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Sample records for 2-hour urokinase regime

  1. Molecular-specific urokinase antibodies

    NASA Technical Reports Server (NTRS)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  2. Development of immunoassays for human urokinase

    NASA Technical Reports Server (NTRS)

    Atassi, M. Zouhair

    1988-01-01

    Radioimmune assays (RIA) and enzyme linked immune assays for measurement of pro-urokinase and the two active forms of the enzyme were developed. Polyclonal and monoclonal antibodies, with desired specificities against preselected synthetic regions of urokinase (UK), were obtained by immunization with the respective synthetic peptides and used to develop RIA for zymogen and the two activated forms of UK.

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

    NASA Technical Reports Server (NTRS)

    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.

  4. Affinity chromatography for purification of two urokinases from human urine.

    PubMed

    Takahashi, R; Akiba, K; Koike, M; Noguchi, T; Ezure, Y

    2000-05-26

    A new affinity chromatography (hydrophobic-mediated affinity chromatography), which was characterized by the matrix having both affinity site to urokinase and hydrophobic site, was established for the purification of urokinase from human urine. The hydrophobic affinity matrix (tentatively named PAS in the text) was prepared by immobilizing 6-aminocaproic acid on Sepharose CL-6B, followed by a coupling p-aminobenzamidine to a part of the hydrophobic site on the matrix. The PAS matrix was applied to the purification of urokinase from human urine, and high- and low-molecular weight pure urokinases were efficiently obtained in high yield by the present method. PMID:10892585

  5. Antibodies Against Three Forms of Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.; Atassi, M. Zouhair

    2007-01-01

    Antibodies that bind to preselected regions of the urokinase molecule have been developed. These antibodies can be used to measure small quantities of each of three molecular forms of urokinase that could be contained in microsamples or conditioned media harvested from cultures of mammalian cells. Previously available antibodies and assay techniques do not yield both clear distinctions among, and measurements of, all three forms. Urokinase is a zymogen that is synthesized in a single-chain form, called ScuPA, which is composed of 411 amino acid residues (see figure). ScuPA has very little enzyme activity, but it can be activated in two ways: (1) by cleavage of the peptide bond lysine 158/isoleucine 159 and the loss of lysine 158 to obtain the high molecular-weight (HMW) form of the enzyme or (2) by cleavage of the bond lysine 135/lysine 136 to obtain the low-molecular-weight (LMW) form of the enzyme. The antibodies in question were produced in mice and rabbits by use of peptides as immunogens. The peptides were selected to obtain antibodies that bind to regions of ScuPA that include the lysine 158/isoleucine 159 and the lysine 135/lysine 136 bonds. The antibodies include monoclonal and polyclonal ones that yield indications as to whether either of these bonds is intact. The polyclonal antibodies include ones that preferentially bind to the HMW or LMW forms of the urokinase molecule. The monoclonal antibodies include ones that discriminate between the ScuPA and the HMW form. A combination of these molecular-specific antibodies will enable simultaneous assays of the ScuPA, HMW, and LMW forms in the same specimen of culture medium.

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

    NASA Technical Reports Server (NTRS)

    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.

  7. Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition

    PubMed Central

    Bernik, Maria B.

    1973-01-01

    Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways—affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis. PMID:4266421

  8. Characterization of a specific anti-human urokinase antibody: Development of a sensitive competition radioimmunoassay for urokinase antigen

    SciTech Connect

    Huber, K.; Kirchheimer, J.; Binder, B.R.

    1984-05-01

    Specific inhibiting IgG antibodies were raised in a rabbit using purified human high molecular weight urokinase as antigen. The antibodies reacted with both high molecular weight and low molecular weight human urokinase using an Ouchterlony double-immunodiffusion technique in such a way that one line of complete identity was obtained. Neither precipitation nor functional inhibition was observed for the tissue-type plasminogen activator. Kinetic studies with plasminogen as a natural high molecular weight substrate or the synthetic low molecular weight p-nitroanilide substrate pyro-Glu-Gly-Arg-pNA revealed, for both substrates, mainly a competitive type of inhibition for the Fab fragments of the specific anti-urokinase antibodies. This characterized anti-urokinase IgG was employed to develop a competitive radioimmunoassay, for human urokinase with /sup 125/I-labeled urokinase as tracer. In this radioimmunoassay, the lower detection limit for urokinase antigen was 10 pg/ml sample; the intrassay variation was 2.8%, and the interassay variation was 5.3%. Applying this radioimmunoassay to plasma samples obtained from healthy young volunteers, urokinase antigen could be measured in a concentration of 7.82 +/- 3.97 ng/ml for mean and 6.66 +/- 2.39 ng/ml for women (mean +/- SD).

  9. Using urokinase to restore patency in double lumen catheters.

    PubMed

    Northsea, C

    1994-08-01

    All hemodialysis patients with temporary or permanent double lumen catheters are at risk for catheter occlusion. Clinical outcomes and cost-effectiveness of using urokinase, a thrombolytic agent, to declot occluded double lumen dialysis catheters were evaluated for 2 years. Patency was restored in 95 of 102 catheters. These data support the use of urokinase to safely and effectively restore patency, thereby extending the length of time a catheter can be used for dialysis.

  10. Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator

    SciTech Connect

    Fibbi, G.; Magnelli, L.; Pucci, M.; Del Rosso, M. )

    1990-03-01

    On the basis of a fibrinolytic assay with {sup 125}I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, the authors have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, they hypothesize that this mechanism may be important in vivo during the process of wound repair.

  11. Urokinase does not prevent abdominal adhesion formation in rats.

    PubMed

    Rivkind, A I; Lieberman, N; Durst, A L

    1985-01-01

    Damage to the fibrinolytic system preventing the resolution of temporary fibrinous adhesions was repeatedly mentioned as an etiological factor in the process of adhesion formation. We experimentally induced abdominal adhesions in rats by gentle scraping of the entire small bowel. Severe adhesions, sometimes accompanied by intestinal obstruction, developed in all of the control animals. Urokinase, a commonly used and potent fibrinolytic agent and a known plasminogen activator, was administered intragastrically, intraperitoneally, or intravenously at various doses ranging from 5,000 to 100,000 U/kg. Urokinase had no effect on the prevention of abdominal adhesions, nor did it reduce the severity or frequency of adhesion formation. PMID:4043158

  12. Fluorescent-Antibody Measurement Of Cancer-Cell Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    1993-01-01

    Combination of laboratory techniques provides measurements of amounts of urokinase in and between normal and cancer cells. Includes use of fluorescent antibodies specific against different forms of urokinase-type plasminogen activator, (uPA), fluorescence microscopy, quantitative analysis of images of sections of tumor tissue, and flow cytometry of different uPA's and deoxyribonucleic acid (DNA) found in suspended-tumor-cell preparations. Measurements provide statistical method for indicating or predicting metastatic potentials of some invasive tumors. Assessments of metastatic potentials based on such measurements used in determining appropriate follow-up procedures after surgical removal of tumors.

  13. Urokinase production by electrophoretically separated cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

    1985-01-01

    Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

  14. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

    PubMed Central

    Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

    1998-01-01

    Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. 
Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. 
Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine. 

 Keywords: urokinase; intestinal epithelium; colon; epithelial proliferation PMID:9824347

  15. Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: colocalization of cell surface urokinase with vinculin

    PubMed Central

    1988-01-01

    Several cell types display binding sites for [125I]urokinase (Vassalli, J.-D., D. Baccino, D. Belin. 1985. J. Cell Biol. 100:86-92) which in certain cases are occupied with endogenous urokinase. These sites appear to focus urokinase at cell surfaces and hence may participate in tissue matrix destruction and cell invasion. Recently Pollanen et al. (1987) demonstrated that the cell surface urokinase of human fibroblasts and fibrosarcoma cells is deposited underneath the cells in strands, apparently at sites of cell-to-substratum contact. Here, using immunofluorescence double labeling, we show that the urokinase strands present on human foreskin fibroblasts are colocalized with strands of vinculin, an intracellular actin-binding protein that is deposited at cell-to-substratum focal adhesion sites. Thus, this indicates linkage of the plasminogen/plasmin system both to sites of cell adhesion and to the cytoskeleton. The urokinase strands on HT 1080 fibrosarcoma cells are more numerous and have shapes that are more tortuous than those on normal fibroblasts. In intact HT 1080 cells, colocalized vinculin strands are obscured by an intense background of soluble vinculin but are apparent on isolated ventral plasma membranes. Certain properties of the urokinase strands suggest that they are related to the [125I]urokinase-binding sites that have been described by several groups: (a) incubating fibroblasts with dexamethasone for 48 h or at pH 3 at 5 degrees C for 10 min greatly decreases the number and intensity of the urokinase strands; (b) strands reappear when glucocorticoid- treated cells are incubated with exogenous 54-kD (but not 35-kD) urokinase, and this process is inhibited by a previously described 16- amino acid peptide that blocks [125I]urokinase binding to the cells. PMID:3129438

  16. Operational Implementation of a 2-Hour Prebreathe Protocol for International Space Station

    NASA Technical Reports Server (NTRS)

    Waligora, James M.; Conkin, J.; Foster, P. P.; Schneider, S.; Loftin, Karin C.; Gernhardt, Michael L.; Vann, R.

    2000-01-01

    Procedures, equipment, and analytical techniques were developed to implement the ground tested 2-hour protocol in-flight operations. The methods are: 1) The flight protocol incorporates additional safety margin over the ground tested protocol. This includes up to 20 min of additional time on enriched O2 during suit purge and pressure check, increased duration of extravehicular activity (EVA) preparation exercise during O2 prebreathing (up to 90 min vs; the tested 24 min), and reduced rates of depressurization. The ground test observations were combined with model projections of the conservative measures (using statistical models from Duke University and NASA JSQ to bound the risk of Type I and Type II decompression sickness (DCS). 2) An inflight exercise device using the in-flight ergometer and elastic tubes for upper body exercise was developed to replicate the dual cycle exercise in the ground trials. 3) A new in-flight breathing system was developed and man-tested. 4) A process to monitor inflight experience with the protocol, including the use of an in-suit Doppler bubble monitor when available, was developed. The results are: 1) The model projections of the conservative factors of the operational protocol were shown to reduce the risk of DCS to levels consistent with the observations of no DCS to date in the shuttle program. 2) Cross over trials of the dual cycle ergometer used in ground tests and the in-flight exercise system verified that02consumption and the % division of work between upper and lower body was not significantly different at the p= 0.05 level. 3) The in-flight breathing system was demonstrated to support work rates generating 75% O2(max) in 95 percentile subjects. 4) An in-flight monitoring plan with acceptance criteria was put in place for the 2-hour prebreathe protocol. And the conclusions are: The 2-hour protocol has been approved for flight, and all implementation efforts are in place to allow use of the protocol as early as flight ISS 7A

  17. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    SciTech Connect

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-03-15

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate.

  18. The role of placental urokinase inhibitor in toxemia of pregnancy.

    PubMed

    Terao, T; Kobayashi, T

    1983-01-01

    The fibrinolysis of the uterus can be reversed during the course of pregnancy. The chief cause of this physiologic change is an increase of urokinase (UK) inhibitor in the placenta. The UK inhibitor also has a pathologic aspect that can influence the course of pregnancy. We have proven that the hypofibrinolysis of toxemic pregnant urine results from increased UK inhibitor. Furthermore, we have shown the existence of UK inhibitor in toxemic pregnant serum and the glomerulus. On the basis of these facts we propose that UK inhibitor leaks into the maternal blood stream from the placenta and inhibits the fibrinolytic activity of UK, forming microthrombuses in the glomerulus. Excess UK inhibitor in the placenta also suppresses the fibrinolytic activity of placental plasminogen activator (PPA). Thus microthrombuses are apt to be formed in both the placenta and glomerulus. Such pathologic inhibition of fibrinolysis strongly influences the course of toxemia. PMID:6360225

  19. Continuous quality improvement: improving hemodialysis catheter patency using urokinase.

    PubMed

    Northsea, C

    1996-12-01

    Opportunities for improvements in patient outcomes through applied continuous quality improvement (CQI) programs are endless and exciting. Improving vascular access outcomes has been a long-standing clinical problem for hemodialysis patients and the nephrology team. During the past few years there has been a dramatic increase in the use of dialysis catheters as permanent accesses for hemodialysis patients. All hemodialysis with dialysis catheters are at risk for catheter occlusion. An innovative, 2-year CQI program was developed, implemented, and designed to improve dialysis catheter patency rates with the use of urokinase. The CQI program resulted in a number of clinical outcomes that were beneficial to the patients and dialysis staff, and were cost-effective to the program.

  20. Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression.

    PubMed Central

    Rao, N K; Shi, G P; Chapman, H A

    1995-01-01

    Binding of urokinase to the glycolipid-anchored urokinase receptor (uPAR) has been implicated in macrophage differentiation. However, no biochemical markers of differentiation have yet been directly linked to uPAR occupancy. As extensive changes in proteolytic profile characterize monocytic differentiation, we have examined the role of uPAR occupancy on protease expression by differentiating phagocytes. Antibodies to either urokinase or to uPAR that prevent receptor binding inhibited induction of cathepsin B in cultured monocytes and both cathepsin B and 92-kD gelatinase mRNA and protein in phorbol diester-stimulated myeloid cells. Mannosamine, an inhibitor of glycolipid anchor assembly, also blocked protease expression. Anti-catalytic urokinase antibodies, excess inactive urokinase, or aprotinin had no effect, indicating that receptor occupancy per se regulated protease expression. Antibodies to the integrins CD11a and CD29 or to the glycolipid-anchored proteins CD14 and CD55 also had no effect. Protease induction was independent of matrix attachment. Antibodies to urokinase or uPAR affected neither the decrease in cathepsin G nor the increase in tumor necrosis factor-alpha in phorbol ester-stimulated cells. These data establish that uPAR is a multifunctional receptor, not only promoting pericellular proteolysis and matrix attachment, but also effecting cysteine- and metallo-protease expression during macrophage differentiation. Images PMID:7615819

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

    PubMed

    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 < 0.05). The expression of huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of semen ejaculate, sperm concentration, and sperm viability. Taken together, our data suggest that huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

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

    PubMed

    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 < 0.05). The expression of huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of semen ejaculate, sperm concentration, and sperm viability. Taken together, our data suggest that huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders. PMID:23960123

  3. The Urine Urokinase Concentration in End Stage Renal Disease with Acquired Renal Cyst

    PubMed Central

    Hong, Sae Yong; Yang, Dong Ho; Lee, Byoung Ho; Ki, Eun Kyong; Chung, Kwang Hoe

    1991-01-01

    To see whether there was any difference in the urine urokinase concentration between acquired cystic kidney disease (ACKD) group and control (non cyst) group in end stage renal disease patients (ESRD), we evaluated fifty ESRD patients who had been maintained on chronic hemodialysis for various period. The urine urokinase concentration was higher in the ACKD group (17.5±14.7 unit/ml, range 13.5–47.0 unit/ml, n=9) than the control group (4.1±3.4 unit/ml, range 0.5–12.0 unit/ml, n=36) (p<0.001), and polycyst group (2.6±1.8 unit/ml, range 1.0–5.1 unit/ml, n=5) (p<0.01). But there was no difference between the control group and polycyst group. In the control group and the ACKD group, there was a direct relation between the dialysis duration and the urokinase concentration and the longer the dialysis duration, the higher the urine urokinase concentration (r squared=0.424, p=0.0001). The hemodialysis duration was longer in the ACKD group (42±17.0 months) than the control group (20.0±12.5 months) (p<0.005). These findings suggest that urokinase may be responsible for cystogenic degeneration in ESRD. PMID:1807367

  4. Application of Molecular Modeling to Urokinase Inhibitors Development

    PubMed Central

    Sulimov, V. B.; Katkova, E. V.; Oferkin, I. V.; Sulimov, A. V.; Romanov, A. N.; Roschin, A. I.; Beloglazova, I. B.; Plekhanova, O. S.; Tkachuk, V. A.; Sadovnichiy, V. A.

    2014-01-01

    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. PMID:24967388

  5. Regime change?

    SciTech Connect

    Pilat, Joseph F.; Budlong-Sylvester, K. W.

    2004-01-01

    Following the 1998 nuclear tests in South Asia and later reinforced by revelations about North Korean and Iraqi nuclear activities, there has been growing concern about increasing proliferation dangers. At the same time, the prospects of radiological/nuclear terrorism are seen to be rising - since 9/11, concern over a proliferation/terrorism nexus has never been higher. In the face of this growing danger, there are urgent calls for stronger measures to strengthen the current international nuclear nonproliferation regime, including recommendations to place civilian processing of weapon-useable material under multinational control. As well, there are calls for entirely new tools, including military options. As proliferation and terrorism concerns grow, the regime is under pressure and there is a temptation to consider fundamental changes to the regime. In this context, this paper will address the following: Do we need to change the regime centered on the Treaty on the Nonproliferation of Nuclear Weapons (NPT) and the International Atomic Energy Agency (IAEA)? What improvements could ensure it will be the foundation for the proliferation resistance and physical protection needed if nuclear power grows? What will make it a viable centerpiece of future nonproliferation and counterterrorism approaches?

  6. Imaging Active Urokinase Plasminogen Activator in Prostate Cancer

    PubMed Central

    LeBeau, Aaron M.; Sevillano, Natalia; Markham, Kate; Winter, Michael B.; Murphy, Stephanie T.; Hostetter, Daniel R.; West, James; Lowman, Henry; Craik, Charles S.; VanBrocklin, Henry F.

    2015-01-01

    The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease expressed by cancer cells and the surrounding tumor microenvironment. Using a human fragment antigen binding phage display library, we identified a human antibody termed U33 that selectively inhibited the active form of the protease urokinase plasminogen activator (uPA, PLAU). In the full-length immunoglobulin form, U33 IgG labeled with near-infrared fluorophores or radionuclides allowed us to non-invasively detect active uPA in prostate cancer xenograft models using optical and single-photon emission computed tomography (SPECT) imaging modalities. U33 IgG labeled with 111In had a remarkable tumor uptake of 43.2% injected dose per gram (%ID/g) 72hr post tail vein injection of the radiolabeled probe in subcutaneous xenografts. Additionally, U33 was able to image active uPA in small soft-tissue and osseous metastatic lesions using a cardiac dissemination prostate cancer model that recapitulated metastatic human cancer. The favorable imaging properties were the direct result of U33 IgG internalization through an uPA receptor mediated mechanism where U33 mimicked the function of the endogenous inhibitor of uPA to gain entry into the cancer cell. Overall, our imaging probe targets a prostate cancer-associated protease, through a unique mechanism, allowing for the non-invasive preclinical imaging of prostate cancer lesions. PMID:25672980

  7. Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency

    PubMed Central

    Chen, Zaixing; Zhao, Runzhen; Zhao, Meimi; Liang, Xinrong; Bhattarai, Deepa; Dhiman, Rohan; Shetty, Sreerama; Idell, Steven

    2014-01-01

    Epithelial sodium channels (ENaC) govern transepithelial salt and fluid homeostasis. ENaC contributes to polarization, apoptosis, epithelial-mesenchymal transformation, etc. Fibrinolytic proteases play a crucial role in virtually all of these processes and are elaborated by the airway epithelium. We hypothesized that urokinase-like plasminogen activator (uPA) regulates ENaC function in airway epithelial cells and tested that possibility in primary murine tracheal epithelial cells (MTE). Both basal and cAMP-activated Na+ flow through ENaC were significantly reduced in monolayers of uPA-deficient cells. The reduction in ENaC activity was further confirmed in basolateral membrane-permeabilized cells. A decrease in the Na+-K+-ATPase activity in the basolateral membrane could contribute to the attenuation of ENaC function in intact monolayer cells. Dysfunctional fluid resolution was seen in uPA-disrupted cells. Administration of uPA and plasmin partially restores ENaC activity and fluid reabsorption by MTEs. ERK1/2, but not Akt, phosphorylation was observed in the cells and lungs of uPA-deficient mice. On the other hand, cleavage of γ ENaC is significantly depressed in the lungs of uPA knockout mice vs. those of wild-type controls. Expression of caspase 8, however, did not differ between wild-type and uPA−/− mice. In addition, uPA deficiency did not alter transepithelial resistance. Taken together, the mechanisms for the regulation of ENaC by uPA in MTEs include augmentation of Na+-K+-ATPase, proteolysis, and restriction of ERK1/2 phosphorylation. We demonstrate for the first time that ENaC may serve as a downstream signaling target by which uPA controls the biophysical profiles of airway fluid and epithelial function. PMID:25172911

  8. Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

    PubMed Central

    Panigada, Mauro; Zacchetti, Lucia; L’Acqua, Camilla; Cressoni, Massimo; Anzoletti, Massimo Boscolo; Bader, Rossella; Protti, Alessandro; Consonni, Dario; D’Angelo, Armando; Gattinoni, Luciano

    2015-01-01

    Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. Methods This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6–13) vs 5 (4–7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93–0.98, p = 0.003). Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality. PMID:26308340

  9. Neuroprotection by urokinase plasminogen activator in the hippocampus.

    PubMed

    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.

  10. Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes.

    PubMed

    Guess, Nicola; Perreault, Leigh; Kerege, Anna; Strauss, Allison; Bergman, Bryan C

    2016-01-01

    Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (β = 0.303, P = 0.018) and 2-hour plasma glucose (β = 0.415, P<0.001), and negatively related to % suppression of hepatic glucose production (β = -0.245, P = 0.049), clamp Rd (β = -0.256, P = 0.001) and NOGD (β = -0.257, P = 0.001). The %kcal from trans fat was also negatively related to clamp Rd (β = -0.209, P = 0.008) and NOGD (β = -0.210, P = 0.008). In contrast, the %kcal from polyunsaturated fat (PUFA) was negatively associated with 2-hour glucose levels (β = -0.383, P = 0.001), and positively related to Rd (β = 0.253, P = 0.007) and NOGD (β = 0.246, P = 0.008). Dietary advice to prevent diabetes should consider the underlying pathophysiology of the prediabetic state.

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

    PubMed

    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 < 0.001), weight (p < 0.001), body volume (BV; p < 0.001), and body density (Db; p < 0.001). Among men, body mass (p < 0.001), body fat percentage (%BF; p < 0.001), and BV (p < 0.001) decreased, whereas Db (p < 0.001) and body temperature (p < 0.001) increased directly after exercise; body mass (p < 0.001) and BV (p < 0.001) remained lower after 2 hours. Among women, body mass (p < 0.001) and BV (p < 0.001) decreased, whereas thoracic gas volume (p = 0.014) and temperature (p < 0.001) increased directly after exercise; body mass (p < 0.001) and BV (p < 0.001) remained lower, whereas %BF (p < 0.001) and Db (p = 0.006) remained higher 2 hours after exercise. These results suggest that a single bout of exercise immediately before Bod Pod testing seems to alter the estimate of %BF, and continues to affect the prediction 2 hours after exercise in women.

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

    PubMed

    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 < 0.001), weight (p < 0.001), body volume (BV; p < 0.001), and body density (Db; p < 0.001). Among men, body mass (p < 0.001), body fat percentage (%BF; p < 0.001), and BV (p < 0.001) decreased, whereas Db (p < 0.001) and body temperature (p < 0.001) increased directly after exercise; body mass (p < 0.001) and BV (p < 0.001) remained lower after 2 hours. Among women, body mass (p < 0.001) and BV (p < 0.001) decreased, whereas thoracic gas volume (p = 0.014) and temperature (p < 0.001) increased directly after exercise; body mass (p < 0.001) and BV (p < 0.001) remained lower, whereas %BF (p < 0.001) and Db (p = 0.006) remained higher 2 hours after exercise. These results suggest that a single bout of exercise immediately before Bod Pod testing seems to alter the estimate of %BF, and continues to affect the prediction 2 hours after exercise in women. PMID:25756324

  13. Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes.

    PubMed

    Guess, Nicola; Perreault, Leigh; Kerege, Anna; Strauss, Allison; Bergman, Bryan C

    2016-01-01

    Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (β = 0.303, P = 0.018) and 2-hour plasma glucose (β = 0.415, P<0.001), and negatively related to % suppression of hepatic glucose production (β = -0.245, P = 0.049), clamp Rd (β = -0.256, P = 0.001) and NOGD (β = -0.257, P = 0.001). The %kcal from trans fat was also negatively related to clamp Rd (β = -0.209, P = 0.008) and NOGD (β = -0.210, P = 0.008). In contrast, the %kcal from polyunsaturated fat (PUFA) was negatively associated with 2-hour glucose levels (β = -0.383, P = 0.001), and positively related to Rd (β = 0.253, P = 0.007) and NOGD (β = 0.246, P = 0.008). Dietary advice to prevent diabetes should consider the underlying pathophysiology of the prediabetic state. PMID:26999667

  14. Increased migration of murine keratinocytes under hypoxia is mediated by induction of urokinase plasminogen activator.

    PubMed

    Daniel, Richard J; Groves, Richard W

    2002-12-01

    One of the key consequences of cutaneous wounding is the development of tissue hypoxia. Recent data have suggested that this is a potent stimulus for increased keratinocyte migration and hence re-epithelialization, although the mechanisms responsible for this remain unclear. In this study we have investigated the relationship between hypoxia, plasminogen activation, and in vitro wound healing. Exposure of keratinocyte cultures to hypoxia resulted in upregulation of urokinase plasminogen activator mRNA and a subsequent increase in urokinase plasminogen activator-mediated plasminogen activation, as determined by indirect chromogenic peptide assay and plasminogen-linked zymography. Analysis of keratinocyte wound healing in vitro confirmed enhanced wound closure in hypoxic cultures compared with normoxic cultures after 16 h. Pretreatment of normoxic and hypoxic cultures with mitomycin C and cytochalasin B indicated that in this system wound closure was due to keratinocyte migration rather than proliferation. Addition of the broad-spectrum serine proteinase inhibitor, p-aminobenzamidine, or the specific urokinase plasminogen activator inhibitors, amiloride and WX-293, significantly reduced wound closure in hypoxic cultures and abrogated the hypoxic enhancement of wound closure. These data indicate a central role for urokinase plasminogen activators in hypoxic keratinocyte migration and suggest a potential mechanism for enhanced re-epithelialization of wounds under low oxygen tensions. PMID:12485432

  15. Urokinase can reduce heparin dose in patients with hypercoagulable states during hemodialysis.

    PubMed

    Ren, Wanjun; Wei, Fang; Sha, Yabin; Wang, Qi; Xie, Lin

    2015-05-01

    Heparin is routinely administered at high doses during hemodialysis to patients with hypercoagulable states. This study aimed to evaluate the safety and efficacy of low-dose heparin in combination with urokinase in this patient population. The presence of a hypercoagulable state was confirmed by thromboelastography. Doses of heparin and urokinase were adjusted based on activated partial thromboplastin time (APTT). Clotting in the extracorporeal circuit was evaluated by a semi-quantitative index. Prothrombin time (PT) and APTT were measured before, during and after dialysis. Kt/V(urea) was used to assess the efficacy of dialysis. D-dimer levels were measured 2 h after the start of hemodialysis. Hemodialysis data with heparin administered alone prior to dialysis were used as control in the present study. With urokinase treatment, the initial dose of heparin was reduced by 45.0 ± 11.4% during hemodialysis and the maintenance dose by 46.8 ± 12.8% compared with heparin alone. No side effects due to urokinase were observed. Bleeding events were rare. Post-dialysis PT (12.99 ± 1.41 vs. 15.22 ± 3.12 s, p = 0.02) and APTT (97.75 ± 43.62 vs. 140.16 ± 30.12 s, p = 0.002) with urokinase plus heparin were significantly shorter than with heparin alone. Finally, during dialysis, D-dimer levels were significantly higher with heparin alone (0.21 ± 0.11 mg/L) than with heparin and urokinase (0.169 ± 0.122 mg/L, p = 0.017). In conclusion, urokinase significantly reduced the dose of heparin required during hemodialysis without any side effects in patients with hypercoagulable states during hemodialysis.

  16. Design of a 2-Hour Prebreathe Protocol for Space Walks (EVAs) from the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    Gernhardt, M. L.; Conkin, J.; Foster, P. P.; Pilmanis, A. A.; Butler, B. D.; Fife, C.; Vann, R. D.; Gerth, W. A.; Loftin, K. C.; Dervay, J.; Waligora, J. M.; Powell, M. R.; Homick, Jerry L. (Technical Monitor)

    2000-01-01

    The majority of extravehicular activities (EVAs) performed from the shuttle use a 10.2 psi staged decompression. The International Space Station (ISS) will operate at 14.7 psi, requiring crews to "campout" in the airlock at 10.2 psi. The constraints associated with campout (crew isolation, oxygen usage, and waste management), provided the rationale to develop a 2-hour prebreathe protocol from 14.7 psi. Previous studies on the affect of microgravity and exercise during prebreathe suggested the feasibility of this approach. Various combinations of adynamia (nonwalking subjects), prebreathe exercise doses, and space suit donning options (10.2 vs. 14.7 psi) were analyzed against timeline and consumable constraints. Prospective decompression sickness (DCS) and venous gas emboli (VGE) accept/reject criteria were defined from statistical 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 (including Grade IV VGE criteria) based on analysis of related medical factors. Monte-Carlo simulation was performed to design a closed sequential, multi-center laboratory trial, including the capability of rejecting the primary protocol and testing at least one alternate exercise dose, within the 2-hour prebreathe. The 2-hour protocol incorporates 0, breathing for 5 0 min at 14.7 psi, including 10 min dual cycle ergometry at 75%VO(2max). It requires an additional 30 minO2breathing during depress from 14.7 to 10.2 psi, followed by a 30-60 min suit donning break at 10.2 psi/26.5% O2. It concludes with a 40 min in-suit O2 prebreathe. The protocol would be accepted for operations, if the incidence of DCS was less than 15% and Grade IV VGE less than 20%, both at 95

  17. Inhibitors of urokinase reduce size of prostate cancer xenografts in severe combined immunodeficient mice.

    PubMed

    Jankun, J; Keck, R W; Skrzypczak-Jankun, E; Swiercz, R

    1997-02-15

    Proteolytic enzymes are required to mediate tumor cell invasion and metastasis. The urokinase plasminogen activator (uPA) is commonly overexpressed by many human cancers. Therefore, uPA is a logical target to inhibit cancer invasion and metastasis. However, uPA inhibitors also reduce tumor growth. We used a mutated form of plasminogen activator inhibitor type 1 to conform a correlation between the inactivation of uPA and tumor size; we have compared these results with the action of p-aminobenzamidine and amiloride, known inhibitors of uPA. Our results show that blocking uPA by uPA inhibitors reduces tumor size in experimental animals. Our molecular simulation of docking inhibitors to the urokinase reveals that all tested small molecule inhibitors bind in proximity of uPA's specificity pocket, a critical site for future search of novel anticancer uPA inhibitors. PMID:9044824

  18. Proteolytic regulation of epithelial sodium channels by urokinase plasminogen activator: cutting edge and cleavage sites.

    PubMed

    Ji, Hong-Long; Zhao, Runzhen; Komissarov, Andrey A; Chang, Yongchang; Liu, Yongfeng; Matthay, Michael A

    2015-02-27

    Plasminogen activator inhibitor 1 (PAI-1) level is extremely elevated in the edematous fluid of acutely injured lungs and pleurae. Elevated PAI-1 specifically inactivates pulmonary urokinase-type (uPA) and tissue-type plasminogen activators (tPA). We hypothesized that plasminogen activation and fibrinolysis may alter epithelial sodium channel (ENaC) activity, a key player in clearing edematous fluid. Two-chain urokinase (tcuPA) has been found to strongly stimulate heterologous human αβγ ENaC activity in a dose- and time-dependent manner. This activity of tcuPA was completely ablated by PAI-1. Furthermore, a mutation (S195A) of the active site of the enzyme also prevented ENaC activation. By comparison, three truncation mutants of the amino-terminal fragment of tcuPA still activated ENaC. uPA enzymatic activity was positively correlated with ENaC current amplitude prior to reaching the maximal level. In sharp contrast to uPA, neither single-chain tPA nor derivatives, including two-chain tPA and tenecteplase, affected ENaC activity. Furthermore, γ but not α subunit of ENaC was proteolytically cleaved at ((177)GR↓KR(180)) by tcuPA. In summary, the underlying mechanisms of urokinase-mediated activation of ENaC include release of self-inhibition, proteolysis of γ ENaC, incremental increase in opening rate, and activation of closed (electrically "silent") channels. This study for the first time demonstrates multifaceted mechanisms for uPA-mediated up-regulation of ENaC, which form the cellular and molecular rationale for the beneficial effects of urokinase in mitigating mortal pulmonary edema and pleural effusions.

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

    NASA Technical Reports Server (NTRS)

    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.; Paloski, William H. (Technical Monitor)

    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%.

  20. Binocular Rivalry Measured 2 Hours After Occlusion Therapy Predicts the Recovery Rate of the Amblyopic Eye in Anisometropic Children

    PubMed Central

    Lunghi, Claudia; Morrone, Maria Concetta; Secci, Jacopo; Caputo, Roberto

    2016-01-01

    Purpose Recent studies on adults have shown that short-term monocular deprivation boosts the deprived eye signal in binocular rivalry, reflecting homeostatic plasticity. Here we investigate whether homeostatic plasticity is present also during occlusion therapy for moderate amblyopia. Methods Binocular rivalry and visual acuity (using Snellen charts for children) were measured in 10 children (mean age 6.2 ± 1 years) with moderate anisometropic amblyopia before the beginning of treatment and at four intervals during occlusion therapy (2 hours, 1, 2, and 5 months). Visual stimuli were orthogonal gratings presented dichoptically through ferromagnetic goggles and children reported verbally visual rivalrous perception. Bangerter filters were applied on the spectacle lens over the best eye for occlusion therapy. Results Two hours of occlusion therapy increased the nonamblyopic eye predominance over the amblyopic eye compared with pretreatment measurements, consistent with the results in adults. The boost of the nonamblyopic eye was still present after 1 month of treatment, steadily decreasing afterward to reach pretreatment levels after 2 months of continuous occlusion. Across subjects, the increase in nonamblyopic eye predominance observed after 2 hours of occlusion correlated (rho = −0.65, P = 0.04) with the visual acuity improvement of the amblyopic eye measured after 2 months of treatment. Conclusions Homeostatic plasticity operates during occlusion therapy for moderate amblyopia and the increase in nonamblyopic eye dominance observed at the beginning of treatment correlates with the amblyopic eye recovery rate. These results suggest that binocular rivalry might be used to monitor visual cortical plasticity during occlusion therapy, although further investigations on larger clinical populations are needed to validate the predictive power of the technique. PMID:27046118

  1. Structural Basis of Interaction Between Urokinase-type Plasminogen Activator and its Receptor

    SciTech Connect

    Barinka,C.; Parry, G.; Callahan, J.; Shaw, D.; Kuo, A.; Cines, B.; Mazar, A.; Lubkowski, J.

    2006-01-01

    Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 {angstrom}. We report the 1.9 {angstrom} crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.

  2. Tirofiban combined with urokinase selective intra-arterial thrombolysis for the treatment of middle cerebral artery occlusion

    PubMed Central

    FENG, LEI; LIU, JUN; LIU, YUNZHEN; CHEN, JIAN; SU, CHUNHAI; LV, CHUANFENG; WEI, YUZHEN

    2016-01-01

    The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group). The recanalization rate, relative-apparent diffusion coefficient (rADC) and neurological function deficit score (NFDS) values were compared among the four groups. The recanalization rate, rADC and NFDS values were improved in the T + UK group compared with the other groups. In summary, the intra-arterial administration of tirofiban combined with urokinase thrombolysis was a more effective intervention in an MCAO model compared with intra-arterial urokinase alone, and may promote reperfusion and reduce infarct volume. PMID:26998029

  3. Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro

    PubMed Central

    Wilson, A; Gibson, P

    2000-01-01

    BACKGROUND—Migration of colonic epithelial cells is important for mucosal repair following injury. The urokinase (u-PA) system regulates migration in other cell types.
AIM—To examine the role of u-PA and its receptor (u-PAR) in colonic epithelial cell migration.
METHODS—Migration was assessed over 24 hours in circular wounds made in confluent monolayers of LIM1215 and Caco-2 human colon cancer cells. The function of u-PA and u-PAR was ablated with antisense oligonucleotides to block expression, with synthetic u-PA peptides to block interaction, and with aprotinin to block u-PA mediated proteolysis.
RESULTS—Migration was stimulated two to threefold by exogenous u-PA, an effect dependent on u-PAR binding but independent of u-PA mediated mitogenesis and proteolysis. Expression of u-PA and u-PAR was inhibited by 80% by the appropriate antisense oligonucleotide. Basal migration and the motogenic effects of butyrate, epidermal growth factor, and phorbol-12-myristate-13-acetate were suppressed by the u-PAR antisense oligonucleotide (40-60%) but were at best minimally affected following inhibition of u-PA expression and binding. 
CONCLUSIONS—In an in vitro model of wounded colonic epithelium, u-PAR promotes cell migration through mechanisms that are not exclusively dependent on u-PA binding. Therefore, u-PA and u-PAR may contribute to colonic mucosal repair in vivo.


Keywords: colon; migration; urokinase; urokinase receptor; epidermal growth factor; butyrate; protein kinase C PMID:10861271

  4. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    PubMed Central

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained.

  5. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration.

    PubMed

    Karnchanasorn, Rudruidee; Huang, Jean; Ou, Horng-Yih; Feng, Wei; Chuang, Lee-Ming; Chiu, Ken C; Samoa, Raynald

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m(2), P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  6. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    PubMed Central

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  7. Urokinase-like plasminogen activator receptor expression on disseminated breast cancer cells.

    PubMed

    Tögel, F; Datta, C; Badbaran, A; Kröger, N; Renges, H; Gieseking, F; Jänicke, F; Zander, A R; Krüger, W

    2001-02-01

    Disseminated tumor cells are detected frequently in bone marrow, peripheral blood, and cytokine-mobilized peripheral blood cell products of women undergoing high-dose therapy for breast cancer. Several attempts were made to purge autografts from contaminating cancer cells; however, the biological and clinical impact of these contaminations has not been clarified so far. Expression of distinct phenotypes is a surrogate marker for metastatic behavior of cancer cells. The expression of the urokinase-like plasminogen activator receptor seems to be a factor of high importance. It is not expressed by normal mammary tissue. Disseminated cancer cells from marrow, blood, and stem cell products have been investigated by double-stain technique for urokinase-like plasminogen activator receptor (uPA-R) expressing cytokeratin-positive cells. uPA-R(+)/CK(+) cells could be found in all qualities of samples; however, significantly less in G-CSF-mobilized peripheral blood stem cells compared to samples of other provenance (p = 0.02). It can be concluded that epithelial cells of malignant phenotype occur in blood, marrow, and autografts of breast cancer patients. Populations of disseminated tumor cells are phenotypically heterogeneous. Reduced uPA-R expression on cancer cells from leukapheresis samples might suggest a less aggressive nature of these cells compared to disseminated cells found in bone marrow. Furthermore, the data suggest that the phenotype of tumor cell contamination in leukapheresis products differs significantly from those of disseminated cancer cells in bone marrow or blood.

  8. A Randomized Clinical Trial of an Intensive Behavior Education Program in Gestational Diabetes Mellitus Women Designed to Improve Glucose Levels on the 2-Hour Oral Glucose Tolerance Test.

    PubMed

    Durnwald, Celeste P; Kallan, Michael J; Allison, Kelly C; Sammel, Mary D; Wisch, Susan; Elovitz, Michal; Parry, Samuel

    2016-10-01

    Objective To evaluate whether women with gestational diabetes mellitus (GDM) enrolled in an intensive behavior education program (IBEP) demonstrate lower mean fasting glucose levels on the 2-hour 75 g oral glucose tolerance test (2-hour OGTT) at 6 to 12 weeks postpartum compared with women who undergo routine GDM management. Study Design A prospective randomized controlled trial of women diagnosed with GDM was conducted. Exclusion criteria were GDM diagnosis ≥ 33 weeks or < 20 weeks. Women were randomly assigned to one of two treatment arms: (1) routine GDM management or (2) an IBEP. Women underwent a 2-hour OGTT at 6 to 12 weeks postpartum. Fisher exact test, t-test, and Wilcoxon rank sum test were used as appropriate. Results Of the 101 women randomized, 49 were assigned to IBEP and 52 received routine GDM management. There was no difference in mean fasting and 2-hour glucose levels on the postpartum 2-hour OGTT between the IBEP and routine management group (88.5 ± 22.9 mg/dL vs. 85.2 ± 13.3 mg/dL, p = 0.49 and 109.8 ± 38.5 mg/dL vs. 109.4 ± 40.8 mg/dL, p = 0.97, respectively). Conclusion GDM women enrolled in a healthy lifestyle intervention program did not demonstrate lower glucose values on the postpartum 2-hour OGTT.

  9. Dual functionality of phosphonic-acid-appended phthalocyanines: inhibitors of urokinase plasminogen activator and anticancer photodynamic agents.

    PubMed

    Venkatramaiah, N; Pereira, Patrícia M R; Almeida Paz, Filipe A; Ribeiro, Carlos A F; Fernandes, Rosa; Tomé, João P C

    2015-11-01

    Phthalocyanines (Pcs) bearing phosphonic acid groups at the periphery exhibit a potential photodynamic effect to induce phototoxicity on human bladder cancer epithelial cells (UM-UC-3). In vitro photophysical and biological studies show high intrinsic ability to inhibit the activity of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9).

  10. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    SciTech Connect

    Murphy, Kenneth D.; McCrohan, Gerard; DeMarta, Deborah A.; Shirodkar, Nitin B.; Kwon, Oun J.; Chopra, Paramjit S.

    1996-03-15

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.

  11. Crystal structure of the urokinase receptor in a ligand-free form.

    PubMed

    Xu, Xiang; Gårdsvoll, Henrik; Yuan, Cai; Lin, Lin; Ploug, Michael; Huang, Mingdong

    2012-03-01

    The urokinase receptor urokinase-type plasminogen activator receptor (uPAR) is a surface receptor capable of not only focalizing urokinase-type plasminogen activator (uPA)-mediated fibrinolysis to the pericellular micro-environment but also promoting cell migration and chemotaxis. Consistent with this multifunctional role, uPAR binds several extracellular ligands, including uPA and vitronectin. Structural studies suggest that uPAR possesses structural flexibility. It is, however, not clear whether this flexibility is an inherent property of the uPAR structure per se or whether it is induced upon ligand binding. The crystal structure of human uPAR in its ligand-free state would clarify this issue, but such information remains unfortunately elusive. We now report the crystal structures of a stabilized, human uPAR (H47C/N259C) in its ligand-free form to 2.4 Å and in complex with amino-terminal fragment (ATF) to 3.2 Å. The structure of uPAR(H47C/N259C) in complex with ATF resembles the wild-type uPAR·ATF complex, demonstrating that these mutations do not perturb the uPA binding properties of uPAR. The present structure of uPAR(H47C/N259C) provides the first structural definition of uPAR in its ligand-free form, which represents one of the biologically active conformations of uPAR as defined by extensive biochemical studies. The domain boundary between uPAR DI-DII domains is more flexible than the DII-DIII domain boundary. Two important structural features are highlighted by the present uPAR structure. First, the DI-DIII domain boundary may face the cell membrane. Second, loop 130-140 of uPAR plays a dynamic role during ligand loading/unloading. Together, these studies provide new insights into uPAR structure-function relationships, emphasizing the importance of the inter-domain dynamics of this modular receptor. PMID:22285761

  12. Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor.

    PubMed

    Trimarchi, Hernán

    2013-11-01

    Primary focal and segmental glomerulosclerosis (FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.

  13. Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect.

    PubMed Central

    Resnati, M; Guttinger, M; Valcamonica, S; Sidenius, N; Blasi, F; Fazioli, F

    1996-01-01

    Physiological concentrations of urokinase plasminogen activator (uPA) stimulated a chemotactic response in human monocytic THP-1 through binding to the urokinase receptor (uPAR). The effect did not require the protease moiety of uPA, as stimulation was achieved also with the N-terminal fragment (ATF), while the 33 kDa low molecular weight uPA was ineffective. Co-immunoprecipitation experiments showed association of uPAR with intracellular kinase(s), as demonstrated by in vitro kinase assays. Use of specific antibodies identified p56/p59hck as a kinase associated with uPAR in THP-1 cell extracts. Upon addition of ATF, p56/p59hck activity was stimulated within 2 min and returned to normal after 30 min. Since uPAR lacks an intracellular domain capable of interacting with intracellular kinase, activation of p56/p59hck must require a transmembrane adaptor. Evidence for this was strongly supported by the finding that a soluble form of uPAR (suPAR) was capable of inducing chemotaxis not only in THP-1 cells but also in cells lacking endogenous uPAR (IC50, 5 pM). However, activity of suPAR require chymotrypsin cleavage between the N-terminal domain D1 and D2 + D3. Chymotrypsin-cleaved suPAR also induced activation of p56/p59hck in THP-1 cells, with a time course comparable with ATF. Our data show that uPA-induced signal transduction takes place via uPAR, involves activation of intracellular tyrosine kinase(s) and requires an as yet undefined adaptor capable of connecting the extracellular ligand binding uPAR to intracellular transducer(s). Images PMID:8612581

  14. Ligand Binding Alters Dimerization and Sequestering of Urokinase Receptors in Raft-Mimicking Lipid Mixtures

    PubMed Central

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

    2014-01-01

    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. PMID:25418095

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

    PubMed

    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.

  16. Urokinase-Type Plasminogen Activator Promotes Dendritic Spine Recovery and Improves Neurological Outcome Following Ischemic Stroke

    PubMed Central

    Wu, Fang; Catano, Marcela; Echeverry, Ramiro; Torre, Enrique; Haile, Woldeab B.; An, Jie; Chen, Changhua; Cheng, Lihong; Nicholson, Andrew; Tong, Frank C.; Park, Jaekeun

    2014-01-01

    Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic stroke in vivo or hypoxia in vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA−/−) or uPAR (uPAR−/−) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA−/− but not in uPAR−/− mice. Diffusion tensor imaging studies indicate that uPA−/− mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS. PMID:25339736

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

    PubMed

    Beaufort, Nathalie; Seweryn, Paulina; de Bentzmann, Sophie; Tang, Aihua; Kellermann, Josef; Grebenchtchikov, Nicolai; Schmitt, Manfred; Sommerhoff, Christian P; Pidard, Dominique; Magdolen, Viktor

    2010-06-15

    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 bacterial proteases might contribute to the activation of this major extracellular proteolytic system, thereby participating in bacterial dissemination. We report that LasB, a thermolysin-like metalloprotease secreted by Ps. aeruginosa, converts the human uPA zymogen into its active form (kcat=4.9 s-1, Km=8.9 microM). Accordingly, whereas the extracellular secretome from the LasB-expressing pseudomonal strain PAO1 efficiently activates pro-uPA, the secretome from the isogenic LasB-deficient strain PDO240 is markedly less potent in pro-uPA activation. Still, both secretomes induce some metalloprotease-independent activation of the human zymogen. The latter involves a serine protease, which we identified via both recombinant protein expression in Escherichia coli and purification from pseudomonal cultures as protease IV (PIV; kcat=0.73 s-1, Km=6.2 microM). In contrast, neither secretomes nor the pure proteases activate Plg. Along with this, LasB converts Plg into mini-Plg and angiostatin, whereas, as reported previously, it processes the uPA receptor, inactivates the plasminogen activator inhibitor 1, and activates pro-matrix metalloproteinase 2. PIV does not target these factors at all. To conclude, LasB and PIV, although belonging to different protease families and displaying quite different substrate specificities, both activate the urokinase-type precursor of the Plg activation cascade. Direct pro-uPA activation, as also reported for other bacterial proteases, might be a frequent phenomenon that contributes to bacterial virulence.

  18. Recovery of urokinase from integrated mammalian cell culture cryogel bioreactor and purification of the enzyme using p-aminobenzamidine affinity chromatography.

    PubMed

    Bansal, Vibha; Roychoudhury, Pradip K; Mattiasson, Bo; Kumar, Ashok

    2006-01-01

    An integrated product recovery system was developed to separate urokinase from the cell culture broth of human kidney cells HT1080. Supermacroporous monolithic cryogels provided ideal matrices with respect to surface and flow properties for use as cell culture scaffold as well as for affinity chromatographic capture step of the enzyme in the integrated system. The urokinase was produced continuously in the reactor running for 4 weeks with continuous circulation of 500 ml of culture medium. The enzyme activity in the culture medium reached to 280 Plough units (PU)/mg protein. Cu(II)-iminodiacetic acid (IDA)-polyacrylamide (pAAm) cryogel column was used to capture urokinase by integrating with the gelatin-coupled pAAm-cryogel bioreactor for HT1080 cell culture. After removing the urokinase capture column from the integrated system the bound protein was eluted. The metal affinity capture step gave 4.5-fold purification of the enzyme thus achieving a specific activity of 1300 PU/mg protein. The enzyme eluate from Cu(II)-IDA-pAAm cryogel capture column was further purified on benzamidine-Sepharose affinity column. This step finally led to a homogeneous preparation of different forms of urokinase in two different elution peaks with a best urokinase activity of 13 550 PU/mg of protein. As compared to initial activity in the cell culture broth, about 26.2- and 48.4-fold increase in specific activity was achieved with enzyme yields corresponding to 32% and 35% in two different peak fractions, respectively. Native electrophoresis and SDS-PAGE showed multiple protein bands corresponding to different forms of the urokinase, which were confirmed by Western blotting and zymography. PMID:16761300

  19. Percutaneous treatment of intrabdominal abscess: urokinase versus saline serum in 100 cases using two surgical scoring systems in a randomized trial.

    PubMed

    Laborda, A; De Gregorio, M A; Miguelena, J M; Medrano, J; Gómez-Arrue, J; Serrano, C; de Blas, I; Gimenez, M; D'Agostino, H

    2009-07-01

    The purpose of this study was to assess whether regular instillation of urokinase during abscess drainage leads to an improved outcome compared to saline irrigation alone. One hundred patients referred for image-guided abdominal abscess drainage were randomized between thrice daily urokinase instillation or saline irrigation alone. At the end of the study, patient medical records were reviewed to determine drainage, study group, Altona (PIA II) and Mannheim (MPI) scoring, duration of drainage, procedure-related complications, hospital stay duration, and clinical outcome. The technical success rate of the percutaneous abscess drainage was 100%. The success or failure of abscess remission did not differ significantly between groups (success rate of 91.5% in the urokinase group vs. 88.8% in the saline group; failure rate was of 8.5 vs. 21.2%, respectively); however, days of drainage, main hospital stay, and overall costs were significantly reduced in patients treated with urokinase compared to the control group (P < 0.05). No adverse effects from urokinase were observed. Surgical scores were a useful homogeneity factor, and MPI showed a good correlation with prognosis, while PIA results did not have a significant correlation. For drainage of complex abscesses (loculations, hemorrhage, viscous material), fibrinolytics safely accelerate drainage and recovery, reducing the length of the hospital stay and, therefore, the total cost. PMID:19190912

  20. Ultrastructural localization of plasma membrane-associated urokinase- type plasminogen activator at focal contacts

    PubMed Central

    1988-01-01

    We have recently shown that urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 are both found extracellularly beneath cultured human skin fibroblasts and HT-1080 sarcoma cells, but in distinct localizations. Here, the ultrastructural distribution of u-PA was studied using immunoferritin electron microscopy. In HT-1080 cells, u-PA on the extracellular aspect of the plasma membrane was detected at sites of direct contact of the cell with the growth substratum beneath all parts of the ventral cell surface. The ferritin-labeled adhesion plaques, which were enriched in submembraneous microfilaments, were frequently seen at the leading lamellae of the cells as well as in lamellipodia and microspikes. Besides the cell-substratum adhesion plaques, ferritin label was detected at cell-cell contact sites. Double-label immunofluorescence showed a striking colocalization of u-PA and vinculin in both HT-1080 cells and WI-38 lung fibroblasts, which is consistent with u-PA being a focal contact component. The u-PA-containing focal contacts of WI-38 cells had no direct codistribution with fibronectin fibrils. In WI-38 cells made stationary by cultivation in a medium containing 0.5% FCS, vinculin plaques became highly elongated and more centrally located, whereas u-PA immunolabel disappeared from such focal adhesions. These findings show that plasma membrane-associated u-PA is an intrinsic component of focal contacts, where, we propose, it enables directional proteolysis for cell migration and invasion. PMID:3123496

  1. [Preparation of novel magnetic dextran affinity adsorbents and their application to purify urokinase].

    PubMed

    Dong, Y S; Liang, F; Yu, X Y; Guo, L A; Chang, J H

    2001-01-01

    The reverse phase suspension and embedment technique were adopted to prepare magnetic dextran microsphere (MDMS). The dispersion medium was mixture of some organic solvents. Span-80 was used as stabilizer. The aqueous dextran with magnetic fluid was suspended in dispersion medium with epichlorohydrin as cross-linking reagent. The mixture was stirred for 30 minutes at room temperature and then heated at 70 degrees C for 4 hours, MDMS was thus obtained. MDMS was activated by epichlorohydrin on which 6-aminohexanoic acid, glycine or ethylene diamine was bonded as spacers. Then it was coupled with p-aminobenzamide, L-arginine methyl ester or guanidohexanoic acid and five magnetic affinity adsorbents were prepared. The MDMS was polydisperse particles with the size of 50-300 meshes and the content of Fe3O4 was about 6.2 per cent in the MDMS. Influence of some parameters such as viscosity and density of organic phase, the volume ratio of organic and aqueous phase, the quantity of surfactant and stirring speed on preparing MDMS was studied. Magnetic affinity adsorbents were used to purify crude urokinase in a bath mode and the effect of coupling reagents and ligands on results of purification was discussed. The bioactivity recovery was 40.0 to 60.7 per cent, the purification-fold was between 14.9 and 32.8, and the adsorptive capacity varies from 89 mg to 121 mg per milliliter of adsorbent. PMID:12541840

  2. Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes

    PubMed Central

    Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D’Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C.; Rastaldi, Maria Pia; Saleem, Moin A.; Mavilio, Domenico; Mikulak, Joanna

    2015-01-01

    Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms’ tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur−/− mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. PMID:26380915

  3. Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes.

    PubMed

    Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D'Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C; Rastaldi, Maria Pia; Saleem, Moin A; Mavilio, Domenico; Mikulak, Joanna

    2015-09-18

    Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur(-/-) mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR.

  4. Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours.

    PubMed Central

    Foucré, D.; Bouchet, C.; Hacène, K.; Pourreau-Schneider, N.; Gentile, A.; Martin, P. M.; Desplaces, A.; Oglobine, J.

    1991-01-01

    The concentrations of cathepsin D (Cath D), urokinase (uPA) and two plasminogen activator inhibitors (PAI-1 and PAI-2) were analysed in the cytosols of 130 human mammary tumours (43 benign tumours and 87 primary and unilateral breast carcinomas). uPA, PAI-1 and PAI-2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay. The median levels of the four parameters were significantly higher in the malignant tumours than in the benign ones. Cath D and uPA increases were 4-fold and 5-fold respectively. PAI-1 and PAI-2 increases were much more important, 74-fold and 29-fold respectively. In malignant tumours, median levels of Cath D and uPA did not vary according to classical prognostic factors (histologic grade, presence or absence of axillary lymph nodes, steroid receptors, UICC stage, tumour size, age, and menopausal status). However, PAI-1 decreased in ER+ and PR+ tumours and PAI-2 increased in menopausal women's tumours. When Cath D, uPA, PAI-1 and PAI-2 levels in malignant tumours were compared, positive correlations were found for all combinations. The implication of plasminogen activator inhibitors in the phenomenon was surprising and merits further investigation using tools other than global antigen measurements in tumours. PMID:1931618

  5. Differential expression of the urokinase receptor (CD87) in arthritic and normal synovial tissues.

    PubMed Central

    Szekanecz, Z; Haines, G K; Koch, A E

    1997-01-01

    AIM: To determine whether the urokinase plasminogen activator receptor (u-PAR; CD87) exhibits a possible pathogenic role in rheumatoid and osteoarthritis. METHODS: A semiquantitative, indirect immunoperoxidase histochemical analysis was performed on frozen synovial tissue sections. The recently characterised monoclonal antibody 10G7 recognising transfectants bearing u-PAR was used. Synovial tissue was obtained from 10 patients with rheumatoid arthritis, 10 patients with osteoarthritis, and four normal subjects. RESULTS: u-PAR was expressed on 70-90% of synovial tissue lining cells and subsynovial, interstitial macrophages from the arthritis patients, but only on a few myeloid cells from the normal subjects. It was also present on more endothelial cells from the rheumatoid and osteoarthritis patients, than from normal synovial tissue. CONCLUSIONS: Plasminogen activators are important in joint destruction underlying arthritis. The up-regulated expression of u-PAR in diseased versus normal synovial tissue suggests a role for this antigen in the inflammatory and angiogenic mechanisms underlying rheumatoid and osteoarthritis. Images PMID:9215148

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

    PubMed

    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.

  7. Expression of MMP-2, MMP-9, and urokinase-type plasminogen activator in cervical intraepithelial neoplasia.

    PubMed

    No, Jae Hong; Jo, Hoenil; Kim, Su-Hyeong; Park, In-Ae; Kang, Daehee; Lee, Chae Hyeong; Han, Seung-Su; Kim, Jae Weon; Park, Noh-Hyun; Kang, Soon-Beom; Song, Yong-Sang

    2009-08-01

    Matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator (uPA) are important factors for cancer invasion and metastasis, degrading the extracellular matrix. They are also associated with angiogenesis. Angiogenic phenotype is another feature of high-grade cervical intraepithelial neoplasia (CIN). However, their associations with the progression of low-grade CIN to high-grade CIN are unexplored. We investigated whether these proteolytic enzyme expressions correlate with the progression of CIN. A total of 39 paraffin-embedded specimens from 10 patients with CIN grade 1, nine with CIN grade 2, and 20 with CIN grade 3 were assessed immunohistochemically by specific antibodies against MMP-2, MMP-9, and uPA. MMP-9 expression was higher in CIN 3 lesions (47.4%) than in CIN 1 (22.2%) and CIN 2 (20.2%) lesions, although the difference failed to reach statistical significance. The expression level of uPA and MMP-2 was not associated with the grade of CIN lesions. Interestingly, we found a significant association between expressions of uPA and MMP-2 (P= 0.028). Our results suggest that MMP-9 might play a role in the progression of CIN.

  8. Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.

    PubMed

    Bao, Ying-Na; Cao, Xue; Luo, Dong-Hua; Sun, Rui; Peng, Li-Xia; Wang, Lin; Yan, Yong-Pan; Zheng, Li-Sheng; Xie, Ping; Cao, Yun; Liang, Ying-Ying; Zheng, Fang-Jing; Huang, Bi-Jun; Xiang, Yan-Qun; Lv, Xing; Chen, Qiu-Yan; Chen, Ming-Yuan; Huang, Pei-Yu; Guo, Ling; Mai, Hai-Qiang; Guo, Xiang; Zeng, Yi-Xin; Qian, Chao-Nan

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target. PMID:24763226

  9. A Urokinase Receptor-Bim Signaling Axis Emerges During EGFR Inhibitor Resistance in Mutant EGFR Glioblastoma

    PubMed Central

    Wykosky, Jill; Hu, Jingjing; Gomez, German G.; Taylor, Tiffany; Villa, Genaro R.; Pizzo, Donald; VandenBerg, Scott R.; Thorne, Amy Haseley; Chen, Clark C.; Mischel, Paul S.; Gonias, Steven. L.; Cavenee, Webster K.; Furnari, Frank B.

    2014-01-01

    EGFR is the most common genetically altered oncogene in glioblastoma (GBM), but small molecule EGFR tyrosine kinase inhibitors (TKIs) have failed to yield durable clinical benefit. Here we show that in two novel model systems of acquired resistance to EGFR TKIs, elevated expression of urokinase plasminogen activator (uPA) drives signaling through the MAPK pathway, which results in suppression of the pro-apoptotic BCL2-family member protein BIM (BCL2L11). In patient-derived GBM cells and genetic GBM models uPA is shown to suppress BIM levels through ERK1/2 phosphorylation, which can be reversed by siRNA mediated knockdown of uPA. TKI-resistant GBMs are re-sensitized to EGFR TKIs by pharmacological inhibition of MEK or a BH3 mimetic drug to replace BIM function. A link between the uPA-uPAR-ERK1/2 pathway and BIM has not been previously demonstrated in GBM, and involvement of this signaling axis in resistance provides rationale for a new strategy to target EGFR TKI-resistant GBM. PMID:25432173

  10. Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition.

    PubMed

    Madunić, Josip; Antica, Mariastefania; Cvjetko, Petra; Požgaj, Lidija; Matulić, Maja

    2016-08-01

    The urokinase plasminogen activator (uPA) system is a complex regulator of extracellular proteolysis which is involved in various physiological and pathological processes. The major components of this system are the serine protease uPA, two inhibitors PAI-1 and PAI-2, and the receptor uPAR. It has been previously shown by several groups that the uPA system has an important role in cancer progression and therefore its possible prognostic and therapeutic value has been evaluated. The aim of this study is to tackle the role of poly(ADP-ribosyl)ation in the induction of uPA activity in a glioblastoma cell line, A1235. This cell line is sensitive to alkylation damage and is a model for drug treatment. The components of the uPA system and the level of DNA damage were analyzed after alkylation agent treatment in combination with poly(ADP-ribose)polymerase-1 (PARP-1) inhibition. Here we show that the increase in uPA activity results from the net balance change between uPA and its inhibitor at mRNA level. Further, PARP-1 inhibition exerts its influence on uPA activity through DNA damage increase. Involvement of several signaling pathways, as well as cell specific regulation influencing the uPA system are discussed.

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

    PubMed

    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.

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

    PubMed Central

    Saleem, Moin A.; Meijers, Björn

    2016-01-01

    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. PMID:27504461

  13. TFRC and ACTB as the best reference genes to quantify Urokinase Plasminogen Activator in breast cancer

    PubMed Central

    2011-01-01

    Background Biomedical researchers have long looked for ways to diagnose and treat cancer patients at the early stages through biomarkers. Although conventional techniques are routinely applied in the detection of biomarkers, attitudes towards using Real-Time PCR techniques in detection of many biomarkers are increasing. Normalization of quantitative Real-Time PCR is necessary to validate non-biological alteration occurring during the steps of RNA quantification. Selection of variably expressed housekeeping genes (HKs) will affect the validity of the data. The aim of the present study was to identify uniformly expressed housekeeping genes in order to use in the breast cancer gene expression studies. Urokinase Plasminogen Activator was used as a gene of interest. Findings The expression of six HKs (TFRC, GUSB, GAPDH, ACTB, HPRT1 and RPLP0) was investigated using geNorm and NormFinder softwares in forty breast tumor, four normal and eight adjacent tissues. RPLP0 and GAPDH revealed maximum M value, while TFRC demonstrated lowest M value. Conclusions In the present study the most and the least stable genes were TFRC and RPLP0 respectively. TFRC and ACTB were verified as the best combination of two genes for breast cancer quantification. The result of this study shows that in each gene expression analysis HKs selection should be done based on experiment conditions. PMID:21702980

  14. Urokinase plasminogen activator receptor-deficient mice demonstrate reduced hyperoxia-induced lung injury.

    PubMed

    van Zoelen, Marieke A D; Florquin, Sandrine; de Beer, Regina; Pater, Jennie M; Verstege, Marleen I; Meijers, Joost C M; van der Poll, Tom

    2009-06-01

    Patients with respiratory failure often require supplemental oxygen therapy and mechanical ventilation. Although both supportive measures are necessary to guarantee adequate oxygen uptake, they can also cause or worsen lung inflammation and injury. Hyperoxia-induced lung injury is characterized by neutrophil infiltration into the lungs. The urokinase plasminogen activator receptor (uPAR) has been deemed important for leukocyte trafficking. To determine the expression and function of neutrophil uPAR during hyperoxia-induced lung injury, uPAR expression was determined on pulmonary neutrophils of mice exposed to hyperoxia. Hyperoxia exposure (O2>80%) for 4 days elicited a pulmonary inflammatory response as reflected by a profound rise in the number of neutrophils that were recovered from bronchoalveolar lavage fluid and lung cell suspensions, as well as increased bronchoalveolar keratinocyte-derived chemokine, interleukin-6, total protein, and alkaline phosphatase levels. In addition, hyperoxia induced the migration of uPAR-positive granulocytes into lungs from wild-type mice compared with healthy control mice (exposed to room air). uPAR deficiency was associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, which was accompanied by a strong reduction in lung injury. Furthermore, in uPAR(-/-) mice, activation of coagulation was diminished. These data suggest that uPAR plays a detrimental role in hyperoxia-induced lung injury and that uPAR deficiency is associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, accompanied by decreased pulmonary injury. PMID:19435793

  15. Loss of Urokinase Receptor Sensitizes Cells to DNA Damage and Delays DNA Repair

    PubMed Central

    Narayanaswamy, Pavan B.; Hodjat, Mahshid; Haller, Hermann; Dumler, Inna; Kiyan, Yulia

    2014-01-01

    DNA damage induced by numerous exogenous or endogenous factors may have irreversible consequences on the cell leading to cell cycle arrest, senescence and cell death. The DNA damage response (DDR) is powerful signaling machinery triggered in response to DNA damage, to provide DNA damage recognition, signaling and repair. Most anticancer drugs induce DNA damage, and DNA repair in turn attenuates therapeutic efficiency of those drugs. Approaches delaying DNA repair are often used to increase efficiency of treatment. Recent data show that ubiquitin-proteasome system is essential for signaling and repair of DNA damage. However, mechanisms providing regulation of proteasome intracellular localization, activity, and recruitment to DNA damage sites are elusive. Even less investigated are the roles of extranuclear signaling proteins in these processes. In this study, we report the involvement of the serine protease urokinase-type plasminogen activator receptor (uPAR) in DDR-associated regulation of proteasome. We show that in vascular smooth muscle cells (VSMC) uPAR activates DNA single strand break repair signaling pathway. We provide evidence that uPAR is essential for functional assembly of the 26S proteasome. We further demonstrate that uPAR mediates DNA damage-induced phosphorylation, nuclear import, and recruitment of the regulatory subunit PSMD6 to proteasome. We found that deficiency of uPAR and PSMD6 delays DNA repair and leads to decreased cell survival. These data may offer new therapeutic approaches for diseases such as cancer, cardiovascular and neurodegenerative disorders. PMID:24987841

  16. Challenges for drug discovery - a case study of urokinase receptor inhibition

    PubMed Central

    Chen, Zhuo; Lin, Lin; Huai, Qing; Huang, Mingdong

    2009-01-01

    Urokinase receptor (uPAR) is a widely recognized target for potential treatment of cancer. The development of uPAR inhibitors has been going on for over a decade. Despite the identification and validation of many highly potent hits using screening or medicinal approaches, none of them has been moved further along the drug discovery pipeline. The development of uPAR inhibitors exemplifies several challenges now faced by drug discovery. These include 1) hydrophobicity and thus poor bioavailability of the inhibitors from screening approaches; 2) specificity of the inhibitor, where a peptidyl inhibitor causes conformational change of the receptor; 3) species specificity, where some inhibitors developed based on the human receptor do not inhibit the murine receptor and thus cannot be validated in mouse models. The recently determined crystal structures of uPAR in complex with its ligand or inhibitor not only provide the structural insight to understand these challenges but also offer a potential solution for further inhibitor development and thus illustrate the importance of structural information in facilitating drug discovery. PMID:20025562

  17. Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

    PubMed

    Cheng, C-C; Lee, Y-F; Lan, J-L; Wu, M-J; Hsieh, T-Y; Lin, N-N; Wang, J-M; Chiu, Y-T

    2013-05-01

    Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics. PMID:23478030

  18. Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

    PubMed

    Cheng, C-C; Lee, Y-F; Lan, J-L; Wu, M-J; Hsieh, T-Y; Lin, N-N; Wang, J-M; Chiu, Y-T

    2013-05-01

    Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics.

  19. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    SciTech Connect

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika . E-mail: angelika.kusch@charite.de

    2007-08-03

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury.

  20. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

    PubMed Central

    Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

    2014-01-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  1. The steady states and dynamics of urokinase-mediated plasmin activation.

    PubMed

    Venkatraman, Lakshmi; Yu, Hanry; Bhowmick, Sourav S; Dewey, Forbes; Tucker-Kellogg, Lisa

    2010-01-01

    Plasmin and urokinase-type plasminogen activator (uPA) are ubiquitous proteases regulating the extracellular environment. They can activate each other via proteolytic cleavage, suggesting the potential for complex dynamic behaviors that could be elucidated by computational modeling. Ordinary differential equations are constructed to model the activation dynamics of plasminogen into plasmin, and single-chain uPA (scUPA) into two-chain uPA (tcUPA). Computational simulations and phase plane analysis reveal two stable steady states for the activation of each protein. Bifurcation analysis shows the in silico system to be bistable. Cell-free experiments verify the system to have ultrasensitive activation behavior, where scUPA is the stimulus and plasmin the output. Furthermore, two significantly different steady states could be seen in vitro for the same stimulus levels, depending on the initial activation level of the plasmin. The switch-like dynamics of the uPA-plasmin system could have potential relevance to many normal and disease processes including angiogenesis, migration and metastasis, wound healing and fibrosis. PMID:19908371

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

    PubMed

    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.

  3. Arctic circulation regimes.

    PubMed

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. PMID:26347536

  4. Arctic circulation regimes

    PubMed Central

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L.

    2015-01-01

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. PMID:26347536

  5. Plasmin-dependent elimination of the growth-factor-like domain in urokinase causes its rapid cellular uptake and degradation.

    PubMed Central

    Poliakov, A; Tkachuk, V; Ovchinnikova, T; Potapenko, N; Bagryantsev, S; Stepanova, V

    2001-01-01

    Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in concert to mediate pericellular proteolysis and to stimulate intracellular signalling responsible for cell migration and proliferation. uPA is composed of three domains, a proteolytic domain (PD), a kringle domain (KD) and a growth-factor-like domain (GFD), the last of which mediates the interaction with uPAR. We demonstrate that uPA, associated with the surface of U937 cells, undergoes plasmin-mediated cleavage of the Lys(46)-Ser(47) bond with elimination of the GFD. Using recombinant forms of uPA, we show that a uPA variant lacking the GFD (r-uPADeltaGFD) and unable to associate with uPAR is rapidly cleared from the cell surface. Binding and internalization of r-uPADeltaGFD are markedly decreased in the presence of 39 kDa receptor-associated protein (RAP), the antagonist of several endocytic receptors of the low-density lipoprotein receptor family, suggesting that this protein clearance pathway is used for r-uPADeltaGFD. In contrast with rapidly internalized r-uPADeltaGFD, the intact recombinant single-chain urokinase with wild-type structure (r-uPAwt) bound to uPAR is retained on the cell surface. Soluble uPAR protects uPA from cleavage by plasmin that results in the elimination of GFD, suggesting that uPAR might protect cell-bound urokinase from plasmin-mediated cleavage between the GFD and KD and subsequent degradation. PMID:11311125

  6. Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator.

    PubMed

    Frederickson, Martyn; Callaghan, Owen; Chessari, Gianni; Congreve, Miles; Cowan, Suzanna R; Matthews, Julia E; McMenamin, Rachel; Smith, Donna-Michelle; Vinković, Mladen; Wallis, Nicola G

    2008-01-24

    Fragment-based lead discovery has been applied to urokinase-type plasminogen activator (uPA). The (R)-enantiomer of the orally active drug mexiletine 5 (a fragment hit from X-ray crystallographic screening) was the chemical starting point. Structure-aided design led to elaborated inhibitors that retained the key interactions of (R)-5 while gaining extra potency by simultaneously occupying neighboring regions of the active site. Subsequent optimization led to 15, a potent, selective, and orally bioavailable inhibitor of uPA. PMID:18163548

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

    PubMed

    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.

  8. Meta-analysis of the urokinase gene 3′-UTR T/C polymorphism and susceptibility to urolithiasis

    PubMed Central

    LI, DAWEI; LIU, JIKAI; REN, JUCHAO; YAN, LEI; LIU, HAINAN; XU, ZHONGHUA

    2013-01-01

    Urokinase is involved in the processes of initiating urinary stones. Several published case-control studies have examined the relationship of urokinase gene 3′-untranslated region (3′-UTR) T/C polymorphism and urolithiasis, but yielded inconsistent findings. In this study, a comprehensive meta-analysis was conducted by pooling relevant studies to obtain reliable conclusions. Studies focusing on the association between urokinase gene 3′-UTR T/C polymorphism and urolithiasis were retrieved through PubMed, Medline, Web of Science and the China National Knowledge Infrastructure platform without any limit on language, until October 2012. Four independent articles were eventually identified as eligible for the final meta-analysis, involving 1,195 subjects. Crude odds ratios (ORs), as well as 95% confidence intervals (CIs), were assessed for the association by either fixed- or random-effects models using RevMan 5.0 software. Significant associations were noted in the ‘TC vs. CC’ codominant model for total population (OR=2.53; 95% CI, 1.43–4.46; P=0.001), Asian population (OR=2.46; 95% CI, 1.38–4.40; P=0.002), male (OR=2.98; 95% CI, 1.43–6.21; P=0.004), Hardy-Weinberg equilibrium (HWE) (OR=2.46; 95% CI, 1.38–4.40; P=0.002) and recurrence (OR=2.66; 95% CI, 1.51–4.67; P=0.00). Statistically significant associations were also observed in the ‘TT+TC vs. CC’ dominant model for the Asian, male, HWE and recurrence population (P<0.05). Additionally, a significant difference was detected in the ‘T vs. C’ allele model for HWE. However, there were no associations in either the ‘TT vs. CC’ codominant model or ‘TT vs. TC+CC’ recessive model. In conclusion, the present meta-analysis suggests that urokinase gene T allele may increase the susceptibility of urolithiasis. PMID:24648951

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

    PubMed Central

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

    2015-01-01

    ABSTRACT Objective: To evaluate the change in respiratory function and functional capacity according to the type of preoperative fasting. Methods: 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. Results: 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. Conclusion: Abbreviation of preoperative fasting time with ingestion of maltodextrin solution is beneficial to pulmonary function and preserves dominant handgrip strength. PMID:26154547

  10. Inhibitors of urokinase type plasminogen activator and cytostatic activity from crude plants extracts.

    PubMed

    Zha, Xueqiang; Diaz, Ricardo; Franco, Jose Javier Rosado; Sanchez, Veronica Forbes; Fasoli, Ezio; Barletta, Gabriel; Carvajal, Augusto; Bansal, Vibha

    2013-01-01

    In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC₅₀ values. The chloroform extract showed the lowest IC₅₀ value (3.52 µg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study.

  11. Urokinase-coated chitosan nanoparticles for thrombolytic therapy: preparation and pharmacodynamics in vivo.

    PubMed

    Jin, Hai-jiang; Zhang, Hao; Sun, Min-li; Zhang, Bai-gen; Zhang, Ji-wei

    2013-11-01

    Blood reperfusion of affected limbs is the most effective therapy for peripheral vascular thrombotic disease, restoring nutrition and blood flow to threatened tissues. Because it is more cost-effective than other thrombolytics, urokinase (UK) is widely used to treat venous thrombosis in China. However, its use is limited because of the risk of UK-related hemorrhagic complications. UK-coated nanoparticles (NPs) may decrease adverse effects while simultaneously increasing thrombolytic benefits. The aim of this study was to combine the sustained-release properties of NPs with the clinical benefits of catheter-directed thrombolysis (CDT) to create a promising new therapy. NPs were prepared via self-assembled chitosan and tripolyphosphate, introduced into a thrombosis model in New Zealand white rabbits, and the ratio of the residual thrombus cross-sectional area to the vascular cross-sectional area was calculated. The NPs had a drug-bearing efficiency of 14.5 ± 1.3%, an encapsulation efficiency of 94.8 ± 2.1% while the particle size of UK-coated NPs was 236 nm. Transmission electron microscopy results showed that the shape of the NPs were spherical and regular. Whether delivered by intravenation or catheter, UK-coated NPs produced a significant increase in the thrombolytic effect compared with free UK and confirmed the superiority of CDT for improving clot lysis over drug-induced systemic thrombolysis. The intravenous NPs caused an abnormal increase in fibrinogen. In conclusion, a water-soluble UK-WCS-NP suspension with good encapsulation efficiency was easily prepared UK-WCS-NPs were capable of maintaining UK activity, provided sustained-release of UK and exhibited better thrombolytic function than free UK. PMID:23728739

  12. Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor

    PubMed Central

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

    2014-01-01

    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 (3) and piperidinone (4) compounds, along with derivatives of previously-identified pyrazole (1) and propylamine (2) compounds. Competition assays revealed that the compounds displaced a fluorescently-labeled peptide (AE147-FAM) with inhibition constant Ki ranging from 6 to 63 μM. Structure-based computational pharmacophore analysis followed by extensive explicit-solvent molecular dynamics simulations and free energy calculations suggested pyrazole-based 1a and piperidinone-based 4 adopt different binding modes, despite their similar two-dimensional structures. In cells, compounds 1b and 1f showed significant inhibition of breast MDA-MB-231 and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but 4b exhibited no cytotoxicity even at concentrations of 100 μM. 1f impaired MDA-MB-231 invasion, adhesion, and migration in a concentration-dependent manner, while 4b inhibited only invasion. 1f inhibited gelatinase (MMP-9) activity in a concentration-dependent manner, while 4b 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 pyrrolidinone and piperidinone (3 and 4b) had no effect. Annexin V staining suggested that the effect of pyrazole-based 1f on proliferation was due to cell killing through an apoptotic mechanism. PMID:24115356

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

    PubMed Central

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

    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 (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. 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 (10.4%) 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 < .001). Multiple logistic regression with odds ratio (OR) for suPAR levels >4.0 ng/ml yielded: schizophrenia, OR: 46.15 95% CI 22.69–93.87, P < .001; age, OR: 1.02 95% CI 0.99–1.02, P = .15; male sex, OR: 0.70 95% CI 0.35–1.36, P = .29; and current smoking, OR: 3.51 95% CI 1.78–6.94, P < .001. Conclusions: Patients with 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. PMID:25154621

  14. A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation.

    PubMed

    Fuentes, Rudy E; Zaitsev, Sergei; Ahn, Hyun Sook; Hayes, Vincent; Kowalska, M Anna; Lambert, Michele P; Wang, Yuhuan; Siegel, Donald L; Bougie, Daniel W; Aster, Richard H; Myers, Daniel D; Stepanova, Victoria; Cines, Douglas B; Muzykantov, Vladimir R; Poncz, Mortimer

    2016-02-01

    The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule-delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi. PMID:26690701

  15. Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice123

    PubMed Central

    Karamanavi, Elisavet; Angelopoulou, Katerina; Lavrentiadou, Sophia; Tsingotjidou, Anastasia; Abas, Zaphiris; Taitzoglou, Ioannis; Vlemmas, Ioannis; Erdman, Suzan E.; Poutahidis, Theofilos

    2014-01-01

    Urokinase-type plasminogen activator (uPA) participates in cancer-related biologic processes, such as wound healing and inflammation. The present study aimed to investigate the effect of uPA deficiency on the long-term outcome of early life episodes of dextran sodium sulfate (DSS)–induced colitis in mice. Wild-type (WT) and uPA-deficient (uPA−/−) BALB/c mice were treated with DSS or remained untreated. Mice were necropsied either 1 week or 7 months after DSS treatment. Colon samples were analyzed by histopathology, immunohistochemistry, ELISA, and real-time polymerase chain reaction. At 7 months, with no colitis evident, half of the uPA−/− mice had large colonic polypoid adenomas, whereas WT mice did not. One week after DSS treatment, there were typical DSS-induced colitis lesions in both WT and uPA−/− mice. The affected colon of uPA−/− mice, however, had features of delayed ulcer re-epithelialization and dysplastic lesions of higher grade developing on the basis of a significantly altered mucosal inflammatory milieu. The later was characterized by more neutrophils and macrophages, less regulatory T cells (Treg), significantly upregulated cytokines, including interleukin-6 (IL-6), IL-17, tumor necrosis factor-α, and IL-10, and lower levels of active transforming growth factor–β1 (TGF-β1) compared to WT mice. Dysfunctional Treg, more robust protumorigenic inflammatory events, and an inherited inability to produce adequate amounts of extracellular active TGF-β1 due to uPA deficiency are interlinked as probable explanations for the inflammatory-induced neoplasmatogenesis in the colon of uPA−/− mice. PMID:24913672

  16. Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells.

    PubMed

    Alfano, Daniela; Gorrasi, Anna; Li Santi, Anna; Ricci, Patrizia; Montuori, Nunzia; Selleri, Carmine; Ragno, Pia

    2015-09-01

    The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3'untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo.

  17. Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis

    PubMed Central

    DING, YOUCHENG; ZHANG, HUI; LU, AIGUO; ZHOU, ZHUQING; ZHONG, MINGAN; SHEN, DONGWEI; WANG, XUJING; ZHU, ZHENGGANG

    2016-01-01

    Peritoneal metastasis is a primary cause of mortality in patients with gastric cancer. Urokinase-type plasminogen activator (uPA) has been demonstrated to be associated with tumor cell metastasis through the degradation of the extracellular matrix. The present study aimed to investigate the mechanisms of the uPA system in gastric cancer with peritoneal metastasis. Expression of uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in four gastric cell lines (AGS, SGC7901, MKN45 and MKN28) was measured by semiquantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting. uPA activity was detected using a uPA activity kit. Peritoneal implantation models of rats were established by injecting four gastric cancer cell lines for the selection of the cancer cells with a high planting potential. Biological behaviors, including adhesion, migration and invasion, were determined using a methyl thiazolyl tetrazolium assay. Expression of the uPA system was observed to be highest in the SGC7901 cells among the four gastric cell lines. uPA activity was observed to be highest in the MKN45 cells and lowest in the AGS cells. Furthermore, peritoneal implantation analysis demonstrated that no peritoneal tumors were identified in the AGS cells, whilst the tumor masses observed in the SGC7901 and MKN45 cells were of different sizes. The survival times of the rats injected with the MKN28 and SGC7901 cells were longer than those of the rats injected with the MKN45 cells. Antibodies for uPA, uPAR and PAI-1 in the uPA system had the ability to inhibit the adhesion, migration and invasion of peritoneal metastasis in the gastric cancer cells. The results of the present study demonstrated that the uPA system was positively associated with peritoneal metastasis in gastric cancer. PMID:27313768

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

    PubMed Central

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan; Wei, Hao; Liu, Shihui; Lund, Ida K.; Høyer-Hansen, Gunilla; Dichek, David A.

    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-accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. Methods and results SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1) or a control antibody. mU1-treated mice were also compared with PBS-treated non-uPA-overexpressing Apoe-null mice. Other SR-uPA mice were treated with one of three doses of a limited-spectrum synthetic MMP inhibitor (XL784) or vehicle. mU1 reduced aortic root intimal lesion area (20%; P = 0.05) and aortic root circumference (12%; P = 0.01). All XL784 doses reduced aortic root intimal lesion area (22–29%) and oil-red-O-positive lesion area (36–42%; P < 0.05 for all doses and both end points), with trends towards reduced aortic root circumference (6–10%). Neither mU1 nor XL784 significantly altered percent aortic surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. Conclusions Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis. PMID:25616415

  19. Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

    PubMed Central

    Zha, Xueqiang; Diaz, Ricardo; Franco, Jose Javier Rosado; Sanchez, Veronica Forbes; Fasoli, Ezio; Barletta, Gabriel; Carvajal, Augusto; Bansal, Vibha

    2014-01-01

    In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 μg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study. PMID:23896619

  20. A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

    PubMed Central

    Fuentes, Rudy E.; Zaitsev, Sergei; Ahn, Hyun Sook; Hayes, Vincent; Kowalska, M. Anna; Lambert, Michele P.; Wang, Yuhuan; Siegel, Donald L.; Bougie, Daniel W.; Aster, Richard H.; Myers, Daniel D.; Stepanova, Victoria; Cines, Douglas B.; Muzykantov, Vladimir R.; Poncz, Mortimer

    2015-01-01

    The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule–delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi. PMID:26690701

  1. Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation.

    PubMed

    Cunningham, Orla; Campion, Suzanne; Perry, V Hugh; Murray, Carol; Sidenius, Nicolai; Docagne, Fabian; Cunningham, Colm

    2009-12-01

    The urokinase plasminogen activator (uPA) receptor (uPAR) is a GPI-linked cell surface protein that facilitates focused plasmin proteolytic activity at the cell surface. uPAR has been detected in macrophages infiltrating the central nervous system (CNS) and soluble uPAR has been detected in the cerebrospinal fluid during a number of CNS pathologies. However, its expression by resident microglial cells in vivo remains uncertain. In this work, we aimed to elucidate the murine CNS expression of uPAR and uPA as well as that of tissue plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) during insults generating distinct and well-characterized inflammatory responses; acute intracerebral lipopolysaccharide (LPS), acute kainate-induced neurodegeneration, and chronic neurodegeneration induced by prion disease inoculation. All three insults induced marked expression of uPAR at both mRNA and protein level compared to controls (naïve, saline, or control inoculum-injected). uPAR expression was microglial in all cases. Conversely, uPA transcription and activity was only markedly increased during chronic neurodegeneration. Dissociation of uPA and uPAR levels in acute challenges is suggestive of additional proteolysis-independent roles for uPAR. PAI-1 was most highly expressed upon LPS challenge, whereas tissue plasminogen activator mRNA was constitutively present and less responsive to all insults studied. These data are novel and suggest much wider involvement of the uPAR/uPA system in CNS function and pathology than previously supposed. PMID:19459212

  2. Urokinase-type plasminogen activator receptor modulates epileptogenesis in mouse model of temporal lobe epilepsy.

    PubMed

    Ndode-Ekane, Xavier Ekolle; Pitkänen, Asla

    2013-06-01

    Mutation in Plaur gene encoding urokinase-type plasminogen activator receptor (uPAR) results in epilepsy and autistic phenotype in mice. In humans, a single nucleotide polymorphism in PLAUR gene represents a risk for autism spectrum disorders. Importantly, the expression of uPAR is elevated in the brain after various epileptogenic insults like traumatic brain injury and status epilepticus. So far, the consequences of altered uPAR expression on brain networks are poorly known. We tested a hypothesis that uPAR regulates post-injury neuronal reorganization and consequent functional outcome, particularly epileptogenesis. Epileptogenesis was induced by intrahippocampal injection of kainate in adult male wild type (Wt) or uPAR knockout (uPAR-/-) mice, and animals were monitored with continuous (24/7) video-electroencephalogram for 30 days. The severity of status epilepticus did not differ between the genotypes. The spontaneous electrographic seizures which developed were, however, longer and their behavioral manifestations were more severe in uPAR-/- than Wt mice. The more severe epilepsy phenotype in uPAR-/- mice was associated with delayed but augmented inflammatory response and more severe neurodegeneration in the hippocampus. Also, the distribution of newly born cells in the dentate gyrus was more scattered, and the recovery of hippocampal blood vessel length from status epilepticus-induced damage was compromised in uPAR-/- mice as compared to Wt mice. Our data demonstrate that a deficiency in uPAR represents a mechanisms which results in the development of a more severe epilepsy phenotype and progressive brain pathology after status epilepticus. We suggest that uPAR represents a rational target for disease-modifying treatments after epileptogenic brain insults. PMID:23263886

  3. Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells

    PubMed Central

    Alfano, Daniela; Gorrasi, Anna; Li Santi, Anna; Ricci, Patrizia; Montuori, Nunzia; Selleri, Carmine; Ragno, Pia

    2015-01-01

    The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3′untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo. PMID:26082201

  4. The urokinase inhibitor p-aminobenzamidine inhibits growth of a human prostate tumor in SCID mice.

    PubMed

    Billström, A; Hartley-Asp, B; Lecander, I; Batra, S; Astedt, B

    1995-05-16

    Malignant cells possess a high degree of proteolytic activity in which the plasminogen activator system plays an important role. An increased expression of urokinase type plasminogen activator (uPA) is of significance for degradation of the extracellular tumor matrix, facilitating invasiveness and growth. Inhibition of the active site of uPA makes it possible to evaluate the significance of uPA in tumor growth. We report here experiments on a uPA-producing human prostate xenograft (DU 145) using a competitive inhibitor of uPA, p-aminobenzamidine. In vitro experiments with DU 145 cells showed that p-aminobenzamidine caused a dose-dependent inhibition of uPA activity. DU 145 cells were inoculated s.c. in SCID mice and, once tumors were established, treatment with p-aminobenzamidine added to drinking water was started and lasted for 23 days. Mice receiving 250 mg/kg/day of p-aminobenzamidine showed a clear decrease in tumor-growth rate compared to the non-treated mice, resulting in 64% lower final tumor weight. In addition, uPA-antigen levels in the membrane fractions of DU 145 tumors from p-aminobenzamidine-treated mice were found to be decreased by 59%. We also show that p-aminobenzamidine has an anti-proliferative effect in cell culture at low cell number, correlating with a dose-dependent decrease in uPA production. In conclusion, we show that a low-molecular-weight uPA-inhibitor, p-aminobenzamidine, has a growth-inhibitory effect on a solid uPA-producing tumor. PMID:7759160

  5. Extracellular alpha 6 integrin cleavage by urokinase-type plasminogen activator in human prostate cancer

    PubMed Central

    Demetriou, Manolis C.; Pennington, Michael E.; Nagle, Raymond B.; Cress, Anne E.

    2009-01-01

    During human prostate cancer progression, the integrin α6β1 (laminin receptor) is expressed on the cancer cell surface during invasion and in lymph node metastases. We previously identified a novel structural variant of the α6 integrin called α6p. This variant was produced on the cell surface and was missing the β-barrel extracellular domain. Using several different concentrations of amiloride, aminobenzamidine and PAI-1 and the urokinase-type plasminogen activator (uPA) function-blocking antibody (3689), we showed that uPA, acting as a protease, is responsible for production of α6p. We also showed that addition of uPA in the culture media of cells that do not produce α6p, resulted in a dose-dependent α6p production. In contrast, the addition of uPA did not result in the cleavage of other integrins. Using α2-antiplasmin and plasmin depleted media, we observed that uPA cleaves the α6 integrin directly. Further, 12-o-tetradecanoyl-phorbol-13-acetate (TPA) induced the production of α6p, and this induction was abolished by PAI-1 but not α2-antiplasmin. Finally, the α6p integrin variant was detected in invasive human prostate carcinoma tissue indicating that this is not a tissue culture phenomenon. These data, taken together, suggest that this is a novel function of uPA, that is, to remove the β-barrel ligand-binding domain of the integrin while preserving its heterodimer association. PMID:15023541

  6. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    PubMed

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications. PMID:24505235

  7. Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

    PubMed Central

    Zhuo, Jingli; Tan, Ee Hong; Yan, Benedict; Tochhawng, Lalchhandami; Jayapal, Manikandan; Koh, Shiuan; Tay, Hwee Kee; Maciver, Sutherland K.; Hooi, Shing Chuan; Salto-Tellez, Manuel; Kumar, Alan Prem; Goh, Yaw Chong; Lim, Yaw Chyn; Yap, Celestial T.

    2012-01-01

    Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. PMID:22927998

  8. Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation.

    PubMed

    Cunningham, Orla; Campion, Suzanne; Perry, V Hugh; Murray, Carol; Sidenius, Nicolai; Docagne, Fabian; Cunningham, Colm

    2009-12-01

    The urokinase plasminogen activator (uPA) receptor (uPAR) is a GPI-linked cell surface protein that facilitates focused plasmin proteolytic activity at the cell surface. uPAR has been detected in macrophages infiltrating the central nervous system (CNS) and soluble uPAR has been detected in the cerebrospinal fluid during a number of CNS pathologies. However, its expression by resident microglial cells in vivo remains uncertain. In this work, we aimed to elucidate the murine CNS expression of uPAR and uPA as well as that of tissue plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) during insults generating distinct and well-characterized inflammatory responses; acute intracerebral lipopolysaccharide (LPS), acute kainate-induced neurodegeneration, and chronic neurodegeneration induced by prion disease inoculation. All three insults induced marked expression of uPAR at both mRNA and protein level compared to controls (naïve, saline, or control inoculum-injected). uPAR expression was microglial in all cases. Conversely, uPA transcription and activity was only markedly increased during chronic neurodegeneration. Dissociation of uPA and uPAR levels in acute challenges is suggestive of additional proteolysis-independent roles for uPAR. PAI-1 was most highly expressed upon LPS challenge, whereas tissue plasminogen activator mRNA was constitutively present and less responsive to all insults studied. These data are novel and suggest much wider involvement of the uPAR/uPA system in CNS function and pathology than previously supposed.

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

    PubMed

    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. PMID:17523079

  10. The tyrosine phosphatase SHP-2 controls urokinase-dependent signaling and functions in human vascular smooth muscle cells

    SciTech Connect

    Kiyan, Julia Haller, Hermann; Dumler, Inna

    2009-04-01

    The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of functional behaviour of human vascular smooth muscle cells (VSMC). uPAR associates with platelet-derived growth factor receptor {beta} (PDGFR-{beta}), which serves as a transmembrane adaptor for uPAR in VSMC, to transduce intracellular signaling and initiate functional changes. The precise and rapid propagation of these signaling cascades demands both strict and flexible regulatory mechanisms that remain unexplored. We provide evidence that the tyrosine phosphatase SHP-2 mediates these processes. uPA regulated SHP-2 phosphorylation, catalytic activity, and its co-localization and association with the PDGFR-{beta}. Active PDGFR-{beta} was required for the uPA-induced SHP-2 phosphorylation. uPAR-directed STAT1 pathway was disturbed in cells expressing SHP-2 inactive mutant. Both, cell proliferation and migration were impaired in VSMC with downregulated SHP-2. Elucidating the underlying mechanisms, we found that uPA induced SHP-2 recruitment to lipid rafts. Disruption of rafts abolished uPA-related control of SHP-2 phosphorylation, its association with PDGFR-{beta} and finally the VSMC functional responses. Our results demonstrate that SHP-2 plays an important role in uPA-directed signaling and functional control of human VSMC and suggest that this phosphatase might contribute to the pathogenesis of the uPA-related vascular remodeling.

  11. Dynamic Treatment Regimes

    PubMed Central

    Chakraborty, Bibhas; Murphy, Susan A.

    2014-01-01

    A dynamic treatment regime consists of a sequence of decision rules, one per stage of intervention, that dictate how to individualize treatments to patients based on evolving treatment and covariate history. These regimes are particularly useful for managing chronic disorders, and fit well into the larger paradigm of personalized medicine. They provide one way to operationalize a clinical decision support system. Statistics plays a key role in the construction of evidence-based dynamic treatment regimes – informing best study design as well as efficient estimation and valid inference. Due to the many novel methodological challenges it offers, this area has been growing in popularity among statisticians in recent years. In this article, we review the key developments in this exciting field of research. In particular, we discuss the sequential multiple assignment randomized trial designs, estimation techniques like Q-learning and marginal structural models, and several inference techniques designed to address the associated non-standard asymptotics. We reference software, whenever available. We also outline some important future directions. PMID:25401119

  12. The serum levels of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction

    PubMed Central

    Wang, Shu-Jin; Qu, Zhong-Sen; Zhang, Qing-De; Li, Liang; Wang, Feng; Zhang, Bin; Wu, Bang-Li; Zhao, Yu-Wu

    2015-01-01

    To investigate the effect of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. 112 cases of uremia complicated with cerebral infarction were randomly divided into the peritoneal dialysate with urokinase treatment group (66 cases) and the conventional treatment group (46 cases). At the same time, 50 cases of healthy people who were more than 45 years old were enrolled in the control group. The basic treatment in both treatment groups was the same. In urokinase therapy group based on the conventional treatment, urokinase was added into peritoneal dialysis fluid, and changes of serum MMP-9, MMP-2 and vWF were observed by drawing blood at different time points within 8 weeks. The changes of serum MMP-2, MMP-9 and vWF were detected by enzyme-linked immunosorbent assay. At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2, vWF were significantly higher (P<0.05, P<0.05, P<0.01). Conventional antiplatelet therapy in brain protection only reduce MMP-9 to the normal range (P>0.05) within 8 weeks. But the MMP-2 and vWF cannot be reduced to the normal range (P<0.01, P<0.01). Low doses of urokinase can reduce MMP-9 (7 d) and MMP-2 (14 d) to the normal range (P>0.05, P>0.05) at the early stage and decrease the vWF to a normal range within 8 weeks (P>0.05). At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2 and vWF increased significantly. Low doses of urokinase dialysis can reduce serum MMP-9, MMP-2, and vWF in acute uremia complicated with cerebral infarction without recurrence of cerebral infarction and cerebral hemorrhagic transformation, indicating that low dose of urokinase peritoneal dialysis may have a certain effect on the early treatment of this disease. PMID:26550224

  13. Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor.

    PubMed Central

    Stacey, K J; Fowles, L F; Colman, M S; Ostrowski, M C; Hume, D A

    1995-01-01

    The mouse urokinase-type plasminogen activator (uPA) gene was used as a model macrophage colony-stimulating factor 1 (CSF-1)-inducible gene to investigate CSF-1 signalling pathways. Nuclear run-on analysis showed that induction of uPA mRNA by CSF-1 and phorbol myristate acetate (PMA) was at the transcriptional level in bone marrow-derived macrophages. CSF-1 and PMA synergized strongly in the induction of uPA mRNA, showing that at least some components of CSF-1 action are mediated independently of protein kinase C. Promoter targets of CSF-1 signalling were investigated with NIH 3T3 cells expressing the human CSF-1 receptor (c-fms). uPA mRNA was induced in these cells by treatment with CSF-1, and a PEA3/AP-1 element at -2.4 kb in the uPA promoter was involved in this response. Ets transcription factors can act through PEA3 sequences, and the involvement of Ets factors in the induction of uPA was confirmed by use of a dominant negative Ets-2 factor. Expression of the DNA binding domain of Ets-2 fused to the lacZ gene product prevented CSF-1-mediated induction of uPA mRNA in NIH 3T3 cells expressing the CSF-1 receptor. Examination of ets-2 mRNA expression in macrophages showed that it was also induced synergistically by CSF-1 and PMA. In the macrophage cell line RAW264, the uPA PEA3/AP-1 element mediated a response to both PMA and cotransfected Ets-2. uPA promoter constructs were induced 60- to 130-fold by Ets-2 expression, and the recombinant Ets-2 DNA binding domain was able to bind to the uPA PEA3/AP-1 element. This work is consistent with a proposed pathway for CSF-1 signalling involving sequential activation of fms, ras, and Ets factors. PMID:7760840

  14. Human retinal pigment epithelial lysis of extracellular matrix: functional urokinase plasminogen activator receptor, collagenase, and elastase.

    PubMed Central

    Elner, Susan G

    2002-01-01

    PURPOSE: To show (1) human retinal pigment epithelial (HRPE) expression of functional urokinase plasminogen activator receptor (uPAR; CD87), (2) HRPE secretion of collagenase and elastase, (3) uPAR-dependent HRPE migration, and (4) uPAR expression in diseased human retinal tissue. METHODS: Immunohistochemistry for uPAR was performed on cultured HRPE cells and in sections of human retina. Double-immunofluorescent staining of live human RPE cells with anti-CR3 antibody (CD11b) was performed to demonstrate the physical proximity of this beta 2 integrin with uPAR and determine whether associations were dependent on RPE confluence and polarity. Extracellular proteolysis by HRPE uPAR was evaluated using fluorescent bodipy-BSA and assessed for specificity by plasminogen activator inhibitor-1 (PAI-1) inhibition. The effect of interleukin-1 beta (IL-1 beta) on uPAR expression was assessed. Collagenase and elastase secretion by unstimulated and IL-1-stimulated HRPE cells was measured by 3H-labelled collagen and elastin cleavage. HRPE-associated collagenase was also assessed by cleavage of fluorescent DQ-collagen and inhibited by phenanthroline. Using an extracellular matrix assay, the roles of uPAR and collagenase in HRPE migration were assessed. RESULTS: Immunoreactive uPAR was detected on cultured HRPE cells and increased by IL-1. On elongated, live HRPE cells, uPAR dissociated from CD11b (CR3) and translocated to anterior poles of migrating cells. Extracellular proteolysis was concentrated at sites of uPAR expression and specifically inhibited by PAI-1. Cultured HRPE cells secreted substantial, functional collagenase and elastase. IL-1 upregulated uPAR, collagenase, and elastase activities. Specific inhibition of uPAR, and to a lesser degree collagenase, reduced HRPE migration in matrix/gel assays. Immunoreactive uPAR was present along the HRPE basolateral membrane in retinal sections and in sections of diseased retinal tissue. CONCLUSIONS: HRPE cells express functional u

  15. Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha.

    PubMed

    Agaphonov, Michael; Romanova, Nina; Sokolov, Sviatoslav; Iline, Anna; Kalebina, Tatyana; Gellissen, Gerd; Ter-Avanesyan, Michael

    2005-11-01

    Human urokinase-type plasminogen activator (uPA) is poorly secreted by yeast cells. Here, we have selected Hansenula polymorpha mutants with increased productivity of active extracellular uPA. Several of the obtained mutants also demonstrated a defect of sorting of carboxypeptidase Y to the vacuole and the mutant loci have been identified in six of them. All these mutations damaged genes involved in protein traffic between the Golgi apparatus and the vacuole, namely PEP3, VPS8, VPS10, VPS17, and VPS35. We have shown that inactivation of the VPS10 gene encoding the vacuolar protein sorting receptor does not increase uPA secretion but stimulates its proteolytic processing. PMID:16181812

  16. A proposal of potent inhibitor for cancer metastasis blocking the pocket of urokinase receptor: ab initio molecular simulations

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    Recent biochemical experiments have elucidated that a variety of proteases play important roles in cancer invasion and metastasis. In particular, binding of urokinase-type plasminogen activator (uPA) to uPA receptor (uPAR) existing on the surface of a cancer cell is considered to be a trigger for cancer invasions. Therefore, the blocking of the binding is expected to inhibit cancer invasion. In previous experiments, several peptides of amino acids were proposed as a potent inhibitor for blocking the binding. In the present study, we obtained stable structures of the solvated complexes with uPAR and the peptides and investigated the specific interactions between uPAR and the peptides by ab initio molecular simulations. Base on these results, we clarified which peptide can bind more strongly to uPAR and proposed a novel potent peptide which can inhibit the uPAR-uPA binding efficiently.

  17. Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis

    PubMed Central

    2014-01-01

    Background Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. Recent studies have proposed that plasma soluble urokinase receptor (suPAR) might be a causative circulating factor but this proposal has caused controversy. This study aimed to measure urinary suPAR levels in patients with primary FSGS and its significance in the pathogenesis of FSGS. Methods Sixty-two patients with primary FSGS, diagnosed between January 2006 and January 2012, with complete clinical and pathologic data were enrolled, together with disease and normal controls. Urinary suPAR levels were measured using commercial ELISA kits and were corrected by urinary creatinine (Cr). The associations between urinary suPAR levels and clinical data at presentation and during follow up were analyzed. Conditionally immortalized human podocytes were used to study the effect of urinary suPAR on activating β3 integrin detected by AP5 staining. Results The urinary suPAR level of patients with primary FSGS (500.56, IQR 262.78 to 1,059.44 pg/μmol Cr) was significantly higher than that of patients with minimal change disease (307.86, IQR 216.54 to 480.18 pg/μmol Cr, P = 0.033), membranous nephropathy (250.23, IQR 170.37 to 357.59 pg/μmol Cr, P <0.001), secondary FSGS (220.45, IQR 149.38 to 335.54 pg/μmol Cr, P <0.001) and normal subjects (183.59, IQR 103.92 to 228.78 pg/μmol Cr, P <0.001). The urinary suPAR level of patients with cellular variant was significantly higher than that of patients with tip variant. The urinary suPAR level in the patients with primary FSGS was positively correlated with 24-hour urine protein (r = 0.287, P = 0.024). During follow up, the urinary suPAR level of patients with complete remission decreased significantly (661.19, IQR 224.32 to 1,115.29 pg/μmol Cr versus 217.68, IQR 121.77 to 415.55 pg/μmol Cr, P = 0.017). The AP5 signal was strongly induced along the cell membrane when human differentiated podocytes were incubated

  18. A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated Urokinase for Studies of Hepatocyte Transplantation

    PubMed Central

    Song, Xijun; Guo, Yushan; Duo, Shuguang; Che, Jie; Wu, Chen; Ochiya, Takahiro; Ding, Mingxiao; Deng, Hongkui

    2009-01-01

    Mouse models of liver injury provide useful tools for studying hepatocyte engraftment and proliferation. A representative model of liver injury is the albumin-urokinase (Alb-uPA) transgenic model, but neonatal lethality hampers its widespread application. To overcome this problem, we generated a transgenic mouse in which transcription of the reverse tetracycline transactivator was (rtTA) driven by the mouse albumin promoter, and backcrossed the rtTA mice onto severe combined immunodeficient (SCID)/bg mice to generate immunodeficient rtTA/SCID mice. We then produced recombinant adenoviruses Ad.TRE-uPA, in which the urokinase was located downstream of the tetracycline response element (TRE). The rtTA/SCID mouse hepatocytes were then infected with Ad.TRE-uPA to establish an inducible liver injury mouse model. In the presence of doxycycline, uPA was exclusively expressed in endogenous hepatocytes and caused extensive liver injury. Enhanced green fluorescent protein-labeled mouse hepatocytes selectively repopulated the rtTA/SCID mouse liver and replaced over 80% of the recipient liver mass after repeated administration of Ad.TRE-uPA. Compared with the original uPA mice, rtTA/SCID mice did not exhibit problems regarding breeding efficiency, and the time window for transplantation was flexible. In addition, we could control the extent of liver injury to facilitate transplantation surgery by regulating the dose of Ad.TRE-uPA. Our inducible mouse model will be convenient for studies of hepatocyte transplantation and hepatic regeneration, and this system will facilitate screening for potential genetic factors critical for engraftment and proliferation of hepatocytes in vivo. PMID:19808649

  19. Relationship of Exercise, Age, and Gender on Decompression Sickness and Venous Gas Emboli During 2-Hour Oxygen Prebreathe Prior to Hypobaric Exposure

    NASA Technical Reports Server (NTRS)

    Conkin, J.; Gernhardt, M. L.; Foster, P. P.; Pilmanis, A. A.; Butler, B. D.; Beltran, E.; Fife, C. E.; Vann, R. D.; Gerth, W. A.; Loftin, K. C.; Paloski, William H. (Technical Monitor)

    2000-01-01

    We evaluated four 2-hour oxygen prebreathe protocols combining adynamia (non-walking) and 4 different amounts of exercise for potential use with extravehicular activity (EVA) on the International Space Station. Phase I: upper and lower body exercises using dual-cycle ergometry (75% VO2 max for 10 min). Phase 11: same ergometry plus 24 min of light exercise that simulated space suit preparations. Phase III: same 24 min of light exercise but no ergometry, and Phase IV: 56 min of light exercise without ergometry. After 80 min on 100% O2, the subjects breathed 26.5% O2 - 73.5% N2 for 30 min at 10.2 psi. All subjects performed a series of upper body exercises from a recumbent position for 4 hrs at 4.3 psi to simulate EVA work. Venous gas emboli (VGE) were monitored every 12 min using precordial Doppler ultrasound. The 39 female and 126 male exposures were analyzed for correlations between decompression sickness (DCS) or VGE, and risk variables. The duration and quantity of exercise during prebreathe inversely relates to DCS and VGE incidence. The type and distribution of the 19 cases of DCS were similar to historical cases. There was no correlation of age, gender, body mass index, or fitness level with greater incidence of DCS or all VGE. However there were more Grade IV VGE in males > 40 years (10 of 19) than in those =< 40 years (3 of 107), with p<0.01 from Fisher's Exact Chi square The latency time for VGE was longer (103 min +/- 56 SD, n = 15 versus 53 min +/- 31, n =13) when the ergometry occurred about 15 min into the prebreathe than when performed at the start of the prebreathe, but the order of the ergometry did not influence the overall DCS and VGE incidence. An increasing amount of exercise during prebreathes reduced the risk of DCS during subsequent exposures to 4.3 psi. Age, gender, or fitness level did not correlate with the incidence of DCS or VGE (combination of Grades I-IV). However males greater than 40 years had a higher incidence of Grade IV VGE.

  20. HbA1c, fasting and 2-hour plasma glucose in current-, ex-, and non-smokers: a meta-analysis

    PubMed Central

    Soulimane, Soraya; Simon, Dominique; Herman, William H; Lange, Celine; Lee, Crystal MY; Colagiuri, Stephen; Shaw, Jonathan E; Zimmet, Paul Z; Magliano, Dianna; Ferreira, Sandra RS; Dong, Yanghu; Zhang, Lei; Jorgensen, Torben; Tuomilehto, Jaakko; Mohan, Viswanathan; Christensen, Dirk L; Kaduka, Lydia; Dekker, Jacqueline M; Nijpels, Giel; Stehouwer, Coen DA; Lantieri, Olivier; Fujimoto, Wilfred Y; Leonetti, Donna L; McNeely, Marguerite J; Borch-Johnsen, Knut; Boyko, Edward J; Vistisen, Dorte; Balkau, Beverley

    2014-01-01

    Aim The relations between smoking and glycaemic parameters are not well explored. We compare HbA1c, fasting plasma glucose (FPG) and 2-hour plasma glucose (2H-PG) in current-, ex- and never-smokers. Methods This meta-analysis used individual data from 16 886 men and 18 539 women without known diabetes, in 12 DETECT-2 consortium studies and in the French D.E.S.I.R. and TELECOM studies. Means of the three glycaemic parameters in current-, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I2 statistic evaluated heterogeneity among studies. Results HbA1c was 0.10 (95%CI:0.08,0.12) % [1.1 (0.9,1.3) mmol/mol] higher in current-smokers and 0.03 (0.01,0.05) % [0.3 (0.1,0.5) mmol/l] higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current- and never-smokers: −0.004 (−0.03,0.02) mmol/l but FPG was higher in ex-smokers: 0.12 (0.09,0.14) mmol/l. In comparison to never-smokers, 2H-PG was lower: −0.44 (−0.52,−0.37) mmol/l in current-smokers, with no difference for ex-smokers: 0.02 (−0.06,0.09) mmol/l. There was a large and unexplained heterogeneity among studies, with I2 always higher than 50%: after stratification by sex and adjustment for age and BMI, I2 changed little. In this study population, current-smokers had a prevalence of diabetes as screened by HbA1c, 1.30% higher and that screened by 2H-PG, 0.52% lower than in comparison to never-smokers. Conclusion Current-smokers had a higher HbA1c and a lower 2H-PG than never-smokers, across this heterogeneous group of studies; this will effect the chances of smokers being diagnosed with diabetes. PMID:24065153

  1. Transradial approach for transcatheter selective superior mesenteric artery urokinase infusion therapy in patients with acute extensive portal and superior mesenteric vein thrombosis.

    PubMed

    Wang, Mao Qiang; Guo, Li Ping; Lin, Han Ying; Liu, Feng Yong; Duan, Feng; Wang, Zhi Jun

    2010-02-01

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 +/- 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 +/- 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 +/- 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

  2. Transradial Approach for Transcatheter Selective Superior Mesenteric Artery Urokinase Infusion Therapy in Patients with Acute Extensive Portal and Superior Mesenteric Vein Thrombosis

    SciTech Connect

    Wang Maoqiang Guo Liping; Lin Hanying; Liu Fengyong; Duan Feng; Wang Zhijun

    2010-02-15

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 {+-} 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 {+-} 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 {+-} 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

  3. Examination Regimes and Student Achievement

    ERIC Educational Resources Information Center

    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…

  4. Mutation of the protein-O-mannosyltransferase enhances secretion of the human urokinase-type plasminogen activator in Hansenula polymorpha.

    PubMed

    Agaphonov, Michael O; Sokolov, Sviatoslav S; Romanova, Nina V; Sohn, Jung-Hoon; Kim, So-Young; Kalebina, Tatyana S; Choi, Eui-Sung; Ter-Avanesyan, Michael D

    2005-10-15

    Human urokinase-type plasminogen activator (uPA) is poorly secreted and aggregates in the endoplasmic reticulum of yeast cells due to inefficient folding. A screen for Hansenula polymorpha mutants with improved uPA secretion revealed a gene encoding a homologue of the Saccharomyces cerevisiae protein-O-mannosyltransferase Pmt1p. Expression of the H. polymorpha PMT1 gene (HpPMT1) abolished temperature sensitivity of the S. cerevisiae pmt1 pmt2 double mutant. As in S. cerevisiae, inactivation of the HpPMT1 gene affected electrophoretic mobility of the O-glycosylated protein, extracellular chitinase. In contrast to S. cerevisiae, disruption of HpPMT1 alone caused temperature sensitivity. Inactivation of the HpPMT1 gene decreased intracellular aggregation of uPA, suggesting that enhanced secretion of uPA was due to improvement of its folding in the endoplasmic reticulum. Unlike most of the endoplasmic reticulum membrane proteins, HpPmt1p possesses the C-terminal KDEL retention signal. PMID:16200504

  5. Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in a general population.

    PubMed

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line Jh; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  6. CHK1 and RAD51 activation after DNA damage is regulated via urokinase receptor/TLR4 signaling

    PubMed Central

    Narayanaswamy, Pavan B; Tkachuk, Sergey; Haller, Hermann; Dumler, Inna; Kiyan, Yulia

    2016-01-01

    Mechanisms of DNA damage and repair signaling are not completely understood that hinder the efficiency of cancer therapy. Urokinase-type plasminogen activator receptor (PLAUR) is highly expressed in most solid cancers and serves as a marker of poor prognosis. We show that PLAUR actively promotes DNA repair in cancer cells. On the contrary, downregulation of PLAUR expression results in delayed DNA repair. We found PLAUR to be essential for activation of Checkpoint kinase 1 (CHK1); maintenance of cell cycle arrest after DNA damage in a TP53-dependent manner; expression, nuclear import and recruitment to DNA-damage foci of RAD51 recombinase, the principal protein involved in the homologous recombination repair pathway. Underlying mechanism implies auto-/paracrine signaling of PLAUR/TLR4 receptor complex leading to activation of CHK1 and DNA repair. The signaling is induced by a danger molecule released by DNA-damaged cells and mediates, at least partially, activation of DNA-damage response. This study describes a new mechanism of DNA repair activation initiated by auto-/paracrine signaling of membrane receptors PLAUR/TLR4. It adds to the understanding of role of PLAUR in cancer and provides a rationale for therapeutic targeting of PLAUR/TLR4 interaction in TP53-positive cancers. PMID:27685627

  7. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders

    PubMed Central

    Toldi, Gergely; Balog, Attila

    2016-01-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

  8. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    PubMed Central

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line JH; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  9. A high-affinity receptor for urokinase plasminogen activator on human keratinocytes: characterization and potential modulation during migration.

    PubMed Central

    McNeill, H; Jensen, P J

    1990-01-01

    Low passage cultures of normal human keratinocytes produce several components of the plasminogen activator/plasmin proteolytic cascade, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and two specific inhibitors. Studies here presented demonstrate that these cells also contain a high-affinity (Kd = 3 x 10(-10) M) plasma membrane-binding site for uPA. High molecular weight uPA, either as the single-chain precursor or two-chain activated form, bound to the receptor; however, low molecular weight (33 kD) uPA, tPA, or epidermal growth factor did not compete for binding, demonstrating specificity. Acid treatment, which removed endogenous uPA from the receptor, was required to detect maximal binding (45,000 sites per cell). To investigate the possibility that the uPA receptor on keratinocytes may be involved in epithelial migration during wound repair, cultures were wounded and allowed to migrate into the wounded site. Binding sites for uPA were localized by autoradiographic analysis of 125I-uPA binding as well as by immunocytochemical studies using anti-uPA IgG. With both techniques uPA binding sites were detected selectively on the plasma membrane of cells at the leading edge of the migrating epithelial sheet. This localization pattern suggests that uPA receptor expression on keratinocytes may be coupled to cell migration during cutaneous wounding. Images PMID:1965151

  10. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders.

    PubMed

    Vasarhelyi, Barna; Toldi, Gergely; Balog, Attila

    2016-04-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

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

    PubMed Central

    Cathelin, Dominique; Placier, Sandrine; Ploug, Michael; Verpont, Marie-Christine; Vandermeersch, Sophie; Luque, Yosu; Hertig, Alexandre; Rondeau, Eric

    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 increases in suPAR concentration result in FSGS-like glomerular lesions and proteinuria. However, whether overexpression of suPAR, per se, contributes to the pathogenesis of FSGS in humans remains controversial. We conducted an independent set of animal experiments in which two different and well characterized forms of recombinant suPAR produced by eukaryotic cells were administered over the short or long term to wild-type (WT) mice. In accordance with the previous study, the delivered suPARs are deposited in the glomeruli. However, such deposition of either form of suPAR in the kidney did not result 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. PMID:24790179

  12. Structure-based Engineering of Species Selectivity in the Interaction Between Urokinase and its Receptor: Implication for Preclinical Cancer Therapy

    SciTech Connect

    Lin, L.; Gardsvoll, H; Huai, Q; Huang, M; Ploug, M

    2010-01-01

    The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface-associated plasminogen activation. Because plasmin activity controls fibrinolysis in a variety of pathological conditions, including cancer and wound healing, several intervention studies have focused on targeting the uPA {center_dot} uPAR interaction in vivo. Evaluations of such studies in xenotransplanted tumor models are, however, complicated by the pronounced species selectivity in this interaction. We now report the molecular basis underlying this difference by solving the crystal structure for the murine uPA {center_dot} uPAR complex and demonstrate by extensive surface plasmon resonance studies that the kinetic rate constants for this interaction can be swapped completely between these orthologs by exchanging only two residues. This study not only discloses the structural basis required for a successful rational design of the species selectivity in the uPA {center_dot} uPAR interaction, which is highly relevant for functional studies in mouse models, but it also suggests the possible development of general inhibitors that will target the uPA {center_dot} uPAR interaction across species barriers.

  13. Great Lakes' regional climate regimes

    NASA Astrophysics Data System (ADS)

    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.

  14. Cloud regimes as phase transitions

    NASA Astrophysics Data System (ADS)

    Stechmann, Samuel N.; Hottovy, Scott

    2016-06-01

    Clouds are repeatedly identified as a leading source of uncertainty in future climate predictions. Of particular importance are stratocumulus clouds, which can appear as either (i) closed cells that reflect solar radiation back to space or (ii) open cells that allow solar radiation to reach the Earth's surface. Here we show that these clouds regimes -- open versus closed cells -- fit the paradigm of a phase transition. In addition, this paradigm characterizes pockets of open cells as the interface between the open- and closed-cell regimes, and it identifies shallow cumulus clouds as a regime of higher variability. This behavior can be understood using an idealized model for the dynamics of atmospheric water as a stochastic diffusion process. With this new conceptual viewpoint, ideas from statistical mechanics could potentially be used for understanding uncertainties related to clouds in the climate system and climate predictions.

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

    PubMed

    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.

  16. alpha-2 Macroglobulin receptor/Ldl receptor-related protein(Lrp)- dependent internalization of the urokinase receptor

    PubMed Central

    1995-01-01

    The GPI-anchored urokinase plasminogen activator receptor (uPAR) does not internalize free urokinase (uPA). On the contrary, uPAR-bound complexes of uPA with its serpin inhibitors PAI-1 (plasminogen activator inhibitor type-1) or PN-1 (protease nexin-1) are readily internalized in several cell types. Here we address the question whether uPAR is internalized as well upon binding of uPA-serpin complexes. Both LB6 clone 19 cells, a mouse cell line transfected with the human uPAR cDNA, and the human U937 monocytic cell line, express in addition to uPAR also the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP/alpha 2-MR) which is required to internalize uPAR-bound uPA-PAI-1 and uPA-PN-1 complexes. Downregulation of cell surface uPAR molecules in U937 cells was detected by cytofluorimetric analysis after uPA-PAI-1 and uPA-PN-1 incubation for 30 min at 37 degrees C; this effect was blocked by preincubation with the ligand of LRP/alpha 2-MR, RAP (LRP/alpha 2-MR- associated protein), known to block the binding of the uPA complexes to LRP/alpha 2-. MR. Downregulation correlated in time with the intracellular appearance of uPAR as assessed by confocal microscopy and immuno-electron microscopy. After 30 min incubation with uPA-PAI-1 or uPA-PN-1 (but not with free uPA), confocal microscopy showed that uPAR staining in permeabilized LB6 clone 19 cells moved from a mostly surface associated to a largely perinuclear position. This effect was inhibited by the LRP/alpha 2-MR RAP. Perinuclear uPAR did not represent newly synthesized nor a preexisting intracellular pool of uPAR, since this fluorescence pattern was not modified by treatment with the protein synthesis inhibitor cycloheximide, and since in LB6 clone 19 cells all of uPAR was expressed on the cell surface. Immuno-electron microscopy confirmed the plasma membrane to intracellular translocation of uPAR, and its dependence on LRP/alpha 2-MR in LB6 clone 19 cells only after

  17. Inhibition of urokinase plasminogen activator “uPA” activity alters ethanol consumption and conditioned place preference in mice

    PubMed Central

    Al Maamari, Elyazia; Al Ameri, Mouza; Al Mansouri, Shamma; Bahi, Amine

    2014-01-01

    Urokinase plasminogen activator, uPA, is a serine protease implicated in addiction to drugs of abuse. Using its specific inhibitor, B428, we and others have characterized the role of uPA in the rewarding properties of psychostimulants, including cocaine and amphetamine, but none have examined the role of uPA in ethanol use disorders. Therefore, in the current study, we extended our observations to the role of uPA in ethanol consumption and ethanol-induced conditioned place preference. The general aim of the present series of experiments was to investigate the effects of the administration of the B428 on voluntary alcohol intake and ethanol conditioned reward. A two-bottle choice, unlimited-access paradigm was used to compare ethanol intake between vehicle- and 3, 10, and 30 mg/kg B428-administered mice. For this purpose, the mice were presented with an ethanol solution (2.5%–20%) and water, at each concentration for 4 days, and their consumption was measured daily. Consumption of saccharin and quinine solutions was also measured. Systemic administration of B428 dose-dependently decreased ethanol intake and preference. Additionally, B428 mice did not differ from vehicle mice in their intake of graded solutions of tastants, suggesting that the uPA inhibition did not alter taste function. Also, ethanol metabolism was not affected following B428 injection. More importantly, 1.5 g/kg ethanol-induced conditioned place preference acquisition was blocked following B428 administration. Taken together, our results are the first to implicate uPA inhibition in the regulation of ethanol consumption and preference, and suggest that uPA may be considered as a possible therapeutic drug target for alcoholism and abstinence. PMID:25258509

  18. Relationship between circulating tumor cells, blood coagulation, and urokinase-plasminogen-activator system in early breast cancer patients.

    PubMed

    Mego, Michal; Karaba, Marian; Minarik, Gabriel; Benca, Juraj; Sedlácková, Tatiana; Tothova, Lubomira; Vlkova, Barbora; Cierna, Zuzana; Janega, Pavol; Luha, Jan; Gronesova, Paulina; Pindak, Daniel; Fridrichova, Ivana; Celec, Peter; Reuben, James M; Cristofanilli, Massimo; Mardiak, Jozef

    2015-01-01

    Cancer is a risk factor for venous thromboembolism (VTE) and plasma d-dimer (DD) and tissue factor (TF) are established VTE associated markers. Circulating tumor cells (CTCs) are associated with the risk of VTE in metastatic breast cancer. This study aimed to correlate CTCs, blood coagulation and the urokinase plasminogen activator (uPA) system in primary breast cancer (PBC) patients. This prospective study included 116 PBC patients treated by primary surgery. CTCs were detected by quantitative RT-PCR assay for expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1, FOXC2). Plasma DD, TF, uPA system proteins were detected by enzyme-linked immunosorbent assays, while expressions of uPA system in surgical specimens were evaluated by immunohistochemistry. CTCs were detected in 27.6% patients. Patients with CTCs had a significantly higher mean plasma DD (ng/mL) than those of patients without CTCs (632.4 versus 365.4, p = 0.000004). There was no association between plasma TF and CTCs. Epithelial CTCs exhibit higher expression of uPA system genes compared to EMT_CTCs. Patients with CTCs had higher plasma uPA proteins than those of patients without CTCs; there was no correlation between tissue expression of uPA system, CTCs, DD or TF levels. In multivariate analysis CTCs and patients age were independent factors associated with plasma DD. We found association between plasma DD and CTCs indicating a potential role for activation of the coagulation cascade in the early metastatic process. CTCs could be directly involved in coagulation activation or increased CTCs could be marker of aggressive disease and increased VTE risk.

  19. Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

    PubMed Central

    Solomayer, E. F.; Diel, I. J.; Wallwiener, D.; Bode, S.; Meyberg, G.; Sillem, M.; Gollan, C.; Kramer, M. D.; Krainick, U.; Bastert, G.

    1997-01-01

    Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases. Images Figure 1 PMID:9310251

  20. Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA-R) in acute myeloid leukemia cells.

    PubMed

    Castagnari, B; Moretti, S; Latorraca, A; Rigolin, G M; Balsamo, R; Lanza, F; Castoldi, G L

    1995-01-01

    The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells. PMID:8519488

  1. Thrombosis recanalization by paeoniflorin through the upregulation of urokinase-type plasminogen activator via the MAPK signaling pathway

    PubMed Central

    YE, SONGSHAN; MAO, BINGYU; YANG, LEI; FU, WEIYUN; HOU, JUNRAN

    2016-01-01

    Paeoniflorin, the major component of Paeonia lactiflora pall, has previously been reported to prevent thrombosis. Plasminogen activator urokinase (uPA) is a serine protease that markedly facilitates normal thrombosis resolution. Paeoniflorin and uPA have been linked to the mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, the influence of paeoniflorin on the expression of uPA was investigated and the underlying regulatory mechanism was preliminarily determined. The prothrombotic state of the model animals treated with paeoniflorin were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, the cytotoxicity of paeoniflorin on human umbilical vein endothelial cell (HUVEC) cultures was estimated using a methyl thiazolyl tetrazolium assay and the possible pathways involved in the interaction between paeoniflorin and uPA were evaluated using western blot analysis. The ELISA results demonstrated that the levels of 6-keto prostaglandin F1a, fibronectin and uPA were significantly upregulated by treatment with paeoniflorin compared with control (P<0.05). By contrast, the expression of fibrinogen, D-dimer and thromboxane B2 were inhibited. With an increase in the concentration of paeoniflorin the cell viability of HUVECs decreased gradually. The results of western blot analysis demonstrated that paeoniflorin increased the phosphorylation of MAPK 14 (p38) and MAPK 8 (JNK). The present study demonstrated that paeoniflorin has the potential to improve the prethrombotic state and recanalize thrombosis by increasing the expression of uPA, which may be mediated via regulation of the p38 and JNK MAPK signaling pathways. However, this treatment effect was dependent on the concentration of paeoniflorin used, an unsuitable concentration of the agent would result in a negative effect on the anti-thrombosis pathways. PMID:27082639

  2. Plasma Soluble Urokinase Receptor Level Is Correlated with Podocytes Damage in Patients with IgA Nephropathy

    PubMed Central

    Zhao, Yanfeng; Liu, Lijun; Huang, Jing; Shi, Sufang; Lv, Jicheng; Liu, Gang; Zhao, Minghui; Zhang, Hong

    2015-01-01

    Background Focal segmental glomerulosclerosis (FSGS) lesions are similar in characteristics to S lesions of the Oxford classification of IgA nephropathy (IgAN) and may predict poor prognosis. In the present study, we aimed to explore the association between plasma soluble urokinase receptor (suPAR) levels and S lesions and podocytes damage in IgAN patients. Methods We enrolled 569 IgAN patients with follow-up data and detected plasma suPAR levels at renal biopsy by enzyme-linked immunosorbent assay. Results Plasma suPAR levels in IgAN patients with or without S lesions did not differ significantly (P = 0.411). However, suPAR levels were positively correlated with proteinuria (r = 0.202, P < 0.001), and negatively correlated with estimated glomerular filtration rate (eGFR, r = –0.236, P < 0.001). In the partial correlation to adjust for eGFR, plasma suPAR levels remained positively correlated with proteinuria (r = 0.112, P = 0.023). In a Cox proportional hazards model, higher levels of plasma suPAR were not associated with poor renal outcome. Plasma suPAR levels of IgAN and primary FSGS patients with nephrotic syndrome were not significantly different (P = 0.306). Plasma suPAR levels in patients with extensive effacement of the epithelial cell foot processes of glomerular podocytes were significantly higher than those with segmental effacement on the basis of comparable eGFR (P = 0.036). Conclusions In IgAN patients, plasma suPAR levels were not associated with S lesions. However, they were positively associated with proteinuria and negatively associated with eGFR. In addition, plasma suPAR levels were positively associated with the effacement degree of the foot processes, which might partially contribute to the development of proteinuria in patients with IgAN. PMID:26167688

  3. A Regime Diagram for Subduction

    NASA Astrophysics Data System (ADS)

    Stegman, D. R.; Farrington, R.; Capitanio, F. A.; Schellart, W. P.

    2009-12-01

    Regime diagrams and associated scaling relations have profoundly influenced our understanding of planetary dynamics. Previous regime diagrams characterized the regimes of stagnant-lid, small viscosity contrast, transitional, and no-convection for temperature-dependent (Moresi and Solomatov, 1995), and non-linear power law rheologies (Solomatov and Moresi, 1997) as well as stagnant-lid, sluggish-lid, and mobile-lid regimes once the finite strength of rock was considered (Moresi and Solomatov, 1998). Scalings derived from such models have been the cornerstone for parameterized models of thermal evolution of rocky planets and icy moons for the past decade. While such a theory can predict the tectonic state of a planetary body, it is still rather incomplete in regards to predicting tectonics. For example, the mobile-lid regime is unspecific as to how continuous lithospheric recycling should occur on a terrestrial planet. Towards this goal, Gerya et al., (2008) advanced a new regime diagram aiming to characterize when subduction would manifest itself as a one-sided or two-sided downwelling and either symmetric or asymmetric. Here, we present a regime diagram for the case of a single-sided, asymmetric type of subduction (most Earth-like type). Using a 3-D numerical model of a free subduction, we describe a total of 5 different styles of subduction that can possibly occur. Each style is distinguished by its upper mantle slab morphology resulting from the sinking kinematics. We provide movies to illustrate the different styles and their progressive time-evolution. In each regime, subduction is accommodated by a combination of plate advance and slab rollback, with associated motions of forward plate velocity and trench retreat, respectively. We demonstrate that the preferred subduction mode depends upon two essential controlling factors: 1) buoyancy of the downgoing plate and 2) strength of plate in resisting bending at the hinge. We propose that a variety of subduction

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

    PubMed Central

    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

  5. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    SciTech Connect

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P. . E-mail: fpchou@csmu.edu.tw

    2006-07-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-{kappa}B, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.

  6. Merging of Rhine flow regimes

    NASA Astrophysics Data System (ADS)

    Boessenkool, Berry; Bronstert, Axel; Bürger, Gerd

    2016-04-01

    The Rhine flow regime is changing: (a) in the alpine nival regime, snow melt floods occur earlier in the year and (b) in the pluvial middle-Rhine regime, rainfall induced flood magnitudes rise. The seasonality of each is currently separated in time, but it is conceivable that this may shift due to climate change. If extremes of both flood types coincide, this would create a new type of hydrologic extreme with disastrous consequences. Quantifying the probability for a future overlap of pluvial and nival floods is therefore of high relevance to society and particularly to reinsurance companies. In order to investigate possible changes in magnitude and timing of flood types, we are developing a chain of physical models for spatio-temporal combination of flood probabilities. As input, we aim to use stochastically downscaled temperature and rainfall extremes from climate model weather projections. Preliminary research shows a six-week forward-shift of peak discharge at the nival gauge Maxau in the past century. The aim of presenting our early-stage work as a poster is to induce an exchange of ideas with fellow scientists in close research disciplines.

  7. Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer.

    PubMed Central

    Yamashita, J.; Ogawa, M.; Yamashita, S.; Nakashima, Y.; Saishoji, T.; Nomura, K.; Inada, K.; Kawano, I.

    1993-01-01

    Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were

  8. Epitope-mapped monoclonal antibodies as tools for functional and morphological analyses of the human urokinase receptor in tumor tissue.

    PubMed Central

    Luther, T.; Magdolen, V.; Albrecht, S.; Kasper, M.; Riemer, C.; Kessler, H.; Graeff, H.; Müller, M.; Schmitt, M.

    1997-01-01

    uPAR (CD87), the receptor for the urokinase-type plasminogen activator (uPA) facilitates tumor cell invasion and metastasis by focusing uPA proteolytic activity to the cell surface. As uPAR exists in various molecular forms, it is desirable to use well defined antibodies for analyses of uPAR antigen expression in human malignant tumors by immunological methods. Therefore, twelve monoclonal antibodies (MAbs) directed against uPAR were generated by using nonglycosylated, recombinant human uPAR (spanning amino acids 1 to 284), expressed in Escherichia coli, as the immunogen. The reaction pattern of these MAbs with the immunogen and a series of carboxyl-terminally truncated versions of uPAR demonstrated that at least six different epitopes of uPAR are recognized. All MAbs reacted under reducing conditions in immunoblot analyses with E. coli-expressed uPA and also with highly glycosylated, functionally intact, recombinant human uPAR expressed in Chinese hamster ovary (CHO) cells. Seven of the MAbs recognized CHO uPAR under nonreducing conditions as well. By flow cytofluorometric analyses, three of these MAbs were shown to bind to native human uPAR present on the cell surface of monocytoid U937 cells with MAb IIIF10 being the best. Saturation of uPAR with uPA on U937 cells completely blocked interaction of MAb IIIF10 with uPAR (mapped epitope, amino acids 52 to 60 of domain I of uPAR). In turn, preincubation of U937 cells with MAb IIIF10 efficiently reduced binding of uPA to uPAR, indicating that the epitope detected by MAb IIIF10 is located within or closely to the uPA-binding site of uPAR, and thus, this site may be a target to influence uPA/uPAR-mediated proteolysis in tumors. Binding of MAbs IID7 or IIIB11 (mapped epitope, amino acids 125 to 132 of domain II of uPAR) to uPAR is not affected when uPAR is occupied by uPA. As these MAbs reacted strongly with cellular uPAR antigen in formalin-fixed paraffin-embedded tumor sections, the domain-II-specific antibodies IID7

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

    PubMed

    Hilty, Matthias Peter; 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

  10. Structural analysis and tissue localization of human C4.4A: a protein homologue of the urokinase receptor.

    PubMed Central

    Hansen, Line V; Gårdsvoll, Henrik; Nielsen, Boye S; Lund, Leif R; Danø, Keld; Jensen, Ole N; Ploug, Michael

    2004-01-01

    C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor (uPAR), was originally identified as a metastasis-associated membrane protein, but little is known about its structural and functional properties. Therefore, we expressed, purified and characterized a soluble truncated form of human C4.4A, and used this protein to produce specific polyclonal anti-C4.4A antibodies. By immunohistochemistry we observed a pronounced surface staining for C4.4A in suprabasal keratinocytes of chronic human wounds and found C4.4A expression markedly upregulated in migrating keratinocytes during re-epithelisation of incisional skin wounds. Phorbol-ester-induced hyperplasia of mouse skin is also accompanied by a significant induction of C4.4A expression in the multilayered, suprabasal keratinocytes. C4.4A contains two Ly-6 (leucocyte antigen 6)/uPAR/alpha-neurotoxin modules. Our recombinant human C4.4A is extensively modified by post-translational glycosylation, which include 5-6 N-linked carbohydrates primarily located in or close to its second Ly-6/uPAR/alpha-neurotoxin module and approximately 15 O-linked carbohydrates clustered in a Ser/Thr/Pro-rich region at the C-terminus. A highly protease-sensitive region (Tyr200-Arg204) is located between these two clusters of N- and O-linked carbohydrates. The natural, glycolipid-anchored C4.4A from amnion membranes of human term placenta exhibits similar properties. Using recombinant, soluble C4.4A or MCF 7 cells, which express significant amounts of GPI-anchored C4.4A, we find no evidence for an interaction between C4.4A and uPA, a property suggested previously for rat C4.4A. Collectively these data indicate that C4.4A, although being a structural homologue of uPAR, is unlikely to have a functional overlap with uPAR. PMID:15012588

  11. Expression and functional role of urokinase-type plasminogen activator receptor in normal and acute leukaemic cells.

    PubMed

    Lanza, F; Castoldi, G L; Castagnari, B; Todd, R F; Moretti, S; Spisani, S; Latorraca, A; Focarile, E; Roberti, M G; Traniello, S

    1998-10-01

    Urokinase-type plasminogen activator receptor (UPA-R-CD87) is a GPI-anchored membrane protein which promotes the generation of plasmin on the surface of many cell types, probably facilitating cellular extravasation and tissue invasion. A flow cytometric quantitative analysis of expression levels for UPA-R was performed on fresh blast cells from patients with acute myeloid leukaemia (AML, n = 74), acute lymphoblastic leukaemia (ALL, n = 24), and biphenotypic leukaemia (BAL, n = 3) using two CD87 monoclonal antibodies (McAbs) (3B10 and VIM5). Peripheral blood and bone marrow (BM) cells from 15 healthy adults served as controls. Using 3B10 McAb, UPA-R was expressed (>99%) by blood monocytes, neutrophils, and BM myelomonocytic precursors in controls, whereas resting T and B lymphocytes, and CD34+ cells were UPA-R negative. We also attempted to clarify whether UPA-R has a role in mediating neutrophil functions. Oriented locomotion induced by different chemotaxins and lysozyme release by granules stimulated with fMLP or PMA were significantly decreased when UPA-R was neutralized by CD87 McAb. In contrast, the anti-UPA-R McAb had no effect on superoxide anion generation of normal neutrophils. Blasts from AML showed a heterogenous pattern of expression for the UPA-R McAbs, with reactivity strictly dependent on FAB subtype. The highest UPA-R expression was seen in the M5 group: all patients tested (n = 20) showed strong positivity for the UPA-R McAb whereas only 12% (3/24) of ALL patients were CD87 positive, and 2/3 of BAL patients showed a dim expression for CD87. The number of receptors expressed by blast cells in 6/74 (8.1%) AML patients was higher than those of normal samples: in addition, since co-expression of UPA-R and CD34 was not found in normal haemopoietic cells, it may be postulated that CD87 can be used alone (when overexpressed) or in combination with CD34 for the detection of minimal residual disease. Results also indicated that patients with UPA

  12. Presence of urokinase in serum-free primary rat hepatocyte cultures and its role in activating hepatocyte growth factor.

    PubMed

    Mars, W M; Kim, T H; Stolz, D B; Liu, M L; Michalopoulos, G K

    1996-06-15

    Serum-free rat hepatocyte cultures can be stimulated to divide by the inactive, single-chain form of hepatocyte growth factor (scHGF), suggesting that hepatocytes contain a protein that can cleave scHGF to its biologically active, two-chain (tcHGF) form. We added radiolabeled scHGF to serum-free cultures and confirmed that tcHGF was being generated. Because scHGF can be cleaved to tcHGF by plasminogen activators (PAs), we next tested the cultures for active PA. Although little PA activity was initially present, the majority was of the urokinase type (u-PA) as determined by neutralization studies using either a polyclonal antibody against u-PA or, since u-PA functions in the context of its receptor (u-PAR), a monoclonal antibody against u-PAR. Considerable PA activity developed within 24 h, which was also neutralizable with antibody. To test whether the active, receptor-bound u-PA from the cell cultures was cleaving scHGF, iodinated scHGF was added to intact cells in the presence of the antibody against u-PAR. Comparison to control cultures determined that the antibody prevented scHGF cleavage. Analysis of cultures treated with HGF, epidermal growth factor, and transforming growth factor alpha (TGF-alpha) alpha showed these growth factors increased the hepatocyte PA activity in parallel with the mRNA for u-PA. TGF-beta had the opposite effect, and when TGF-beta was added to the culture system, conversion of scHGF to tcHGF was prevented in concert with the production of the type 1 PA inhibitor. When liver remnants from hepatectomized animals were assayed for active TGF-beta, elevated protein was found just prior to the appearance of PA inhibitor 1 message and protein. Collectively, our data show that in culture, active u-PA is present and cleaves scHGF to tcHGF in the context of its receptor. It also suggests that modulation of u-PA activity by various growth factors is relevant for regulating cleavage of scHGF to tcHGF both in vitro and in vivo.

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

    PubMed Central

    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

  14. Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes

    PubMed Central

    Magnussen, Synnøve; Hadler-Olsen, Elin; Latysheva, Nadezhda; Pirila, Emma; Steigen, Sonja E.; Hanes, Robert; Salo, Tuula; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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

  15. Preparation and antitumor effect of a toxin-linked conjugate targeting vascular endothelial growth factor receptor and urokinase plasminogen activator

    PubMed Central

    Xiang, Ying; Li, Qiying; Huang, Dehong; Tang, Xianjun; Wang, Li; Shi, Yang; Zhang, Wenjun; Yang, Tao; Xiao, Chunyan

    2015-01-01

    The aberrant signaling activation of vascular endothelial growth factor receptor (VEGFR) and urokinase plasminogen activator (uPA) is a common characteristic of many tumors, including lung cancer. Accordingly, VEGFR and uPA have emerged as attractive targets for tumor. KDR (Flk-1/VEGFR-2), a member of the VEGFR family, has been recognized as an important target for antiangiogenesis in tumor. In this study, a recombinant immunotoxin was produced to specifically target KDR-expressing tumor vascular endothelial cells and uPA-expressing tumor cells and mediate antitumor angiogenesis and antitumor effect. Based on its potent inhibitory effect on protein synthesis, Luffin-beta (Lβ) ribosome-inactivating protein was selected as part of a recombinant fusion protein, a single-chain variable fragment against KDR (KDRscFv)-uPA cleavage site (uPAcs)-Lβ-KDEL (named as KPLK). The KDRscFv-uPAcs-Lβ-KDEL (KPLK) contained a single-chain variable fragment (scFv) against KDR, uPAcs, Lβ, and the retention signal for endoplasmic reticulum proteins KDEL (Lys-Asp-Glu-Leu). The KPLK-expressing vector was expressed in Escherichia coli, and the KPLK protein was isolated with nickel affinity chromatography and gel filtration chromatography. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis test demonstrated KPLK was effectively expressed. Result of in vitro cell viability assay on non-small cell lung cancer (NSCLC) H460 cell line (uPA-positive cell) revealed that KPLK significantly inhibited cell proliferation, induced apoptosis, and accumulated cells in S and G2/M phases, but the normal cell line (human submandibular gland cell) was unaffected. These effects were enhanced when uPA was added to digest KPLK to release Lβ. For in vivo assay of KPLK, subcutaneous xenograft tumor model of nude mice were established with H460 cells. Growth of solid tumors was significantly inhibited in animals treated with KPLK up to 21 days, tumor weights were decreased, and the expression of

  16. The thermal regime of Venus

    SciTech Connect

    Solomatov, V.S.; Zharkov, V.N. )

    1990-04-01

    In the present numerical modeling study of the thermal evolution of Venus, the mantle is taken to be composed of independently convecting upper and lower mantles. A novel parameterization is used which takes into account recent numerical investigations in media with complex rheology. The parameters of the convecting planet in the asymptotic regime do not depend on initial conditions, and are ascertained analytically. Convection in the lower part of the crust is demonstrated to be involved in regions having specific crustal composition; heat transfer to the surface is primarily via advection by magmas that are produced by melting of the lower layers of the crust. 50 refs.

  17. Breddin's graph for tectonic regimes

    NASA Astrophysics Data System (ADS)

    Célérier, Bernard; Séranne, Michel

    2001-05-01

    A simple graphical method is proposed to infer the tectonic regime from a fault and slip data set. An abacus is overlaid on a plot of the rake versus strike of the data. This yields the horizontal principal stress directions and a constraint on the stress tensor aspect ratio, in a manner similar to Breddin's graph for two-dimensional strain analysis. The main requirement is that one of the principal stress directions is close to the vertical. This method is illustrated on monophase synthetic and natural data, but is also expected to help sort out multiphase data sets.

  18. The New English Quality Assurance Regime

    ERIC Educational Resources Information Center

    Brown, Roger

    2011-01-01

    England is developing a new quality assurance regime that will come into effect in October 2011. A new funding regime will operate from the following year, together with new rules to ease the participation of private higher education providers. This article describes and analyses the new quality and funding regimes. It argues that the greater…

  19. Adaptation in Collaborative Governance Regimes

    NASA Astrophysics Data System (ADS)

    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. Different regimes of dynamic wetting

    NASA Astrophysics Data System (ADS)

    Gustav, Amberg; Wang, Jiayu; Do-Quang, Minh; Shiomi, Junichiro; Physiochemical fluid mechanics Team; Maruyama-Chiashi Laboratory Team

    2014-11-01

    Dynamic wetting, as observed when a droplet contacts a dry solid surface, is important in various engineering processes, such as printing, coating, and lubrication. Our overall aim is to investigate if and how the detailed properties of the solid surface influence the dynamics of wetting. Here we discuss how surface roughness influences the initial dynamic spreading of a partially wetting droplet by studying the spreading on a solid substrate patterned with microstructures just a few micrometers in size. This is complemented by matching numerical simulations. We present a parameter map, based on the properties of the liquid and the solid surface, which identifies qualitatively different spreading regimes, where the spreading speed is limited by either the liquid viscosity, the surface properties, or the liquid inertia. The peculiarities of the different spreading regimes are studied by detailed numerical simulations, in conjuction with experiments. This work was financially supported in part by, the Japan Society for the Promotion of Science (J.W. and J.S) and Swedish Governmental Agency for Innovation Systems (M.D.-Q. and G.A).

  1. Adaptation in collaborative governance regimes.

    PubMed

    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.

  2. Optimization of Crystals of an Inhibitory Antibody of Urokinase Plasminogen Activator Receptor (uPAR) with Hydrogen Peroxide and Low Protein Concentration

    SciTech Connect

    Li, Yongdong; Shi, Xiaoli; Parry, Graham; Chen, Liqing; Callahan, Jennifer A.; Mazar, Andrew P.; Huang, Mingdong

    2010-07-19

    Optimization of protein crystal formation is often a necessary step leading to diffraction-quality crystals to enable collection of a full X-ray data set. Typical protein crystal optimization involves screening different components, e.g., pH, precipitants, and additives of the precipitant solution. Here we present an example using an inhibitory antibody of urokinase plasminogen activator receptor (uPAR) where such procedures did not yield diffracting crystals. In contrast, it was the treatment of the protein with hydrogen peroxide incubation and the protein concentration reduction that were found to be key factors in obtaining diffracting crystals. Final crystals diffracted to 1.75 {angstrom}, and belong to orthorhombic P212121 space group with unit cell parameters a = 37.162 {angstrom}, b = 84.474 {angstrom}, c = 134.030 {angstrom}, and contain one molecule of Fab fragment of anti-uro kinase receptor antibody in the asymmetric unit.

  3. Stimulation of urokinase-type plasminogen activator receptor expression by PMA requires JNK1-dependent and -independent signaling modules.

    PubMed

    Gum, R; Juarez, J; Allgayer, H; Mazar, A; Wang, Y; Boyd, D

    1998-07-16

    The urokinase-type plasminogen activator receptor (u-PAR) has been implicated in tumor progression, and previous studies have shown that the expression of this gene is strongly up-regulated by PMA. Although the signaling mechanism by which PMA modulates u-PAR expression is not known, the effect of this phorbol ester on the expression of other genes has been ascribed to activation of the c-Raf-1-ERK signaling pathway. However, in the current study we examined an alternate possibility that the inductive effect of PMA on u-PAR expression also required a JNK1-dependent signaling cascade usually associated with stress-inducing stimuli. PMA treatment of the u-PAR-deficient OVCAR-3 ovarian cancer cells, which contain low JNK activities, resulted in a rapid (5 min) increase in JNK activity. Maximal JNK activity (12-fold induction) occurred after 30 min; this preceding the earliest detected rise in u-PAR protein (2 h). Dose-response studies with PMA also indicated that the increased JNK activity was tightly correlated with elevated u-PAR protein levels. The stimulation of u-PAR promoter activity by PMA required an intact upstream AP-1 motif (-184) and in PMA-treated cells this motif was bound with c-Jun as indicated from mobility shift assays. PMA up-regulated the c-Jun trans acting activity as indicated by the higher activity of a GAL4-regulated luciferase reporter in phorbol-ester-treated cells co-transfected with an expression vector encoding the c-Jun transactivation domain fused to the GAL4 DNA-binding domain. The ability of PMA to stimulate u-PAR promoter activity was effectively titrated out by the co-expression of either a kinase-defective JNK1 or a dominant negative MEKK1 the latter being an upstream activator of JNK1. Conversely, u-PAR promoter activity was stimulated by the co-expression of a constitutively active MEKK1 and this induction was antagonized by the inclusion of the kinase-defective JNK1 plasmid. We also determined the biological significance of the

  4. The Role of Urokinase Plasminogen Activator and Plasmin Activator Inhibitor-1 on Vein Wall Remodeling in Experimental Deep Vein Thrombosis

    PubMed Central

    Baldwin, Joe F.; Sood, Vikram; Elfline, Megan A.; Luke, Cathy E.; Dewyer, Nicholas A.; Diaz, Jose A.; Myers, Dan D.; Wakefield, Thomas; Henke, Peter K.

    2012-01-01

    OBJECTIVE Deep vein thrombosis (DVT) resolution instigates an inflammatory response, resulting in vessel wall damage and scarring. Urokinase-plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), are integral components of the fibrinolytic system, essential for VT resolution. This study determined the vein wall response when exposed to increased and decreased plasmin activity. Methods A mouse inferior vena cava (IVC) ligation model in uPA −/− or PAI-1 −/− and their genetic wild types (B6/SvEv and C57/BL6, respectively) was used to create stasis thrombi, with tissue harvest at either 8 or 21d. Tissue analysis included gene expression of vascular smooth muscle cells (alpha SMA [αSMA], SM22) and endothelial marker (CD31), by real time PCR, ELISA, matrix metalloproteinase (MMP) -2 and 9 activity by zymography and vein wall collagen by picrosirius red histological analysis. A P < .05 was considered significant. RESULTS Thrombi were significantly larger in both 8d and 21d uPA −/− as compared to WT, and were significantly smaller in both 8 and 21d PAI-1 −/− as compared to WT. Correspondingly, 8d plasmin levels were reduced in half in uPA −/− and increased 3 fold in PAI-1 −/− when compared to respective WT thrombi (P < .05, N = 5 – 6). The endothelial marker CD31 was elevated 2 fold in PAI-1 −/− mice at 8d, but reduced 2.5 fold at 21d in uPA −/− as compared with WT (P = .02, N = 5 – 6), suggesting less endothelial preservation. Vein wall VSMC gene expression showed that 8d and 21d PAI-1 −/− mice had 2.3 and 3.8 fold more SM22 and 1.8 and 2.3 fold more αSMA expression than respective WT (P < .05, N = 5 – 7), as well as 1.8 fold increased αSMA (+) cells (N = 3 – 5, P ≤ .05). No significant difference in MMP2 or 9 activity was found in the PAI-1 −/− mice compared with WT, while 5.4 fold more MMP9 was present in 21d WT than 21d uPA −/− (P = .03, N = 5). Lastly, collagen was ~2 fold

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

    PubMed

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai; Luo, Zhipu; Li, Rui; Gårdsvoll, Henrik; de Lorenzi, Valentina; Sidenius, Nicolai; Huang, Mingdong; Ploug, Michael

    2015-12-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane protein often expressed in the microenvironment of invasive solid cancers and high levels are generally associated with poor patient prognosis (Kriegbaum et al., 2011 [1]). uPAR is organized 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 specificities using this protein as antigen; (3) mapping the functional epitope on uPAR for these mAbs by surface plasmon resonance with a complete library of purified single-site uPAR mutants (Zhao et al., 2015; Gårdsvoll et al., 2006 [5,6]); and finally (4) solving the three-dimensional structures for one of these mAbs by X-ray crystallography alone and in complex with uPAR [deposited in the PDB database as 4QTH and 4QTI, respectively].

  6. Urokinase-type Plasminogen Activator-like Proteases in Teleosts Lack Genuine Receptor-binding Epidermal Growth Factor-like Domains*

    PubMed Central

    Bager, René; Kristensen, Thomas K.; Jensen, Jan K.; Szczur, Agnieszka; Christensen, Anni; Andersen, Lisbeth M.; Johansen, Jesper S.; Larsen, Niels; Baatrup, Erik; Huang, Mingdong; Ploug, Michael; Andreasen, Peter A.

    2012-01-01

    Plasminogen activation catalyzed by urokinase-type plasminogen activator (uPA) plays an important role in normal and pathological tissue remodeling processes. Since its discovery in the mid-1980s, the cell membrane-anchored urokinase-type plasminogen activator receptor (uPAR) has been believed to be central to the functions of uPA, as uPA-catalyzed plasminogen activation activity appeared to be confined to cell surfaces through the binding of uPA to uPAR. However, a functional uPAR has so far only been identified in mammals. We have now cloned, recombinantly produced, and characterized two zebrafish proteases, zfuPA-a and zfuPA-b, which by several criteria are the fish orthologs of mammalian uPA. Thus, both proteases catalyze the activation of fish plasminogen efficiently and both proteases are inhibited rapidly by plasminogen activator inhibitor-1 (PAI-1). But zfuPA-a differs from mammalian uPA by lacking the exon encoding the uPAR-binding epidermal growth factor-like domain; zfuPA-b differs from mammalian uPA by lacking two cysteines of the epidermal growth factor-like domain and a uPAR-binding sequence comparable with that found in mammalian uPA. Accordingly, no zfuPA-b binding activity could be found in fish white blood cells or fish cell lines. We therefore propose that the current consensus of uPA-catalyzed plasminogen activation taking place on cell surfaces, derived from observations with mammals, is too narrow. Fish uPAs appear incapable of receptor binding in the manner known from mammals and uPA-catalyzed plasminogen activation in fish may occur mainly in solution. Studies with nonmammalian vertebrate species are needed to obtain a comprehensive understanding of the mechanism of plasminogen activation. PMID:22733817

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

    PubMed

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai; Luo, Zhipu; Li, Rui; Gårdsvoll, Henrik; de Lorenzi, Valentina; Sidenius, Nicolai; Huang, Mingdong; Ploug, Michael

    2015-12-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane protein often expressed in the microenvironment of invasive solid cancers and high levels are generally associated with poor patient prognosis (Kriegbaum et al., 2011 [1]). uPAR is organized 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 specificities using this protein as antigen; (3) mapping the functional epitope on uPAR for these mAbs by surface plasmon resonance with a complete library of purified single-site uPAR mutants (Zhao et al., 2015; Gårdsvoll et al., 2006 [5,6]); and finally (4) solving the three-dimensional structures for one of these mAbs by X-ray crystallography alone and in complex with uPAR [deposited in the PDB database as 4QTH and 4QTI, respectively]. PMID:26504891

  8. Permafrost and the geothermal regime

    NASA Astrophysics Data System (ADS)

    Lachenbruch, A. H.; Marshall, B. V.

    Permafrost is the region in the solid earth where the temperature is below 0 C summer and winter. Within this region, water usually occurs as ice, often in massive segregated forms, although capillary water, brines, and gas hydrates also occur. The frozen condition renders permafrost impermeable to water flow, subject to brittle fracture under seasonally induced thermal stress, and subject to mechanical failure and flow when thawed by natural processes or disturbed by man. Hence an understanding of the factors controlling the geothermal regime is necessary for an understanding of geomorphic processes and for successful design of engineering structures such as roadways, heated buildings, pipelines, and oil wells in permafrost terrains. Studies of these factors are greatly simplified by the general absence of heat transfer by flowing ground water; temperatures are estimated with confidence from heat-conduction theory if the ground surface temperature, regional heat flow, and thermal properties are known.

  9. Propagation Regime of Iron Dust Flames

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

    A flame propagating through an iron-dust mixture can propagate in two asymptotic regimes. When the characteristic time of heat transfer between particles is much smaller than the characteristic time of particle combustion, the flame propagates in the continuum regime where the heat released by reacting particles can be modelled as a space-averaged function. In contrast, when the characteristic time of heat transfer is much larger than the particle reaction time, the flame can no longer be treated as a continuum due to dominating effects associated with the discrete nature of the particle reaction. The discrete regime is characterized by weak dependence of the flame speed on the oxygen concentration compared to the continuum regime. The discrete regime is observed in flames propagating through an iron dust cloud within a gas mixture containing xenon, while the continuum regime is obtained when xenon is substituted with helium.

  10. Discriminatory Proofreading Regimes in Nonequilibrium Systems

    NASA Astrophysics Data System (ADS)

    Murugan, Arvind; Huse, David A.; Leibler, Stanislas

    2014-04-01

    We use ideas from kinetic proofreading, an error-correcting mechanism in biology, to identify new kinetic regimes in nonequilibrium systems. These regimes are defined by the sensitivity of the occupancy of a state of the system to a change in its energy. In biological contexts, higher sensitivity corresponds to stronger discrimination between molecular substrates with different energetics competing in the same reaction. We study this discriminatory ability in systems with discrete states that are connected by a general network of transitions. We find multiple regimes of different discriminatory ability when the energy of a given state of the network is varied. Interestingly, the occupancy of the state can even increase with its energy, corresponding to an "antiproofreading" regime. The number and properties of such discriminatory regimes are limited by the topology of the network. Finally, we find that discriminatory regimes can be changed without modifying any "hard-wired" structural aspects of the system but rather by simply changing external chemical potentials.

  11. Regimes of suprathermal electron transport

    SciTech Connect

    Glinsky, M.E.

    1995-07-01

    Regimes of the one-dimensional (1-D) transport of suprathermal electrons into a cold background plasma are delineated. A well ordered temporal progression is found through eras where {ital J}{center_dot}{ital E} heating, hot electron--cold electron collisional heating, and diffusive heat flow dominate the cold electron energy equation. Scaling relations for how important quantities such as the width and temperature of the heated layer of cold electrons evolve with time are presented. These scaling relations are extracted from a simple 1-D model of the transport which can be written in dimensionless form with one free parameter. The parameter is shown to be the suprathermal electron velocity divided by the drift velocity of cold electrons which balances the suprathermal current. Special attention is paid to the assumptions which allow the reduction from the collisional Vlasov equation, using a Fokker--Planck collision operator, to this simple model. These model equations are numerically solved and compared to both the scaling relations and a more complete multigroup electron diffusion transport. Implications of the scaling relations on fast ion generation, magnetic field generation, and electric field inhibition of electron transport are examined as they apply to laser heated plasmas. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  12. Multistability of synchronous regimes in rotator ensembles.

    PubMed

    Kryukov, A K; Petrov, V S; Osipov, G V; Kurths, J

    2015-12-01

    We study collective dynamics in rotator ensembles and focus on the multistability of synchronous regimes in a chain of coupled rotators. We provide a detailed analysis of the number of coexisting regimes and estimate in particular, the synchronization boundary for different types of individual frequency distribution. The number of wave-based regimes coexisting for the same parameters and its dependence on the chain length are estimated. We give an analytical estimation for the synchronization frequency of the in-phase regime for a uniform individual frequency distribution. PMID:26723160

  13. Regimes of DNA confined in a nanochannel

    NASA Astrophysics Data System (ADS)

    Dai, Liang; Doyle, Patrick

    2014-03-01

    Scaling regimes for polymers confined to tubular channels are well established when the channel cross-sectional dimension is either very small (Odjik regime) or large (classic de Gennes regime) relative to the polymer Kuhn length. In the literature, there is no clear consensus regarding the intermediate region and if subregimes even exist to connect these two classic bounding regimes. The confluence of emerging single DNA mapping technologies and a resurged interest in the fundamental properties of confined polymers has led to extensive research in this area using DNA as a model system. Due to the DNA molecule's properties and limitations of nanofabrication, most experiments are performed in this intermediate regime with channel dimensions of a few Kuhn lengths. Here we use simulations and theory to reconcile conflicting theories and show that there are indeed extended de Gennes, partial alignment and hairpin regimes located between the two classic regimes. Simulations results for both chain extension and free energy support the existence of these regimes. This research was supported by the National Research Foundation Singapore through the Singapore MIT Alliance for Research and Technology's research program in BioSystems and Micromechanics, the National Science Foundation (CBET-1335938).

  14. FISHER INFORMATION AND ECOSYSTEM REGIME CHANGES

    EPA Science Inventory

    Following Fisher’s work, we propose two different expressions for the Fisher Information along with Shannon Information as a means of detecting and assessing shifts between alternative ecosystem regimes. Regime shifts are a consequence of bifurcations in the dynamics of an ecosys...

  15. Capacitance densitometer for flow regime identification

    DOEpatents

    Shipp, Jr., Roy L.

    1978-01-01

    This invention relates to a capacitance densitometer for determining the flow regime of a two-phase flow system. A two-element capacitance densitometer is used in conjunction with a conventional single-beam gamma densitometer to unambiguously identify the prevailing flow regime and the average density of a flowing fluid.

  16. Discrete fluorescent saturation regimes in multilevel systems

    NASA Technical Reports Server (NTRS)

    Kastner, S. O.; Bhatia, A. K.

    1988-01-01

    Using models of multilevel atoms, the fluorescent process was examined for the ratio of the photooxidation rate, Pij, to the collisional oxidation rate, Cij, in the pumped resonance transition i-j. It is shown that, in the full range of the parameter Pij/Cij, there exist three distinct regimes (I, II, and III) which may be usefully exploited. These regimes are defined, respectively, by the following conditions: Pij/Cij smaller than about 1; Pij/Cij much greater than 1 and Pij much lower than Cki; and Pij/Cij much greater than 1 and Pij much higher than Cki, where Cki is the collisional rate populating the source level i. The only regime which is characterized by the sensitivity of fluorescent-fluorescent line intensity ratios to Pij is regime I. If regime III is reached, even fluorescent-nonfluorescent line ratios become independent of Pij. The analysis is applied to the resonant photoexcitation of a carbonlike ion.

  17. Snowpack regimes of the Western United States

    NASA Astrophysics Data System (ADS)

    Trujillo, Ernesto; Molotch, Noah P.

    2014-07-01

    Snow accumulation and melt patterns play a significant role in the water, energy, carbon, and nutrient cycles in the montane environments of the Western United States. Recent studies have illustrated that changes in the snow/rainfall apportionments and snow accumulation and melt patterns may occur as a consequence of changes in climate in the region. In order to understand how these changes may affect the snow regimes of the region, the current characteristics of the snow accumulation and melt patterns must be identified. Here we characterize the snow water equivalent (SWE) curve formed by the daily SWE values at 766 snow pillow stations in the Western United States, focusing on several metrics of the yearly SWE curves and the relationships between the different metrics. The metrics are the initial snow accumulation and snow disappearance dates, the peak snow accumulation and date of peak, the length of the snow accumulation season, the length of the snowmelt season, and the snow accumulation and snowmelt slopes. Three snow regimes emerge from these results: a maritime, an intermountain, and a continental regime. The maritime regime is characterized by higher maximum snow accumulations reaching 300 cm and shorter accumulation periods of less than 220 days. Conversely, the continental regime is characterized by lower maximum accumulations below 200 cm and longer accumulation periods reaching over 260 days. The intermountain regime lies in between. The regions that show the characteristics of the maritime regime include the Cascade Mountains, the Klamath Mountains, and the Sierra Nevada Mountains. The intermountain regime includes the Eastern Cascades slopes and foothills, the Blue Mountains, Northern and Central basins and ranges, the Columbia Mountains/Northern Rockies, the Idaho Batholith, and the Canadian Rockies. Lastly, the continental regime includes the Middle and Southern Rockies, and the Wasatch and Uinta Mountains. The implications of snow regime

  18. Abrupt climate-independent fire regime changes

    USGS Publications Warehouse

    Pausas, Juli G.; Keeley, Jon E.

    2014-01-01

    Wildfires have played a determining role in distribution, composition and structure of many ecosystems worldwide and climatic changes are widely considered to be a major driver of future fire regime changes. However, forecasting future climatic change induced impacts on fire regimes will require a clearer understanding of other drivers of abrupt fire regime changes. Here, we focus on evidence from different environmental and temporal settings of fire regimes changes that are not directly attributed to climatic changes. We review key cases of these abrupt fire regime changes at different spatial and temporal scales, including those directly driven (i) by fauna, (ii) by invasive plant species, and (iii) by socio-economic and policy changes. All these drivers might generate non-linear effects of landscape changes in fuel structure; that is, they generate fuel changes that can cross thresholds of landscape continuity, and thus drastically change fire activity. Although climatic changes might contribute to some of these changes, there are also many instances that are not primarily linked to climatic shifts. Understanding the mechanism driving fire regime changes should contribute to our ability to better assess future fire regimes.

  19. Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

    PubMed Central

    Witte, J H de; Foekens, J A; Brünner, N; Heuvel, J J T M; Tienoven, ThH van; Look, M P; Klijn, J G M; Geurts-Moespot, A; Grebenchtchikov, N; Benraad, ThJ; Sweep, C G J

    2001-01-01

    Using a previously developed enzyme-linked immunosorbent assay (ELISA), the levels of the receptor for urokinase-type plasminogen activator (uPAR) were determined in cytosols and corresponding membrane pellets derived from 878 primary breast tumours. The levels of uPAR in the pellet extracts were more than 3-fold higher than those measured in the cytosols (P< 0.001). Moreover, the uPAR levels in the two types of extracts were weakly, though significantly, correlated with each other (rS= 0.20, P< 0.001). In Cox univariate analysis, high cytosolic levels of uPAR were significantly associated with reduced overall survival (OS) and relapse-free survival (RFS). The levels of uPAR in pellet extracts appeared not to be related with patient survival. In multivariate analysis, elevated levels of uPAR measured in cytosols and pellet extracts were found to be independent predictors of poor OS, not RFS. The prediction of poor prognosis on the basis of high uPAR levels emphasizes its important role in plasmin-mediated degradation of extracellular matrix proteins during cancer invasion and metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11437407

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

    PubMed

    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. PMID:20502321

  1. Human single-chain urokinase is activated by the omptins PgtE of Salmonella enterica and Pla of Yersinia pestis despite mutations of active site residues.

    PubMed

    Järvinen, Hanna M; Laakkonen, Liisa; Haiko, Johanna; Johansson, Tiira; Juuti, Katri; Suomalainen, Marjo; Buchrieser, Carmen; Kalkkinen, Nisse; Korhonen, Timo K

    2013-08-01

    Fibrinolysis is important in cell migration and tightly regulated by specific inhibitors and activators; of the latter, urokinase (uPA) associates with enhancement of cell migration. Active uPA is formed through cleavage of the single-chain uPA (scuPA). The Salmonella enterica strain 14028R cleaved human scuPA at the peptide bond Lys158-Ile159, the site cleaved also by the physiological activator human plasmin. The cleavage led to activation of scuPA, while no cleavage or activation were detected with the mutant strain 14028R lacking the omptin protease PgtE. Complementation and expression studies confirmed the role of PgtE in scuPA activation. Similar cleavage and activation of scuPA were detected with recombinant Escherichia coli expressing the omptin genes pla from Yersinia pestis, ompT and ompP from E. coli, sopA from Shigella flexneri, and leo from Legionella pneumophila. For these omptins the activation of scuPA is the only shared function so far detected. Only poor cleavage and activation of scuPA were seen with YcoA of Y. pestis and YcoB of Yersinia pseudotuberculosis that are considered to be proteolytically inactive omptin variants. Point mutations of active site residues in Pla and PgtE had different effects on the proteolysis of plasminogen and of scuPA, indicating versatility in omptin proteolysis.

  2. High Expression of Urokinase-Type Plasminogen Activator Is Associated with Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast

    PubMed Central

    Kim, Eun Young; Do, Sung-Im; Hyun, Keehoon; Park, Yong Lai; Kim, Dong-Hoon; Chae, Seoung Wan; Sohn, Jin Hee

    2016-01-01

    Purpose In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer. Methods Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen. Results Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001). Conclusion Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC. PMID:27382391

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

    PubMed

    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.

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

    PubMed

    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 < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

  5. Macromolecular interaction on a cAMP responsive region in the urokinase-type plasminogen activator gene: a role of protein phosphorylation.

    PubMed Central

    von der Ahe, D; Pearson, D; Nagamine, Y

    1990-01-01

    We have studied the regulation of urokinase-type plasminogen activator gene expression by cAMP in LLC-PK1 cells. We found a cAMP responsive region 3.4 kb upstream of the transcription initiation site, which comprised three protein-binding domains designated A, B, and C. Domains A and B both contain a sequence, TGACG, homologous to a consensus cAMP response element (CRE; TGACGTCA). Effective cAMP-mediated induction was achieved when these two domains were linked with domain C, which by itself did not confer cAMP responsiveness to a heterologous promoter nor contained CRE-like sequence, suggesting a functional cooperation among these domains. Results of competition studies using gel retardation and DNase I footprinting assays suggest that there is a protein-protein interaction between a CRE binding protein and a domain C binding protein. In gel retardation assays, binding of a nuclear protein to domains A and B was strongly augmented by addition of the catalytic subunit of cAMP-dependent protein kinase, whereas the protein binding to domain C was slightly inhibited, suggesting that protein phosphorylation is involved in the regulation of protein-DNA interaction. Images PMID:2159633

  6. The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index.

    PubMed

    Ng, Hien Fuh; Chin, Kin Fah; Chan, Kok-Gan; Ngeow, Yun Fong

    2015-06-01

    suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity. PMID:26284904

  7. Increased metalloprotease activity in the epileptogenic lesion--Lobectomy reduces metalloprotease activity and urokinase-type uPAR circulating levels.

    PubMed

    Quirico-Santos, Thereza; Nascimento Mello, Angélica; Casimiro Gomes, Aline; de Carvalho, Lian Pontes; de Souza, Jorge Marcondes; Alves-Leon, Soniza

    2013-11-13

    Inflammation influences the pathogenesis of seizures by boosting neuronal degeneration of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). This work aimed to determine the activity of metalloproteases (MMPs) in brain tissue fragments of TLE-HS patients and the effect of lobectomy on circulating inflammatory biomarkers. Surgical fragments (n=4) from epileptogenic focus (EF) e perilesion area (PL), and control hippocampus from autopsy (n=5) were processed for glial protein (GFAP), activated microglia (IB4) immunohistochemistry, and metalloprotease activity (MMP-2, -9). Perilesional area showed GFAP positive cells with morphology of activate astrocyte and reactive gliosis nearby the lesion. In the lesion foci, astrocytes had altered cytoarchitecture with disorganized stroma suggestive of necrosis, and numerous mononuclear cells with few projections and morphological characteristics of activate microglia. Analysis of MMP-9 and MMP-2 in the sera before and after hippocampectomy confirmed the inflammatory pattern of TLE-HS, with high MMP-9 activity; high MMP-9/TIMP-1 and urokinase uPAR plasma levels before lobectomy but low after surgery. Maintenance of MMP-2 activity indicates persistent tissue remodeling in both groups. The present work shows that patients with chronic and medically intractable TLE-HS that undergone amigdalo-hippocampectomy for removal of epileptogenic lesion had a clinical enduring benefit of lack seizure recurrence for up to a year, and consistent reduction of proteases (MMP-9 and uPAR) activation that participate as important inflammatory epileptogenic inducers.

  8. Docosahexaenoic Acid Inhibits Tumor Promoter-Induced Urokinase-Type Plasminogen Activator Receptor by Suppressing PKCδ- and MAPKs-Mediated Pathways in ECV304 Human Endothelial Cells

    PubMed Central

    Lian, Sen; Xia, Yong; Nguyen, Thi Thinh; Ung, Trong Thuan; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

    2016-01-01

    The overexpression of urokinase-type plasminogen activator receptor (uPAR) is associated with inflammation and virtually all human cancers. Despite the fact that docosahexaenoic acid (DHA) has been reported to possess anti-inflammatory and anti-tumor properties, the negative regulation of uPAR by DHA is still undefined. Here, we investigated the effect of DHA on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced uPAR expression and the underlying molecular mechanisms in ECV304 human endothelial cells. DHA concentration-dependently inhibited TPA-induced uPAR. Specific inhibitors and mutagenesis studies showed that PKCδ, JNK1/2, Erk1/2, NF-κB, and AP-1 were critical for TPA-induced uPAR expression. Application of DHA suppressed TPA-induced translocation of PKCδ, activation of the JNK1/2 and Erk1/2 signaling pathways, and subsequent AP-1 and NF-κB transactivation. In conclusion, these observations suggest a novel role for DHA in reducing uPAR expression and cell invasion by inhibition of PKCδ, JNK1/2, and Erk1/2, and the reduction of AP-1 and NF-κB activation in ECV304 human endothelial cells. PMID:27654969

  9. Regimes of validity for balanced models

    NASA Astrophysics Data System (ADS)

    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.

  10. Earth Regime Network Evolution Study (ERNESt)

    NASA Technical Reports Server (NTRS)

    Menrad, Bob

    2016-01-01

    Speaker and Presenter at the Lincoln Laboratory Communications Workshop on April 5, 2016 at the Massachusetts Institute of Technology Lincoln Laboratory in Lexington, MA. A visual presentation titled Earth Regimes Network Evolution Study (ERNESt).

  11. Historical fire regime in southern California

    USGS Publications Warehouse

    Keeley, Jon E.; Fotheringham, Connie J.

    2003-01-01

    The historical variability in fire regime is a conservative indicator of ecosystem sustainability. Understanding the natural role of fire in chaparral ecosystems is therefore necessary for effective fire management.

  12. Snowpack Regimes of the Western United States

    NASA Astrophysics Data System (ADS)

    Trujillo, E.; Molotch, N. P.

    2011-12-01

    Snow accumulation and melt patterns play a significant role in the water, energy, carbon and nutrient cycles in the montane environments of the Western United States. Recent studies have illustrated that changes in the snow/rainfall apportionments, and snow accumulation and melt patterns may occur as a consequence of changes in climate in the region. In order to understand how these changes may affect the snow regimes of the region, the current characteristics of the snow accumulation and melt patterns must be identified. Here, we characterize the snow water equivalent (SWE) curve formed by the daily SWE values at over seven hundred snow pillow stations in the Western U.S., focusing on several metrics of the yearly SWE curves and the cross relationships between the different metrics. The metrics include the initial snow accumulation and meltout dates, the peak accumulation and date of peak, the time from initial accumulation to peak, the time from peak to meltout, the accumulation and melt slopes, and the daily rates of accumulation and melt. Three distinct regimes emerge from these results: a maritime, an intermediate (intercontinental), and a continental regime. The maritime regime is characterized by higher maximum snow accumulations reaching 300 cm and shorter accumulation periods of less than 220 days, while on the other hand; the continental regime is characterized by lower maximum accumulations below 200 cm and longer accumulation periods reaching over 260 days. The intercontinental regime lies in between. Several other differences are identified between the metrics of the SWE curve in these regimes. The regions that show the characteristics of the maritime regime include the Cascade Mountains, the Klamath Mountains, and the Sierra Nevada Mountains. The intercontinental regime includes the Northern and Central basins and ranges, the Idaho Batholith, the Northern Rockies and the Blue Mountains. Lastly, the Continental regime includes the Middle and Southern

  13. Electron transport fluxes in potato plateau regime

    SciTech Connect

    Shaing, K.C.; Hazeltine, R.D.

    1997-12-01

    Electron transport fluxes in the potato plateau regime are calculated from the solutions of the drift kinetic equation and fluid equations. It is found that the bootstrap current density remains finite in the region close to the magnetic axis, although it decreases with increasing collision frequency. This finite amount of the bootstrap current in the relatively collisional regime is important in modeling tokamak startup with 100{percent} bootstrap current. {copyright} {ital 1997 American Institute of Physics.}

  14. Identifying natural flow regimes using fish communities

    NASA Astrophysics Data System (ADS)

    Chang, Fi-John; Tsai, Wen-Ping; Wu, Tzu-Ching; Chen, Hung-kwai; Herricks, Edwin E.

    2011-10-01

    SummaryModern water resources management has adopted natural flow regimes as reasonable targets for river restoration and conservation. The characterization of a natural flow regime begins with the development of hydrologic statistics from flow records. However, little guidance exists for defining the period of record needed for regime determination. In Taiwan, the Taiwan Eco-hydrological Indicator System (TEIS), a group of hydrologic statistics selected for fisheries relevance, is being used to evaluate ecological flows. The TEIS consists of a group of hydrologic statistics selected to characterize the relationships between flow and the life history of indigenous species. Using the TEIS and biosurvey data for Taiwan, this paper identifies the length of hydrologic record sufficient for natural flow regime characterization. To define the ecological hydrology of fish communities, this study connected hydrologic statistics to fish communities by using methods to define antecedent conditions that influence existing community composition. A moving average method was applied to TEIS statistics to reflect the effects of antecedent flow condition and a point-biserial correlation method was used to relate fisheries collections with TEIS statistics. The resulting fish species-TEIS (FISH-TEIS) hydrologic statistics matrix takes full advantage of historical flows and fisheries data. The analysis indicates that, in the watersheds analyzed, averaging TEIS statistics for the present year and 3 years prior to the sampling date, termed MA(4), is sufficient to develop a natural flow regime. This result suggests that flow regimes based on hydrologic statistics for the period of record can be replaced by regimes developed for sampled fish communities.

  15. A holistic view of marine regime shifts

    PubMed Central

    Conversi, Alessandra; Dakos, Vasilis; Gårdmark, Anna; Ling, Scott; Folke, Carl; Mumby, Peter J.; Greene, Charles; Edwards, Martin; Blenckner, Thorsten; Casini, Michele; Pershing, Andrew; Möllmann, Christian

    2015-01-01

    Understanding marine regime shifts is important not only for ecology but also for developing marine management that assures the provision of ecosystem services to humanity. While regime shift theory is well developed, there is still no common understanding on drivers, mechanisms and characteristic of abrupt changes in real marine ecosystems. Based on contributions to the present theme issue, we highlight some general issues that need to be overcome for developing a more comprehensive understanding of marine ecosystem regime shifts. We find a great divide between benthic reef and pelagic ocean systems in how regime shift theory is linked to observed abrupt changes. Furthermore, we suggest that the long-lasting discussion on the prevalence of top-down trophic or bottom-up physical drivers in inducing regime shifts may be overcome by taking into consideration the synergistic interactions of multiple stressors, and the special characteristics of different ecosystem types. We present a framework for the holistic investigation of marine regime shifts that considers multiple exogenous drivers that interact with endogenous mechanisms to cause abrupt, catastrophic change. This framework takes into account the time-delayed synergies of these stressors, which erode the resilience of the ecosystem and eventually enable the crossing of ecological thresholds. Finally, considering that increased pressures in the marine environment are predicted by the current climate change assessments, in order to avoid major losses of ecosystem services, we suggest that marine management approaches should incorporate knowledge on environmental thresholds and develop tools that consider regime shift dynamics and characteristics. This grand challenge can only be achieved through a holistic view of marine ecosystem dynamics as evidenced by this theme issue.

  16. Learning Flow Regimes from Snapshot Data

    NASA Astrophysics Data System (ADS)

    Hemati, Maziar

    2015-11-01

    Fluid flow regimes are often categorized based on the qualitative patterns observed by visual inspection of the flow field. For example, bluff body wakes are traditionally classified based on the number and groupings of vortices shed per cycle (e.g., 2S, 2P, P+S), as seen in snapshots of the vorticity field. Subsequently, the existence and nature of these identified flow regimes can be explained through dynamical analyses of the fluid mechanics. Unfortunately, due to the need for manual inspection, the approach described above can be impractical for studies that seek to learn flow regimes from large volumes of numerical and/or experimental snapshot data. Here, we appeal to established techniques from machine learning and data-driven dynamical systems analysis to automate the task of learning flow regimes from snapshot data. Moreover, by appealing to the dynamical structure of the fluid flow, this approach also offers the potential to reveal flow regimes that may be overlooked by visual inspection alone. Here, we will introduce the methodology and demonstrate its capabilities and limitations in the context of several model flows.

  17. Gradual regime shifts in fairy circles

    PubMed Central

    Zelnik, Yuval R.; Meron, Ehud; Bel, Golan

    2015-01-01

    Large responses of ecosystems to small changes in the conditions—regime shifts—are of great interest and importance. In spatially extended ecosystems, these shifts may be local or global. Using empirical data and mathematical modeling, we investigated the dynamics of the Namibian fairy circle ecosystem as a case study of regime shifts in a pattern-forming ecosystem. Our results provide new support, based on the dynamics of the ecosystem, for the view of fairy circles as a self-organization phenomenon driven by water–vegetation interactions. The study further suggests that fairy circle birth and death processes correspond to spatially confined transitions between alternative stable states. Cascades of such transitions, possible in various pattern-forming systems, result in gradual rather than abrupt regime shifts. PMID:26362787

  18. Massive superstring scatterings in the Regge regime

    SciTech Connect

    He Song; Lee, Jen-Chi; Takahashi, Keijiro; Yang Yi

    2011-03-15

    We calculate four classes of high-energy massive string scattering amplitudes of fermionic string theory at arbitrary mass levels in the Regge regime (RR). We show that all four leading order amplitudes in the RR can be expressed in terms of the Kummer function of the second kind. Based on the summation algorithm of a set of extended signed Stirling number identities, we show that all four ratios calculated previously by the method of decoupling of zero-norm states among scattering amplitudes in the Gross regime can be extracted from this Kummer function in the RR. Finally, we conjecture and give evidence that the existence of these four Gross regime ratios in the RR persists to subleading orders in the Regge expansion of all high-energy fermionic string scattering amplitudes.

  19. Gradual regime shifts in fairy circles.

    PubMed

    Zelnik, Yuval R; Meron, Ehud; Bel, Golan

    2015-10-01

    Large responses of ecosystems to small changes in the conditions--regime shifts--are of great interest and importance. In spatially extended ecosystems, these shifts may be local or global. Using empirical data and mathematical modeling, we investigated the dynamics of the Namibian fairy circle ecosystem as a case study of regime shifts in a pattern-forming ecosystem. Our results provide new support, based on the dynamics of the ecosystem, for the view of fairy circles as a self-organization phenomenon driven by water-vegetation interactions. The study further suggests that fairy circle birth and death processes correspond to spatially confined transitions between alternative stable states. Cascades of such transitions, possible in various pattern-forming systems, result in gradual rather than abrupt regime shifts. PMID:26362787

  20. Spin glasses in the nonextensive regime

    NASA Astrophysics Data System (ADS)

    Wittmann, Matthew; Young, A. P.

    2012-04-01

    Spin systems with long-range interactions are “nonextensive” if the strength of the interactions falls off sufficiently slowly with distance. It has been conjectured for ferromagnets and, more recently, for spin glasses that, everywhere in the nonextensive regime, the free energy is exactly equal to that for the infinite range model in which the characteristic strength of the interaction is independent of distance. In this paper we present the results of Monte Carlo simulations of the one-dimensional long-range spin glasses in the nonextensive regime. Using finite-size scaling, our results for the transition temperatures are consistent with this prediction. We also propose and provide numerical evidence for an analogous result for diluted long-range spin glasses in which the coordination number is finite, namely, that the transition temperature throughout the nonextensive regime is equal to that of the infinite-range model known as the Viana-Bray model.

  1. Mental hospital regime in England and Wales.

    PubMed

    Andoh, B

    1996-01-01

    Although non-private conventional mental hospitals in England and Wales have been in existence for about two centuries, the literature on the actual regimes in those hospitals is not enormous. Since Goffman's Asylums, things have changed in North America, the United Kingdom and elsewhere. However, not much has been written about the present position. This article (based on qualitative data collected over 12 months) describes the regimes in three conventional mental hospitals in S.E. England. It covers hospital policy on the admission of a patient, daily ward routine, the open-door policy, fire precautions, close observation, seclusion, search of patients and their belongings and the handling of patients' correspondence. It concludes that the regimes are reasonable.

  2. Gradual regime shifts in fairy circles.

    PubMed

    Zelnik, Yuval R; Meron, Ehud; Bel, Golan

    2015-10-01

    Large responses of ecosystems to small changes in the conditions--regime shifts--are of great interest and importance. In spatially extended ecosystems, these shifts may be local or global. Using empirical data and mathematical modeling, we investigated the dynamics of the Namibian fairy circle ecosystem as a case study of regime shifts in a pattern-forming ecosystem. Our results provide new support, based on the dynamics of the ecosystem, for the view of fairy circles as a self-organization phenomenon driven by water-vegetation interactions. The study further suggests that fairy circle birth and death processes correspond to spatially confined transitions between alternative stable states. Cascades of such transitions, possible in various pattern-forming systems, result in gradual rather than abrupt regime shifts.

  3. Massive superstring scatterings in the Regge regime

    NASA Astrophysics Data System (ADS)

    He, Song; Lee, Jen-Chi; Takahashi, Keijiro; Yang, Yi

    2011-03-01

    We calculate four classes of high-energy massive string scattering amplitudes of fermionic string theory at arbitrary mass levels in the Regge regime (RR). We show that all four leading order amplitudes in the RR can be expressed in terms of the Kummer function of the second kind. Based on the summation algorithm of a set of extended signed Stirling number identities, we show that all four ratios calculated previously by the method of decoupling of zero-norm states among scattering amplitudes in the Gross regime can be extracted from this Kummer function in the RR. Finally, we conjecture and give evidence that the existence of these four Gross regime ratios in the RR persists to subleading orders in the Regge expansion of all high-energy fermionic string scattering amplitudes.

  4. Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients

    PubMed Central

    de Witte, J H; Sweep, C G J; Klijn, J G M; Grebenschikov, N; Peters, H A; Look, M P; van Tienoven, Th H; Heuvel, J J T M; van Putten, W L J; Benraad, Th J; Foekens, J A

    1999-01-01

    To evaluate the clinical relevance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) measured by a recently developed enzyme-linked immunosorbent assay (ELISA), we analysed both components in samples derived from 892 patients with primary breast cancer (median follow-up 99 months). The assays were performed in cytosolic extracts as well as in corresponding detergent extracts of pellets obtained after ultracentrifugation, which was carried out when preparing the cytosolic fractions for routine steroid hormone receptor determination. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.60, P < 0.0001 for uPA and rs = 0.65, P < 0.0001 for PAI-1). Furthermore, strong correlations were found between the levels of both uPA (rs = 0.85, P < 0.0001) and PAI-1 (rs = 0.90, P < 0.0001) in the cytosols and their levels previously measured with ELISAs based on commercial reagents. In both Cox univariate and multivariate analysis, high cytosolic levels of uPA or PAI-1 were significantly associated with increased rates of relapse and death. The levels of uPA and PAI-1 in the pellet extracts also provided prognostic information, although to a lesser extent compared with the cytosolic extracts. The prediction of prognosis on the basis of uPA and PAI-1 assessed by an alternative ELISA once again emphasizes the established prognostic role and usefulness of these parameters in selection of breast cancer patients at high or low risk of recurrence. © 1999 Cancer Research Campaign PMID:10098758

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

    PubMed

    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. PMID:24681666

  6. Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.

    PubMed

    Schmalfeldt, B; Prechtel, D; Härting, K; Späthe, K; Rutke, S; Konik, E; Fridman, R; Berger, U; Schmitt, M; Kuhn, W; Lengyel, E

    2001-08-01

    Proteases are linked to the malignant phenotype of different solid tumors. Therefore, the expression of the matrix metalloproteinase (MMP)-2 and MMP-9 and of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) in the progression of ovarian cancer was investigated. Gelatinolytic activity and protein expression of MMP-2 and MMP-9 were analyzed in tissue extracts of 19 cystadenomas and 18 low malignant potential (LMP) tumors, as well as 41 primary tumors of advanced ovarian cancer stage International Federation of Gynecology and Obstetrics IIIc/IV and their corresponding omentum metastases by quantitative gelatin zymography and Western blot. In the same tissue extracts, antigen levels of uPA and its inhibitor PAI-1 were determined by ELISA. Protein expression of pro-MMP-2 (72 kDa) and pro-MMP-9 (92 kDa as well as antigen levels of uPA and PAI-1 were low in benign ovarian tumors but increased significantly from LMP tumors to advanced ovarian cancers. The highest values of all of the proteolytic factors were detected in omentum metastases. Active MMP-2 enzyme (62 kDa) was detected only in ovarian cancer (66%) and corresponding metastases (93%) but never in benign or LMP tumors. The activation rate of MMP-2 to its active isoform was higher in the metastases. Comparing both proteolytic systems, higher PAI-1 concentrations were consistently found in cancers with high pro-MMP-9 expression. These data indicate that members of the plasminogen activator system, as well as the metalloproteinases MMP-2/9, increase with growing malignant potential of ovarian tumors. These findings are of particular relevance to the development of protease inhibitors as new therapeutic approaches in ovarian cancer.

  7. FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line.

    PubMed

    Hamaguchi, M; Morishita, Y; Takahashi, I; Ogura, M; Takamatsu, J; Saito, H

    1991-01-01

    We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation. PMID:1845845

  8. Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China

    PubMed Central

    Guo, Shui-Ming; Han, Min; Chen, Mei-Xue; Ning, Yong; Pei, Guang-Chang; Li, Yue-Qiang; Dai, Wei; Ge, Shu-Wang; Deng, Yuan-Jun; Guo, Yan-Yan; Li, Xiao-Qing; Haller, Hermann; Xu, Gang; Rong, Song

    2015-01-01

    Background Soluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN). Methods We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. Results We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions. Conclusions Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN. PMID:26380984

  9. Follicle-stimulating hormone and cyclic AMP induce transcription from the human urokinase promoter in primary cultures of mouse Sertoli cells.

    PubMed

    Rossi, P; Grimaldi, P; Blasi, F; Geremia, R; Verde, P

    1990-06-01

    The hormonal regulation of the human urokinase type plasminogen activator (uPA) gene has been studied by introducing into mouse and rat Sertoli cell primary cultures a recombinant plasmid, in which the transcription regulatory elements of the cloned human uPA gene drive the expression of the bacterial chloramphenicol-acetyl-transferase gene. It was found to be expressed and regulated by FSH and (Bu)2cAMP in the mouse cells only, in agreement with data on the expression of the endogenous gene in rat and mouse gonads. The stimulation of transcription by FSH was evident in cultures from 13-day-old but not from 18-day-old mice, even though (Bu)2cAMP induction could be observed at both ages. Phorbol-myristate acetate was found to activate the human uPA promoter in Sertoli cell cultures from mice of both ages, even though the effect was less evident in cultures of 18-day-old animals. Deletion analysis of the human uPA 5'-flanking region showed that the distal enhancer element is not needed for (Bu)2cAMP induction, and that at least two promoter regions are involved in (Bu)2cAMP induced transcription. One of these cAMP responsive regions lies between nucleotides -72 and -29 from the CAP site. The sequence of this region would suggest the binding of transcription factor AP-2, a cell-specific mediator of both cAMP and phorbol esters action on gene expression. However, these sequences do not mediate phorbol ester activation of human uPA promoter in mouse Sertoli cells.

  10. Hepatocytes buried in the cirrhotic livers of patients with biliary atresia proliferate and function in the livers of urokinase-type plasminogen activator-NOG mice.

    PubMed

    Suemizu, Hiroshi; Nakamura, Kazuaki; Kawai, Kenji; Higuchi, Yuichiro; Kasahara, Mureo; Fujimoto, Junichiro; Tanoue, Akito; Nakamura, Masato

    2014-09-01

    The pathogenesis of biliary atresia (BA), which leads to end-stage cirrhosis in most patients, has been thought to inflame and obstruct the intrahepatic and extrahepatic bile ducts. BA is not believed to be caused by abnormalities in parenchymal hepatocytes. However, there has been no report of a detailed analysis of hepatocytes buried in the cirrhotic livers of patients with BA. Therefore, we evaluated the proliferative potential of these hepatocytes in immunodeficient, liver-injured mice [the urokinase-type plasminogen activator (uPA) transgenic NOD/Shi-scid IL2rγnull (NOG); uPA-NOG strain]. We succeeded in isolating viable hepatocytes from the livers of patients with BA who had various degrees of fibrosis. The isolated hepatocytes were intrasplenically transplanted into the livers of uPA-NOG mice. The hepatocytes of only 3 of the 9 BA patients secreted detectable amounts of human albumin in sera when they were transplanted into mice. However, human leukocyte antigen-positive hepatocyte colonies were detected in 7 of the 9 mice with hepatocyte transplants from patients with BA. We demonstrated that hepatocytes buried in the cirrhotic livers of patients with BA retained their proliferative potential. A liver that was reconstituted with hepatocytes from patients with BA was shown to be a functioning human liver with a drug-metabolizing enzyme gene expression pattern that was representative of mature human liver and biliary function, as ascertained by fluorescent dye excretion into the bile canaliculi. These results imply that removing the primary etiology via an earlier portoenterostomy may increase the quantity of functionally intact hepatocytes remaining in a cirrhotic liver and may contribute to improved outcomes.

  11. A urokinase-type plasminogen activator-inhibiting cyclic peptide with an unusual P2 residue and an extended protease binding surface demonstrates new modalities for enzyme inhibition.

    PubMed

    Hansen, Martin; Wind, Troels; Blouse, Grant E; Christensen, Anni; Petersen, Helle H; Kjelgaard, Signe; Mathiasen, Lisa; Holtet, Thor L; Andreasen, Peter A

    2005-11-18

    To find new principles for inhibiting serine proteases, we screened phage-displayed random peptide repertoires with urokinase-type plasminogen activator (uPA) as the target. The most frequent of the isolated phage clones contained the disulfide bridge-constrained sequence CSWRGLENHRMC, which we designated upain-1. When expressed recombinantly with a protein fusion partner, upain-1 inhibited the enzymatic activity of uPA competitively with a temperature and pH-dependent K(i), which at 25 degrees C and pH 7.4 was approximately 500 nm. At the same conditions, the equilibrium dissociation constant K(D), monitored by displacement of p-aminobenzamidine from the specificity pocket of uPA, was approximately 400 nm. By an inhibitory screen against other serine proteases, including trypsin, upain-1 was found to be highly selective for uPA. The cyclical structure of upain-1 was indispensable for uPA binding. Alanine-scanning mutagenesis identified Arg(4) of upain-1 as the P(1) residue and indicated an extended binding interaction including the specificity pocket and the 37-, 60-, and 97-loops of uPA and the P(1), P(2), P(3)', P(4)', and the P(5)' residues of upain-1. Substitution with alanine of the P(2) residue, Trp(3), converted upain-1 into a distinct, although poor, uPA substrate. Upain-1 represents a new type of uPA inhibitor that achieves selectivity by targeting uPA-specific surface loops. Most likely, the inhibitory activity depends on its cyclical structure and the unusual P(2) residue preventing the scissile bond from assuming a tetrahedral geometry and thus from undergoing hydrolysis. Peptide-derived inhibitors such as upain-1 may provide novel mechanistic information about enzyme-inhibitor interactions and alternative methodologies for designing effective protease inhibitors. PMID:16141208

  12. Plasminogen-stimulated airway smooth muscle cell proliferation is mediated by urokinase and annexin A2, involving plasmin-activated cell signalling

    PubMed Central

    Stewart, A G; Xia, Y C; Harris, T; Royce, S; Hamilton, J A; Schuliga, M

    2013-01-01

    BACKGROUND AND PURPOSE The conversion of plasminogen into plasmin by interstitial urokinase plasminogen activator (uPA) is potentially important in asthma pathophysiology. In this study, the effect of uPA-mediated plasminogen activation on airway smooth muscle (ASM) cell proliferation was investigated. EXPERIMENTAL APPROACH Human ASM cells were incubated with plasminogen (0.5–50 μg·mL−1) or plasmin (0.5–50 mU·mL−1) in the presence of pharmacological inhibitors, including UK122, an inhibitor of uPA. Proliferation was assessed by increases in cell number or MTT reduction after 48 h incubation with plasmin(ogen), and by earlier increases in [3H]-thymidine incorporation and cyclin D1 expression. KEY RESULTS Plasminogen (5 μg·mL−1)-stimulated increases in cell proliferation were attenuated by UK122 (10 μM) or by transfection with uPA gene-specific siRNA. Exogenous plasmin (5 mU·mL−1) also stimulated increases in cell proliferation. Inhibition of plasmin-stimulated ERK1/2 or PI3K/Akt signalling attenuated plasmin-stimulated increases in ASM proliferation. Furthermore, pharmacological inhibition of cell signalling mediated by the EGF receptor, a receptor trans-activated by plasmin, also reduced plasmin(ogen)-stimulated cell proliferation. Knock down of annexin A2, which has dual roles in both plasminogen activation and plasmin-signal transduction, also attenuated ASM cell proliferation following incubation with either plasminogen or plasmin. CONCLUSIONS AND IMPLICATIONS Plasminogen stimulates ASM cell proliferation in a manner mediated by uPA and involving multiple signalling pathways downstream of plasmin. Targeting mediators of plasminogen-evoked ASM responses, such as uPA or annexin A2, may be useful in the treatment of asthma. PMID:24111848

  13. Epithelial and Stromal Cell Urokinase Plasminogen Activator Receptor Expression Differentially Correlates with Survival in Rectal Cancer Stages B and C Patients

    PubMed Central

    Ahn, Seong Beom; Chan, Charles; Dent, Owen F.; Mohamedali, Abidali; Kwun, Sun Young; Clarke, Candice; Fletcher, Julie; Chapuis, Pierre H.; Nice, Edouard C.; Baker, Mark S.

    2015-01-01

    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. PMID:25692297

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

    PubMed Central

    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

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

    PubMed Central

    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

  16. Procedures for the quantitative protein determination of urokinase and its inhibitor, PAI-1, in human breast cancer tissue extracts by ELISA.

    PubMed

    Schmitt, Manfred; Sturmheit, Alexandra S; Welk, Anita; Schnelldorfer, Christel; Harbeck, Nadia

    2006-01-01

    The determination of the protein content of urokinase-type plasminogen activator (uPA) and its inhibitor, PAI-1, in breast cancer tissue extracts is used clinically to identify patients at risk to experience disease recurrence (metastasis) or early death. The serine protease uPA, in concert with its inhibitor PAI-1, promotes tumor cell adhesion, migration, and proliferation, as well as extracellular matrix degradation and, thus, facilitates tumor cell invasion and metastasis. The various technical steps to recover uPA and PAI-1 protein from archived breast cancer tissues and to quantitatively determine uPA and PAI-1 protein content in tumor tissue extracts by enzyme-linked immunosorbent assay (ELISA) are described in detail. The technical steps involved require fresh-frozen breast cancer tissue, a dismembrator machine (ball mill) to pulverize the tissue in the frozen state, detergent (Triton X-100) containing Tris-buffered saline to extract uPA and PAI-1 from the pulverized breast cancer tissue, an ultracentrifuge to separate the detergent fraction from cellular debris, uPA and PAI-1 ELISA kits, protein determination reagents, and a 96-well spectrophotometer (ELISA reader) to assess uPA, PAI-1, and total protein in the detergent extract. The uPA/PAI-1 ELISAs and the protein determination format described are robust and highly sensitive. In addition to the macromethod of tissue disintegration, we present a simple but sensitive micro-extraction procedure using cryostat sections or core biopsies as the source of breast cancer tissue. Such a technique allows rapid and quantitative determination of uPA and PAI-1, even in small breast cancer specimens.

  17. Statistical regimes of random laser fluctuations

    SciTech Connect

    Lepri, Stefano; Cavalieri, Stefano; Oppo, Gian-Luca; Wiersma, Diederik S.

    2007-06-15

    Statistical fluctuations of the light emitted from amplifying random media are studied theoretically and numerically. The characteristic scales of the diffusive motion of light lead to Gaussian or power-law (Levy) distributed fluctuations depending on external control parameters. In the Levy regime, the output pulse is highly irregular leading to huge deviations from a mean-field description. Monte Carlo simulations of a simplified model which includes the population of the medium demonstrate the two statistical regimes and provide a comparison with dynamical rate equations. Different statistics of the fluctuations helps to explain recent experimental observations reported in the literature.

  18. Synchronization regimes in conjugate coupled chaotic oscillators.

    PubMed

    Karnatak, Rajat; Ramaswamy, Ram; Prasad, Awadhesh

    2009-09-01

    Nonlinear oscillators that are mutually coupled via dissimilar (or conjugate) variables display distinct regimes of synchronous behavior. In identical chaotic oscillators diffusively coupled in this manner, complete synchronization occurs only by chaos suppression when the coupled subsystems drive each other into a regime of periodic dynamics. Furthermore, the coupling does not vanish but acts as an "internal" drive. When the oscillators are mismatched, phase synchronization occurs, while in a master slave configuration, generalized synchrony results. These effects are demonstrated in a system of coupled chaotic Rossler oscillators.

  19. Anomalous Hall effect in localization regime

    NASA Astrophysics Data System (ADS)

    Wu, Lin; Zhu, Kai; Yue, Di; Tian, Yuan; Jin, Xiaofeng

    2016-06-01

    The anomalous Hall effect in the ultrathin film regime is investigated in Fe(001)(1-3 nm) films epitaxial on MgO(001). The logarithmic localization correction to longitudinal resistivity and anomalous Hall resistivity are observed at low temperature. We identify that the coefficient of skew scattering has a reduction from metallic to localized regime, while the contribution of side jump has inconspicuous change except for a small drop below 10 K. Furthermore, we discover that the intrinsic anomalous Hall conductivity decreases with the reduction of thickness below 2 nm. Our results provide unambiguous experimental evidence to clarify the problem of localization correction to the anomalous Hall effect.

  20. Collective working regimes for coupled heat engines.

    PubMed

    Jiménez de Cisneros, B; Hernández, A Calvo

    2007-03-30

    Arrays of coupled heat engines are proposed as a paradigmatic model to study the trade-off between individual and collective behavior in linear irreversible thermodynamics. The analysis reveals the existence of a control parameter which selects different operation regimes of the whole array. In particular, the regimes of maximum efficiency and maximum power are considered, giving for the latter a general derivation of the Curzon-Ahlborn efficiency which surprisingly does not depend on whether or not the individual engines in the array work at maximum power.

  1. Supercurrent in the quantum Hall regime

    NASA Astrophysics Data System (ADS)

    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.

  2. Supercurrent in the quantum Hall regime.

    PubMed

    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

    2016-05-20

    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. PMID:27199424

  3. Convective Regimes in Crystallizing Basaltic Magma Chambers

    NASA Astrophysics Data System (ADS)

    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

  4. Delinating Thermohaline Double-Diffusive Rayleigh Regimes

    NASA Astrophysics Data System (ADS)

    Graf, T.; Walther, M.; Kolditz, O.; Liedl, R.

    2013-12-01

    In natural systems, convective flow induced from density differences may occur in near-coastal aquifers, atmospheric boundary layers, oceanic streams or within the earth crust. Whether an initially stable, diffusive regime evolves into a convective (stable or chaotic) regime, or vice versa, depends on the system's framing boundary conditions. A conventional parameter to express the relation between diffusive and convective forces of such a density-driven regime is Rayleigh number (Ra). While most systems are mainly dominated by only a single significant driving force (i.e. only temperature or salinity), some systems need to consider two boundary processes (e.g. deep, thus warm, haline flow in porous media). In that case, a two-dimensional, 'double-diffusive' Rayleigh system can be defined. Nield (1998) postulated a boundary between diffusive and convective regime at RaT + RaC = 4pi^2 in the first quadrant (Q1), with Rayleigh numbers for temperature and concentration respectively. The boundary in the forth quadrant (Q4) could not exactly be determined, yet the approximate position estimated. Simulations with HydroGeoSphere (Therrien, 2010) using a vertical, quadratic, homogeneous, isotropic setup confirmed the existence of the 4pi^2-boundary and revealed additional regimes (diffusive, single-roll, double-roll, chaotic) in Q1. Also, non-chaotic, oscillating patterns could be identified in Q4. More detailed investigations with OpenGeoSys (Kolditz, 2012) confirmed the preceding HGS results, and, using a 1:10-scaled domain (height:length), uncovered even more distinctive regimes (diffusive, minimum ten roles, supposely up to 25 roles, and chaotic?) in Q1, while again, oscillating patterns were found in the transition zone between diffusive and chaotic regimes in Q4. Output of numerical simulations from Q1 and Q4 show the mentioned regimes (diffusive, stable-convective, stable-oscillatory, chaotic) while results are displayed in context of a possible delination between

  5. Intermediate scaling regime for multilayer epitaxial growth

    NASA Astrophysics Data System (ADS)

    Ross, Richard S.; Gyure, Mark F.

    2000-04-01

    We explore the layer-by-layer (Frank-van der Merwe) growth regime within the context of a discrete solid-on-solid kinetic Monte Carlo model. Our results demonstrate a nontrivial scaling of the lattice step edge density, a quantity that oscillates about a nominally constant value prior to the onset of kinetic roughening. This value varies with the ratio of the surface diffusivity to the deposition flux, R≡D/F, as a nearly perfect power law over a wide range of R. This ``intermediate'' scaling regime extends in coverage from one to at least a few tens of monolayers, which is exactly the regime of most importance to the growth of device-quality semiconductor quantum heterostructures. Comparison with lowest-order linear theories for height fluctuations demonstrates the validity of the Wolf-Villain mean-field theory for the description of lattice step density and ``in-plane'' structure for all coverages down to the first monolayer of growth. However, the mean-field theory does not fully account for the surface width in this regime and consequently does not quantitatively predict the observed step density scaling.

  6. Prolonged Instability Prior to a Regime Shift

    PubMed Central

    Spanbauer, Trisha L.; Allen, Craig R.; Angeler, David G.; Eason, Tarsha; Fritz, Sherilyn C.; Garmestani, Ahjond S.; Nash, Kirsty L.; Stone, Jeffery R.

    2014-01-01

    Regime shifts are generally defined as the point of ‘abrupt’ change in the state of a system. However, a seemingly abrupt transition can be the product of a system reorganization that has been ongoing much longer than is evident in statistical analysis of a single component of the system. Using both univariate and multivariate statistical methods, we tested a long-term high-resolution paleoecological dataset with a known change in species assemblage for a regime shift. Analysis of this dataset with Fisher Information and multivariate time series modeling showed that there was a∼2000 year period of instability prior to the regime shift. This period of instability and the subsequent regime shift coincide with regional climate change, indicating that the system is undergoing extrinsic forcing. Paleoecological records offer a unique opportunity to test tools for the detection of thresholds and stable-states, and thus to examine the long-term stability of ecosystems over periods of multiple millennia. PMID:25280010

  7. Forest damage and snow avalanche flow regime

    NASA Astrophysics Data System (ADS)

    Feistl, T.; Bebi, P.; Christen, M.; Margreth, S.; Diefenbach, L.; Bartelt, P.

    2015-06-01

    Snow avalanches break, uproot and overturn trees causing damage to forests. The extent of forest damage provides useful information on avalanche frequency and intensity. However, impact forces depend on avalanche flow regime. In this paper, we define avalanche loading cases representing four different avalanche flow regimes: powder, intermittent, dry and wet. Using a numerical model that simulates both powder and wet snow avalanches, we study documented events with forest damage. First we show that in the powder regime, although the applied impact pressures can be small, large bending moments in the tree stem can be produced due to the torque action of the blast. The impact area of the blast extends over the entire tree crown. We find that, powder clouds with velocities over 20 m s-1 can break tree stems. Second we demonstrate that intermittent granular loadings are equivalent to low-density uniform dry snow loadings under the assumption of homogeneous particle distributions. The intermittent regime seldom controls tree breakage. Third we calculate quasi-static pressures of wet snow avalanches and show that they can be much higher than pressures calculated using dynamic pressure formulas. Wet snow pressure depends both on avalanche volume and terrain features upstream of the tree.

  8. Forest damage and snow avalanche flow regime

    NASA Astrophysics Data System (ADS)

    Feistl, T.; Bebi, P.; Christen, M.; Margreth, S.; Diefenbach, L.; Bartelt, P.

    2015-01-01

    Snow avalanches break, uproot and overturn trees causing damage to forests. The extent of forest damage provides useful information on avalanche frequency and intensity. However, impact forces depend on avalanche flow regime. In this paper, we define avalanche loading cases representing four different avalanche flow regimes: powder, intermittent, dry and wet. In the powder regime, the blast of the cloud can produce large bending moments in the tree stem because of the impact area extending over the entire tree crown. We demonstrate that intermittent granular loadings are equivalent to low-density uniform dry snow loadings under the assumption of homogeneous particle distributions. In the wet snow case, avalanche pressure is calculated using a quasi-static model accounting for the motion of plug-like wet snow flows. Wet snow pressure depends both on avalanche volume and terrain features upstream of the tree. Using a numerical model that simulates both powder and wet snow avalanches, we study documented events with forest damage. We find (1) powder clouds with velocities over 20 m s-1 can break tree stems, (2) the intermittent regime seldom controls tree breakage and (3) quasi-static pressures of wet snow avalanches can be much higher than pressures calculated using dynamic pressure formulas.

  9. Knowledge Regimes and Contradictions in Education Reforms

    ERIC Educational Resources Information Center

    Aasen, Petter; Prøitz, Tine Sophie; Sandberg, Nina

    2014-01-01

    The article outlines a theoretical framework for understanding education policy and education reforms based on the concept of knowledge regimes. The concept refers to understandings and definitions of governance and procedural aspects, manners of governing and curriculum issues, thus it comprises contents, structures, and processes of education…

  10. Two limiting regimes of interacting Bessel processes

    NASA Astrophysics Data System (ADS)

    Andraus, Sergio; Katori, Makoto; Miyashita, Seiji

    2014-06-01

    We consider the interacting Bessel processes, a family of multiple-particle systems in one dimension where particles evolve as individual Bessel processes and repel each other via a log-potential. We consider two limiting regimes for this family on its two main parameters: the inverse temperature β and the Bessel index ν. We obtain the time-scaled steady-state distributions of the processes for the cases where β or ν are large but finite. In particular, for large β we show that the steady-state distribution of the system corresponds to the eigenvalue distribution of the β-Laguerre ensembles of random matrices. We also estimate the relaxation time to the steady state in both cases. We find that in the freezing regime β → ∞, the scaled final positions of the particles are locked at the square root of the zeroes of the Laguerre polynomial of parameter ν - 1/2 for any initial configuration, while in the regime ν → ∞, we prove that the scaled final positions of the particles converge to a single point. In order to obtain our results, we use the theory of Dunkl operators, in particular the intertwining operator of type B. We derive a previously unknown expression for this operator and study its behaviour in both limiting regimes. By using these limiting forms of the intertwining operator, we derive the steady-state distributions, the estimations of the relaxation times and the limiting behaviour of the processes.

  11. A Global Classification of Contemporary Fire Regimes

    NASA Astrophysics Data System (ADS)

    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.

  12. Taxonomy of potential international safeguards regimes

    SciTech Connect

    Lemley, J.R.; Allentuck, J.

    1994-08-01

    Since the International Atomic Energy Agency`s (IAEA) search for the components of Iraq`s nuclear weapons program under the auspices of the United Nations Security Council, a consensus for enhancing, strengthening or expanding the scope of international safeguards has developed. Some of the enhanced safeguards concepts which have been suggested include the following: short-notice, challenge, and random inspections; effluent monitoring in onsite, near site, and fly-by modes; local and wide-area environmental monitoring; and utilization of data from space-platform sensors. Potential safeguards regimes can be classified according to the functional and technical criteria which would be necessary for implementation of various enhanced safeguards concepts. While the nature of the regime which will emerge cannot be predicted, the classification of possible regimes according to major characteristics can be useful for identifying functional criteria and implementation challenges, focusing development efforts on the functional criteria, and planning for efficient use of safeguards resources. Precedents established in previously negotiated treaties -- the Chemical Weapons Convention, the Treaty on Conventional Forces in Europe, START, and Open Skies -- are examined with regard to enhancement of the international safeguards regime for nuclear and other weapons of mass destruction. Bilateral, multilateral and regional integration of enhanced safeguards elements is considered.

  13. The future of the nuclear nonproliferation regime.

    SciTech Connect

    Pilat, Joseph F.

    2004-01-01

    Following the 1998 nuclear tests in South Asia and later reinforced by revelations about North Korean and Iraqi nuclear activities, there has been growing concern about increasing proliferation dangers. At the same time, the prospects of radiological/nuclear terrorism are seen to be rising - since 9/11, concern over a proliferation/terrorism nexus has never been higher. In the face of this growing danger, there are urgent calls for stronger measures to strengthen the current international nuclear nonproliferation regime, including recommendations to place civilian processing of weapon-useable material under multinational control. As well, there are calls for entirely new tools, including military options. As proliferation and terrorism concerns grow, the regime is under pressure and there is a temptation to consider fundamental changes to the regime. In this context, this paper will address the following: Do we need to change the regime centered on the Treaty on the Nonproliferation of Nuclear Weapons (NPT) and the International Atomic Energy Agency (IAEA)? What improvements could ensure it will be the foundation for the proliferation resistance and physical protection needed if nuclear power grows? What will make it a viable centerpiece of future nonproliferation and counterterrorism approaches?

  14. Regimes of turbulence without an energy cascade

    PubMed Central

    Barenghi, C. F.; Sergeev, Y. A.; Baggaley, A. W.

    2016-01-01

    Experiments and numerical simulations of turbulent 4He and 3He-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 turbulence generated by injection of vortex rings at low temperatures. Our models justify the hydrodynamical description of quantum turbulence and shed light into an unexpected regime of vortex dynamics. PMID:27761005

  15. Regime Shifts in the Anthropocene: Drivers, Risks, and Resilience

    PubMed Central

    Rocha, Juan Carlos; Peterson, Garry D.; Biggs, Reinette

    2015-01-01

    Many ecosystems can experience regime shifts: surprising, large and persistent changes in the function and structure of ecosystems. Assessing whether continued global change will lead to further regime shifts, or has the potential to trigger cascading regime shifts has been a central question in global change policy. Addressing this issue has, however, been hampered by the focus of regime shift research on specific cases and types of regime shifts. To systematically assess the global risk of regime shifts we conducted a comparative analysis of 25 generic types of regime shifts across marine, terrestrial and polar systems; identifying their drivers, and impacts on ecosystem services. Our results show that the drivers of regime shifts are diverse and co-occur strongly, which suggests that continued global change can be expected to synchronously increase the risk of multiple regime shifts. Furthermore, many regime shift drivers are related to climate change and food production, whose links to the continued expansion of human activities makes them difficult to limit. Because many regime shifts can amplify the drivers of other regime shifts, continued global change can also be expected to increase the risk of cascading regime shifts. Nevertheless, the variety of scales at which regime shift drivers operate provides opportunities for reducing the risk of many types of regime shifts by addressing local or regional drivers, even in the absence of rapid reduction of global drivers. PMID:26267896

  16. Regime shifts in the anthropocene: drivers, risks, and resilience.

    PubMed

    Rocha, Juan Carlos; Peterson, Garry D; Biggs, Reinette

    2015-01-01

    Many ecosystems can experience regime shifts: surprising, large and persistent changes in the function and structure of ecosystems. Assessing whether continued global change will lead to further regime shifts, or has the potential to trigger cascading regime shifts has been a central question in global change policy. Addressing this issue has, however, been hampered by the focus of regime shift research on specific cases and types of regime shifts. To systematically assess the global risk of regime shifts we conducted a comparative analysis of 25 generic types of regime shifts across marine, terrestrial and polar systems; identifying their drivers, and impacts on ecosystem services. Our results show that the drivers of regime shifts are diverse and co-occur strongly, which suggests that continued global change can be expected to synchronously increase the risk of multiple regime shifts. Furthermore, many regime shift drivers are related to climate change and food production, whose links to the continued expansion of human activities makes them difficult to limit. Because many regime shifts can amplify the drivers of other regime shifts, continued global change can also be expected to increase the risk of cascading regime shifts. Nevertheless, the variety of scales at which regime shift drivers operate provides opportunities for reducing the risk of many types of regime shifts by addressing local or regional drivers, even in the absence of rapid reduction of global drivers.

  17. Regime shifts in the anthropocene: drivers, risks, and resilience.

    PubMed

    Rocha, Juan Carlos; Peterson, Garry D; Biggs, Reinette

    2015-01-01

    Many ecosystems can experience regime shifts: surprising, large and persistent changes in the function and structure of ecosystems. Assessing whether continued global change will lead to further regime shifts, or has the potential to trigger cascading regime shifts has been a central question in global change policy. Addressing this issue has, however, been hampered by the focus of regime shift research on specific cases and types of regime shifts. To systematically assess the global risk of regime shifts we conducted a comparative analysis of 25 generic types of regime shifts across marine, terrestrial and polar systems; identifying their drivers, and impacts on ecosystem services. Our results show that the drivers of regime shifts are diverse and co-occur strongly, which suggests that continued global change can be expected to synchronously increase the risk of multiple regime shifts. Furthermore, many regime shift drivers are related to climate change and food production, whose links to the continued expansion of human activities makes them difficult to limit. Because many regime shifts can amplify the drivers of other regime shifts, continued global change can also be expected to increase the risk of cascading regime shifts. Nevertheless, the variety of scales at which regime shift drivers operate provides opportunities for reducing the risk of many types of regime shifts by addressing local or regional drivers, even in the absence of rapid reduction of global drivers. PMID:26267896

  18. Genistein reduces tumor necrosis factor alpha-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells.

    PubMed

    van Hinsbergh, V W; Vermeer, M; Koolwijk, P; Grimbergen, J; Kooistra, T

    1994-11-01

    The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PAI-1 induced by these inflammatory mediators in human endothelial cells in vitro, and partially reduces the basal PAI-1 production by these cells. These effects of genistein were accompanied by a decrease in PAI-1 mRNA and in a suppression of the PAI-1 transcription rate as shown by run-on assay. A specific action of genistein, probably by inhibiting a tyrosine protein kinase, is likely, because the structural genistein analogue daidzein, which has a low tyrosine protein kinase inhibitor activity, did not inhibit PAI-1 synthesis. Vanadate, a tyrosine protein phosphatase inhibitor, increased PAI-1 production. The effect of genistein on PAI-1 synthesis was rather selective. Herbimycin A also reduced PAI-1 synthesis, but several other tyrosine protein kinase inhibitors, namely tyrphostin A47, methyl-2,5-dihydroxy-cinnamate, and compound 5, were unable to do so. All these tyrosine protein kinase inhibitors reduced basic fibroblast growth factor (b-FGF)-induced [3H]thymidine incorporation in endothelial cells. This indicates that the effect of genistein on PAI-1 transcription proceeds independently of its effect on mitogenesis. In contrast to TNF-alpha-induced PAI-1 production, the transcription and synthesis of urokinase-type plasminogen activator (u-PA) was not inhibited by genistein. A TNF-alpha-mutant (Trp32Thr86TNF alpha) that specifically recognizes the 55-kD TNF-receptor, mimicked the effects of TNF alpha on both PAI-1 and u-PA. Because genistein affected PAI-1, but not u-PA induced by this mutant, involvement of different TNF-receptors cannot underlie the difference in the effects of genistein on PAI-1 and u-PA synthesis. Because genistein also

  19. Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells.

    PubMed

    Kim, Mi H; Yoo, Hyung S; Kim, Mi Y; Jang, Hee J; Baek, Min K; Kim, Hyeong R; Kim, Kyung K; Shin, Boo A; Ahn, Bong W; Jung, Young D

    2007-04-01

    The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H2O2 content, as determined using H2O2-sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H2O2 and uPAR expression. In addition, exogenous H2O2 was found to increase uPAR mRNA expression and its promoter activity. Site-directed mutagenesis of the potential NF-kappaB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-kappaB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutated-type NF-kappaB-inducing kinase and I-kappaB, and a specific inhibitor of NF-kappaB (BAY11-7082) decreased the H. pylori-induced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-kappaB. With the aid of NAC and H2O2, it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-kappaB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-kappaB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells.

  20. 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

    SciTech Connect

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do

    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

  1. H-Ras Increases Urokinase Expression and Cell Invasion in Genetically Modified Human Astrocytes Through Ras/Raf/MEK Signaling Pathway

    PubMed Central

    ZHAO, YUNGE; XIAO, AIZHEN; DIPIERRO, CHARLES G.; ABDEL-FATTAH, RANA; AMOS, SAMSON; REDPATH, GERARD T.; CARPENTER, JOAN E.; PIEPER, RUSSELL O.; HUSSAINI, ISA M.

    2008-01-01

    Previous study reported that the activation of Ras pathway cooperated with E6/E7-mediated inactivation of p53/pRb to transform immortalized normal human astrocytes (NHA/hTERT) into intracranial tumors strongly resembling human astrocytomas. The mechanism of how H-Ras contributes to astrocytoma formation is unclear. Using genetically modified NHA cells (E6/E7/hTERT and E6/E7/hTERT/Ras cells) as models, we investigated the mechanism of Ras-induced tumorigenesis. The overexpression of constitutively active H-RasV12 in E6/E7/hTERT cells robustly increased the levels of urokinase plasminogen activator (uPA) mRNA, protein, activity and invasive capacity of the E6/E7/hTERT/Ras cells. However, the expressions of MMP-9 and MMP-2 did not significantly change in the E6/E7/hTERT and E6/E7/hTERT/Ras cells. Furthermore, E6/E7/hTERT/Ras cells also displayed higher level of uPA activity and were more invasive than E6/E7/hTERT cells in 3D culture, and formed an intracranial tumor mass in a NOD-SCID mouse model. uPA specific inhibitor (B428) and uPA neutralizing antibody decreased uPA activity and invasion in E6/E7/hTERT/Ras cells. uPA-deficient U-1242 glioblastoma cells were less invasive in vitro and exhibited reduced tumor growth and infiltration into normal brain in xenograft mouse model. Inhibitors of Ras (FTA), Raf (Bay 54−9085) and MEK (UO126), but not of phosphatidylinositol 3-kinase (PI3K) (LY294002) and of protein kinase C (BIM) pathways, inhibited uPA activity and cell invasion. Our results suggest that H-Ras increased uPA expression and activity via the Ras/Raf/MEK signaling pathway leading to enhanced cell invasion and this may contribute to increased invasive growth properties of astrocytomas. PMID:18383343

  2. mRNAs encoding urokinase-type plasminogen activator and plasminogen activator inhibitor-1 are elevated in the mouse brain following kainate-mediated excitation.

    PubMed

    Masos, T; Miskin, R

    1997-07-01

    Urokinase-type plasminogen activator (uPA) is an inducible extracellular serine protease implicated in fibrinolysis and in tissue remodeling. Recently, we have localized uPA mRNA strictly in limbic structures and the parietal cortex of the adult mouse brain. Here, we tested whether the systemic treatment of mice with kainic acid (KA), an amino acid inducing limbic seizures, could elevate in the brain mRNAs encoding uPA and its specific inhibitor, plasminogen activator inhibitor-1 (PAI-1), a major antifibrinolytic agent. Brain sections encompassing the hippocampus were tested through in situ hybridization using radiolabeled riboprobes specific for the two mRNA species. The results showed that KA greatly enhanced both mRNA species in sites of limbic structures and cortex. However, in the hypothalamus and brain blood vessels only PAI-1 mRNA was elevated. Those were also the only two locations where PAI-1 mRNA was detected in the non-treated control brain, although at a low level. For both mRNAs, KA enhancement was first evident 2-4 h after treatment, and it was most prolonged in the hippocampal area, where prominent hybridization signals persisted for three days. Here, both mRNAs were initially elevated in the hilar region of the dentate gyrus and in the molecular and oriens layers; however, PAI-1 mRNA became evident throughout the area, while uPA mRNA became especially pronounced in the CA3/CA4 subfield. In the cortex both mRNA types were induced, but only uPA mRNA was elevated in the retrosplenial cortex, and also in the subiculum. In the amygdaloid complex, uPA mRNA was restricted to the basolateral nucleus, whereas PAI-1 mRNA was seen throughout the structure, however, excluding this nucleus. These data show that seizure activity enhances the expression of uPA and PAI-1 genes in the brain; the patterns of enhancement suggest that the protease and its inhibitor may act in brain plasticity in synchrony, however, also independently of each other. Furthermore, the

  3. A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

    SciTech Connect

    Sasaki, Hiroshi; Klotz, Laurence H.; Sugar, Linda M.; Kiss, Alexander; Venkateswaran, Vasundara

    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

  4. Dominant takeover regimes for genetic algorithms

    NASA Technical Reports Server (NTRS)

    Noever, David; Baskaran, Subbiah

    1995-01-01

    The genetic algorithm (GA) is a machine-based optimization routine which connects evolutionary learning to natural genetic laws. The present work addresses the problem of obtaining the dominant takeover regimes in the GA dynamics. Estimated GA run times are computed for slow and fast convergence in the limits of high and low fitness ratios. Using Euler's device for obtaining partial sums in closed forms, the result relaxes the previously held requirements for long time limits. Analytical solution reveal that appropriately accelerated regimes can mark the ascendancy of the most fit solution. In virtually all cases, the weak (logarithmic) dependence of convergence time on problem size demonstrates the potential for the GA to solve large N-P complete problems.

  5. The change of resurfacing regimes on Venus

    NASA Astrophysics Data System (ADS)

    Ivanov, M. A.

    2015-01-01

    The change of volcanic resurfacing regimes on Venus is discussed. The frequency-size distribution of the regional and lobate plains fields suggest that regional plains had likely been formed due to lava flooding. The geological ratios of impact craters with plains units of different ages are analyzed. Only 3% of the craters located on the older regional plains are found to be embayed by plains material. About 50% of the craters located on the younger lobate plains are found to be embayed by plains lavas. Both the frequency-size distribution of the regional plains fields and the number of embayed craters indicate their catastrophic formation. For lobate plains, these parameters indicate a gradual and time-stretched accumulation of their material. Thus, the volcanic resurfacing regimes must have been changing radically throughout the observable portion of the geological history of Venus.

  6. Steady and transient regimes in hydropower plants

    NASA Astrophysics Data System (ADS)

    Gajic, A.

    2013-12-01

    Hydropower plant that has been in operation for about 30 years has to be reconstructed. They have already installed 12 Kaplan turbines, the largest in the world at that time. The existing CAM relationship was determined based on hydraulic model tests and checked by efficiency on-site tests. It was also tested based on turbine bearing vibrations. In order to discover vibrations and long cracks on stay vanes detailed on-site measurements were performed. Influence of the modification of the trailing edges on the dynamic stresses of the stay vanes is also shown. In order to improve power output transient regimes were analyzed, both experimentally and numerically. Reversible hydropower plant, a pioneer in Europe since it was the first Pump storage power plant constructed with the highest head pump-turbines in the world. Analyses of transient regimes discover some problems with S-shaped characteristics coupled with non-symmetrical penstock.

  7. Marginal Mean Models for Dynamic Regimes

    PubMed Central

    Murphy, S. A.; van der Laan, M. J.; Robins, J. M.

    2009-01-01

    A dynamic treatment regime is a list of rules for how the level of treatment will be tailored through time to an individual’s changing severity. In general, individuals who receive the highest level of treatment are the individuals with the greatest severity and need for treatment. Thus there is planned selection of the treatment dose. In addition to the planned selection mandated by the treatment rules, the use of staff judgment results in unplanned selection of the treatment level. Given observational longitudinal data or data in which there is unplanned selection, of the treatment level, the methodology proposed here allows the estimation of a mean response to a dynamic treatment regime under the assumption of sequential randomization. PMID:20019887

  8. The optomechanical instability in the quantum regime

    NASA Astrophysics Data System (ADS)

    Ludwig, Max; Kubala, Björn; Marquardt, Florian

    2008-09-01

    We consider a generic optomechanical system, consisting of a driven optical cavity and a movable mirror attached to a cantilever. Systems of this kind (and analogues) have been realized in many recent experiments. It is well known that these systems can exhibit an instability towards a regime where the cantilever settles into self-sustained oscillations. In this paper, we briefly review the classical theory of the optomechanical instability, and then discuss the features arising in the quantum regime. We solve numerically a full quantum master equation for the coupled system, and use it to analyze the photon number, the cantilever's mechanical energy, the phonon probability distribution and the mechanical Wigner density, as a function of experimentally accessible control parameters. When a suitable dimensionless 'quantum parameter' is sent to zero, the results of the quantum mechanical model converge towards the classical predictions. We discuss this quantum-to-classical transition in some detail.

  9. Bose polarons in the strongly interacting regime

    NASA Astrophysics Data System (ADS)

    Kedar, Dhruv; Hu, Ming-Guang; van de Graaff, Michael; Corson, John; Cornell, Eric; Jin, Deborah

    2016-05-01

    Impurities immersed in and interacting with a Bose-Einstein condensate (BEC) are predicted to form quasiparticle excitations called Bose polarons. I will present experimental evidence of Bose polarons in cold atoms obtained using radio-frequency spectroscopy to measure the excitation spectrum of fermionic K-40 impurities interacting with a BEC of Rb-87 atoms. We use an interspecies Feshbach resonance to tune the interactions between the impurities and the bosons, and we take data in the strongly interacting regime.

  10. The kinetic regime of the Vicsek model

    NASA Astrophysics Data System (ADS)

    Chepizhko, A. A.; Kulinskii, V. L.

    2009-12-01

    We consider the dynamics of the system of self-propelling particles modeled via the Vicsek algorithm in continuum time limit. It is shown that the alignment process for the velocities can be subdivided into two regimes: "fast" kinetic and "slow" hydrodynamic ones. In fast kinetic regime the alignment of the particle velocity to the local neighborhood takes place with characteristic relaxation time. So, that the bigger regions arise with the velocity alignment. These regions align their velocities thus giving rise to hydrodynamic regime of the dynamics. We propose the mean-field-like approach in which we take into account the correlations between density and velocity. The comparison of the theoretical predictions with the numerical simulations is given. The relation between Vicsek model in the zero velocity limit and the Kuramoto model is stated. The mean-field approach accounting for the dynamic change of the neighborhood is proposed. The nature of the discontinuity of the dependence of the order parameter in case of vectorial noise revealed in Gregorie and Chaite, Phys. Rev. Lett., 92, 025702 (2004) is discussed and the explanation of it is proposed.

  11. Understanding the Early Regime of Drop Spreading.

    PubMed

    Mitra, Surjyasish; Mitra, Sushanta K

    2016-09-01

    We present experimental data to characterize the spreading of a liquid drop on a substrate kept submerged in another liquid medium. They reveal that drop spreading always begins in a regime dominated by drop viscosity where the spreading radius scales as r ∼ t with a nonuniversal prefactor. This initial viscous regime either lasts in its entirety or switches to an intermediate inertial regime where the spreading radius grows with time following the well-established inertial scaling of r ∼ t(1/2). This latter case depends on the characteristic viscous length scale of the problem. In either case, the final stage of spreading, close to equilibrium, follows Tanner's law. Further experiments performed on the same substrate kept in ambient air reveal a similar trend, albeit with limited spatiotemporal resolution, showing the universal nature of the spreading behavior. It is also found that, for early times of spreading, the process is similar to coalescence of two freely suspended liquid drops, making the presence of the substrate and consequently the three-phase contact line insignificant. PMID:27513708

  12. Lubrication regimes in lumbar total disc arthroplasty.

    PubMed

    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.

  13. Constructing an interdisciplinary flow regime recommendation

    USGS Publications Warehouse

    Bartholow, J.M.

    2010-01-01

    It is generally agreed that river rehabilitation most often relies on restoring a more natural flow regime, but credibly defining the desired regime can be problematic. I combined four distinct methods to develop and refine month-by-month and event-based flow recommendations to protect and partially restore the ecological integrity of the Cache la Poudre River through Fort Collins, Colorado. A statistical hydrologic approach was used to summarize the river's natural flow regime and set provisional monthly flow targets at levels that were historically exceeded 75% of the time. These preliminary monthly targets were supplemented using results from three Poudre-specific disciplinary studies. A substrate maintenance flow model was used to better define the high flows needed to flush accumulated sediment from the river's channel and help sustain the riparian zone in this snowmelt-dominated river. A hydraulic/habitat model and a water temperature model were both used to better define the minimum flows necessary to maintain a thriving cool water fishery. The result is a range of recommended monthly flows and daily flow guidance illustrating the advantage of combining a wide range of available disciplinary information, supplemented by judgment based on ecological principles and a general understanding of river ecosystems, in a highly altered, working river. ?? 2010 American Water Resources Association.

  14. Three-dimensional null point reconnection regimes

    SciTech Connect

    Priest, E. R.; Pontin, D. I.

    2009-12-15

    Recent advances in theory and computational experiments have shown the need to refine the previous categorization of magnetic reconnection at three-dimensional null points--points at which the magnetic field vanishes. We propose here a division into three different types, depending on the nature of the flow near the spine and fan of the null. The spine is an isolated field line which approaches the null (or recedes from it), while the fan is a surface of field lines which recede from it (or approach it). So-called torsional spine reconnection occurs when field lines in the vicinity of the fan rotate, with current becoming concentrated along the spine so that nearby field lines undergo rotational slippage. In torsional fan reconnection field lines near the spine rotate and create a current that is concentrated in the fan with a rotational flux mismatch and rotational slippage. In both of these regimes, the spine and fan are perpendicular and there is no flux transfer across spine or fan. The third regime, called spine-fan reconnection, is the most common in practice and combines elements of the previous spine and fan models. In this case, in response to a generic shearing motion, the null point collapses to form a current sheet that is focused at the null itself, in a sheet that locally spans both the spine and fan. In this regime the spine and fan are no longer perpendicular and there is flux transfer across both of them.

  15. THE DYNAMIC REGIME CONCEPT FOR ECOSYSTEM MANAGEMENT AND RESTORATION

    EPA Science Inventory

    Dynamic regimes of ecosystems are multidimensional basis of attraction, characterized by particular species communities and ecosystems processes. Ecosystem patterns and processes rarely respond linerarly to disturbances, and the nonlinear cynamic regime concept offers a more real...

  16. FISHER INFORMATION OF DYNAMIC REGIME TRANSITIONS IN ECOLOGICAL SYSTEMS

    EPA Science Inventory

    Ecosystems often exhibit transitions between multiple dynamic regimes (or steady states). As ecosystems experience perturbations of varying regularity and intensity, they may either remain within the state space neighborhood of the current regime, or ?flip? into the neighborhood ...

  17. The discrete regime of flame propagation

    NASA Astrophysics Data System (ADS)

    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

  18. River Flow Regimes and Effective Discharge

    NASA Astrophysics Data System (ADS)

    Basso, S.; Sprocati, R.; Frascati, A.; Marani, M.; Schirmer, M.; Botter, G.

    2015-12-01

    The concept of effective discharge is widespread in geomorphology and river engineering and restoration. For example, it is used to design the most stable channel configuration, to estimate sedimentation rate and lifespan of reservoirs and to characterize the hydrologic forcing in models studying long-term evolution of rivers. Accordingly, the effective discharge has been the focus of countless empirical, theoretical and numerical studies, which found it to vary among catchments as a function of climate, landscape and river morphology, type of transport (dissolved, suspended or bedload), and of streamflow variability. The heterogeneity of the effective discharge values observed in different catchments challenges a thorough understanding of its pivotal drivers, and a consistent framework which explains observations carried out in different geographic areas is still lacking. In the present work, the observed diversity is explained in terms of the underlying heterogeneity of river flow regimes, by linking effective discharge to attributes of the sediment rating curve and to streamflow variability, as resulting from climatic and landscape drivers. An analytic expression of the effective ratio (i.e. the ratio between effective discharge and mean streamflow) is provided, which captures observed values of effective discharge for suspended sediment transport in a set of catchments of the continental United States. The framework disentangles hydrologic and landscape controls on effective discharge, and highlights distinct effective ratios of persistent and erratic hydrologic regimes (respectively characterized by low and high flow variability), attributable to intrinsically different streamflow dynamics. Clusters of river catchments characterized by similar streamflow dynamics can be identified. The framework provides an opportunity for first-order estimates of effective discharge in rivers belonging to different areas, based on the type of flow regime.

  19. Bose Polarons in the Strongly Interacting Regime.

    PubMed

    Hu, Ming-Guang; Van de Graaff, Michael J; Kedar, Dhruv; Corson, John P; Cornell, Eric A; Jin, Deborah S

    2016-07-29

    When an impurity is immersed in a Bose-Einstein condensate, impurity-boson interactions are expected to dress the impurity into a quasiparticle, the Bose polaron. We superimpose an ultracold atomic gas of ^{87}Rb with a much lower density gas of fermionic ^{40}K impurities. Through the use of a Feshbach resonance and radio-frequency spectroscopy, we characterize the energy, spectral width, and lifetime of the resultant polaron on both the attractive and the repulsive branches in the strongly interacting regime. The width of the polaron in the attractive branch is narrow compared to its binding energy, even as the two-body scattering length diverges. PMID:27517776

  20. Efficiency of Rectification: Reversible vs. Irreversible Regimes

    NASA Astrophysics Data System (ADS)

    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.

  1. Bose Polarons in the Strongly Interacting Regime

    NASA Astrophysics Data System (ADS)

    Hu, Ming-Guang; Van de Graaff, Michael J.; Kedar, Dhruv; Corson, John P.; Cornell, Eric A.; Jin, Deborah S.

    2016-07-01

    When an impurity is immersed in a Bose-Einstein condensate, impurity-boson interactions are expected to dress the impurity into a quasiparticle, the Bose polaron. We superimpose an ultracold atomic gas of 87Rb with a much lower density gas of fermionic 40 impurities. Through the use of a Feshbach resonance and radio-frequency spectroscopy, we characterize the energy, spectral width, and lifetime of the resultant polaron on both the attractive and the repulsive branches in the strongly interacting regime. The width of the polaron in the attractive branch is narrow compared to its binding energy, even as the two-body scattering length diverges.

  2. Imperfect relativistic mirrors in the quantum regime

    SciTech Connect

    Mendonça, J. T.; Serbeto, A.; Galvão, R. M. O.

    2014-05-15

    The collective backscattering of intense laser radiation by energetic electron beams is considered in the relativistic quantum regime. Exact solutions for the radiation field are obtained, for arbitrary electron pulse shapes and laser intensities. The electron beams act as imperfect nonlinear mirrors on the incident laser radiation. This collective backscattering process can lead to the development of new sources of ultra-short pulse radiation in the gamma-ray domain. Numerical examples show that, for plausible experimental conditions, intense pulses of gamma-rays, due to the double Doppler shift of the harmonics of the incident laser radiation, can be produced using the available technology, with durations less than 1 as.

  3. 22 CFR 120.29 - Missile Technology Control Regime.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Missile Technology Control Regime. 120.29... DEFINITIONS § 120.29 Missile Technology Control Regime. (a) For purposes of this subchapter, Missile Technology Control Regime (MTCR) means the policy statement between the United States, the United...

  4. 22 CFR 120.29 - Missile Technology Control Regime.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Missile Technology Control Regime. 120.29... DEFINITIONS § 120.29 Missile Technology Control Regime. (a) For purposes of this subchapter, Missile Technology Control Regime (MTCR) means the policy statement between the United States, the United...

  5. 22 CFR 120.29 - Missile Technology Control Regime.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Missile Technology Control Regime. 120.29... DEFINITIONS § 120.29 Missile Technology Control Regime. (a) For purposes of this subchapter, Missile Technology Control Regime (MTCR) means the policy statement between the United States, the United...

  6. 22 CFR 120.29 - Missile Technology Control Regime.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Missile Technology Control Regime. 120.29... DEFINITIONS § 120.29 Missile Technology Control Regime. (a) For purposes of this subchapter, Missile Technology Control Regime (MTCR) means the policy statement between the United States, the United...

  7. 22 CFR 120.29 - Missile Technology Control Regime.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Missile Technology Control Regime. 120.29... DEFINITIONS § 120.29 Missile Technology Control Regime. (a) For purposes of this subchapter, Missile Technology Control Regime (MTCR) means the policy statement among the United States, the United Kingdom,...

  8. The relationship between void waves and flow regime transition

    SciTech Connect

    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.

  9. Kinetic studies on novel plasminogen activators. Demonstration of fibrin enhancement for hybrid enzymes comprising the A-chain of plasmin (Lys-78) and B-chain of tissue-type plasminogen activator (Ile-276) or urokinase (Ile-159).

    PubMed Central

    Fears, R; Dodd, I; Ferres, H; Robinson, J H

    1990-01-01

    The activation of plasminogen by two novel hybrid enzymes, constructed from the A-chain of plasmin and the B-chains of tissue-type plasminogen activator (t-PA) or urokinase, was compared with the activation by the parent enzymes. Basal kinetic constants for 'Lys-plasminogen' (human plasminogen with N-terminal lysine) and 'Glu-plasminogen' (human plasminogen with N-terminal glutamic acid) activation were similar to those of the parent activators. The Km for plasminogen turnover for both hybrid enzymes was considerably decreased in the presence of both soluble fibrin and a mimic, a CNBr digest of fibrinogen. These enhancements and the related apparent negative co-operativity are similar to the behaviour of t-PA itself. The results are discussed with regard to the molecular features involved in the mechanism of fibrin stimulation. PMID:2139324

  10. Elastic regimes of subisostatic athermal fiber networks.

    PubMed

    Licup, A J; Sharma, A; MacKintosh, F C

    2016-01-01

    Athermal models of disordered fibrous networks are highly useful for studying the mechanics of elastic networks composed of stiff biopolymers. The underlying network architecture is a key aspect that can affect the elastic properties of these systems, which include rich linear and nonlinear elasticity. Existing computational approaches have focused on both lattice-based and off-lattice networks obtained from the random placement of rods. It is not obvious, a priori, whether the two architectures have fundamentally similar or different mechanics. If they are different, it is not clear which of these represents a better model for biological networks. Here, we show that both approaches are essentially equivalent for the same network connectivity, provided the networks are subisostatic with respect to central force interactions. Moreover, for a given subisostatic connectivity, we even find that lattice-based networks in both two and three dimensions exhibit nearly identical nonlinear elastic response. We provide a description of the linear mechanics for both architectures in terms of a scaling function. We also show that the nonlinear regime is dominated by fiber bending and that stiffening originates from the stabilization of subisostatic networks by stress. We propose a generalized relation for this regime in terms of the self-generated normal stresses that develop under deformation. Different network architectures have different susceptibilities to the normal stress but essentially exhibit the same nonlinear mechanics. Such a stiffening mechanism has been shown to successfully capture the nonlinear mechanics of collagen networks. PMID:26871101

  11. Revealing the quantum regime in tunnelling plasmonics.

    PubMed

    Savage, Kevin J; Hawkeye, Matthew M; Esteban, Rubén; Borisov, Andrei G; Aizpurua, Javier; Baumberg, Jeremy J

    2012-11-22

    When two metal nanostructures are placed nanometres apart, their optically driven free electrons couple electrically across the gap. The resulting plasmons have enhanced optical fields of a specific colour tightly confined inside the gap. Many emerging nanophotonic technologies depend on the careful control of this plasmonic coupling, including optical nanoantennas for high-sensitivity chemical and biological sensors, nanoscale control of active devices, and improved photovoltaic devices. But for subnanometre gaps, coherent quantum tunnelling becomes possible and the system enters a regime of extreme non-locality in which previous classical treatments fail. Electron correlations across the gap that are driven by quantum tunnelling require a new description of non-local transport, which is crucial in nanoscale optoelectronics and single-molecule electronics. Here, by simultaneously measuring both the electrical and optical properties of two gold nanostructures with controllable subnanometre separation, we reveal the quantum regime of tunnelling plasmonics in unprecedented detail. All observed phenomena are in good agreement with recent quantum-based models of plasmonic systems, which eliminate the singularities predicted by classical theories. These findings imply that tunnelling establishes a quantum limit for plasmonic field confinement of about 10(-8)λ(3) for visible light (of wavelength λ). Our work thus prompts new theoretical and experimental investigations into quantum-domain plasmonic systems, and will affect the future of nanoplasmonic device engineering and nanoscale photochemistry.

  12. Variety of synchronous regimes in neuronal ensembles

    NASA Astrophysics Data System (ADS)

    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.

  13. Option pricing with regime switching by trinomial tree method

    NASA Astrophysics Data System (ADS)

    Yuen, Fei Lung; Yang, Hailiang

    2010-02-01

    We present a fast and simple tree model to price simple and exotic options in Markov Regime Switching Model (MRSM) with multi-regime. We modify the trinomial tree model of Boyle (1986) [12] by controlling the risk neutral probability measure in different regime states to ensure that the tree model can accommodate the data of all different regimes at the same time preserving its combining tree structure. In MRSM, the market might not be complete, therefore we provide some ideas and discussions on managing the regime switching risk in support of our results.

  14. Distinct Transport Regimes for Two Elastically Coupled Molecular Motors

    NASA Astrophysics Data System (ADS)

    Berger, Florian; Keller, Corina; Klumpp, Stefan; Lipowsky, Reinhard

    2012-05-01

    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.

  15. Dynamic regime marginal structural mean models for estimation of optimal dynamic treatment regimes, Part I: main content.

    PubMed

    Orellana, Liliana; Rotnitzky, Andrea; Robins, James M

    2010-01-01

    Dynamic treatment regimes are set rules for sequential decision making based on patient covariate history. Observational studies are well suited for the investigation of the effects of dynamic treatment regimes because of the variability in treatment decisions found in them. This variability exists because different physicians make different decisions in the face of similar patient histories. In this article we describe an approach to estimate the optimal dynamic treatment regime among a set of enforceable regimes. This set is comprised by regimes defined by simple rules based on a subset of past information. The regimes in the set are indexed by a Euclidean vector. The optimal regime is the one that maximizes the expected counterfactual utility over all regimes in the set. We discuss assumptions under which it is possible to identify the optimal regime from observational longitudinal data. Murphy et al. (2001) developed efficient augmented inverse probability weighted estimators of the expected utility of one fixed regime. Our methods are based on an extension of the marginal structural mean model of Robins (1998, 1999) which incorporate the estimation ideas of Murphy et al. (2001). Our models, which we call dynamic regime marginal structural mean models, are specially suitable for estimating the optimal treatment regime in a moderately small class of enforceable regimes of interest. We consider both parametric and semiparametric dynamic regime marginal structural models. We discuss locally efficient, double-robust estimation of the model parameters and of the index of the optimal treatment regime in the set. In a companion paper in this issue of the journal we provide proofs of the main results.

  16. Stable operating regime for traveling wave devices

    DOEpatents

    Carlsten, Bruce E.

    2000-01-01

    Autophase stability is provided for a traveling wave device (TWD) electron beam for amplifying an RF electromagnetic wave in walls defining a waveguide for said electromagnetic wave. An off-axis electron beam is generated at a selected energy and has an energy noise inherently arising from electron gun. The off-axis electron beam is introduced into the waveguide. The off-axis electron beam is introduced into the waveguide at a second radius. The waveguide structure is designed to obtain a selected detuning of the electron beam. The off-axis electron beam has a velocity and the second radius to place the electron beam at a selected distance from the walls defining the waveguide, wherein changes in a density of the electron beam due to the RF electromagnetic wave are independent of the energy of the electron beam to provide a concomitant stable operating regime relative to the energy noise.

  17. Nonlinear regimes of forced magnetic reconnection

    SciTech Connect

    Vekstein, G.; Kusano, K.

    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.

  18. Regime Changes in California Temperature Trends

    NASA Astrophysics Data System (ADS)

    Cordero, E. C.; Kessomkiat, W.; Mauget, S.

    2008-12-01

    Annual and seasonal temperature trends are analyzed for California using surface data from the US Historical Climate Network and the larger COOP network. While trends in Tmax and Tmin both show warming over the last 50 years, the temporal and spatial structure of these trends is quite different. An analysis using Mann Whitney U statistics reveals that the patterns of warming and cooling from individual stations have a distinct temporal signature that differs between Tmax and Tmin. Significant cooling trends in Tmin are found between 1920-1958, while significant warming only starts after the 1970s. In contrast, Tmax trends show a more variable pattern of warming and cooling between 1920-1980, with California wide warming only occurring after 1980. These results suggest regime changes in California temperature trends that could only occur through large scale forcing. A discussion of the various forcing mechanisms contributing to California trends and their spatial and temporal variability will be presented.

  19. Supercurrent in the quantum Hall regime

    NASA Astrophysics Data System (ADS)

    Wei, Ming-Tso; Amet, François; Ke, Chung-Ting; Borzenets, Ivan; Wang, Jiyingmei; Watanabe, Keji; Taniguchi, Takashi; Deacon, Russell; Yamamoto, Michihisa; Bomze, Yuriy; Tarucha, Seigo; Finkelstein, Gleb

    Combining superconductivity and the quantum Hall (QH) effect is a promising route for creating new types of topological excitations. Despite this potential, signatures of superconductivity in the quantum Hall regime remain scarce, and a superconducting current through a QH weak link has so far eluded experimental observation. Here we demonstrate the existence of a novel type of Josephson coupling through a QH region at magnetic fields as high as 2 Tesla. The supercurrent is mediated by states encompassing QH edge channels, which are flowing on opposite sides of the sample. The edges are coupled together by the hybrid electron-hole modes at the interfaces between the QH region and the superconducting contacts. These chiral modes, which share some features with Majorana modes, are formed when electron and hole edge states are mixed by the superconductor.

  20. Environment Flow Assessment with Flow Regime Transition

    NASA Astrophysics Data System (ADS)

    Su, J.; Ho, C. C.; Chang, L. C.

    2015-12-01

    To avoid worsen river and estuarine ecosystems cause by overusing water resources, environmental flows conservation is applied to reduce the impact of river environment. Environmental flows refer to water provided within a river, wetland or coastal zone to sustain ecosystems and benefits to human wellbeing. Environment flow assessment is now widely accepted that a naturally variable flow regime, rather than just a minimum low flow. In this study, we propose four methods, experience method, Tenant method, hydraulic method and habitat method to assess the environmental flow of base flow, flush flow and overbank flow with different discharge, frequency and occurrence period. Dahan River has been chosen as a case to demonstrate the assessment mechanism. The alternatives impact analysis of environment and human water used provides a reference for stakeholders when holding an environmental flow consultative meeting.

  1. Alumina strength degradation in the elastic regime

    SciTech Connect

    Furnish, M.D.; Chhabildas, L.C.

    1997-08-01

    Measurements of Kanel et. al. [1991] have suggested that deviatoric stresses in glasses shocked to nearly the Hugoniot Elastic limit (HEL) relax over a time span of microseconds after initial loading. Failure (damage) waves have been inferred on the basis of these measurements using time-resolved manganin normal and transverse stress gauges. Additional experiments on glass by other researchers, using time-resolved gauges, high-speed photography and spall strength determinations have also lead to the same conclusions. In the present study the authors have conducted transmitted-wave experiments on high-quality Coors AD995 alumina shocked to roughly 5 and 7 GPa (just below or at the HEL). The material is subsequently reshocked to just above its elastic limit. Results of these experiments do show some evidence of strength degradation in the elastic regime.

  2. Different spreading regimes of spray-flames

    NASA Astrophysics Data System (ADS)

    Suard, Sylvain; Haldenwang, Pierre; Nicoli, Colette

    2004-05-01

    We present a minimal model of spray combustion to investigate a flame front propagating through a fuel-lean mixture of fuel vapor, droplets and air. The model relies on a main control parameter, Da, named the Damkoehler number, which allows us to take into account a large variety of fuel sprays. Numerical results reveal, as a function of Da, a wide range of spray-flame structures, including the classical gaseous premixed flame, a specific regime controlled by vaporisation, and a pulsating mode of propagation. The latter appears when the vaporisation is smaller than (or equal to) the reaction time, and it occurs even with a unit Lewis number. To cite this article: S. Suard et al., C. R. Mecanique 332 (2004).

  3. Evolution of the water regime of Phobos

    SciTech Connect

    Fanale, F.P.; Salvail, J.R. )

    1990-12-01

    In the present model of Phobos water regime evolution, a time-dependent solar insolation is influenced by both decreasing solar output over geologic time and the Mars and Phobos cycles of eccentricity and obliquity, which vary over 100,000-1,000,000 year time scales. The results presented address model cases which assume (1) a homogeneous distribution of water ice, and (2) a driving of water ice toward the surface by the internal thermal gradient near the poles. A two-dimensional model is used to compute temperatures, heat and vapor fluxes, and ice removal/deposition rates, for the case of uniform ice distribution throughout Phobos. The results obtained indicate that a substantial amount of vapor is produced within 1 km of the surface. 15 refs.

  4. Classification of Arctic, Mid-Latitude and Tropical Clouds in the Mixed-Phase Temperature Regime

    NASA Astrophysics Data System (ADS)

    Costa, Anja; Afchine, Armin; Luebke, Anna; Meyer, Jessica; Dorsey, James R.; Gallagher, Martin W.; Ehrlich, André; Wendisch, Manfred; Krämer, Martina

    2016-04-01

    The degree of glaciation and the sizes and habits of ice particles formed in mixed-phase clouds remain not fully understood. However, these properties define the mixed clouds' radiative impact on the Earth's climate and thus a correct representation of this cloud type in global climate models is of importance for an improved certainty of climate predictions. This study focuses on the occurrence and characteristics of two types of clouds in the mixed-phase temperature regime (238-275K): coexistence clouds (Coex), in which both liquid drops and ice crystals exist, and fully glaciated clouds that develop in the Wegener-Bergeron-Findeisen regime (WBF clouds). We present an extensive dataset obtained by the Cloud and Aerosol Particle Spectrometer NIXE-CAPS, covering Arctic, mid-latitude and tropical regions. In total, we spent 45.2 hours within clouds in the mixed-phase temperature regime during five field campaigns (Arctic: VERDI, 2012 and RACEPAC, 2014 - Northern Canada; mid-latitude: COALESC, 2011 - UK and ML-Cirrus, 2014 - central Europe; tropics: ACRIDICON, 2014 - Brazil). We show that WBF and Coex clouds can be identified via cloud particle size distributions. The classified datasets are used to analyse temperature dependences of both cloud types as well as range and frequencies of cloud particle concentrations and sizes. One result is that Coex clouds containing supercooled liquid drops are found down to temperatures of -40 deg C only in tropical mixed clouds, while in the Arctic and mid-latitudes no liquid drops are observed below about -20 deg C. In addition, we show that the cloud particles' aspherical fractions - derived from polarization signatures of particles with diameters between 20 and 50 micrometers - differ significantly between WBF and Coex clouds. In Coex clouds, the aspherical fraction of cloud particles is generally very low, but increases with decreasing temperature. In WBF clouds, where all cloud particles are ice, about 20-40% of the cloud

  5. Deterministic-random separation in nonstationary regime

    NASA Astrophysics Data System (ADS)

    Abboud, D.; Antoni, J.; Sieg-Zieba, S.; Eltabach, M.

    2016-02-01

    In rotating machinery vibration analysis, the synchronous average is perhaps the most widely used technique for extracting periodic components. Periodic components are typically related to gear vibrations, misalignments, unbalances, blade rotations, reciprocating forces, etc. Their separation from other random components is essential in vibration-based diagnosis in order to discriminate useful information from masking noise. However, synchronous averaging theoretically requires the machine to operate under stationary regime (i.e. the related vibration signals are cyclostationary) and is otherwise jeopardized by the presence of amplitude and phase modulations. A first object of this paper is to investigate the nature of the nonstationarity induced by the response of a linear time-invariant system subjected to speed varying excitation. For this purpose, the concept of a cyclo-non-stationary signal is introduced, which extends the class of cyclostationary signals to speed-varying regimes. Next, a "generalized synchronous average'' is designed to extract the deterministic part of a cyclo-non-stationary vibration signal-i.e. the analog of the periodic part of a cyclostationary signal. Two estimators of the GSA have been proposed. The first one returns the synchronous average of the signal at predefined discrete operating speeds. A brief statistical study of it is performed, aiming to provide the user with confidence intervals that reflect the "quality" of the estimator according to the SNR and the estimated speed. The second estimator returns a smoothed version of the former by enforcing continuity over the speed axis. It helps to reconstruct the deterministic component by tracking a specific trajectory dictated by the speed profile (assumed to be known a priori).The proposed method is validated first on synthetic signals and then on actual industrial signals. The usefulness of the approach is demonstrated on envelope-based diagnosis of bearings in variable

  6. Late Quaternary fire regimes of Australasia

    NASA Astrophysics Data System (ADS)

    Mooney, S. D.; Harrison, S. P.; Bartlein, P. J.; Daniau, A.-L.; Stevenson, J.; Brownlie, K. C.; Buckman, S.; Cupper, M.; Luly, J.; Black, M.; Colhoun, E.; D'Costa, D.; Dodson, J.; Haberle, S.; Hope, G. S.; Kershaw, P.; Kenyon, C.; McKenzie, M.; Williams, N.

    2011-01-01

    We have compiled 223 sedimentary charcoal records from Australasia in order to examine the temporal and spatial variability of fire regimes during the Late Quaternary. While some of these records cover more than a full glacial cycle, here we focus on the last 70,000 years when the number of individual records in the compilation allows more robust conclusions. On orbital time scales, fire in Australasia predominantly reflects climate, with colder periods characterized by less and warmer intervals by more biomass burning. The composite record for the region also shows considerable millennial-scale variability during the last glacial interval (73.5-14.7 ka). Within the limits of the dating uncertainties of individual records, the variability shown by the composite charcoal record is more similar to the form, number and timing of Dansgaard-Oeschger cycles as observed in Greenland ice cores than to the variability expressed in the Antarctic ice-core record. The composite charcoal record suggests increased biomass burning in the Australasian region during Greenland Interstadials and reduced burning during Greenland Stadials. Millennial-scale variability is characteristic of the composite record of the sub-tropical high pressure belt during the past 21 ka, but the tropics show a somewhat simpler pattern of variability with major peaks in biomass burning around 15 ka and 8 ka. There is no distinct change in fire regime corresponding to the arrival of humans in Australia at 50 ± 10 ka and no correlation between archaeological evidence of increased human activity during the past 40 ka and the history of biomass burning. However, changes in biomass burning in the last 200 years may have been exacerbated or influenced by humans.

  7. 29 CFR 2530.200b-2 - Hour of service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... employment relationship has terminated) due to vacation, holiday, illness, incapacity (including disability...). (C) Employee C spent 3 weeks on a paid vacation. C's salary is established at an annual rate but is... spent 2 weeks on vacation, for which he was paid $150. Although D has no regular work schedule, the...

  8. 29 CFR 2530.200b-2 - Hour of service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... employment relationship has terminated) due to vacation, holiday, illness, incapacity (including disability...). (C) Employee C spent 3 weeks on a paid vacation. C's salary is established at an annual rate but is... spent 2 weeks on vacation, for which he was paid $150. Although D has no regular work schedule, the...

  9. 29 CFR 2530.200b-2 - Hour of service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... employment relationship has terminated) due to vacation, holiday, illness, incapacity (including disability...). (C) Employee C spent 3 weeks on a paid vacation. C's salary is established at an annual rate but is... spent 2 weeks on vacation, for which he was paid $150. Although D has no regular work schedule, the...

  10. 29 CFR 2530.200b-2 - Hour of service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... employment relationship has terminated) due to vacation, holiday, illness, incapacity (including disability...). (C) Employee C spent 3 weeks on a paid vacation. C's salary is established at an annual rate but is... spent 2 weeks on vacation, for which he was paid $150. Although D has no regular work schedule, the...

  11. 29 CFR 2530.200b-2 - Hour of service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... employment relationship has terminated) due to vacation, holiday, illness, incapacity (including disability...). (C) Employee C spent 3 weeks on a paid vacation. C's salary is established at an annual rate but is... spent 2 weeks on vacation, for which he was paid $150. Although D has no regular work schedule, the...

  12. Fasting and 2-Hour Plasma Glucose and Insulin

    PubMed Central

    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

  13. Using decision lists to construct interpretable and parsimonious treatment regimes.

    PubMed

    Zhang, Yichi; Laber, Eric B; Tsiatis, Anastasios; Davidian, Marie

    2015-12-01

    A treatment regime formalizes personalized medicine as a function from individual patient characteristics to a recommended treatment. A high-quality treatment regime can improve patient outcomes while reducing cost, resource consumption, and treatment burden. Thus, there is tremendous interest in estimating treatment regimes from observational and randomized studies. However, the development of treatment regimes for application in clinical practice requires the long-term, joint effort of statisticians and clinical scientists. In this collaborative process, the statistician must integrate clinical science into the statistical models underlying a treatment regime and the clinician must scrutinize the estimated treatment regime for scientific validity. To facilitate meaningful information exchange, it is important that estimated treatment regimes be interpretable in a subject-matter context. We propose a simple, yet flexible class of treatment regimes whose members are representable as a short list of if-then statements. Regimes in this class are immediately interpretable and are therefore an appealing choice for broad application in practice. We derive a robust estimator of the optimal regime within this class and demonstrate its finite sample performance using simulation experiments. The proposed method is illustrated with data from two clinical trials. PMID:26193819

  14. Using Decision Lists to Construct Interpretable and Parsimonious Treatment Regimes

    PubMed Central

    Zhang, Yichi; Laber, Eric B.; Tsiatis, Anastasios; Davidian, Marie

    2015-01-01

    Summary A treatment regime formalizes personalized medicine as a function from individual patient characteristics to a recommended treatment. A high-quality treatment regime can improve patient outcomes while reducing cost, resource consumption, and treatment burden. Thus, there is tremendous interest in estimating treatment regimes from observational and randomized studies. However, the development of treatment regimes for application in clinical practice requires the long-term, joint effort of statisticians and clinical scientists. In this collaborative process, the statistician must integrate clinical science into the statistical models underlying a treatment regime and the clinician must scrutinize the estimated treatment regime for scientific validity. To facilitate meaningful information exchange, it is important that estimated treatment regimes be interpretable in a subject-matter context. We propose a simple, yet flexible class of treatment regimes whose members are representable as a short list of if-then statements. Regimes in this class are immediately interpretable and are therefore an appealing choice for broad application in practice. We derive a robust estimator of the optimal regime within this class and demonstrate its finite sample performance using simulation experiments. The proposed method is illustrated with data from two clinical trials. PMID:26193819

  15. Rheological equations in asymptotic regimes of granular flow

    USGS Publications Warehouse

    Chen, C.-L.; Ling, C.-H.

    1998-01-01

    This paper assesses the validity of the generalized viscoplastic fluid (GVF) model in light of the established constitutive relations in two asymptotic flow regimes, namely, the macroviscous and grain-inertia regimes. A comprehensive review of the literature on constitutive relations in both regimes reveals that except for some material constants, such as the coefficient of restitution, the normalized shear stress in both regimes varies only with the grain concentration, C. It is found that Krieger-Dougherty's relative viscosity, ??*(C), is sufficiently coherent among the monotonically nondecreasing functions of C used in describing the variation of the shear stress with C in both regimes. It not only accurately represents the C-dependent relative viscosity of a suspension in the macroviscous regime, but also plays a role of the radial distribution function that describes the statistics of particle collisions in the grain-inertia regime. Use of ??*(C) alone, however, cannot link the two regimes. Another parameter, the shear-rate number, N, is needed in modelling the rheology of neutrally buoyant granular flows in transition between the two asymptotic regimes. The GVF model proves compatible with most established relations in both regimes.

  16. Characterization of fire regime in Sardinia (Italy)

    NASA Astrophysics Data System (ADS)

    Bacciu, V. M.; Salis, M.; Mastinu, S.; Masala, F.; Sirca, C.; Spano, D.

    2012-12-01

    In the last decades, a number of Authors highlighted the crucial role of forest fires within Mediterranean ecosystems, with impacts both negative and positive on all biosphere components and with reverberations on different scales. Fire determines the landscape structure and plant composition, but it is also the cause of enormous economic and ecological damages, beside the loss of human life. In Sardinia (Italy), the second largest island of the Mediterranean Basin, forest fires are perceived as one of the main environmental and social problems, and data are showing that the situation is worsening especially within the rural-urban peripheries and the increasing number of very large forest fires. The need for information concerning forest fire regime has been pointed out by several Authors (e.g. Rollins et al., 2002), who also emphasized the importance of understanding the factors (such as weather/climate, socio-economic, and land use) that determine spatial and temporal fire patterns. These would be used not only as a baseline to predict the climate change effect on forest fires, but also as a fire management and mitigation strategy. The main aim of this paper is, thus, to analyze the temporal and spatial patterns of fire occurrence in Sardinia (Italy) during the last three decades (1980-2010). For the analyzed period, fire statistics were provided by the Sardinian Forest Service (CFVA - Corpo Forestale e di Vigilanza Ambientale), while weather data for eight weather stations were obtained from the web site www.tutiempo.it. For each station, daily series of precipitation, mean, maximum and minimum temperature, relative humidity and wind speed were available. The present study firstly analyzed fire statistics (burned area and number of fires) according to the main fire regime characteristics (seasonality, fire return interval, fire incidence, fire size distribution). Then, fire and weather daily values were averaged to obtain monthly, seasonal and annual values, and

  17. Guidance for evaluating and recommending temperature regimes to protect fish

    USGS Publications Warehouse

    Armour, Carl L.

    1991-01-01

    Procedures are presented for evaluating temperature regimes for fish. Although examples pertain to spring chinook salmon (Oncorhynchus tshawytscha), the principles apply to other species. Basic temperature tolerance relationships for fish are explained and three options are described for comparing alternative temperature regimes. The options are to base comparisons on experimental temperature tolerance results, suitability of a simulated temperature regime for key life stages, or population statistics and predicated responses to simulated temperatures.

  18. Random nanolasing in the Anderson localized regime

    NASA Astrophysics Data System (ADS)

    Liu, J.; Garcia, P. D.; Ek, S.; Gregersen, N.; Suhr, T.; Schubert, M.; Mørk, J.; Stobbe, S.; Lodahl, P.

    2014-04-01

    The development of nanoscale optical devices for classical and quantum photonics is affected by unavoidable fabrication imperfections that often impose performance limitations. However, disorder may also enable new functionalities, for example in random lasers, where lasing relies on random multiple scattering. The applicability of random lasers has been limited due to multidirectional emission, lack of tunability, and strong mode competition with chaotic fluctuations due to a weak mode confinement. The regime of Anderson localization of light has been proposed for obtaining stable multimode random lasing, and initial work concerned macroscopic one-dimensional layered media. Here, we demonstrate on-chip random nanolasers where the cavity feedback is provided by the intrinsic disorder. The strong confinement achieved by Anderson localization reduces the spatial overlap between lasing modes, thus preventing mode competition and improving stability. This enables highly efficient, stable and broadband wavelength-controlled lasers with very small mode volumes. Furthermore, the complex interplay between gain, dispersion-controlled slow light, and disorder is demonstrated experimentally for a non-conservative random medium. The statistical analysis shows a way towards optimizing random-lasing performance by reducing the localization length, a universal parameter.

  19. CSDP: The seismology of continental thermal regimes

    SciTech Connect

    Aki, K.

    1990-05-01

    This is a progress report for the past one year of research (year 3 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. The past year has been extremely productive especially in the area of interpretation theory, including the following two major break-throughs. One is the derivation of an integral equation for time-dependent power spectra, which unified all the existing theories on seismic scattering (including the radiative transfer theory for total energy and single and multiple scattering theories based on the ray approach) and offers more complete and economical solutions to the problems of seismic scattering and attenuation. The other is the new formula for synthetic seismograms for layered media with irregular interfaces, combining the T-matrix method for an arbitrary shaped inclusion and the method of global generalized reflection/transmission coefficients for layered media. Both breakthroughs will enable us to deal with seismic observations in complex earth structures more efficiently and accurately. In the area of experimental studies, we discovered seismic guided waves trapped in the San Andreas fault near Parkfield, California. 54 refs., 14 figs.

  20. Global fishery prospects under contrasting management regimes.

    PubMed

    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

    2016-05-01

    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.

  1. Global fishery prospects under contrasting management regimes

    PubMed Central

    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

  2. RF Profile Control for Sustained Plasma Regimes

    NASA Astrophysics Data System (ADS)

    Hosea, J.; Bernabei, S.; Leblanc, B.; Majeski, R.; Menard, J.; Ono, M.; Phillips, C. K.; Schilling, G.; Wilson, J. R.

    1999-11-01

    For advancing plasma operation regimes for AT tokamaks and steady state concepts, as well as for forming and sustaining alternate concepts, it is necessary to provide control of the spatial profiles for the important plasma parameters - pressure, current, etc.. RF techniques offer considerable promise for providing this control and should be further developed as rapidly as possible within the well established tokamak program for forming a basis for application to all confinement concepts. Notably, IBW promises to provide internal transport barrier control if the coupling physics can be understood and efficient antenna coupling to the Bernstein wave can be developed. We will review the IBW experience and discuss possible explanations and solutions for the coupling problems encountered. In particular, the competing roles of parametric decay instability and surface mode excitation will be examined in order to elucidate the increase in surface power losses for the larger devices DIII-D and TFTR. Also, issues which need to be understood for employing ICRF and LH techniques to best advantage, such as antenna bombardment and energetic electron excitation, respectively, will be outlined.

  3. Global fishery prospects under contrasting management regimes.

    PubMed

    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

    2016-05-01

    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

  4. Characterizing wildfire regimes in the United States

    PubMed Central

    Malamud, Bruce D.; Millington, James D. A.; Perry, George L. W.

    2005-01-01

    Wildfires statistics for the conterminous United States (U.S.) are examined in a spatially and temporally explicit manner. We use a high-resolution data set consisting of 88,916 U.S. Department of Agriculture Forest Service wildfires over the time period 1970-2000 and consider wildfire occurrence as a function of ecoregion (land units classified by climate, vegetation, and topography), ignition source (anthropogenic vs. lightning), and decade. For the conterminous U.S., we (i) find that wildfires exhibit robust frequency-area power-law behavior in 18 different ecoregions; (ii) use normalized power-law exponents to compare the scaling of wildfire-burned areas between ecoregions, finding a systematic change from east to west; (iii) find that wildfires in the eastern third of the U.S. have higher power-law exponents for anthropogenic vs. lightning ignition sources; and (iv) calculate recurrence intervals for wildfires of a given burned area or larger for each ecoregion, allowing for the classification of wildfire regimes for probabilistic hazard estimation in the same vein as is now used for earthquakes. PMID:15781868

  5. Cluster analysis of multiple planetary flow regimes

    NASA Technical Reports Server (NTRS)

    Mo, Kingtse; Ghil, Michael

    1987-01-01

    A modified cluster analysis method was developed to identify spatial patterns of planetary flow regimes, and to study transitions between them. This method was applied first to a simple deterministic model and second to Northern Hemisphere (NH) 500 mb data. The dynamical model is governed by the fully-nonlinear, equivalent-barotropic vorticity equation on the sphere. Clusters of point in the model's phase space are associated with either a few persistent or with many transient events. Two stationary clusters have patterns similar to unstable stationary model solutions, zonal, or blocked. Transient clusters of wave trains serve as way stations between the stationary ones. For the NH data, cluster analysis was performed in the subspace of the first seven empirical orthogonal functions (EOFs). Stationary clusters are found in the low-frequency band of more than 10 days, and transient clusters in the bandpass frequency window between 2.5 and 6 days. In the low-frequency band three pairs of clusters determine, respectively, EOFs 1, 2, and 3. They exhibit well-known regional features, such as blocking, the Pacific/North American (PNA) pattern and wave trains. Both model and low-pass data show strong bimodality. Clusters in the bandpass window show wave-train patterns in the two jet exit regions. They are related, as in the model, to transitions between stationary clusters.

  6. Regime shifts in models of dryland vegetation.

    PubMed

    Zelnik, Yuval R; Kinast, Shai; Yizhaq, Hezi; Bel, Golan; Meron, Ehud

    2013-12-13

    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 of 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-soil domains expand into vegetated domains. The significance of these findings is that, while models belonging to the first group can only exhibit abrupt shifts, models belonging to the second group can also exhibit gradual and incipient shifts. A discussion of open problems concludes the paper.

  7. Regime shifts in models of dryland vegetation.

    PubMed

    Zelnik, Yuval R; Kinast, Shai; 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 of 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-soil domains expand into vegetated domains. The significance of these findings is that, while models belonging to the first group can only exhibit abrupt shifts, models belonging to the second group can also exhibit gradual and incipient shifts. A discussion of open problems concludes the paper.

  8. Flow regimes in a trapped vortex cell

    NASA Astrophysics Data System (ADS)

    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.

  9. The seismology of geothermal regimes. Final report

    SciTech Connect

    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.

  10. CSDP: Seismology of continental thermal regime

    SciTech Connect

    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.

  11. Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the Wnt signaling pathway

    PubMed Central

    Ma, Zhi-Gang; Lv, Xiao-Dan; Zhan, Ling-Ling; Chen, Lan; Zou, Qi-Yuan; Xiang, Ji-Qiao; Qin, Jiao-Li; Zhang, Wei-Wei; Zeng, Zhao-Jing; Jin, Hui; Jiang, Hai-Xing; Lv, Xiao-Ping

    2016-01-01

    AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) with human urokinase-type plasminogen activator (uPA) on liver fibrosis, and to investigate the mechanism of gene therapy. METHODS: BMSCs transfected with adenovirus-mediated human urokinase plasminogen activator (Ad-uPA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson’s staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and mRNA expression levels. RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type III were markedly decreased, whereas the levels of serum albumin were increased by uPA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while uPA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area (16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment (12.38% ± 2.27%) and was further reduced by uPA-BMSCs treatment (8.31% ± 1.21%). Both protein and mRNA expression of β-catenin, Wnt4 and Wnt5a was down-regulated in liver tissues following uPA gene modified BMSCs treatment when compared with the model animals. CONCLUSION: Transplantation of uPA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with uPA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt

  12. Magnetised Kelvin-Helmholtz instability in the intermediate regime between subsonic and supersonic regimes

    SciTech Connect

    Henri, P.; Califano, F.; Pegoraro, F.; Faganello, M.

    2012-07-15

    The understanding of the dynamics at play at the Earth's Magnetopause, the boundary separating the Earth's magnetosphere and the solar wind plasmas, is of primary importance for space plasma modeling. We focus our attention on the low latitude flank of the magnetosphere where the velocity shear between the magnetosheath and the magnetospheric plasmas is the energetic source of Kelvin-Helmholtz instability. On the shoulder of the resulting vortex chain, different secondary instabilities are at play depending on the local plasma parameters and compete with the vortex pairing process. Most important, secondary instabilities, among other magnetic reconnection, control the plasma mixing as well as the entry of solar wind plasma in the magnetosphere. We make use of a two-fluid model, including the Hall term and the electron mass in the generalized Ohm's law, to study the 2D non-linear evolution of the Kelvin-Helmholtz instability at the magnetosheath-magnetosphere interface, in the intermediate regime between subsonic and supersonic regimes. We study the saturation mechanisms, depending on the density jump across the shear layer and the magnetic field strength in the plane. In the presence of a weak in-plane magnetic field, the dynamics of the Kelvin-Helmholtz rolled-up vortices self-consistently generates thin current sheets where reconnection instability eventually enables fast reconnection to develop. Such a system enables to study guide field multiple-island collisionless magnetic reconnection as embedded in a large-scale dynamic system, unlike the classical static, ad hoc reconnection setups. In this regime, reconnection is shown to inhibit the vortex pairing process. This study provides a clear example of nonlinear, cross-scale, collisionless plasma dynamics.

  13. FISHER INFORMATION AS A METRIC FOR SUSTAINABLE REGIMES

    EPA Science Inventory

    The important question in sustainability is not whether the world is sustainable, but whether a humanly acceptable regime of the world is sustainable. We propose Fisher Information as a metric for the sustainability of dynamic regimes in complex systems. The quantity now known ...

  14. Water use regimes: Characterizing direct human interaction with hydrologic systems

    USGS Publications Warehouse

    Weiskel, P.K.; Vogel, R.M.; Steeves, P.A.; Zarriello, P.J.; DeSimone, L.A.; Ries, Kernell G.

    2007-01-01

    [1] The sustainability of human water use practices is a rapidly growing concern in the United States and around the world. To better characterize direct human interaction with hydrologic systems (stream basins and aquifers), we introduce the concept of the water use regime. Unlike scalar indicators of anthropogenic hydrologic stress in the literature, the water use regime is a two-dimensional, vector indicator that can be depicted on simple x-y plots of normalized human withdrawals (hout) versus normalized human return flows (hin). Four end-member regimes, natural-flow-dominated (undeveloped), human-flow-dominated (churned), withdrawal-dominated (depleted), and return-flow-dominated (surcharged), are defined in relation to limiting values of hout and hin. For illustration, the water use regimes of 19 diverse hydrologic systems are plotted and interpreted. Several of these systems, including the Yellow River Basin, China, and the California Central Valley Aquifer, are shown to approach particular end-member regimes. Spatial and temporal regime variations, both seasonal and long-term, are depicted. Practical issues of data availability and regime uncertainty are addressed in relation to the statistical properties of the ratio estimators hout and hin. The water use regime is shown to be a useful tool for comparative water resources assessment and for describing both historic and alternative future pathways of water resource development at a range of scales. Copyright 2007 by the American Geophysical Union.

  15. A Tale of Two Regimes: Instrumentality and Commons Access

    ERIC Educational Resources Information Center

    Toly, Noah J.

    2005-01-01

    Technical developments have profound social and environmental impacts. Both are observed in the implications of regimes of instrumentality for commons access regimes. Establishing social, material, ecological, intellectual, and moral infrastructures, technologies are partly constitutive of commons access and may militate against governance…

  16. IDENTIFICATION OF REGIME SHIFTS IN TIME SERIES USING NEIGHBORHOOD STATISTICS

    EPA Science Inventory

    The identification of alternative dynamic regimes in ecological systems requires several lines of evidence. Previous work on time series analysis of dynamic regimes includes mainly model-fitting methods. We introduce two methods that do not use models. These approaches use state-...

  17. Global regime shift dynamics of catastrophic sea urchin overgrazing

    PubMed Central

    Ling, S. D.; Scheibling, R. E.; Rassweiler, A.; Johnson, C. R.; Shears, N.; Connell, S. D.; Salomon, A. K.; Norderhaug, K. M.; Pérez-Matus, A.; Hernández, J. C.; Clemente, S.; Blamey, L. K.; Hereu, B.; Ballesteros, E.; Sala, E.; Garrabou, J.; Cebrian, E.; Zabala, M.; Fujita, D.; Johnson, L. E.

    2015-01-01

    A pronounced, widespread and persistent regime shift among marine ecosystems is observable on temperate rocky reefs as a result of sea urchin overgrazing. Here, we empirically define regime-shift dynamics for this grazing system which transitions between productive macroalgal beds and impoverished urchin barrens. Catastrophic in nature, urchin overgrazing in a well-studied Australian system demonstrates a discontinuous regime shift, which is of particular management concern as recovery of desirable macroalgal beds requires reducing grazers to well below the initial threshold of overgrazing. Generality of this regime-shift dynamic is explored across 13 rocky reef systems (spanning 11 different regions from both hemispheres) by compiling available survey data (totalling 10 901 quadrats surveyed in situ) plus experimental regime-shift responses (observed during a total of 57 in situ manipulations). The emergent and globally coherent pattern shows urchin grazing to cause a discontinuous ‘catastrophic’ regime shift, with hysteresis effect of approximately one order of magnitude in urchin biomass between critical thresholds of overgrazing and recovery. Different life-history traits appear to create asymmetry in the pace of overgrazing versus recovery. Once shifted, strong feedback mechanisms provide resilience for each alternative state thus defining the catastrophic nature of this regime shift. Importantly, human-derived stressors can act to erode resilience of desirable macroalgal beds while strengthening resilience of urchin barrens, thus exacerbating the risk, spatial extent and irreversibility of an unwanted regime shift for marine ecosystems.

  18. Extractive Regimes: Toward a Better Understanding of Indonesian Development

    ERIC Educational Resources Information Center

    Gellert, Paul K.

    2010-01-01

    This article proposes the concept of an extractive regime to understand Indonesia's developmental trajectory from 1966 to 1998. The concept contributes to world-systems, globalization, and commodity-based approaches to understanding peripheral development. An extractive regime is defined by its reliance on extraction of multiple natural resources…

  19. Disciplinary Regimes of "Care" and Complementary Alternative Education

    ERIC Educational Resources Information Center

    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…

  20. FISHER INFORMATION AS A METRIC FOR SUSTAINABLE SYSTEM REGIMES

    EPA Science Inventory

    The important question in sustainability is not whether the world is sustainable, but whether a humanly acceptable regime of the world is sustainable. We propose Fisher Information as a metric for the sustainability of dynamic regimes in complex systems. The quantity now known ...

  1. Plasma Physics Regimes in Tokamaks with Li Walls

    SciTech Connect

    L.E. Zakharo; N.N. Gorelenkov; R.B. White; S.I. Krasheninnikov; G.V. Pereverzev

    2003-08-21

    Low recycling regimes with a plasma limited by a lithium wall surface suggest enhanced stability and energy confinement, both necessary for tokamak reactors. These regimes could make ignition feasible in compact tokamaks. Ignited Spherical Tokamaks (IST), self-sufficient in the bootstrap current, are introduced as a necessary step for development of the physics and technology of power reactors.

  2. Detection and Assessment of Ecosystem Regime Shifts from Fisher Information

    EPA Science Inventory

    Ecosystem regime shifts, which are long-term system reorganizations, have profound implications for sustainability. There is a great need for indicators of regime shifts, particularly methods that are applicable to data from real systems. We have developed a form of Fisher info...

  3. Bargaining among Nations: Culture, History, and Perceptions in Regime Formation.

    ERIC Educational Resources Information Center

    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)

  4. Flow regimes in a single dimple on the channel surface

    NASA Astrophysics Data System (ADS)

    Kovalenko, G. V.; Terekhov, V. I.; Khalatov, A. A.

    2010-12-01

    The boundaries of the domains of existence of flow regimes past single dimples made as spherical segments on a flat plate are determined with the use of available experimental results. Regimes of a diffuser-confuser flow, a horseshoe vortex, and a tornado-like vortex in the dimple are considered. Neither a horseshoe vortex nor a tornado-like vortex is observed in dimples with the relative depth smaller than 0.1. Transformations from the diffuser-confuser flow regime to the horseshoe vortex regime and from the horseshoe vortex flow to the tornado-like vortex flow are found to depend not only on the Reynolds number, but also on the relative depth of the spherical segment. Dependences for determining the boundaries of the regime existence domains are proposed, and parameters at which the experimental results can be generalized are given.

  5. Monitoring and diagnostics systems for nuclear power plant operating regimes

    SciTech Connect

    Abagyan, A.A.; Dmitriev, V.M.; Klebanov, L.A.; Kroshilin, A.E.; Larin, E.P.; Morozov, S.K.

    1988-05-01

    The development of new monitoring and diagnostics systems for Soviet reactors is discussed. An experimental test station is described where industrial operation of new experimental systems can be conducted for purposes of bringing their performance to the level of standard Soviet systems for monitoring reactor operation regimes and equipment resources. The requirements and parameters of the systems are described on a unit-by-unit basis, including the sensor reading monitoring unit, the vibroacoustic monitoring unit, the noise monitoring unit, the accident regime identification unit, and the nonstationary regime monitoring unit. Computer hardware and software requirements are discussed. The results of calculational and experimental research on two complex nonstationary regimes of reactor operation are given. The accident regimes identification unit for the VVER-1000 is analyzed in detail.

  6. Human influence on California fire regimes

    USGS Publications Warehouse

    Syphard, A.D.; Radeloff, V.C.; Keeley, J.E.; Hawbaker, T.J.; Clayton, M.K.; Stewart, S.I.; Hammer, R.B.

    2007-01-01

    Periodic wildfire maintains the integrity and species composition of many ecosystems, including the mediterranean-climate shrublands of California. However, human activities alter natural fire regimes, which can lead to cascading ecological effects. Increased human ignitions at the wildland-urban interface (WUI) have recently gained attention, but fire activity and risk are typically estimated using only biophysical variables. Our goal was to determine how humans influence fire in California and to examine whether this influence was linear, by relating contemporary (2000) and historic (1960-2000) fire data to both human and biophysical variables. Data for the human variables included fine-resolution maps of the WUI produced using housing density and land cover data. Interface WUI, where development abuts wildland vegetation, was differentiated from intermix WUI, where development intermingles with wildland vegetation. Additional explanatory variables included distance to WUI, population density, road density, vegetation type, and ecoregion. All data were summarized at the county level and analyzed using bivariate and multiple regression methods. We found highly significant relationships between humans and fire on the contemporary landscape, and our models explained fire frequency (R2 = 0.72) better than area burned (R2 = 0.50). Population density, intermix WUI, and distance to WUI explained the most variability in fire frequency, suggesting that the spatial pattern of development may be an important variable to consider when estimating fire risk. We found nonlinear effects such that fire frequency and area burned were highest at intermediate levels of human activity, but declined beyond certain thresholds. Human activities also explained change in fire frequency and area burned (1960-2000), but our models had greater explanatory power during the years 1960-1980, when there was more dramatic change in fire frequency. Understanding wildfire as a function of the

  7. Human influence on California fire regimes.

    PubMed

    Syphard, Alexandra D; Radeloff, Volker C; Keeley, Jon E; Hawbaker, Todd J; Clayton, Murray K; Stewart, Susan I; Hammer, Roger B

    2007-07-01

    Periodic wildfire maintains the integrity and species composition of many ecosystems, including the mediterranean-climate shrublands of California. However, human activities alter natural fire regimes, which can lead to cascading ecological effects. Increased human ignitions at the wildland-urban interface (WUI) have recently gained attention, but fire activity and risk are typically estimated using only biophysical variables. Our goal was to determine how humans influence fire in California and to examine whether this influence was linear, by relating contemporary (2000) and historic (1960-2000) fire data to both human and biophysical variables. Data for the human variables included fine-resolution maps of the WUI produced using housing density and land cover data. Interface WUI, where development abuts wildland vegetation, was differentiated from intermix WUI, where development intermingles with wildland vegetation. Additional explanatory variables included distance to WUI, population density, road density, vegetation type, and ecoregion. All data were summarized at the county level and analyzed using bivariate and multiple regression methods. We found highly significant relationships between humans and fire on the contemporary landscape, and our models explained fire frequency (R2 = 0.72) better than area burned (R2 = 0.50). Population density, intermix WUI, and distance to WUI explained the most variability in fire frequency, suggesting that the spatial pattern of development may be an important variable to consider when estimating fire risk. We found nonlinear effects such that fire frequency and area burned were highest at intermediate levels of human activity, but declined beyond certain thresholds. Human activities also explained change in fire frequency and area burned (1960-2000), but our models had greater explanatory power during the years 1960-1980, when there was more dramatic change in fire frequency. Understanding wildfire as a function of the

  8. Mercury's thermal evolution and core crystallization regime

    NASA Astrophysics Data System (ADS)

    Rivoldini, A.; Van Hoolst, T.; Dumberry, M.; Steinle-Neumann, G.

    2015-10-01

    Unlike the Earth, where the liquid core isentrope is shallower than the core liquidus, at the lower pressures inside Mercury's core the isentrope can be steeper than the melting temperature. As a consequence, upon cooling, the isentrope may first enter a solid stability field near the core mantle boundary and produce ironrich snow that sinks under gravity and produces buoyant upwellings of iron depleted fluid. Similar to bottom up crystallization, crystallization initiated near the top might generate sufficient buoyancy flux to drive magnetic field generation by compositional convection.In this study we model Mercury's thermal evolution by taking into account the formation of iron-rich snow to assess when the conditions for an internally magnetic field can be satisfied. We employ a thermodynamic consistent description of the iron high-pressure phase diagram and thermoelastic properties of iron alloys as well as the most recent data about the thermal conductivity of core materials. We use a 1-dimensional parametrized thermal evolution model in the stagnant lid regime for the mantle (e.g. [1]) that is coupled to the core. The model for the mantle takes into account the formation of the crust due to melting at depth. Mantle convection is driven by heat producing radioactive elements, heat loss from secular cooling and from the heat supplied by the core. The heat generated inside the core is mainly provided from secular cooling, from the latent heat released at iron freezing, and from gravitational energy resulting form the release of light elements at the inner core-outer core boundary as well as from the sinking of iron-rich snow and subsequent upwellings of light elements in the snow zone. If the heat flow out of the core is smaller than the heat transported along the core isentrope a thermal boundary will from at the top of the outer core. To determine the extension of the convecting region inside the liquid core we calculate the convective power [2]. Finally, we

  9. Tropical precipitation regimes and mechanisms of regime transitions: contrasting two aquaplanet general circulation models

    NASA Astrophysics Data System (ADS)

    Oueslati, Boutheina; Bellon, Gilles

    2013-05-01

    The atmospheric general circulation models ARPEGE-climate and LMDz are used in an aquaplanet configuration to study the response of a zonally symmetric atmosphere to a range of sea surface temperature (SST) forcing. We impose zonally-symmetric SST distributions that are also symmetric about the equator, with varying off-equatorial SST gradients. In both models, we obtain the characteristic inter-tropical convergence zone (ITCZ) splitting that separates two regimes of equilibrium (in terms of precipitations): one with one ITCZ over the equator for large SST gradients in the tropics, and one with a double ITCZ for small tropical SST gradients. Transition between these regimes is mainly driven by changes in the low-level convergence that are forced by the SST gradients. Model-dependent, dry and moist feedbacks intervene to reinforce or weaken the effect of the SST forcing. In ARPEGE, dry advective processes reinforce the SST forcing, while a competition between sensible heat flux and convective cooling provides a complex feedback on the SST forcing in the LMDz. It is suggested that these feedbacks influence the location of the transition in the parameter range.

  10. The catalytic domain of endogenous urokinase-type plasminogen activator is required for the mitogenic activity of platelet-derived and basic fibroblast growth factors in human vascular smooth muscle cells.

    PubMed

    Padró, Teresa; Mesters, Rolf M; Dankbar, Berno; Hintelmann, Heike; Bieker, Ralf; Kiehl, Michael; Berdel, Wolfgang E; Kienast, Joachim

    2002-05-01

    Emerging data suggest that urokinase-type plasminogen activator (UPA), beyond its role in pericellular proteolysis, may also act as a mitogen. We investigated the function of endogenous UPA in mediating the mitogenic effects of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) on human vascular smooth muscle cells (SMC). Growth-arrested SMC constitutively expressed UPA, but UPA expression and secretion increased several times upon stimulation with either PDGF or bFGF. Inhibition of endogenous UPA with a polyclonal antibody significantly reduced DNA synthesis and proliferation of PDGF or bFGF stimulated SMC, this effect already being evident when the cells entered S-phase. The proliferative activity of endogenous UPA was dependent on a functional catalytic domain as demonstrated by inhibition experiments with a specific monoclonal antibody (394OA) and p-aminobenzamidine, respectively. In contrast, neither plasmin generation nor binding of UPA to its receptor (CD87) were required for UPA-mediated mitogenic effects. The results demonstrate that endogenous UPA is not only overexpressed in SMC upon stimulation with PDGF/bFGF, but also mediates the mitogenic activity of the growth factors in a catalytic-domain-dependent manner. Specific inhibition of this UPA domain may represent an attractive target for pharmacological interventions in atherogenesis and restenosis after angioplasty. PMID:11956327

  11. A robust method for estimating optimal treatment regimes.

    PubMed

    Zhang, Baqun; Tsiatis, Anastasios A; Laber, Eric B; Davidian, Marie

    2012-12-01

    A treatment regime is a rule that assigns a treatment, among a set of possible treatments, to a patient as a function of his/her observed characteristics, hence "personalizing" treatment to the patient. The goal is to identify the optimal treatment regime that, if followed by the entire population of patients, would lead to the best outcome on average. Given data from a clinical trial or observational study, for a single treatment decision, the optimal regime can be found by assuming a regression model for the expected outcome conditional on treatment and covariates, where, for a given set of covariates, the optimal treatment is the one that yields the most favorable expected outcome. However, treatment assignment via such a regime is suspect if the regression model is incorrectly specified. Recognizing that, even if misspecified, such a regression model defines a class of regimes, we instead consider finding the optimal regime within such a class by finding the regime that optimizes an estimator of overall population mean outcome. To take into account possible confounding in an observational study and to increase precision, we use a doubly robust augmented inverse probability weighted estimator for this purpose. Simulations and application to data from a breast cancer clinical trial demonstrate the performance of the method. PMID:22550953

  12. Estimating Optimal Treatment Regimes from a Classification Perspective

    PubMed Central

    Tsiatis, Anastasios A.; Davidian, Marie; Zhang, Min; Laber, Eric

    2013-01-01

    A treatment regime maps observed patient characteristics to a recommended treatment. Recent technological advances have increased the quality, accessibility, and volume of patient-level data; consequently, there is a growing need for powerful and flexible estimators of an optimal treatment regime that can be used with either observational or randomized clinical trial data. We propose a novel and general framework that transforms the problem of estimating an optimal treatment regime into a classification problem wherein the optimal classifier corresponds to the optimal treatment regime. We show that commonly employed parametric and semi-parametric regression estimators, as well as recently proposed robust estimators of an optimal treatment regime can be represented as special cases within our framework. Furthermore, our approach allows any classification procedure that can accommodate case weights to be used without modification to estimate an optimal treatment regime. This introduces a wealth of new and powerful learning algorithms for use in estimating treatment regimes. We illustrate our approach using data from a breast cancer clinical trial. PMID:23645940

  13. Estimating Optimal Treatment Regimes from a Classification Perspective.

    PubMed

    Zhang, Baqun; Tsiatis, Anastasios A; Davidian, Marie; Zhang, Min; Laber, Eric

    2012-01-01

    A treatment regime maps observed patient characteristics to a recommended treatment. Recent technological advances have increased the quality, accessibility, and volume of patient-level data; consequently, there is a growing need for powerful and flexible estimators of an optimal treatment regime that can be used with either observational or randomized clinical trial data. We propose a novel and general framework that transforms the problem of estimating an optimal treatment regime into a classification problem wherein the optimal classifier corresponds to the optimal treatment regime. We show that commonly employed parametric and semi-parametric regression estimators, as well as recently proposed robust estimators of an optimal treatment regime can be represented as special cases within our framework. Furthermore, our approach allows any classification procedure that can accommodate case weights to be used without modification to estimate an optimal treatment regime. This introduces a wealth of new and powerful learning algorithms for use in estimating treatment regimes. We illustrate our approach using data from a breast cancer clinical trial. PMID:23645940

  14. River flow regimes and vegetation dynamics along a river transect

    NASA Astrophysics Data System (ADS)

    Doulatyari, Behnam; Basso, Stefano; Schirmer, Mario; Botter, Gianluca

    2014-11-01

    Ecohydrological processes occurring within fluvial landscapes are strongly affected by natural streamflow variability. In this work the patterns of vegetation biomass in two rivers characterized by contrasting flow regimes were investigated by means of a comprehensive stochastic model which explicitly couples catchment-scale hydroclimatic processes, morphologic attributes of the river transect and in-stream bio-ecological features. The hydrologic forcing is characterized by the probability distribution (pdf) of streamflows and stages resulting from stochastic precipitation dynamics, rainfall-runoff transformation and reach scale morphologic attributes. The model proved able to reproduce the observed pdf of river flows and stages, as well as the pattern of exposure/inundation along the river transect in both regimes. Our results suggest that in persistent regimes characterized by reduced streamflow variability, mean vegetation biomass is chiefly controlled by the pattern of groundwater availability along the transect, leading to a marked transition between aquatic and terrestrial environments. Conversely, erratic regimes ensure wider aquatic-terrestrial zones in which optimal elevation ranges for species with different sensitivity to flooding and access to groundwater are separated. Patterns of mean biomass in erratic regimes were found to be more sensitive to changes in the underlying hydroclimatic conditions, notwithstanding the reduced responsiveness of the corresponding flow regimes. The framework developed highlights the important role played by streamflow regimes in shaping riverine environments, and may eventually contribute to identifying the influence of landscape, climate and morphologic features on in-stream ecological dynamics.

  15. An Examination of the Nature of Global MODIS Cloud Regimes

    NASA Technical Reports Server (NTRS)

    Oreopoulos, Lazaros; Cho, Nayeong; Lee, Dongmin; Kato, Seiji; Huffman, George J.

    2014-01-01

    We introduce global cloud regimes (previously also referred to as "weather states") derived from cloud retrievals that use measurements by the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument aboard the Aqua and Terra satellites. The regimes are obtained by applying clustering analysis on joint histograms of retrieved cloud top pressure and cloud optical thickness. By employing a compositing approach on data sets from satellites and other sources, we examine regime structural and thermodynamical characteristics. We establish that the MODIS cloud regimes tend to form in distinct dynamical and thermodynamical environments and have diverse profiles of cloud fraction and water content. When compositing radiative fluxes from the Clouds and the Earth's Radiant Energy System instrument and surface precipitation from the Global Precipitation Climatology Project, we find that regimes with a radiative warming effect on the atmosphere also produce the largest implied latent heat. Taken as a whole, the results of the study corroborate the usefulness of the cloud regime concept, reaffirm the fundamental nature of the regimes as appropriate building blocks for cloud system classification, clarify their association with standard cloud types, and underscore their distinct radiative and hydrological signatures.

  16. Marine regime shifts: drivers and impacts on ecosystems services

    PubMed Central

    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.

  17. Toward a Physical Characterization of Raindrop Collision Outcome Regimes

    NASA Technical Reports Server (NTRS)

    Testik, F. Y.; Barros, Ana P.; Bilven, Francis L.

    2011-01-01

    A comprehensive raindrop collision outcome regime diagram that delineates the physical conditions associated with the outcome regimes (i.e., bounce, coalescence, and different breakup types) of binary raindrop collisions is proposed. The proposed diagram builds on a theoretical regime diagram defined in the phase space of collision Weber numbers We and the drop diameter ratio p by including critical angle of impact considerations. In this study, the theoretical regime diagram is first evaluated against a comprehensive dataset for drop collision experiments representative of raindrop collisions in nature. Subsequently, the theoretical regime diagram is modified to explicitly describe the dominant regimes of raindrop interactions in (We, p) by delineating the physical conditions necessary for the occurrence of distinct types of collision-induced breakup (neck/filament, sheet, disk, and crown breakups) based on critical angle of impact consideration. Crown breakup is a subtype of disk breakup for lower collision kinetic energy that presents distinctive morphology. Finally, the experimental results are analyzed in the context of the comprehensive collision regime diagram, and conditional probabilities that can be used in the parameterization of breakup kernels in stochastic models of raindrop dynamics are provided.

  18. Past and Future Drought Regimes in Turkey

    NASA Astrophysics Data System (ADS)

    Sen, Burak; Topcu, Sevilay; Turkes, Murat; Sen, Baha

    2010-05-01

    Climate variability in the 20th century was characterized by apparent precipitation variability at both temporal and spatial scales. In addition to the well-known characteristic seasonal and year-to-year variability, some marked and long-term changes in precipitation occurred in Turkey, particularly after the early 1970s. Drought, originating from a deficiency of precipitation over an extended time period (which is usually a season or more) has become a recurring phenomenon in Turkey in the past few decades. Spatially coherent with the significant drought events since early 1970s, water stress and shortages for all water user sectors have also reached their critical points in Turkey. Analyzing the historical occurrence of drought provides an understanding of the range of climate possibilities for a country, resulting in more informed management decision-making. However, future projections about spatial and temporal changes in drought characteristics such as frequency, intensity and duration can be challenging for developing appropriate mitigation and adaptation strategies. Hence, the objectives of this study are (i) to analyze the spatial and temporal dimensions of historical droughts in Turkey, (2) to predict potential intensity, frequency and duration of droughts in Turkey for the future (2070-2100). The Standardized Precipitation Index (SPI) and the Percent to Normal Index (PNI) have been used to assess the drought characteristics. Rainfall datasets for the reference period, 1960-1990, were acquired from 52 stations (representative of all kinds of regions with different rainfall regimes in the country) of the Turkish State Meteorological Service (TSMS). The future rainfall series for the 2070-2100 period were simulated using a regional climate model (RegCM3) for IPCC's SRESS-A2 scenario conditions. For verification of RegCM3 simulations, the model was performed for the reference period and simulated rainfall data were used for computing two drought indices (SPI

  19. On chaotic flow regimes in a rotating spherical layer

    NASA Astrophysics Data System (ADS)

    Zhilenko, D. Yu.; Krivonosova, O. É.; Nikitin, N. V.

    2008-12-01

    We present results of an experimental investigation and numerical simulations of chaotic flow regimes in a layer of a viscous incompressible fluid confined between counter-rotating spherical boundaries. The turbulent flow velocity pulsation profiles obtained by straightforward calculations are qualitatively similar to the analogous profiles known for a flat mixing layer. At the boundaries of their formation, chaotic flow regimes are characterized by a continuous spectrum of velocity pulsations and a high correlation dimension ( D > 8), in contrast to the chaotic regimes observed in an analogous layer with one (inner) rotating boundary.

  20. Multiple planetary flow regimes in the Southern Hemisphere

    NASA Technical Reports Server (NTRS)

    Yoden, Shigeo; Shiotani, Masato; Hirota, Isamu

    1987-01-01

    Low-frequency variations in the general circulation of the Southern Hemisphere during 1983 were studied using daily geopotential height and temperature analyses for 12 pressure levels from 1000 mb up to 50 mb, performed by the National Meteorological Center of Japan. Results disclosed the presence, in the Southern Hemisphere troposphere, of an irregular fluctuation of two zonal mean geostrophic wind patterns (named single-jet and double-jet regimes) during wintertime. The fluctuation is characterized by the persistence of one geostrophic wind regime, with characteristic duration of a month, followed by a rather rapid transition to another regime.

  1. Boundary between stable and unstable regimes of accretion. Ordered and chaotic unstable regimes

    NASA Astrophysics Data System (ADS)

    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.

  2. Regime shifts and resilience in China's coastal ecosystems.

    PubMed

    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.

  3. Fixed points, stable manifolds, weather regimes, and their predictability

    SciTech Connect

    Deremble, Bruno; D'Andrea, Fabio; Ghil, Michael

    2009-10-27

    In a simple, one-layer atmospheric model, we study the links between low-frequency variability and the model’s fixed points in phase space. The model dynamics is characterized by the coexistence of multiple ''weather regimes.'' To investigate the transitions from one regime to another, we focus on the identification of stable manifolds associated with fixed points. We show that these manifolds act as separatrices between regimes. We track each manifold by making use of two local predictability measures arising from the meteorological applications of nonlinear dynamics, namely, ''bred vectors'' and singular vectors. These results are then verified in the framework of ensemble forecasts issued from clouds (ensembles) of initial states. The divergence of the trajectories allows us to establish the connections between zones of low predictability, the geometry of the stable manifolds, and transitions between regimes.

  4. Stochastic regimes in very-low-frequency fluidic oscillator

    NASA Astrophysics Data System (ADS)

    Tesař, Václav

    2016-03-01

    Paper discusses interesting unexpected stochastic regimes discovered in a fluidic oscillator designed for operation at very low oscillation frequencies - without the inconvenience of the long feedback loops needed in standard low-frequency oscillator designs. The new oscillator contains a pair of bistable turn-down active valves operating in anti-parallel — essentially analogous to Abraham & Bloch electric "multibrateur" invented in 1919. Three different self-excited oscillation regimes were found. In the order of increasing supplied flow rate, these regimes are characterised by: (A) generation of stochastic-duration multi-pulse packs, (B) generation of individual pulses with a degree of periodicity, and (C) regime with randomly appearing flow pulses separated by intervals of the order of seconds.

  5. The role of transients in weather regimes and transitions

    SciTech Connect

    Reinhold, B.; Yang, Shuting )

    1993-05-01

    Transition of weather regimes is examined in a highly simplified model. Two completely distinct internal methods of transition are identified. The first is a synoptically triggered large-scale instability, while the second is an energy inconsistency between the large-scale and synoptic scales that does not allow the two scales to equilibrate. In the atmosphere, the first case appears as a sudden propagation and damping (or vice versa) of the large-scale pattern with no obvious warning, while the second is consistent with the synoptician's description of a regime being disrupted by a single catastrophic event such as explosive cyclogenesis. The first method is always fast (on a synoptic time scale), while the second does not have to be, though often is. By examining what causes the regimes to fail, one can better understand the role of the transients during all phases of weather regimes. 27 refs., 5 figs.

  6. Fixed points, stable manifolds, weather regimes, and their predictability.

    PubMed

    Deremble, Bruno; D'Andrea, Fabio; Ghil, Michael

    2009-12-01

    In a simple, one-layer atmospheric model, we study the links between low-frequency variability and the model's fixed points in phase space. The model dynamics is characterized by the coexistence of multiple "weather regimes." To investigate the transitions from one regime to another, we focus on the identification of stable manifolds associated with fixed points. We show that these manifolds act as separatrices between regimes. We track each manifold by making use of two local predictability measures arising from the meteorological applications of nonlinear dynamics, namely, "bred vectors" and singular vectors. These results are then verified in the framework of ensemble forecasts issued from "clouds" (ensembles) of initial states. The divergence of the trajectories allows us to establish the connections between zones of low predictability, the geometry of the stable manifolds, and transitions between regimes.

  7. Regime shifts and resilience in China's coastal ecosystems.

    PubMed

    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. PMID:26286204

  8. The effect of refrigerants in the mixed lubrication regime

    SciTech Connect

    Mizuhara, Kazuyuki; Tomimoto, Makoto

    1997-12-31

    Because of environmental concerns, CFC (chlorofluorocarbon) refrigerants must be replaced with HFCs (hydrofluorocarbons). As a result, many tribological problems are caused especially in rotary piston compressors. To solve the problem, the effects of refrigerants on friction and wear characteristics of the oil and refrigerant mixtures at the mixed lubrication regime are investigated. The difference in refrigerants are clearly observed not only in boundary but also in the mixed lubrication regime. The effects of operating conditions on sliding conditions and experimental results are also discussed. It is concluded that for practical application where long life is essential, experiments must be conducted under the mixed lubrication regime. Also, the importance of defining the lubrication regime in terms of film parameter is emphasized.

  9. Diffusion dependent focusing regimes in peak mode counterflow isotachophoresis

    NASA Astrophysics Data System (ADS)

    GanOr, Nethanel; Rubin, Shimon; Bercovici, Moran

    2015-07-01

    We present an analytical, numerical, and experimental study of pressure driven counterflow isotachophoresis (ITP). We study solutions to the Nernst-Planck equations in the axi-symmetric and radially dependent case, in the leading order of negligible body forces. We provide a simple model that describes the ITP interface shape for Poiseuille-type counterflows, and an asymptotic model which captures two distinct sample focusing regimes of peak mode ITP. We validate the existence of these regimes using numerical simulations and map the conditions under which each of the focal regions dominates. In particular, we demonstrate numerically that a species diffusivity is a key parameter determining its focusing regime. We experimentally show that this allows spatial separation of co-focusing species having distinctly different diffusivities. We further demonstrate that while dispersion associated with counterflow is typically considered to reduce peak concentrations, certain focusing regimes allow a net gain in sample concentration over the non-dispersed case.

  10. Fixed points, stable manifolds, weather regimes, and their predictability

    DOE PAGESBeta

    Deremble, Bruno; D'Andrea, Fabio; Ghil, Michael

    2009-10-27

    In a simple, one-layer atmospheric model, we study the links between low-frequency variability and the model’s fixed points in phase space. The model dynamics is characterized by the coexistence of multiple ''weather regimes.'' To investigate the transitions from one regime to another, we focus on the identification of stable manifolds associated with fixed points. We show that these manifolds act as separatrices between regimes. We track each manifold by making use of two local predictability measures arising from the meteorological applications of nonlinear dynamics, namely, ''bred vectors'' and singular vectors. These results are then verified in the framework of ensemblemore » forecasts issued from clouds (ensembles) of initial states. The divergence of the trajectories allows us to establish the connections between zones of low predictability, the geometry of the stable manifolds, and transitions between regimes.« less

  11. FISHER INFORMATION AND DYNAMIC REGIME CHANGES IN ECOLOGICAL SYTEMS

    EPA Science Inventory

    Ecosystems often exhibit transitions between dynamic regimes (or steady states), such as the conversion of oligotrophic to eutrophic conditions and associated aquatic ecological communities, due to natural (or increasingly) anthropogenic disturbances. As ecosystems experience per...

  12. AN APPROACH FOR CLASSIFYING TIDAL REGIMES BASED ON TIDAL CONSTITUENTS

    EPA Science Inventory

    Tidal fluctuations can be one of the dominant physical processes in estuaries. This paper presents a numerical classification of tidal regimes that can be used to summarize local conditions and facilitate comparisons among locations. Tide predictions are customarily calculated ...

  13. Brownian colloids in underdamped and overdamped regimes with nonhomogeneous temperature

    NASA Astrophysics Data System (ADS)

    Sancho, J. M.

    2015-12-01

    The motion of Brownian particles when temperature is spatially dependent is studied by stochastic simulations and theoretical analysis. Nonequilibrium steady probability distributions Ps t(z ,v ) for both underdamped and overdamped regimes are analyzed. The existence of local kinetic energy equipartition theorem is also discussed. The transition between both regimes is characterized by a dimensionless friction parameter. This study is applied to three physical systems of colloidal particles.

  14. Synchronous marine pelagic regime shifts in the Northern Hemisphere

    PubMed Central

    Beaugrand, G.; Conversi, A.; Chiba, S.; Edwards, M.; Fonda-Umani, S.; Greene, C.; Mantua, N.; Otto, S. A.; Reid, P. C.; Stachura, M. M.; Stemmann, L.; Sugisaki, H.

    2015-01-01

    Regime shifts are characterized by sudden, substantial and temporally persistent changes in the state of an ecosystem. They involve major biological modifications and often have important implications for exploited living resources. In this study, we examine whether regime shifts observed in 11 marine systems from two oceans and three regional seas in the Northern Hemisphere (NH) are synchronous, applying the same methodology to all. We primarily infer marine pelagic regime shifts from abrupt shifts in zooplankton assemblages, with the exception of the East Pacific where ecosystem changes are inferred from fish. Our analyses provide evidence for quasi-synchronicity of marine pelagic regime shifts both within and between ocean basins, although these shifts lie embedded within considerable regional variability at both year-to-year and lower-frequency time scales. In particular, a regime shift was detected in the late 1980s in many studied marine regions, although the exact year of the observed shift varied somewhat from one basin to another. Another regime shift was also identified in the mid- to late 1970s but concerned less marine regions. We subsequently analyse the main biological signals in relation to changes in NH temperature and pressure anomalies. The results suggest that the main factor synchronizing regime shifts on large scales is NH temperature; however, changes in atmospheric circulation also appear important. We propose that this quasi-synchronous shift could represent the variably lagged biological response in each ecosystem to a large-scale, NH change of the climatic system, involving both an increase in NH temperature and a strongly positive phase of the Arctic Oscillation. Further investigation is needed to determine the relative roles of changes in temperature and atmospheric pressure patterns and their resultant teleconnections in synchronizing regime shifts at large scales.

  15. Laboratory experiment on boundaries of upper stage plane bed regime

    NASA Astrophysics Data System (ADS)

    Zrostlík, Štěpán; Matoušek, Václav

    2016-04-01

    Results are discussed of laboratory experiments on criteria determining the transition between the regime of dunes and the upper stage plane bed (UPB) regime and the transition between the UPB regime and the regime of wavy flow. The experiments were carried for 3 fractions of plastic material and two fractions of glass beads in a broad range of flow conditions (different discharges of water and solids and longitudinal bed slopes) in a tilting flume. The experiments reveal that, contrary to expectations, a constant value of the Shields parameter is not an appropriate criterion for the transition between the dune regime and the UPB regime. Furthermore, the transition appears to be insensitive to the total discharge of solids and water. Instead, the criterion seems to be well represented by a constant value of the average transport concentration of sediment (the ratio of volumetric discharge of solids and volumetric discharge of mixture). The experimental results exhibit a very tight correlation between the transport concentration and the longitudinal bed slope. Hence, a constant value of the bed slope can be considered an appropriate criterion for the transition. The transition between the UPB regime and the wavy regime (significant waves develop but they are not always standing waves) is found at a constant value of Froude number, which is in agreement with literature, although it is found at a higher value than the literature usually suggests (Fr = 1.2 instead of 1.0). Hence, the transition occurs in the super-critical flow but it is not necessarily associated with the critical flow.

  16. Ignition Regime for Fusion in a Degenerate Plasma

    SciTech Connect

    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.

  17. Equatorial atmospheric weather regimes: Their structure and role

    SciTech Connect

    Connors, V.S.

    1991-01-01

    Infrared radiance measurements by the Geostationary Operational Environmental Satellite (GOES-6) from April 1986 through April 1987 are used to characterize and identify distinct regimes of persistent, large-scale cloudiness patterns over the Amazon Basin. These tropical weather regimes are responsible for the continental-scale atmospheric processes that transport air, trace gases, and heat from the Amazon Basin. The cloud patterns are represented by both scene-scale parameters, such as the cloud-free area and the value of the 'clear sky peak' in a histogram, and textural measures, such as contrast of cloudy area and homogeneity or cloudy area. Correlation analyses of the attribute arrays determined that only 9 of the original 15 cloud pattern descriptors are required for the cluster analyses. Seventy-six percent of the satellite images are classified into 1 of 14 weather regimes which persist for periods that range from 3 to 15 days each. The dominant weather regimes are described by the recurrence and duration of the events, by the rainfall produced and energy released to the tropical atmosphere, and by the composite kinematic and thermodynamic analyses. While the classification analyses identified a range of organized weather conditions in the Amazon Basin, two weather regimes, each occurring in separate seasons, dominate the year. The prominent dry season regime (A) occurs 11 times, persists for 25 percent of the year, produces 81 percent of the dry season rainfall, and 7 percent of the energy export necessary to balance the global heat budget. The prominent wet season regime (B) occurs 8 times, persists for 18 percent of the year, delivers about 30 percent of the wet season rainfall, and 16 percent of the energy export requirement. Because the dry season regime (A) draws nearly half of its water vapor supply from local sources, a vital link may exist between the rainforest ecosystem and the dry season rainfall.

  18. Sensitivity of streamflows to hydroclimatic fluctuations: resilience and regime shifts

    NASA Astrophysics Data System (ADS)

    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.

  19. Triggered dynamics in a model of different fault creep regimes

    PubMed Central

    Kostić, Srđan; Franović, Igor; Perc, Matjaž; Vasović, Nebojša; Todorović, Kristina

    2014-01-01

    The study is focused on the effect of transient external force induced by a passing seismic wave on fault motion in different creep regimes. Displacement along the fault is represented by the movement of a spring-block model, whereby the uniform and oscillatory motion correspond to the fault dynamics in post-seismic and inter-seismic creep regime, respectively. The effect of the external force is introduced as a change of block acceleration in the form of a sine wave scaled by an exponential pulse. Model dynamics is examined for variable parameters of the induced acceleration changes in reference to periodic oscillations of the unperturbed system above the supercritical Hopf bifurcation curve. The analysis indicates the occurrence of weak irregular oscillations if external force acts in the post-seismic creep regime. When fault motion is exposed to external force in the inter-seismic creep regime, one finds the transition to quasiperiodic- or chaos-like motion, which we attribute to the precursory creep regime and seismic motion, respectively. If the triggered acceleration changes are of longer duration, a reverse transition from inter-seismic to post-seismic creep regime is detected on a larger time scale. PMID:24954397

  20. Modeling of a Two-Regime Crystallization in a Multicomponent

    SciTech Connect

    Mazzanti, G.; Marangoni, A; Idziak, S

    2008-01-01

    The kinetics of phase transitions of milk fat triacylglycerols, as model multicomponent lipid systems, were studied under shear in a Couette cell at 17 C, 17.5 C and 20 C under shear rates ranging from 0 to 2880s-1 using synchrotron X-ray diffraction. Two-dimensional diffraction patterns were captured during the crystallization process. No effect of shear on onset time for phase a from the liquid was observed. Afterwards a two-regime crystallization process was observed. During the first regime, as observed in other systems, shear reduced the onset time of the phase transition from phase a to 2880s-. The model previously developed for palm oil (ODE model) worked well to describe this regime, confirming the general value of the proposed ODE model. However, the ODE model did not satisfactorily describe the second regime. We found that, as the system gets closer to equilibrium, the growth regime becomes controlled by diffusion, manifested by the kinetics following a {radical}t dependence. This regime was found to be consistent with a mechanism combining step growth at a kink with progressive selection of the crystallizing moieties. This mechanism is in agreement with the displacement of the diffraction peak positions, which revealed how increased shear rate promotes the crystallization of the higher melting fraction affecting the composition of the crystallites.

  1. Regimes of the magnetized Rayleigh{endash}Taylor instability

    SciTech Connect

    Winske, D.

    1996-11-01

    Hybrid simulations with kinetic ions and massless fluid electrons are used to investigate the linear and nonlinear behavior of the magnetized Rayleigh{endash}Taylor instability in slab geometry with the plasma subject to a constant gravity. Three regimes are found, which are determined by the magnitude of the complex frequency {omega}={omega}{sub {ital r}}+{ital i}{gamma}. For {vert_bar}{omega}{vert_bar}{lt}{Omega}{sub {ital i}}({Omega}{sub {ital i}}= ion gyrofrequency), one finds the typical behavior of the usual fluid regime, namely the development of {open_quote}{open_quote}mushroom-head{close_quote}{close_quote} spikes and bubbles in the density and a strongly convoluted boundary between the plasma and magnetic field, where the initial gradient is not relaxed much. A second regime, where {vert_bar}{omega}{vert_bar}{approximately}0.1{Omega}{sub {ital i}}, is characterized by the importance of the Hall term. Linearly, the developing flute modes are more finger-like and tilted along the interface; nonlinearly, clump-like structures form, leading to a significant broadening of the interface. The third regime is characterized by unmagnetized ion behavior, with {vert_bar}{omega}{vert_bar}{approximately}{Omega}{sub {ital i}}. Density clumps, rather than flutes, form in the linear stage, while nonlinearly, longer-wavelength modes that resemble those in fluid regime dominate. Finite Larmor radius stabilization of short-wavelength modes is observed in each regime. {copyright} {ital 1996 American Institute of Physics.}

  2. Do family policy regimes matter for children's well-being?

    PubMed

    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. PMID:21692245

  3. O-regime dynamics and modeling in Tore Supra

    SciTech Connect

    Turco, F.; Giruzzi, G.; Imbeaux, F.; Udintsev, V. S.; Artaud, J. F.; Barana, O.; Dumont, R.; Mazon, D.; Segui, J.-L.

    2009-06-15

    The regime of nonlinear temperature oscillations (O-regime), characteristic of noninductive discharges on Tore Supra [Equipe 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 T{sub e}(r) where the equation coefficients are functions of j and T{sub e} 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.

  4. Assessing the Institution of the Nuclear Nonproliferation Regime

    SciTech Connect

    Toomey, Christopher

    2010-05-14

    The nuclear nonproliferation regime is facing a crisis of effectiveness. During the Cold War, the regime was relatively effective in stemming the proliferation of nuclear weapons and building an institutional structure that could, under certain conditions, ensure continued success. However, in the evolving global context, the traditional approaches are becoming less appropriate. Globalization has introduced new sets of stresses on the nonproliferation regime, such as the rise of non-state actors, broadening extensity and intensity of supply chains, and the multipolarization of power. This evolving global context demands an analytical and political flexibility in order to meet future threats. Current institutional capabilities established during the Cold War are now insufficient to meet the nonproliferation regime’s current and future needs. The research was based on information gathered through interviews and reviews of the relevant literature, and two dominant themes emerged. First, that human security should be integrated into the regime to account for the rise of non-state actors and networked violence. Second, confidence in the regime’s overall effectiveness has eroded at a time where verification-based confidence is becoming more essential. The research postulates that a critical analysis of the regime that fully utilizes institutional theory, with its focus on rules, normative structures, and procedures will be essential to adapting the regime to the current global context, building mechanisms for generating trust, creating better enforcement, and providing flexibility for the future.

  5. Oscillations of a highly discrete breather with a critical regime

    PubMed

    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.

  6. Dynamic regime marginal structural mean models for estimation of optimal dynamic treatment regimes, Part II: proofs of results.

    PubMed

    Orellana, Liliana; Rotnitzky, Andrea; Robins, James M

    2010-03-03

    In this companion article to "Dynamic Regime Marginal Structural Mean Models for Estimation of Optimal Dynamic Treatment Regimes, Part I: Main Content" [Orellana, Rotnitzky and Robins (2010), IJB, Vol. 6, Iss. 2, Art. 7] we present (i) proofs of the claims in that paper, (ii) a proposal for the computation of a confidence set for the optimal index when this lies in a finite set, and (iii) an example to aid the interpretation of the positivity assumption.

  7. North Sea wind climate in changing weather regimes

    NASA Astrophysics Data System (ADS)

    Anders, Ivonne; Rockel, Burkhardt

    2015-04-01

    Results from regional climate models (RCMs) are getting more and more important in future wind climate assessment. From RCMs often only the daily wind speed is available, but no information on prevailing wind direction of each day. Weather regime classification can close this gap and models ability of simulating surface wind speed can be analysed in detail. Several objective regime classifications have been investigated to be a sufficient diagnostic tool to evaluate the present wind climate at the German and Dutch coastal area of the North Sea. The classification by Jenkinson and Collison (1977) uses values for mean sea level pressure at 16 locations centered over the North Sea. Beside the predefined 8 prevailed wind directions and the two possibilities on cyclonic or anticyclonic turbulence, 2x8 hybrid weather types can be defined. In this way 27 different regimes can be distinguished including a class of non-classifiable cases. The 27 regimes could be reduced to a number of 11 by allotting the hybrid types to the directional or the centered types. As the classification is carried out for the North Sea based on ERA40 mean sea level pressure the different regimes clearly reflect the mean wind characteristics at the stations. Comparing the wind roses for the individual observations leads to the assumption that the regime classification described before fits the requirements to carry out the regime dependent evaluation of the RCMs with a focus on the German and Dutch coast. Trends in the occurrence of the regimes in the winter period of 1961 to 2000 show an increase of the regimes with Western and Southwestern wind directions and a decrease of wind events from Eastern directions in the North Sea. The trend is dominated by the strong positive phase of the NAO especially in the months January to March starting in the beginning of the 1980s. Due to the applied method ERA40 and the RCMs do not necessarily show the same regime at each day. The agreement among the RCM

  8. AN INDEX TO DETECT EXTERNALLY-FORCED DYNAMIC REGIME SHIFTS IN ECOSYSTEMS

    EPA Science Inventory

    The concept of dynamic regimes, and nonlinear shifts between regimes, has gained acceptance and importance in ecosystem research. Regimes in ecosystems are identified as states with characteristic species abundances and abiotic conditions. Ecosystems are maintained in particular ...

  9. USING FISHER INFORMATION TO DETECT GRADUAL AND RAPID ECOSYSTEM REGIME SHIFTS

    EPA Science Inventory

    As ecosystems experience perturbations of varying regularity and intensity, they may either remain within the state space neighborhood of the current regime, or "flip" into the neighborhood of a regime with different characteristics. Although the possibility of such regime shifts...

  10. Regime shifts in North Sea and Baltic Sea: A comparison

    NASA Astrophysics Data System (ADS)

    Dippner, Joachim W.; Möller, Caroline; Hänninen, Jari

    2012-12-01

    The ICES subdivisions in the North Sea (SD IIIa, SD IVa, and SD IVb) and the subdivisions in the Baltic Sea (SD 29, SD 27/28-2, and SD 25/26) are selected to compare the response in long term monitoring data (1970-2000) with respect to climate regime shifts. A modified AMOEBA model is applied to the data sets to identify the status and development of the North Sea and Baltic Sea system during two recent regime shifts. Biological regime shifts can be identified 1989/1990 in SD IIIa in the North Sea and in SD 25/26 in the Baltic Sea. A synchronous appearance of regime shifts could only be identified in the central and southern Baltic Sea for both regime shifts 1975/76 and 1989/90 where the AMOEBA model indicated a high similarity in ecosystem response. A clear difference was identified in the response of the North Sea and the Baltic Sea. Inter-annual and inter-decadal variability as well as regime shifts are driven in the Baltic Sea by direct atmospheric forcing only. In contrast, the changes in the North Sea are influenced by both the direct atmospheric forcing and the indirect forcing from the changes in North Atlantic. The fact that regime shifts as well as their synchronous appearance can be identified with the AMOEBA model might be of major interest for the management of sustainable use of ecosystem goods and services, the development of ecosystem approach to management and the implementation of the Marine Strategy Framework Directive (MSFD) of the European Union (EU).

  11. Transient response of Salix cuttings to changing water level regimes

    NASA Astrophysics Data System (ADS)

    Gorla, L.; Signarbieux, C.; Turberg, P.; Buttler, A.; Perona, P.

    2015-03-01

    Sustainable water management requires an understanding of the effects of flow regulation on riparian ecomorphological processes. We investigated the transient response of Salix viminalis by examining the effect of water-level regimes on its above-ground and below-ground biomass. Four sets of Salix cuttings, three juveniles (in the first growing season) and one mature (1 year old), were planted and initially grown under the same water-level regime for 1 month. We imposed three different water-level regime treatments representing natural variability, a seasonal trend with no peaks, and minimal flow (characteristic of hydropower) consisting of a constant water level and natural flood peaks. We measured sap flux, stem water potential, photosynthesis, growth parameters, and final root architecture. The mature cuttings were not affected by water table dynamics, but the juveniles displayed causal relationships between the changing water regime, plant growth, and root distribution during a 2 month transient period. For example, a 50% drop in mean sap flux corresponded with a -1.5 Mpa decrease in leaf water potential during the first day after the water regime was changed. In agreement with published field observations, the cuttings concentrated their roots close to the mean water table of the corresponding treatment, allowing survival under altered conditions and resilience to successive stress events. Juvenile development was strongly impacted by the minimum flow regime, leading to more than 60% reduction of both above-ground and below-ground biomass, with respect to the other treatments. Hence, we suggest avoiding minimum flow regimes where Salix restoration is prioritized.

  12. Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2 -9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways.

    PubMed

    Lu, Kung-Wen; Chen, Jung-Chou; Lai, Tung-Yuan; Yang, Jai-Sing; Weng, Shu-Wen; Ma, Yi-Shih; Lu, Pei-Jung; Weng, Jing-Ru; Chueh, Fu-Shin; Wood, W Gibson; Chung, Jing-Gung

    2011-05-01

    Gypenosides (Gyp), found in Gynostemma pentaphyllum Makino, has been used as a folk medicine in the Chinese population for centuries and is known to have diverse pharmacologic effects, including anti-proliferative and anti-cancer actions. However, the effects of Gyp on prevention from invasion and migration of oral cancer cells are still unsatisfactory. The purpose of this study was to investigate effects of Gyp treatment on migration and invasion of SAS human oral cancer cells. SAS cells were cultured in the presence of 90 and 180 μg/mL Gyp for 24 and 48 hours. Gyp induced cytotoxic effects and inhibited SAS cells migration and invasion in dose- and time-dependent response. Wound-healing assay and boyden chamber assay were carried out to investigate Gyp-inhibited migration and invasion of SAS cells. Gyp decreased the abundance of several proteins, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/ 2), matrix metalloproteinase-9, -2 (MMP-9, -2), sevenless homolog (SOS), Ras, urokinase-type plasminogen activator (uPA), focal adhesion kinase (FAK) and RAC-alpha serine/threonine-protein kinase (Akt), in a time-dependent manner. In addition, Gyp decreased mRNA levels of MMP-2, MMP-7, MMP-9 but did not affect FAK and Rho A mRNA levels in SAS cells. These results provide evidences for the role of Gyp as a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of oral cancer cells. The inhibition of NF-κB and MMP-2, -7 and -9 signaling may be one of the mechanisms that is present in Gyp-inhibited cancer cell invasion and migration.

  13. Cadmium induces urokinase-type plasminogen activator receptor expression and the cell invasiveness of human gastric cancer cells via the ERK-1/2, NF-κB, and AP-1 signaling pathways.

    PubMed

    Khoi, Pham Ngoc; Xia, Yong; Lian, Sen; Kim, Ho Dong; Kim, Do Hyun; Joo, Young Eun; Chay, Kee-Oh; Kim, Kyung Keun; Jung, Young Do

    2014-10-01

    Cadmium exposure has been linked to human cancers, including stomach cancer. In this study, the effects of cadmium on urokinase-type plasminogen activator receptor (uPAR) expression in human gastric cancer cells and the underlying signal transduction pathways were investigated. Cadmium induced uPAR expression in a time- and concentration-dependent manner. Cadmium also induced uPAR promoter activity. Additionally, cadmium induced the activation of extracellular signal regulated kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and the activation of c-Jun amino terminal kinase (JNK). A specific inhibitor of MEK-1 (PD98059) inhibited cadmium-induced uPAR expression, while JNK and p38 MAPK inhibitors did not. Expression vectors encoding dominant-negative MEK-1 (pMCL-K97M) also prevented cadmium-induced uPAR promoter activity. Site-directed mutagenesis and electrophoretic mobility shift studies showed that sites for the transcription factors nuclear factor (NF)-κB and activator protein-1 (AP-1) were involved in cadmium-induced uPAR transcription. Suppression of the cadmium-induced uPAR promoter activity by a mutated-type NF-κB-inducing kinase and I-κB and an AP-1 decoy oligonucleotide confirmed that the activation of NF-κB and AP-1 are essential for cadmium-induced uPAR upregulation. Cells pretreated with cadmium showed markedly enhanced invasiveness and this effect was partially abrogated by uPAR-neutralizing antibodies and by inhibitors of ERK-1/2, NF-κB, and AP-1. These results suggest that cadmium induces uPAR expression via ERK-1/2, NF-κB, and AP-1 signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS cells.

  14. Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

    PubMed Central

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion. PMID:23940799

  15. A serpin-induced extensive proteolytic susceptibility of urokinase-type plasminogen activator implicates distortion of the proteinase substrate-binding pocket and oxyanion hole in the serpin inhibitory mechanism.

    PubMed

    Egelund, R; Petersen, T E; Andreasen, P A

    2001-02-01

    The formation of stable complexes between serpins and their target serine proteinases indicates formation of an ester bond between the proteinase active-site serine and the serpin P1 residue [Egelund, R., Rodenburg, K.W., Andreasen, P.A., Rasmussen, M.S., Guldberg, R.E. & Petersen, T.E. (1998) Biochemistry 37, 6375-6379]. An important question concerning serpin inhibition is the contrast between the stability of the ester bond in the complex and the rapid hydrolysis of the acyl-enzyme intermediate in general serine proteinase-catalysed peptide bond hydrolysis. To answer this question, we used limited proteolysis to detect conformational differences between free urokinase-type plasminogen activator (uPA) and uPA in complex with plasminogen activator inhibitor-1 (PAI-1). Whereas the catalytic domain of free uPA, pro-uPA, uPA in complex with non-serpin inhibitors and anhydro-uPA in a non-covalent complex with PAI-1 was resistant to proteolysis, the catalytic domain of PAI-1-complexed uPA was susceptible to proteolysis. The cleavage sites for four different proteinases were localized in specific areas of the C-terminal beta-barrel of the catalytic domain of uPA, providing evidence that the serpin inhibitory mechanism involves a serpin-induced massive rearrangement of the proteinase active site, including the specificity pocket, the oxyanion hole, and main-chain binding area, rendering the proteinase unable to complete the normal hydrolysis of the acyl-enzyme intermediate. The distorted region includes the so-called activation domain, also known to change conformation on zymogen activation.

  16. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

    PubMed

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.

  17. RNAi-mediated Downregulation of Urokinase Plasminogen Activator Receptor (uPAR) and Matrix Metalloprotease-9 (MMP-9) in Human Breast Cancer Cells Results in Decreased Tumor Invasion, Angiogenesis and Growth

    PubMed Central

    Kunigal, Sateesh; Lakka, Sajani S.; Gondi, Christopher S.; Estes, Norman; Rao, Jasti S.

    2007-01-01

    The serine protease urokinase-type plasminogen activator (uPA) plays a significant role in tumor cell invasion and metastasis when bound to its specific receptor, uPAR (also known as CD87). In addition to the uPA-uPAR system, matrix metalloproteinases (MMPs) are involved in tumor cell invasion and metastasis. In this study, we achieved specific inhibition of uPAR and MMP-9 using RNAi technology. We introduced small interfering RNA (siRNA) to downregulate the expression of uPAR and MMP-9 (pUM) in breast cancer cell lines (MDA MB 231 and ZR 75 1). In vitro angiogenesis studies indicated a decrease in the angiogenic potential of the treated cells; in particular, a remarkable decrease was observed in the cells treated with bicistronic construct (pUM) in comparision to the controls. Additionally, bicistronic construct inhibited the formation of capillary-like structures in in vivo models of angiogenesis. Similarly, the invasive potential and migration decreased dramatically when treated with the bicistronic construct as shown by matrigel invasion and migration assays. These results suggest a synergistic effect from the simultaneous downregulation of uPAR and MMP-9. We also assessed the levels of phosphorylated forms of MAPK, ERK, and AKT signaling pathway molecules and found reduction in the levels of these molecules in cells treated with the bicistronic construct as compared to the control cells. Furthermore, targeting both uPAR and MMP-9 totally regressed orthotopic breast tumors in nude mice. In conclusion, our results provide evidence that the simultaneous downregulation of uPAR and MMP-9 using RNAi technology may provide an effective tool for breast cancer therapy. PMID:17657740

  18. Regime switching model for financial data: Empirical risk analysis

    NASA Astrophysics Data System (ADS)

    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. Early regimes of water capillary flow in slit silica nanochannels.

    PubMed

    Oyarzua, Elton; Walther, Jens H; Mejía, Andrés; Zambrano, Harvey A

    2015-06-14

    Molecular dynamics simulations are conducted to investigate the initial stages of spontaneous imbibition of water in slit silica nanochannels surrounded by air. An analysis is performed for the effects of nanoscopic confinement, initial conditions of liquid uptake and air pressurization on the dynamics of capillary filling. The results indicate that the nanoscale imbibition process is divided into three main flow regimes: an initial regime where the capillary force is balanced only by the inertial drag and characterized by a constant velocity and a plug flow profile. In this regime, the meniscus formation process plays a central role in the imbibition rate. Thereafter, a transitional regime takes place, in which, the force balance has significant contributions from both inertia and viscous friction. Subsequently, a regime wherein viscous forces dominate the capillary force balance is attained. Flow velocity profiles identify the passage from an inviscid flow to a developing Poiseuille flow. Gas density profiles ahead of the capillary front indicate a transient accumulation of air on the advancing meniscus. Furthermore, slower capillary filling rates computed for higher air pressures reveal a significant retarding effect of the gas displaced by the advancing meniscus.

  20. Hydrological minimal model for fire regime assessment in Mediterranean ecosystem

    NASA Astrophysics Data System (ADS)

    Ursino, N.; Rulli, M. C.

    2012-04-01

    A new model for Mediterranean forest fire regime assessment is presented and discussed. The model is based on the experimental evidence that fire is due to both hydrological and ecological processes and the relative role of fuel load versus fuel moisture is an important driver in fire ecology. Diverse scenarios are analyzed where either the hydrological forcing or the feedback between fire and hydrological characterization of the site is changed. The model outcome demonstrates that the two way interaction between hydrological processes, biology and fire regime drives the ecosystem toward a typical fire regime that may be altered either by an evolution of the biological characterization of the site or by a change of the hydrological forcing. This tenet implies that not every fire regime is compatible with the ecohydrological characterization of the site under study. This means that natural (non antropogenic) fire cannot be modeled as an arbitrary external forcing because the coupled hydrological and biological processes determines its statistical characterization, and conversely, the fire regime affects the soil moisture availability and the outcome of different species competition under possible water stress. The new modelling approach presented here, when provided by a proper model parameterization, can advance the capability in predicting and managing fires in ecosystems influenced by climate and land use changes.

  1. Shear Capacity as Prognostic of Nocturnal Boundary Layer Regimes

    NASA Astrophysics Data System (ADS)

    van Hooijdonk, Ivo; Donda, Judith; Bosveld, Fred; Moene, Arnold; Clercx, Herman; van de Wiel, Bas

    2015-04-01

    After sunset the surface temperature can drop rapidly in some nights and may lead to ground frost. This sudden drop is closely related to the occurrence of fundamentally different behaviour of turbulence in the nocturnal boundary layer. Recent theoretical findings predict the appearance of two different regimes: the continuously turbulent (weakly stable) boundary layer and the relatively 'quiet' (very stable) boundary layer. Field observations from a large number of nights (approx. 4500 in total) are analysed using an ensemble averaging technique. The observations support the existence of these two fundamentally different regimes: weakly stable (turbulent) nights rapidly reach a steady state (within 2-3 hours). In contrast, very stable nights reach a steady state much later after a transition period (2-6 hours). During this period turbulence is weak and non-stationary. To characterise the regime a new parameter is introduced: the Shear Capacity. This parameter compares the actual shear after sunset with the minimum shear needed to sustain continuous turbulence. In turn, the minimum shear is dictated by the heat flux demand at the surface (net radiative cooling), so that the Shear Capacity combines flow information with knowledge on the boundary condition. It is shown that the Shear Capacity enables prediction of the flow regimes. The prognostic strength of this non-dimensional parameter appears to outperform the traditional ones like z/L and Ri as regime indicator.

  2. Burning plasma regime for Fussion-Fission Research Facility

    NASA Astrophysics Data System (ADS)

    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.

  3. THE IMPACT OF THE GLOBAL NUCLEAR SAFETY REGIME IN BRAZIL

    SciTech Connect

    Almeida, C.

    2004-10-06

    A turning point of the world nuclear industry with respect to safety occurred due to the accident at Chernobyl, in 1986. A side from the tragic personal losses and the enormous financial damage, the Chernobyl accident has literally demonstrated that ''a nuclear accident anywhere is an accident everywhere''. The impact was felt immediately by the nuclear industry, with plant cancellations (e.g. Austria), elimination of national programs (e.g. Italy) and general construction delays. However, the reaction of the nuclear industry was equally immediate, which led to the proposal and establishment of a Global Nuclear Safety Regime. This regime is composed of biding international safety conventions, globally accepted safety standard, and a voluntary peer review system. In a previous work, the author has presented in detail the components of this Regime, and briefly discussed its impact in the Brazilian nuclear power organizations, including the Regulatory Body. This work, on the opposite, briefly reviews the Global Nuclear Safety Regime, and concentrates in detail in the discussion of its impact in Brazil, showing how it has produced some changes, and where the peer pressure regime has failed to produce real results.

  4. Soil magnetic susceptibility reflects soil moisture regimes and the adaptability of tree species to these regimes

    USGS Publications Warehouse

    Wang, J.-S.; Grimley, D.A.; Xu, C.; Dawson, J.O.

    2008-01-01

    Flooded, saturated or poorly drained soils are frequently anaerobic, leading to dissolution of the strongly magnetic minerals, magnetite and maghemite, and a corresponding decrease in soil magnetic susceptibility (MS). In this study of five temperate deciduous forests in east-central Illinois, USA, mean surface soil MS was significantly higher adjacent to upland tree species (31 ?? 10-5 SI) than adjacent to floodplain or lowland tree species (17 ?? 10-5 SI), when comparing regional soils with similar parent material of loessal silt. Although the sites differ in average soil MS for each tree species, the relative order of soil MS means for associated tree species at different locations is similar. Lowland tree species, Celtis occidentalis L., Ulmus americana L., Acer saccharinum L., Carya laciniosa (Michx. f.) Loud., and Fraxinus pennsylvanica Marsh. were associated with the lowest measured soil MS mean values overall and at each site. Tree species' flood tolerance rankings increased significantly, as soil MS values declined, the published rankings having significant correlations with soil MS values for the same species groups. The three published classifications of tree species' flood tolerance were significantly correlated with associated soil MS values at all sites, but most strongly at Allerton Park, the site with the widest range of soil drainage classes and MS values. Using soil MS measurements in forests with soil parent material containing similar initial levels of strongly magnetic minerals can provide a simple, rapid and quantitative method to classify soils according to hydric regimes, including dry conditions, and associated plant composition. Soil MS values thus have the capacity to quantify the continuum of hydric tolerances of tree species and guide tree species selection for reforestation. ?? 2007 Elsevier B.V. All rights reserved.

  5. Shifts in fisheries management: adapting to regime shifts

    PubMed Central

    King, Jacquelynne R.; McFarlane, Gordon A.; Punt, André E.

    2015-01-01

    For many years, fisheries management was based on optimizing yield and maintaining a target biomass, with little regard given to low-frequency environmental forcing. However, this policy was often unsuccessful. In the last two to three decades, fisheries science and management have undergone a shift towards balancing sustainable yield with conservation, with the goal of including ecosystem considerations in decision-making frameworks. Scientific understanding of low-frequency climate–ocean variability, which is manifested as ecosystem regime shifts and states, has led to attempts to incorporate these shifts and states into fisheries assessment and management. To date, operationalizing these attempts to provide tactical advice has met with limited success. We review efforts to incorporate regime shifts and states into the assessment and management of fisheries resources, propose directions for future investigation and outline a potential framework to include regime shifts and changes in ecosystem states into fisheries management.

  6. Theoretical study of the crossover into hydrodynamic regime in graphene

    NASA Astrophysics Data System (ADS)

    Ho, Derek; Yudhistira, Indra; Hu, Ben Yu-Kuang; Adam, Shaffique

    Experiments on graphene have recently succeeded in entering the hydrodynamic regime, as demonstrated by successful observations of strong violation of Wiedemann-Franz law, the Gurzhi effect and electronic Poiseuille flow. It is known that electronic systems enter the hydrodynamic regime when electron-electron scattering dominates over electron-impurity and electron-phonon scattering. However, a quantitative study of this transition from the Fermi liquid to hydrodynamic regime is still lacking. In view of this, we quantitatively analyze the electron-electron, electron-impurity and electron-phonon scattering rates as a function of temperature, charge doping and disorder (charge puddle) strength. This yields a quantitative understanding of the onset of hydrodynamic electronic behavior in graphene samples. This work is supported by the National Research Foundation of Singapore under its Fellowship program (NRF-NRFF2012-01) and by the Singapore Ministry of Education and Yale-NUS College through Grant No. R-607-265-01312.

  7. Supercurrent in the quantum Hall regime, part II

    NASA Astrophysics Data System (ADS)

    Amet, Francois; Ke, Chung Ting; Borzenets, Ivan; Wang, Jiyingmei; Watanabe, Kenji; Taniguchi, Takashi; Deacon, Russel; Yamamoto, Michihisa; Bomze, Yuriy; Tarucha, Seigo; Finkelstein, Gleb

    A novel promising route for creating topological states and excitations is to combine superconductivity and the quantum Hall effect. Despite this potential, signatures of superconductivity in the quantum Hall regime remain scarce, and a superconducting current through a Landau-quantized two-dimensional electron gas has so far eluded experimental observation. High-mobility graphene/BN heterostructures exhibit the quantum Hall effect at relatively low field and are therefore particularly suitable to study the fate of the Josephson effect in that regime. Here, we report the observation of a superconducting current through graphene at fields as high as 2 Tesla. In that regime, the normal-state resistance is quantized but pockets of superconductivity still persist at small current bias. We will describe their bias and temperature dependence. Magnetic field interference patterns in the supercurrent inform on possible mechanisms mediating this supercurrent.

  8. Living dangerously on borrowed time during slow, unrecognized regime shifts.

    PubMed

    Hughes, Terry P; Linares, Cristina; Dakos, Vasilis; van de Leemput, Ingrid A; van Nes, Egbert H

    2013-03-01

    Regime shifts from one ecological state to another are often portrayed as sudden, dramatic, and difficult to reverse. Yet many regime shifts unfold slowly and imperceptibly after a tipping point has been exceeded, especially at regional and global scales. These long, smooth transitions between equilibrium states are easy to miss, ignore, or deny, confounding management and governance. However, slow responses by ecosystems after transgressing a dangerous threshold also affords borrowed time - a window of opportunity to return to safer conditions before the new state eventually locks in and equilibrates. In this context, the most important challenge is a social one: convincing enough people to confront business-as-usual before time runs out to reverse unwanted regime shifts even after they have already begun.

  9. Nonlinear-optical frequency-doubling metareflector: pulsed regime

    NASA Astrophysics Data System (ADS)

    Popov, A. K.; Myslivets, S. A.

    2016-01-01

    The properties of backward-wave second-harmonic metareflector operating in pulse regime are investigated. It is made of metamaterial which enables phase matching of contra-propagating fundamental and second-harmonic waves. References are given to the works that prove such a possibility. Physical principles underlying differences in the proposed and standard settings as well as between continuous-wave and pulsed regimes are discussed. Pulsed regime is more practicable and has a broader scope of applications. A set of partial differential equations which describe such a reflector with the account for losses are solved numerically. It is shown that unlike second-harmonic generation in standard settings, contra-propagating pulse of second harmonic may become much longer than the incident fundamental one and the difference grows with decrease in the input pulse length as compared to thickness of the metaslab. The revealed properties are important for applications and may manifest themselves beyond the optical wavelength range.

  10. Inhomogeneous stationary and oscillatory regimes in coupled chaotic oscillators.

    PubMed

    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.

  11. Laser-nucleus interactions: The quasi-adiabatic regime

    NASA Astrophysics Data System (ADS)

    Pálffy, Adriana; Buss, Oliver; Hoefer, Axel; Weidenmüller, Hans A.

    2015-10-01

    The interaction between nuclei and a strong zeptosecond laser pulse with coherent MeV photons is investigated theoretically. We provide a first semiquantitative study of the quasi-adiabatic regime where the photon absorption rate is comparable to the nuclear equilibration rate. In that regime, multiple photon absorption leads to the formation of a compound nucleus in the so-far unexplored regime of excitation energies several hundred MeV above the yrast line. The temporal dynamics of the process is investigated by means of a set of master equations that account for dipole absorption, stimulated dipole emission, neutron decay, and induced fission in a chain of nuclei. That set is solved numerically by means of state-of-the-art matrix exponential methods also used in nuclear fuel burn-up and radioactivity transport calculations. Our quantitative estimates predict the excitation path and range of nuclei reached by neutron decay and provide relevant information for the layout of future experiments.

  12. Living dangerously on borrowed time during slow, unrecognized regime shifts.

    PubMed

    Hughes, Terry P; Linares, Cristina; Dakos, Vasilis; van de Leemput, Ingrid A; van Nes, Egbert H

    2013-03-01

    Regime shifts from one ecological state to another are often portrayed as sudden, dramatic, and difficult to reverse. Yet many regime shifts unfold slowly and imperceptibly after a tipping point has been exceeded, especially at regional and global scales. These long, smooth transitions between equilibrium states are easy to miss, ignore, or deny, confounding management and governance. However, slow responses by ecosystems after transgressing a dangerous threshold also affords borrowed time - a window of opportunity to return to safer conditions before the new state eventually locks in and equilibrates. In this context, the most important challenge is a social one: convincing enough people to confront business-as-usual before time runs out to reverse unwanted regime shifts even after they have already begun. PMID:22995893

  13. Challenges in Finding AGNs in the Low Luminosity Regime

    NASA Astrophysics Data System (ADS)

    Satyapal, Shobita; Abel, Nick; Secrest, Nathan; Singh, Amrit; Ellison, Sara

    2016-08-01

    Low luminosity AGNs are an important component of the AGN population. They are often found in the lowest mass galaxies or galaxies that lack classical bulges, a demographic that places important constraints to models of supermassive black hole seed formation and merger-free models of AGN fueling. The detection of AGNs in this low luminosity regime is challenging both because star formation in the host galaxy can dominate the optical spectrum and gas and dust can obscure the central engine at both optical and X-ray wavelengths. Thus while mid-infrared color selection and X-ray observations at energies <10 keV are often powerful tools in uncovering optically unidentified AGNs at higher luminosities, this is not the case in the low luminosity regime. In this talk, I will review the effectiveness of uncovering AGNs in the low luminosity regime using multiwavength investigations, with a focus on infrared spectroscopic signatures.

  14. Temporal evolution of flow regimes in urbanizing basins

    NASA Astrophysics Data System (ADS)

    Mejia, A.; Rossel, F.; Gironas, J. A.; Jovanovic, T.

    2014-12-01

    We characterize the temporal evolution of the flow regime of urbanizing basins. By urbanizing basins, we mean basins that have experienced urban growth during their observation period. To represent the flow regime, we use flow duration curves (FDCs). We compute the FDCs using a stochastic model of daily streamflow for urban basins. In this case, the model aids in discerning the influence of key factors (e.g., climate, land use change, stormwater managenment conditions, and the slow and fast properties of the hydrologic response) on streamflow. To implement the model, we first divide the complete observation period of a given urban basin into intervals of equal duration, e.g. 5 years. Subsequently, we apply the model to each interval and this is how we capture the influence of land use changes and climatic fluctuations on the flow regime. We apply this modeling framework to 14 urbanizing basins in the Baltimore-Washington DC region. Results from this application indicate consistent changes in the temporal evolution of the altered flow regimes, which can largely be explained by the progressive redistribution with urban growth of water from slow subsurface runoff and evapotranspiration to fast urban runoff. We also use the modeling framework to determine indicators of ecohydrological alteration for urbanizing basins. The application of these indicators to our study area suggests that the flow regime is sensitive to alterations up to a certain level of urbanization after which sensitivity seems to level off. The flow regime also seems to be relatively more resistant to alterations for both the smaller and larger levels of urbanization considered. In the future, we would like to extend the application of the proposed modeling framework to other metropolitan areas.

  15. Energy regimes and the development of the European Community

    SciTech Connect

    Hadjilambrinos, C.J.

    1993-01-01

    Energy policy has historically played an important role in the development of the European Community (EC). This study examines the reasons for the choice of coal and atomic energy as regimes of integration, analyzes their impact on the institutions and political traditions of the EC, and evaluates their consistency with the principles of democratic governance. Functionalist theory has provided the idealogical foundations for the European Coal and Steel Community and the European Atomic Energy Community. Functionalist theorists advocate technocracy as the means for overcoming the conflicts inherent in traditional political processes. Coal and atomic energy were chosen as regimes of integration because of their technocratic character and the importance attached to them as the dominant energy source of the time and the perceived source of energy abundance in the near future. Energy regimes could not be removed from the political context of national governance. Hard energy regimes, which include coal and atomic energy, are technocratic policies which exclude ordinary citizens from the exercise of power and intensify international conflict. An institutional analysis of the French and Danish electricity regimes demonstrates that their political characteristics are incompatible with the principles of democratic governance. It is also demonstrated that the characteristics of soft energy regimes (e.g., conservation and renewables) are compatible with these principles and are based on cooperation. An analysis of the EC's energy policy demonstrates that a soft energy path represents a concept of integration which distributes decision-making power among various levels of governance. A hard energy path would concentrate power in the hands of a technocratic elite. The pursuit of a soft energy path by the EC would enhance significantly the opportunities for political integration.

  16. Regime independent coupled-wave equations in anisotropic photorefractive media

    NASA Astrophysics Data System (ADS)

    Daly, K. R.; D'Alessandro, G.; Kaczmarek, M.

    2009-06-01

    An extension to coupled wave theory suitable for all regimes of diffraction is presented. The model assumes that the refractive index grating has an arbitrary profile in one direction and is periodic (but not necessarily sinusoidal) in the other. Higher order diffracted terms are considered and appropriate mismatch terms dealt with. It is shown that this model is analytically equivalent to both the Bragg and Raman-Nath regime coupling models under an appropriate set of assumptions. This model is applied to cases such as optical coupling in liquid crystal cells with photoconductive layers. Its predictions are successfully compared to finite element simulations of the full Maxwell’s equations.

  17. Using Clustering to Establish Climate Regimes from PCM Output

    NASA Technical Reports Server (NTRS)

    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

  18. The transition between the niche and neutral regimes in ecology

    PubMed Central

    Fisher, Charles K.; Mehta, Pankaj

    2014-01-01

    An ongoing debate in ecology concerns the impacts of ecological drift and selection on community assembly. Here, we show that there is a transition in diverse ecological communities between a selection-dominated regime (the niche phase) and a drift-dominated regime (the neutral phase). Simulations and analytic arguments show that the niche phase is favored in communities with large population sizes and relatively constant environments, whereas the neutral phase is favored in communities with small population sizes and fluctuating environments. Our results demonstrate how apparently neutral populations may arise even in communities inhabited by species with varying traits. PMID:25157131

  19. Orbital magnetoconductance in the variable-range-hopping regime

    NASA Technical Reports Server (NTRS)

    Sivan, U.; Entin-Wohlman, O.; Imry, Y.

    1988-01-01

    The orbital magnetoconductance (MC) in the variable-range-hopping (VRH) regime is evaluated by use of a model which approximately takes into account the interference among random paths in the hopping process. Instead of logarithmic averaging the MC is obtained by the critical percolating resistor method. The small-field MC is quadratic in H; it is positive deep in the VRH regime and changes sign when the zero-field conductivity is high enough. This behavior (except for the sign change) and the relevant magnetic field scale are in agreement with recent experiments. The calculated MC is always positive for strong fields and is predicted to saturate at sufficiently large fields.

  20. Strong and moderate nonlinear El Niño regimes

    NASA Astrophysics Data System (ADS)

    Takahashi, Ken; Dewitte, Boris

    2016-03-01

    It has been previously proposed that two El Niño (EN) regimes, strong and moderate, exist but the historical observational record is too short to establish this conclusively. Here, 1200 years of simulations with the GFDL CM2.1 model allowed us to demonstrate their existence in this model and, by showing that the relevant dynamics are also evident in observations, we present a stronger case for their existence in nature. In CM2.1, the robust bimodal probability distribution of equatorial Pacific sea surface temperature (SST) indices during EN peaks provides evidence for the existence of the regimes, which is also supported by a cluster analysis of these same indices. The observations agree with this distribution, with the EN of 1982-1983 and 1997-1998 corresponding to the strong EN regime and all the other observed EN to the moderate regime. The temporal evolution of various indices during the observed strong EN agrees very well with the events in CM2.1, providing further validation of this model as a proxy for nature. The two regimes differ strongly in the magnitude of the eastern Pacific warming but not much in the central Pacific. Observations and model agree in the existence of a finite positive threshold in the SST anomaly above which the zonal wind response to warming is strongly enhanced. Such nonlinearity in the Bjerknes feedback, which increases the growth rate of EN events if they reach sufficiently large amplitude, is very likely the essential mechanism that gives rise to the existence of the two EN regimes. Oceanic nonlinear advection does not appear essential for the onset of strong EN. The threshold nonlinearity could make the EN regimes very sensitive to stochastic forcing. Observations and model agree that the westerly wind stress anomaly in the central equatorial Pacific in late boreal summer has a substantial role determining the EN regime in the following winter and it is suggested that a stochastic component at this time was key for the

  1. Champagne experiences various rhythmical bubbling regimes in a flute.

    PubMed

    Liger-Belair, Gérard; Tufaile, Alberto; Jeandet, Philippe; Sartorelli, José-Carlos

    2006-09-20

    Bubble trains are seen rising gracefully from a few points on the glass wall (called nucleation sites) whenever champagne is poured into a glass. As time passes during the gas-discharging process, the careful observation of some given bubble columns reveals that the interbubble distance may change suddenly, thus revealing different rhythmical bubbling regimes. Here, it is reported that the transitions between the different bubbling regimes of some nucleation sites during gas discharging is a process which may be ruled by a strong interaction between tiny gas pockets trapped inside the nucleation site and/or also by an interaction between the tiny bubbles just blown from the nucleation site.

  2. Primary Thermometry in the Intermediate Coulomb Blockade Regime

    NASA Astrophysics Data System (ADS)

    Feshchenko, A. V.; Meschke, M.; Gunnarsson, D.; Prunnila, M.; Roschier, L.; Penttilä, J. S.; Pekola, J. P.

    2013-10-01

    We investigate Coulomb blockade thermometers (CBT) in an intermediate temperature regime, where measurements with enhanced accuracy are possible due to the increased magnitude of the differential conductance dip. Previous theoretical results show that corrections to the half width and to the depth of the measured conductance dip of a sensor are needed, when leaving the regime of weak Coulomb blockade towards lower temperatures. In the present work, we demonstrate experimentally that the temperature range of a CBT sensor can be extended by employing these corrections without compromising the primary nature or the accuracy of the thermometer.

  3. Phase contrast and operation regimes in multifrequency atomic force microscopy

    SciTech Connect

    Santos, Sergio

    2014-04-07

    In amplitude modulation atomic force microscopy the attractive and the repulsive force regimes induce phase shifts above and below 90°, respectively. In the more recent multifrequency approach, however, multiple operation regimes have been reported and the theory should be revisited. Here, a theory of phase contrast in multifrequency atomic force microscopy is developed and discussed in terms of energy transfer between modes, energy dissipation and the kinetic energy and energy transfer associated with externally driven harmonics. The single frequency virial that controls the phase shift might undergo transitions in sign while the average force (modal virial) remains positive (negative)

  4. Cool, high-density regime for poloidal divertors

    SciTech Connect

    Petravic, M.; Post, D.; Heifetz, D.; Schmidt, J.

    1981-08-01

    Calculations have been performed which demonstrate the possibility of operating poloidal divertors at high densities and low temperatures. This operating regime is caused primarily by ionization of recycling neutral gas near the divertor neutralizer plate which amplifies the input particle flux thereby raising the plasma density and lowering the plasma temperature. Low temperature, high density operation of poloidal divertors would ease the design requirements for future large tokamaks such as INTOR or FED by reducing the erosion rate in the divertor and reducing the neutral density and the associated charge exchange erosion near the main plasma. This regime may have already been observed on several divertor and limiter experiments.

  5. Predictive mapping of the natural flow regimes of France

    NASA Astrophysics Data System (ADS)

    Snelder, Ton H.; Lamouroux, Nicolas; Leathwick, John R.; Pella, Hervé; Sauquet, Eric; Shankar, Ude

    2009-06-01

    SummaryHydrologic variability is important in sustaining a variety of ecological processes in streams and rivers. Natural flow regime classifications group streams and rivers that are relatively homogeneous with respect to flow variability and have been promoted as a method of defining units for management of river flows. Although there has been considerable interest in classifying natural flow regimes, there has been less emphasis given to developing accurate methods of extrapolating these classifications to locations without flow data. We developed a method of mapping flow regime classes using boosted regression trees (BRT) that automatically fits non-linear functions and interactions between explanatory variables of flow regimes, both of which can be expected when comparing responses between complex systems such as watersheds. A natural flow regimes classification of continental France was developed from cluster analysis of 157 hydrological indices derived from 763 gauging stations representing unmodified flows. BRT models were used to predict the likelihood of gauging stations belonging to each class based on the watershed characteristics. These models were used to extrapolate the natural flow regime classification to all segments of a national river network. The performance of the BRT models were compared with other methods of assigning locations to flow regime classes, including the use of geographically contiguous regions, linear discriminant analysis (LDA) and classification and regression trees (CART). The "fitted" misclassification rate (associated with model fits) for assignment based on the BRT models was 13% whereas the fitted misclassification rates for geographically contiguous regions, LDA and CART were 52%, 44% and 39% respectively. A "predictive" misclassification rate (calculated for new cases) was estimated for assignments based on the BRT, LDA and CART models using cross validation analysis. For assignment based on the BRT models, the mean

  6. Simple bounds from the perturbative regime of inflation

    SciTech Connect

    Leblond, Louis; Shandera, Sarah E-mail: sarah@phys.columbia.edu

    2008-08-15

    We examine the conditions under which a perturbative expansion around an inflating background is valid. When inflation is driven by a single field with a general sound speed, we find a lower limit on the sound speed related to the amplitude of the inflationary power spectrum. Generalizing the sound speed constraints to include scale dependence can limit the number of e-folds obtained in the perturbative regime and restrict otherwise apparently viable models. We also show that, for models with a low sound speed, eternal inflation cannot occur in the perturbative regime.

  7. Terahertz Quantum Plasmonics of Nanoslot Antennas in Nonlinear Regime.

    PubMed

    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.

  8. Using Clustering to Establish Climate Regimes from PCM Output

    NASA Astrophysics Data System (ADS)

    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

  9. Explicit mapping of acoustic regimes for wind instruments

    NASA Astrophysics Data System (ADS)

    Missoum, Samy; Vergez, Christophe; Doc, Jean-Baptiste

    2014-09-01

    This paper proposes a methodology to map the various acoustic regimes of wind instruments. The maps can be generated in a multidimensional space consisting of design, control parameters, and initial conditions. The boundaries of the maps are obtained explicitly in terms of the parameters using a Support Vector Machine (SVM) classifier as well as a dedicated adaptive sampling 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.

  10. Terahertz Quantum Plasmonics of Nanoslot Antennas in Nonlinear Regime.

    PubMed

    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. PMID:26372787

  11. Geothermal regimes at Clearlake California: A preliminary review

    SciTech Connect

    Burns, K.L.; Potter, R.M.; Zyvoloski, G.

    1992-01-01

    Three distinct geothermal regimes are inferred in the vicinity of the city of Clearlake, California. The first is a conductive heat flow regime, the second is a fault-controlled hot spring flow of magmatic'' fluids, and the third is a resurgent flow of meteoric warm water. The conductive heat flow results in flat, horizontal isotherms. The hot spring generates a localized spike in the isotherms. The advective disturbance carries heat laterally to a fault-line resurgence, lowering the apparent heat flow at the surface.

  12. Geothermal regimes at Clearlake California: A preliminary review

    SciTech Connect

    Burns, K.L.; Potter, R.M.; Zyvoloski, G.

    1992-08-01

    Three distinct geothermal regimes are inferred in the vicinity of the city of Clearlake, California. The first is a conductive heat flow regime, the second is a fault-controlled hot spring flow of ``magmatic`` fluids, and the third is a resurgent flow of meteoric warm water. The conductive heat flow results in flat, horizontal isotherms. The hot spring generates a localized spike in the isotherms. The advective disturbance carries heat laterally to a fault-line resurgence, lowering the apparent heat flow at the surface.

  13. Safe Fast Reactor Based on Nuclear Burning Wave Regime

    SciTech Connect

    Fomin, S.; Mel'nik, Yu.; Pilipenko, V.; Shul'ga, N.

    2006-07-01

    The deterministic approach for describing the phenomenon of self-sustained regime of nuclear burning wave in a fast critical reactor is developed. The results of calculations of the space-time evolution of neutron flux and the fuel burn-up in such a system are presented. (authors)

  14. Ranking Regime and the Future of Vernacular Scholarship

    ERIC Educational Resources Information Center

    Ishikawa, Mayumi

    2014-01-01

    World university rankings and their global popularity present a number of far-reaching impacts for vernacular scholarship. This article employs a multidimensional approach to analyze the ranking regime's threat to local scholarship and knowledge construction through a study of Japanese research universities. First, local conditions that have…

  15. Towards an Orderly Exit Regime in English Higher Education

    ERIC Educational Resources Information Center

    Fisher, Andrew

    2016-01-01

    In a competitive market, the exit of those suppliers who cannot offer an attractive product at an attractive price is seen as desirable. However, the consequences for consumers when their own supplier leaves the market in an unplanned or disorderly way may be undesirable. Exit regimes exist in regulated markets to ensure that consumers are not…

  16. Morphodynamic regime and long-term evolution of meandering rivers

    NASA Astrophysics Data System (ADS)

    Frascati, Alessandro; Lanzoni, Stefano

    2009-06-01

    In the present contribution we focus our attention on the long-term behavior of meandering rivers, a very common pattern in nature. This class of dynamical systems is driven by the coexistence of various intrinsically nonlinear mechanisms which determine the possible occurrence of two different morphodynamic regimes: the subresonant and the superresonant regimes. Investigating the full range of morphodynamic conditions, we objectively compare the morphologic characteristics exhibited by synthetically generated and observed planimetric patterns. The analysis is carried out examining, through principal component analysis, a suitable set of morphological variables. We show that even in the presence of the strong filtering action exerted by cutoff processes, a closer, although not yet complete, similarity with natural meandering planforms can be achieved only by adopting a flow field model which accounts for the full range of morphodynamic regimes. We also introduce a new morphodynamic length scale, ?m, associated with spatially oscillating disturbances. Once normalized with this length scale, the relevant morphologic features of the simulated long-term patterns (e.g., the probability density function of local curvature and the geometric characteristics of oxbow lakes) tend to collapse on two distinct behaviors, depending on the dominant morphologic regime.

  17. Two regimes in the regularity of sunspot number

    SciTech Connect

    Shapoval, A.; Shnirman, M.

    2013-12-20

    Sunspot numbers WN display quasi-periodical variations that undergo regime changes. These irregularities could indicate a chaotic system and be measured by Lyapunov exponents. We define a functional λ (an 'irregularity index') that is close to the (maximal) Lyapunov exponent for dynamical systems and well defined for series with a random component: this allows one to work with sunspot numbers. We compute λ for the daily WN from 1850 to 2012 within 4 yr sliding windows: λ exhibit sharp maxima at solar minima and secondary maxima at solar maxima. This pattern is reflected in the ratio R of the amplitudes of the main versus secondary peaks. Two regimes have alternated in the past 150 yr, R1 from 1850 to 1915 (large λ and R values) and R2 from 1935 to 2005 (shrinking difference between main and secondary maxima, R values between 1 and 2). We build an autoregressive model consisting of Poisson noise plus an 11 yr cycle and compute its irregularity index. The transition from R1 to R2 can be reproduced by strengthening the autocorrelation a of the model series. The features of the two regimes are stable for model and WN with respect to embedding dimension and delay. Near the time of the last solar minimum (∼2008), the irregularity index exhibits a peak similar to the peaks observed before 1915. This might signal a regime change back from R2 to R1 and the onset of a significant decrease of solar activity.

  18. Consequences of more extreme precipitation regimes for terrestrial ecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Amplification of the hydrological cycle, as a consequence of global warming, will be manifest not only by alterations in total annual precipitation, but also through more extreme precipitation regimes characterized by fewer, but larger rainfall events and more severe intervening drought periods. Ba...

  19. Initiation of detonation regimes in hybrid two-phase mixtures

    NASA Astrophysics Data System (ADS)

    Khasainov, B. A.; Veyssiere, B.

    1996-06-01

    The problem of detonation initiation is studied in the case of hybrid two-phase mixtures consisting of a hydrogen-air gaseous mixture with suspended fine aluminium particles. In preceding works on this subject, investigation of the steady propagation regimes has shown that three main propagation regimes could exist: the Pseudo-Gas Detonation (PGD), the Single-Front Detonation (SFD), and the Double-Front Detonation (DFD). In the present study, a one-dimensional unsteady numerical code has been improved to study the build-up of the detonation in a heterogeneous solid particle gas mixture contained in a tube. The initiation is simulated by the deposition of a given energy in a point source explosion, and the formation of the detonation is observed over distances of 15 m to 30 m. As the code has been designed to run on a micro-computer, memory limitations preclude sufficient accuracy for quantitative results, however, good qualitative agreement has been found with the results of the steady analysis. In addition, it has been demonstrated that when both PGD and SFD could exist at the same particle concentration, the PGD regime was unstable and was able to exist only over a limited distance (a few meters): after some time, the reaction of aluminium particles in the unsteady flow perturbs the leading wave and accelerates it to the SFD regime. Influence of particle diameter and of initiation energy are examined.

  20. Politics, welfare regimes, and population health: controversies and evidence.

    PubMed

    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. PMID:21899562

  1. Dynamic Financial Constraints: Distinguishing Mechanism Design from Exogenously Incomplete Regimes.

    PubMed

    Karaivanov, Alexander; Townsend, Robert M

    2014-05-01

    We formulate and solve a range of dynamic models of constrained credit/insurance that allow for moral hazard and limited commitment. We compare them to full insurance and exogenously incomplete financial regimes (autarky, saving only, borrowing and lending in a single asset). We develop computational methods based on mechanism design, linear programming, and maximum likelihood to estimate, compare, and statistically test these alternative dynamic models with financial/information constraints. Our methods can use both cross-sectional and panel data and allow for measurement error and unobserved heterogeneity. We estimate the models using data on Thai households running small businesses from two separate samples. We find that in the rural sample, the exogenously incomplete saving only and borrowing regimes provide the best fit using data on consumption, business assets, investment, and income. Family and other networks help consumption smoothing there, as in a moral hazard constrained regime. In contrast, in urban areas, we find mechanism design financial/information regimes that are decidedly less constrained, with the moral hazard model fitting best combined business and consumption data. We perform numerous robustness checks in both the Thai data and in Monte Carlo simulations and compare our maximum likelihood criterion with results from other metrics and data not used in the estimation. A prototypical counterfactual policy evaluation exercise using the estimation results is also featured.

  2. The Harrison Diffusion Kinetics Regimes in Solute Grain Boundary Diffusion

    SciTech Connect

    Belova, Irina; Fiedler, T; Kulkarni, Nagraj S; Murch, Prof. Graeme

    2012-01-01

    Knowledge of the limits of the principal Harrison kinetics regimes (Type-A, B and C) for grain boundary diffusion is very important for the correct analysis of the depth profiles in a tracer diffusion experiment. These regimes for self-diffusion have been extensively studied in the past by making use of the phenomenological Lattice Monte Carlo (LMC) method with the result that the limits are now well established. The relationship of those self-diffusion limits to the corresponding ones for solute diffusion in the presence of solute segregation to the grain boundaries remains unclear. In the present study, the influence of solute segregation on the limits is investigated with the LMC method for the well-known parallel grain boundary slab model by showing the equivalence of two diffusion models. It is shown which diffusion parameters are useful for identifying the limits of the Harrison kinetics regimes for solute grain boundary diffusion. It is also shown how the measured segregation factor from the diffusion experiment in the Harrison Type-B kinetics regime may differ from the global segregation factor.

  3. Dynamic Financial Constraints: Distinguishing Mechanism Design from Exogenously Incomplete Regimes.

    PubMed

    Karaivanov, Alexander; Townsend, Robert M

    2014-05-01

    We formulate and solve a range of dynamic models of constrained credit/insurance that allow for moral hazard and limited commitment. We compare them to full insurance and exogenously incomplete financial regimes (autarky, saving only, borrowing and lending in a single asset). We develop computational methods based on mechanism design, linear programming, and maximum likelihood to estimate, compare, and statistically test these alternative dynamic models with financial/information constraints. Our methods can use both cross-sectional and panel data and allow for measurement error and unobserved heterogeneity. We estimate the models using data on Thai households running small businesses from two separate samples. We find that in the rural sample, the exogenously incomplete saving only and borrowing regimes provide the best fit using data on consumption, business assets, investment, and income. Family and other networks help consumption smoothing there, as in a moral hazard constrained regime. In contrast, in urban areas, we find mechanism design financial/information regimes that are decidedly less constrained, with the moral hazard model fitting best combined business and consumption data. We perform numerous robustness checks in both the Thai data and in Monte Carlo simulations and compare our maximum likelihood criterion with results from other metrics and data not used in the estimation. A prototypical counterfactual policy evaluation exercise using the estimation results is also featured. PMID:25246710

  4. Search Regimes and the Industrial Dynamics of Science

    ERIC Educational Resources Information Center

    Bonaccorsi, Andrea

    2008-01-01

    The article addresses the issue of dynamics of science, in particular of new sciences born in twentieth century and developed after the Second World War (information science, materials science, life science). The article develops the notion of search regime as an abstract characterization of dynamic patterns, based on three dimensions: the rate of…

  5. Microgravity Flow Regime Data: Buoyancy and Mixing Apparatus Effects

    NASA Astrophysics Data System (ADS)

    Shephard, Adam; Best, Frederick

    2010-01-01

    Zero-g two-phase flow data set qualification and flight experiment design have not been standardized and as a result, agreement among researchers has not been reached regarding what experimental conditions adequately approximate those of microgravity. The effects of buoyancy forces and mixing apparatus on the flow regime transitions are presented in this study. The gravity conditions onboard zero-g aircraft are at best 10-3 g which is used to approximate the 10-5 g conditions of microgravity, thus the buoyancy forces present on zero-g aircraft can become significantly large and unrepresentative of microgravity. When buoyancy forces approach those of surface tension forces, buoyancy induced coalescence occurs. When discussing flow regime transitions, these large buoyancy forces lead to flow regime transitions which otherwise would not occur. The buoyancy attributes of the two-phase flow data sets available in the literature are evaluated to determine which data sets exhibit buoyancy induced transitions. Upon comparison of the representative data sets, the affects of different mixing apparatus can be seen in the superficial velocity flow regime maps.

  6. Transport processes in magnetically confined plasmas in the nonlinear regime

    SciTech Connect

    Sonnino, Giorgio

    2006-06-15

    A field theory approach to transport phenomena in magnetically confined plasmas is presented. The thermodynamic field theory (TFT), previously developed for treating the generic thermodynamic system out of equilibrium, is applied to plasmas physics. Transport phenomena are treated here as the effect of the field linking the thermodynamic forces with their conjugate flows combined with statistical mechanics. In particular, the Classical and the Pfirsch-Schlueter regimes are analyzed by solving the thermodynamic field equations of the TFT in the weak-field approximation. We found that, the TFT does not correct the expressions of the ionic heat fluxes evaluated by the neoclassical theory in these two regimes. On the other hand, the fluxes of matter and electronic energy (heat flow) is further enhanced in the nonlinear Classical and Pfirsch-Schlueter regimes. These results seem to be in line with the experimental observations. The complete set of the electronic and ionic transport equations in the nonlinear Banana regime, is also reported. A paper showing the comparison between our theoretic results and the experimental observations in the JET machine is currently in preparation.

  7. Nonlinear transport processes in tokamak plasmas. I. The collisional regimes

    SciTech Connect

    Sonnino, Giorgio; Peeters, Philippe

    2008-06-15

    An application of the thermodynamic field theory (TFT) to transport processes in L-mode tokamak plasmas is presented. The nonlinear corrections to the linear ('Onsager') transport coefficients in the collisional regimes are derived. A quite encouraging result is the appearance of an asymmetry between the Pfirsch-Schlueter (P-S) ion and electron transport coefficients: the latter presents a nonlinear correction, which is absent for the ions, and makes the radial electron coefficients much larger than the former. Explicit calculations and comparisons between the neoclassical results and the TFT predictions for Joint European Torus (JET) plasmas are also reported. It is found that the nonlinear electron P-S transport coefficients exceed the values provided by neoclassical theory by a factor that may be of the order 10{sup 2}. The nonlinear classical coefficients exceed the neoclassical ones by a factor that may be of order 2. For JET, the discrepancy between experimental and theoretical results for the electron losses is therefore significantly reduced by a factor 10{sup 2} when the nonlinear contributions are duly taken into account but, there is still a factor of 10{sup 2} to be explained. This is most likely due to turbulence. The expressions of the ion transport coefficients, determined by the neoclassical theory in these two regimes, remain unaltered. The low-collisional regimes, i.e., the plateau and the banana regimes, are analyzed in the second part of this work.

  8. Welfare Attitudes and Social Expenditure: Do Regimes Shape Public Opinion?

    ERIC Educational Resources Information Center

    Jakobsen, Tor Georg

    2011-01-01

    This article examines the link between regime types, social expenditure, and welfare attitudes. By employing data on 19 countries taken from the World Values Survey, the main aim is to see to what degree the institutions of a country affect the attitudes of its citizens. According to Esping-Andersen ("The three worlds of welfare capitalism".…

  9. Shear-driven Dynamo Waves in the Fully Nonlinear Regime

    NASA Astrophysics Data System (ADS)

    Pongkitiwanichakul, P.; Nigro, G.; Cattaneo, F.; Tobias, S. M.

    2016-07-01

    Large-scale dynamo action is well understood when the magnetic Reynolds number (Rm) is small, but becomes problematic in the astrophysically relevant large Rm limit since the fluctuations may control the operation of the dynamo, obscuring the large-scale behavior. Recent works by Tobias & Cattaneo demonstrated numerically the existence of large-scale dynamo action in the form of dynamo waves driven by strongly helical turbulence and shear. Their calculations were carried out in the kinematic regime in which the back-reaction of the Lorentz force on the flow is neglected. Here, we have undertaken a systematic extension of their work to the fully nonlinear regime. Helical turbulence and large-scale shear are produced self-consistently by prescribing body forces that, in the kinematic regime, drive flows that resemble the original velocity used by Tobias & Cattaneo. We have found four different solution types in the nonlinear regime for various ratios of the fluctuating velocity to the shear and Reynolds numbers. Some of the solutions are in the form of propagating waves. Some solutions show large-scale helical magnetic structure. Both waves and structures are permanent only when the kinetic helicity is non-zero on average.

  10. Globalisation, the "Idea of a University" and Its Ethical Regimes

    ERIC Educational Resources Information Center

    Marginson, Simon

    2007-01-01

    This paper sketches the impact of globalisation and internationalisation on the terrain of values and ethics in higher education. The first part of the paper discusses values and ethics in higher education in relation to the "Idea of a University", and identifies the ethical regimes essential to the functioning of HEIs as knowledge-forming…

  11. Root response of Jerusalem artichoke genotypes to different water regimes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine effects of drought on selected root growth parameters and develop relationships between root parameters and tuber yield for selected Jerusalem artichoke (JA) genotypes. Three water regimes (Field capacity, 50% available water (AW) and 25% AW) and five JA...

  12. Political Regime and Human Capital: A Cross-Country Analysis

    ERIC Educational Resources Information Center

    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…

  13. FISHER INFORMATION AND DYNAMIC REGIME CHANGES IN ECOLOGICAL SYSTEMS

    EPA Science Inventory

    Fisher Information and Dynamic Regime Changes in Ecological Systems
    Abstract for the 3rd Conference of the International Society for Ecological Informatics
    Audrey L. Mayer, Christopher W. Pawlowski, and Heriberto Cabezas

    The sustainable nature of particular dynamic...

  14. Connectivity, regime shifts and the resilience of coral reefs

    NASA Astrophysics Data System (ADS)

    Elmhirst, Toby; Connolly, Sean R.; Hughes, Terry P.

    2009-12-01

    Connectivity of larvae among metapopulations in open marine systems can be a double-edged sword, allowing for the colonization and replenishment of both desirable and undesirable elements of interacting species-rich assemblages. This article studies the effect of recruitment by coral and macroalgae on the resilience of grazed reef ecosystems. In particular, we focus on how larval connectivity affects regime shifts between alternative assemblages that are dominated either by corals or by macroalgae. Using a model with bistability dynamics, we show that recruitment of coral larvae erodes the resilience of a macroalgae-dominated ecosystem when grazing is high, but has negligible effect when grazing is low. Conversely, recruitment by macroalgae erodes the resilience of a coral-dominated ecosystem when grazing is low, leading to a regime shift to macroalgae. Thus, spillover of coral recruits from highly protected areas will not restore coral cover or prevent flips to macroalgae in the surrounding seascape if grazing levels in these areas are depleted, but may be pivotal for re-building coral populations if grazing is high. Fishing restrictions and the re-introduction of herbivores should therefore be a prime conservation objective for preventing undesirable regime shifts. Connectivity by some components of coral reef assemblages (e.g., macroalgae, pathogens, crown-of-thorns starfish) may be detrimental to sustaining reefs, especially where overfishing and other drivers have eroded their resilience, making them more vulnerable to a regime shift.

  15. Dynamics of liquid drops coalescing in the inertial regime.

    PubMed

    Sprittles, James E; Shikhmurzaev, Yulii D

    2014-06-01

    We examine the dynamics of two coalescing liquid drops in the "inertial regime," where the effects of viscosity are negligible and the propagation of the front of the bridge connecting the drops can be considered as "local." The solution fully computed in the framework of classical fluid mechanics allows this regime to be identified, and the accuracy of the approximating scaling laws proposed to describe the propagation of the bridge to be established. It is shown that the scaling law known for this regime has a very limited region of accuracy, and, as a result, in describing experimental data it has frequently been applied outside its limits of applicability. The origin of the scaling law's shortcoming appears to be the fact that it accounts for the capillary pressure due only to the longitudinal curvature of the free surface as the driving force for the process. To address this deficiency, the scaling law is extended to account for both the longitudinal and azimuthal curvatures at the bridge front, which, fortuitously, still results in an explicit analytic expression for the front's propagation speed. This expression is shown to offer an excellent approximation for both the fully computed solution and for experimental data from a range of flow configurations for a remarkably large proportion of the coalescence process. The derived formula allows one to predict the speed at which drops coalesce for the duration of the inertial regime, which should be useful for the analysis of experimental data. PMID:25019880

  16. Syria: The Consolidation of the Asad Regime, 1970-1975.

    ERIC Educational Resources Information Center

    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)

  17. Dynamic Financial Constraints: Distinguishing Mechanism Design from Exogenously Incomplete Regimes*

    PubMed Central

    Karaivanov, Alexander; Townsend, Robert M.

    2014-01-01

    We formulate and solve a range of dynamic models of constrained credit/insurance that allow for moral hazard and limited commitment. We compare them to full insurance and exogenously incomplete financial regimes (autarky, saving only, borrowing and lending in a single asset). We develop computational methods based on mechanism design, linear programming, and maximum likelihood to estimate, compare, and statistically test these alternative dynamic models with financial/information constraints. Our methods can use both cross-sectional and panel data and allow for measurement error and unobserved heterogeneity. We estimate the models using data on Thai households running small businesses from two separate samples. We find that in the rural sample, the exogenously incomplete saving only and borrowing regimes provide the best fit using data on consumption, business assets, investment, and income. Family and other networks help consumption smoothing there, as in a moral hazard constrained regime. In contrast, in urban areas, we find mechanism design financial/information regimes that are decidedly less constrained, with the moral hazard model fitting best combined business and consumption data. We perform numerous robustness checks in both the Thai data and in Monte Carlo simulations and compare our maximum likelihood criterion with results from other metrics and data not used in the estimation. A prototypical counterfactual policy evaluation exercise using the estimation results is also featured. PMID:25246710

  18. Politics, welfare regimes, and population health: controversies and evidence.

    PubMed

    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.

  19. Regimes of flow induced vibration for tandem, tethered cylinders

    NASA Astrophysics Data System (ADS)

    Nave, Gary; Stremler, Mark

    2015-11-01

    In the wake of a bluff body, there are a number of dynamic response regimes that exist for a trailing bluff body depending on spacing, structural restoring forces, and the mass-damping parameter m* ζ . For tandem cylinders with low values of m* ζ , two such regimes of motion are Gap Flow Switching and Wake Induced Vibration. In this study, we consider the dynamics of a single degree-of-freedom rigid cylinder in the wake of another in these regimes for a variety of center-to-center cylinder spacings (3-5 diameters) and Reynolds numbers (4,000-11,000). The system consists of a trailing cylinder constrained to a circular arc around a fixed leading cylinder, which, for small angle displacements, bears a close resemblance to the transversely oscillating cylinders found more commonly in existing literature. From experiments on this system, we compare and contrast the dynamic response within these two regimes. Our results show sustained oscillations in the absence of a structural restoring force in all cases, providing experimental support for the wake stiffness assumption, which is based on the mean lift toward the center line of flow.

  20. Local-field correction in the strong-coupling regime

    SciTech Connect

    Hien, Tran Minh; Dung, Ho Trung; Welsch, Dirk-Gunnar

    2011-04-15

    The influence of the local-field correction on the strong atom-field coupling regime are investigated using the real-cavity model. The atom is positioned at the center of a multilayer sphere. Three types of mirrors are considered: perfectly reflecting, Lorentz band gap, and Bragg-distributed ones, with special emphasis on experimental practicability. In particular, the influence of the local field on the spectral resonance lines, the Rabi oscillation frequency and decay rate, and the condition indicating the occurrence of the strong-coupling regime are studied in detail. It is shown that the local-field correction gives rise to a structureless plateau in the density of states of the electromagnetic field. The level of the plateau rises with increasing material density and/or absorption, which may eventually destroy the strong-coupling regime. The effect of the local field is especially pronounced at high-material densities due to direct energy transfer from the guest atom to the medium. At lower material density and/or absorption, variation of the material density does not seem to affect much the strong-coupling regime, except for a small shift in the resonance frequency.

  1. Velocity Regimes for Sphere Penetration of Granular Materials

    NASA Astrophysics Data System (ADS)

    Omidvar, Mehdi; Bless, Stephan; Guzman, Ivan; Iskander, Magued

    2014-03-01

    Penetration of granular materials as a function of velocity is made complex by transitions where one or another physical process is dominant. At the lowest velocity, bearing resistance (which depends on friction and depth) is dominant, then dynamic Coulomb friction, then inertial resistance, then particle crushing. There is also a special regime where resistance is very high during the first radius of penetration, probably due to shock wave effects. These transitions are very evident in penetration of dry sand, between 0 and 300 m/s, as revealed by measurements of deceleration and the final depth of penetration. With crushed quartz particles, the particle crushing regime is not observed. Additionally, in saturated sand, the crushing regime appears to be suppressed. The regime where particles are crushed corresponds to an increase in penetration resistance, and this plays a large role in the relative difficulty in penetration of dry as opposed to wet materials. Measurements of deceleration give rise to estimates of average stress in the granular materials. For the case of sand, the threshold for comminution is at about 100 MPa, and this is also where significant crushing of sand is seen in triaxial compression experiments. Funded by Defense Threat Reduction Agency grant HDTRA1-10-1-0049.

  2. Accessing Imagined Communities and Reinscribing Regimes of Truth

    ERIC Educational Resources Information Center

    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…

  3. Civic Capacity in Educational Reform Efforts: Emerging and Established Regimes in Rust Belt Cities

    ERIC Educational Resources Information Center

    Mitra, Dana L.; Frick, William C.

    2011-01-01

    Using urban regime theory, the article examines two Rust Belt cities that tried to break the cycle of social reproduction in their communities by reforming their schools. The article contributes to the development of urban regime theory by comparing an "emerging" regime to an "established" regime. The comparison highlights the interdependent…

  4. Effects of two long-term mowing regimes on vegetation

    USGS Publications Warehouse

    Perry, M.C.; Deller, A.S.

    2000-01-01

    Wildlife managers have for many years been interested in the role of mowing as a management technique to benefit wildlife. Two long-term mowing regimes (60 years of similar management) were evaluated at Patuxent Research Refuge during the summer of 1997 to better understand the influence of mowing on vegetation communities. Mowing ceased in 1997 due to reduction in maintenance funds, which facilitated the identification of mature grasses. The previous mowing regimes included (1) lawn areas that had been mowed with rotary mowers approximately every 24 weeks and (2) meadow areas that had been mowed approximately once a year with a brushhog. Each regime had two replications. Vegetation was sampled in 20, 1 m2 plots per area (n=80) and percent cover visually estimated by species. The percent ground cover of the dominant vegetation on the lawn area was 40.0% red fescue (Festuca rubra), 26.5% white clover (Trifolium repens), and 18.0% Kentucky blue grass (Poa pratensis). The percent ground cover of the dominant vegetation in the meadow area was 33.2% meadow fescue (Festuca elatior), 9.9% sweet vernal grass (Anthoxanthum odoratum), 9.2% orchard grass (Dactylis glomerata), 6.3% Japanese honeysuckle (Lonicera japonica), and 5.2% red fescue. The sites were sampled again in 1999 with the major difference being the absence of white clover in the lawn areas, believed to be a result of the drought conditions in recent years. All percent ground covers for the dominant vegetation were significantly different (P<0.01) between the two mowing regimes. Species richness was higher in both years in the meadow regime (74, 62) versus the lawn regime (33, 23). Frequently mowed lawn areas may provide better grazing forage for herbivores, such as geese, rabbits, and deer, however, meadow areas may provide greater plant biomass (232 vs. 63 g/m2) and greater diversity of plant species. The meadow regime also appeared to have greater seed production and cover, which is favored by a wider

  5. Classification of river regimes: A context for hydroecology

    USGS Publications Warehouse

    Osterkamp, W.R.; Friedman, J.M.

    2000-01-01

    Over the past 30 years, ecologists have demostrated the importance of flow and temperature as primary variables in driving running water, riparian and floodplain ecosystems. As it is important to assess the size and timing of discharge variations in relation to those in temperature, a method is proposed that uses multivariate techniques to separately classify annual discharge and temperature regimes according to their 'shape' and 'magnitude', and which then combines the classifications. This paper: (i) describes a generally applicable method; (ii) tests the method by applying it to riparian systems on four British rivers using a 20-year record (1977-97) of flow and air temperature: (iii) proposes a hydroecological interpretation of the classification; (iv) considers the degree to which the methodology might provide information to support the design of ecologically acceptable flow regimes. 'Regimes' are defined for discharge and air temperature using monthly mean data. The results of applying the classification procedure to four British rivers indicates that the 'typical' regimes for each of the four catchments are composite features produced by a small number of clearly defined annual types that reflect interannual variability in hydroclimatological conditions. Annual discharge patterns are dominated by three 'shape' classes (accounting for 94% of the station years: class A, early (November) peak; class B, intermediate (December-January) peak; and class C, late (March) peak) and one 'magnitude' class (70% of the station years fall into class 3, intermediate), with two subordinate 'magnitude' classes: low-flow years (18%) and high flow years (12%). For air temperature, annual patterns are classified evenly into three 'shape' and four 'magnitude' classes. It is argued that this variety of flow-temperature patterns is important for sustaining ecosystem integrity and for establishing benchmark flow regimes and associated frequencies to aid river management. Copyright

  6. Fire regime characterization in Mediterranean ecosystems of Southern Italy

    NASA Astrophysics Data System (ADS)

    Lanorte, A.; Lasaponara, R.

    2009-04-01

    This paper addresses the wildfire regime in Mediterranean ecosystems of Southern Italy. Fire regimes refer to average fire conditions (including fire size, fire density, fire frequency, fire seasonality, fire intensity, fire severity, fire thresholds, etc.) occurring over a long period of time. Information on spatial pattern of forest fire locations is a key point in the study of the dynamics of fire disturbance, and allows us to improve the knowledge of past and current role of fire. Historical evidence clearly shows what did happen and this can fruitfully help to understand what is happening and what could happen in the next future. Mapping fire regimes is very challenging, because fire ocurrence features are the expression of the interactions between climate, fire, vegetation, topography, social factors. The main objective of this work is to provide a comprehensive characterization of the fire regime in Italy based on a recently updated national wildfire database. Fire data were obtained from the Italian National Forestry Service. This national database is comprised of information contained in individual fire reports completed for every fire that occurs on public lands in the Italian peninsula. Complete data were only available for 1996-2006 at the time we accessed the database, which determined the years we analysed. The primary fire history variables that we reported were number of fires, area burned, burning time and duration, and fire size (average size of individual fires) The wildfire records (wildfire area, location, time, vegetation) were analysed with other environmental (fuel availability and type), topographic features, and meteorological/climatological data. Results of our analysis could help better understand the different factors on the wildfire regime in Mediterranean ecosystems of Southern Italy.

  7. Early warning of atmospheric regime transitions using transfer operators

    NASA Astrophysics Data System (ADS)

    Tantet, Alexis; Dijkstra, Henk

    2015-04-01

    The existence of persistent midlatitude atmospheric regimes, such as blocking events, with time scales larger than 5-10 days and indications of preferred transition paths between them motivates the development of early-warning indicators of regime transitions. Here, we use a barotropic model of the northern midlatitudes winter flow to study such meta-stable regimes. We look at estimates of transfer operators acting on densities evolving on a reduced phase space spanned by the first Empirical Orthogonal Functions of the streamfunction and develop an early-warning indicator of zonal to blocked flow transition. The study of the spectra of transfer operators estimated for different lags reveals a multi-level structure in the flow as well as the effect of memory on the reduced dynamics due to past interactions between the resolved and unresolved variables. The slowest motions in the reduced phase space are thereby found to have time scales larger than 8 days and to behave as Markovian for larger lags. These motions are associated with meta-stable regimes and their transitions and can be detected as almost-invariant sets of the transfer operator. The early-warning indicator is based on the action on an initial density of products of the transfer operators estimated for sufficiently long lags, making use of the semi-group property of these operators and shows relatively good Peirce skill score. From the energy budget of the model, we are able to explain the meta-stability of the regimes and the existence of preferred transition paths as the manifestation of barotropic instability. Finally, even though the model is highly simplified, the skill of the early warning indicator is promising, suggesting that the transfer operator approach can be used in parallel to an operational deterministic model for stochastic prediction or to assess forecast uncertainty.

  8. Climate change and future fire regimes: Examples from California

    USGS Publications Warehouse

    Keeley, Jon E.; Syphard, Alexandra D.

    2016-01-01

    Climate and weather have long been noted as playing key roles in wildfire activity, and global warming is expected to exacerbate fire impacts on natural and urban ecosystems. Predicting future fire regimes requires an understanding of how temperature and precipitation interact to control fire activity. Inevitably this requires historical analyses that relate annual burning to climate variation. Fuel structure plays a critical role in determining which climatic parameters are most influential on fire activity, and here, by focusing on the diversity of ecosystems in California, we illustrate some principles that need to be recognized in predicting future fire regimes. Spatial scale of analysis is important in that large heterogeneous landscapes may not fully capture accurate relationships between climate and fires. Within climatically homogeneous subregions, montane forested landscapes show strong relationships between annual fluctuations in temperature and precipitation with area burned; however, this is strongly seasonal dependent; e.g., winter temperatures have very little or no effect but spring and summer temperatures are critical. Climate models that predict future seasonal temperature changes are needed to improve fire regime projections. Climate does not appear to be a major determinant of fire activity on all landscapes. Lower elevations and lower latitudes show little or no increase in fire activity with hotter and drier conditions. On these landscapes climate is not usually limiting to fires but these vegetation types are ignition-limited. Moreover, because they are closely juxtaposed with human habitations, fire regimes are more strongly controlled by other direct anthropogenic impacts. Predicting future fire regimes is not rocket science; it is far more complicated than that. Climate change is not relevant to some landscapes, but where climate is relevant, the relationship will change due to direct climate effects on vegetation trajectories, as well as

  9. The human dimension of fire regimes on Earth

    USGS Publications Warehouse

    Bowman, David M.J.S.; Balch, Jennifer; Artaxo, Paulo; Bond, William J.; Cochrane, Mark A.; D'Antonio, Carla M.; DeFries, Ruth; Johnston, Fay H.; Keeley, Jon E.; Krawchuk, Meg A.; Kull, Christian A.; Michelle, Mack; Moritz, Max A.; Pyne, Stephen; Roos, Christopher I.; Scott, Andrew C.; Sodhi, Navjot S.; Swetnam, Thomas W.

    2011-01-01

    Humans and their ancestors are unique in being a fire-making species, but 'natural' (i.e. independent of humans) fires have an ancient, geological history on Earth. Natural fires have influenced biological evolution and global biogeochemical cycles, making fire integral to the functioning of some biomes. Globally, debate rages about the impact on ecosystems of prehistoric human-set fires, with views ranging from catastrophic to negligible. Understanding of the diversity of human fire regimes on Earth in the past, present and future remains rudimentary. It remains uncertain how humans have caused a departure from 'natural' background levels that vary with climate change. Available evidence shows that modern humans can increase or decrease background levels of natural fire activity by clearing forests, promoting grazing, dispersing plants, altering ignition patterns and actively suppressing fires, thereby causing substantial ecosystem changes and loss of biodiversity. Some of these contemporary fire regimes cause substantial economic disruptions owing to the destruction of infrastructure, degradation of ecosystem services, loss of life, and smoke-related health effects. These episodic disasters help frame negative public attitudes towards landscape fires, despite the need for burning to sustain some ecosystems. Greenhouse gas-induced warming and changes in the hydrological cycle may increase the occurrence of large, severe fires, with potentially significant feedbacks to the Earth system. Improved understanding of human fire regimes demands: (1) better data on past and current human influences on fire regimes to enable global comparative analyses, (2) a greater understanding of different cultural traditions of landscape burning and their positive and negative social, economic and ecological effects, and (3) more realistic representations of anthropogenic fire in global vegetation and climate change models. We provide an historical framework to promote understanding

  10. The human dimension of fire regimes on Earth.

    PubMed

    Bowman, David M J S; Balch, Jennifer; Artaxo, Paulo; Bond, William J; Cochrane, Mark A; D'Antonio, Carla M; Defries, Ruth; Johnston, Fay H; Keeley, Jon E; Krawchuk, Meg A; Kull, Christian A; Mack, Michelle; Moritz, Max A; Pyne, Stephen; Roos, Christopher I; Scott, Andrew C; Sodhi, Navjot S; Swetnam, Thomas W; Whittaker, Robert

    2011-12-01

    Humans and their ancestors are unique in being a fire-making species, but 'natural' (i.e. independent of humans) fires have an ancient, geological history on Earth. Natural fires have influenced biological evolution and global biogeochemical cycles, making fire integral to the functioning of some biomes. Globally, debate rages about the impact on ecosystems of prehistoric human-set fires, with views ranging from catastrophic to negligible. Understanding of the diversity of human fire regimes on Earth in the past, present and future remains rudimentary. It remains uncertain how humans have caused a departure from 'natural' background levels that vary with climate change. Available evidence shows that modern humans can increase or decrease background levels of natural fire activity by clearing forests, promoting grazing, dispersing plants, altering ignition patterns and actively suppressing fires, thereby causing substantial ecosystem changes and loss of biodiversity. Some of these contemporary fire regimes cause substantial economic disruptions owing to the destruction of infrastructure, degradation of ecosystem services, loss of life, and smoke-related health effects. These episodic disasters help frame negative public attitudes towards landscape fires, despite the need for burning to sustain some ecosystems. Greenhouse gas-induced warming and changes in the hydrological cycle may increase the occurrence of large, severe fires, with potentially significant feedbacks to the Earth system. Improved understanding of human fire regimes demands: (1) better data on past and current human influences on fire regimes to enable global comparative analyses, (2) a greater understanding of different cultural traditions of landscape burning and their positive and negative social, economic and ecological effects, and (3) more realistic representations of anthropogenic fire in global vegetation and climate change models. We provide an historical framework to promote understanding

  11. The human dimension of fire regimes on Earth.

    PubMed

    Bowman, David M J S; Balch, Jennifer; Artaxo, Paulo; Bond, William J; Cochrane, Mark A; D'Antonio, Carla M; Defries, Ruth; Johnston, Fay H; Keeley, Jon E; Krawchuk, Meg A; Kull, Christian A; Mack, Michelle; Moritz, Max A; Pyne, Stephen; Roos, Christopher I; Scott, Andrew C; Sodhi, Navjot S; Swetnam, Thomas W; Whittaker, Robert

    2011-12-01

    Humans and their ancestors are unique in being a fire-making species, but 'natural' (i.e. independent of humans) fires have an ancient, geological history on Earth. Natural fires have influenced biological evolution and global biogeochemical cycles, making fire integral to the functioning of some biomes. Globally, debate rages about the impact on ecosystems of prehistoric human-set fires, with views ranging from catastrophic to negligible. Understanding of the diversity of human fire regimes on Earth in the past, present and future remains rudimentary. It remains uncertain how humans have caused a departure from 'natural' background levels that vary with climate change. Available evidence shows that modern humans can increase or decrease background levels of natural fire activity by clearing forests, promoting grazing, dispersing plants, altering ignition patterns and actively suppressing fires, thereby causing substantial ecosystem changes and loss of biodiversity. Some of these contemporary fire regimes cause substantial economic disruptions owing to the destruction of infrastructure, degradation of ecosystem services, loss of life, and smoke-related health effects. These episodic disasters help frame negative public attitudes towards landscape fires, despite the need for burning to sustain some ecosystems. Greenhouse gas-induced warming and changes in the hydrological cycle may increase the occurrence of large, severe fires, with potentially significant feedbacks to the Earth system. Improved understanding of human fire regimes demands: (1) better data on past and current human influences on fire regimes to enable global comparative analyses, (2) a greater understanding of different cultural traditions of landscape burning and their positive and negative social, economic and ecological effects, and (3) more realistic representations of anthropogenic fire in global vegetation and climate change models. We provide an historical framework to promote understanding

  12. Geographical factors affecting variability of precipitation regime in Iran

    NASA Astrophysics Data System (ADS)

    Sabziparvar, A. A.; Movahedi, S.; Asakereh, H.; Maryanaji, Z.; Masoodian, S. A.

    2015-04-01

    This study compares the precipitation regimes by using harmonic analysis during the last four decades (1965-2004). We used the measured precipitation data from 428 rain-gauge sites and weather stations distributed across Iran by applying 15 × 15 km spatial grids to generate the interpolated data. Data validations were carried out by statistical tests. In this study, first three harmonics of precipitation variances were evaluated. Variability of precipitation regime was explored by using three harmonic analysis methods. In addition, the effect of geographical factors (GF) (site elevation, latitude, and longitude) affecting the precipitation regime (P) was verified by multivariate regression method. The resulted regression equation between P and GF for spring showed the highest correlation coefficient ( r = 0.79). For other seasons, r was lower than for spring and varied between 0.26 (summer) to 0.58 (autumn). Analysis of the first harmonic proved that the main precipitation regime in Iran tends to concentrate in one specific season (winter) as a result of large-scale Mediterranean systems passing over the country. In other words, the first harmonic is able to explain most of the precipitation variations which are caused by large-scale atmospheric circulation. For all the three harmonics, variances of precipitation were mainly a function of the geographical factors. This effect was more evident in the third harmonic; in such a way that increasing the latitudes caused higher precipitation variance. This means that the precipitation regime in northern sites is more sensitive to the local factors than those of southern sites. The results of this research can be used for reliable estimation of precipitation in ungauged sites.

  13. Vegetation management with fire modifies peatland soil thermal regime.

    PubMed

    Brown, Lee E; Palmer, Sheila M; Johnston, Kerrylyn; Holden, Joseph

    2015-05-01

    Vegetation removal with fire can alter the thermal regime of the land surface, leading to significant changes in biogeochemistry (e.g. carbon cycling) and soil hydrology. In the UK, large expanses of carbon-rich upland environments are managed to encourage increased abundance of red grouse (Lagopus lagopus scotica) by rotational burning of shrub vegetation. To date, though, there has not been any consideration of whether prescribed vegetation burning on peatlands modifies the thermal regime of the soil mass in the years after fire. In this study thermal regime was monitored across 12 burned peatland soil plots over an 18-month period, with the aim of (i) quantifying thermal dynamics between burned plots of different ages (from <2 to 15 + years post burning), and (ii) developing statistical models to determine the magnitude of thermal change caused by vegetation management. Compared to plots burned 15 + years previously, plots recently burned (<2-4 years) showed higher mean, maximum and range of soil temperatures, and lower minima. Statistical models (generalised least square regression) were developed to predict daily mean and maximum soil temperature in plots burned 15 + years prior to the study. These models were then applied to predict temperatures of plots burned 2, 4 and 7 years previously, with significant deviations from predicted temperatures illustrating the magnitude of burn management effects. Temperatures measured in soil plots burned <2 years previously showed significant statistical disturbances from model predictions, reaching +6.2 °C for daily mean temperatures and +19.6 °C for daily maxima. Soil temperatures in plots burnt 7 years previously were most similar to plots burned 15 + years ago indicating the potential for soil temperatures to recover as vegetation regrows. Our findings that prescribed peatland vegetation burning alters soil thermal regime should provide an impetus for further research to understand the consequences of thermal regime

  14. Quantifying Floods of a Flood Regime in Space and Time

    NASA Astrophysics Data System (ADS)

    Whipple, A. A.; Fleenor, W. E.; Viers, J. H.

    2015-12-01

    Interaction between a flood hydrograph and floodplain topography results in spatially and temporally variable conditions important for ecosystem process and function. Individual floods whose frequency and dimensionality comprise a river's flood regime contribute to that variability and in aggregate are important drivers of floodplain ecosystems. Across the globe, water management actions, land use changes as well as hydroclimatic change associated with climate change have profoundly affected natural flood regimes and their expression within the floodplain landscape. Homogenization of riverscapes has degraded once highly diverse and productive ecosystems. Improved understanding of the range of flood conditions and spatial variability within floodplains, or hydrospatial conditions, is needed to improve water and land management and restoration activities to support the variable conditions under which species adapted. This research quantifies the flood regime of a floodplain site undergoing restoration through levee breaching along the lower Cosumnes River of California. One of the few lowland alluvial rivers of California with an unregulated hydrograph and regular floodplain connectivity, the Cosumnes River provides a useful test-bed for exploring river-floodplain interaction. Representative floods of the Cosumnes River are selected from previously-established flood types comprising the flood regime and applied within a 2D hydrodynamic model representing the floodplain restoration site. Model output is analyzed and synthesized to quantify and compare conditions in space and time, using metrics such as depth and velocity. This research establishes methods for quantifying a flood regime's floodplain inundation characteristics, illustrates the role of flow variability and landscape complexity in producing heterogeneous floodplain conditions, and suggests important implications for managing more ecologically functional floodplains.

  15. Numerical simulation of flows from free molecular regime to continuum regime by a DVM with streaming and collision processes

    NASA Astrophysics Data System (ADS)

    Yang, L. M.; Shu, C.; Wu, J.; Wang, Y.

    2016-02-01

    A discrete velocity method (DVM) with streaming and collision processes is presented in this work for simulation of flows from free molecular regime to continuum regime. The present scheme can be considered as a semi-Lagrangian like scheme. At first, we follow the conventional DVM to discretize the phase velocity space by a number of discrete velocities. Then, for each discrete velocity, the kinetic equation with BGK-Shakhov model is integrated in space and time within one time step. As a result, a simple algebraic formulation can be obtained, and its solution can be marched in time by the streaming and collision processes. However, differently from the conventional semi-Lagrangian scheme, the present scheme uses the MUSCL approach with van Albada limiter in the process of reconstructing the distribution function at the surrounding points of the cell center, and the transport distance is controlled in order to avoid extrapolation. This makes the present scheme be capable of simulating the hypersonic rarefied flows. In addition, as compared to the unified gas kinetic scheme (UGKS), the present scheme is simpler and easier for implementation. Thus, the computational efficiency can be improved accordingly. To validate the proposed numerical scheme, test examples from free molecular regime to continuum regime are simulated. Numerical results showed that the present scheme can predict the flow properties accurately even for hypersonic rarefied flows.

  16. Stochastic Parametrisations and Regime Behaviour of Atmospheric Models

    NASA Astrophysics Data System (ADS)

    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

  17. Scalable quantum memory in the ultrastrong coupling regime.

    PubMed

    Kyaw, T H; Felicetti, S; Romero, G; Solano, E; Kwek, L-C

    2015-01-01

    Circuit quantum electrodynamics, consisting of superconducting artificial atoms coupled to on-chip resonators, represents a prime candidate to implement the scalable quantum computing architecture because of the presence of good tunability and controllability. Furthermore, recent advances have pushed the technology towards the ultrastrong coupling regime of light-matter interaction, where the qubit-resonator coupling strength reaches a considerable fraction of the resonator frequency. Here, we propose a qubit-resonator system operating in that regime, as a quantum memory device and study the storage and retrieval of quantum information in and from the Z2 parity-protected quantum memory, within experimentally feasible schemes. We are also convinced that our proposal might pave a way to realize a scalable quantum random-access memory due to its fast storage and readout performances. PMID:25727251

  18. Periodic and aperiodic regimes in coupled dissipative chemical oscillators

    NASA Astrophysics Data System (ADS)

    Schreiber, Igor; Holodniok, Martin; Kubíček, Milan; Marek, Miloš

    1986-05-01

    Dynamic behavior of two identical reaction cells with linear symmetric coupling is studied in detail. The standard model reaction scheme "Brusselator" is used as the description of the kinetics. The uncoupled cells can exhibit either a stable stationary state or stable periodic oscillations. A number of stationary and periodic oscillatory patterns arise as a result of the coupling. A non-homogeneous spatio-temporal organization includes homoclinic and heteroclinic oscillations as well as chaotic regimes. Numerical continuation algorithms are used to determine the dependence of stationary and periodic solutions on parameters. Stable stationary nonhomogeneous regimes exist typically at intermediate levels of coupling intensity. The nonhomogeneous periodic solutions arise either via Hopf bifurcatios from stationary solutions or via period-doubling bifurcations from the homogeneous periodic solutions. The results obtained may serve as a standard for the study of the behavior of other coupled systems in which either a stable stationary state or stable oscillations exist in the single cell.

  19. Plasma regimes in the deep geomagnetic tail - ISEE 3

    NASA Technical Reports Server (NTRS)

    Bame, S. J.; Anderson, R. C.; Asbridge, J. R.; Baker, D. N.; Feldman, W. C.; Gosling, J. T.; Hones, E. W., Jr.; Mccomas, D. J.; Zwickl, R. D.

    1983-01-01

    The spacecraft remained close to or within a previously unexplored part of the distant (60-220 earth radii) geomagnetic tail nearly continuously from January 1 to March 30, 1983. Analysis of the data reveals that all of the plasma regimes identified previously with near-earth measurements (plasma sheet, low-latitude boundary layer, plasma mantle, lobe, and magnetosheath) remain recognizable in the distant tail. These regimes, however, are found to be intermingled in a more chaotic fashion than near the earth. Within the plasma sheet at approximately 200 earth radii, typical flow velocities are about 500 km/s tailward, considerably higher than in the near-earth plasma sheet. Earthward flow within the plasma sheet is observed occasionally, indicating the temporary presence of a neutral line beyond 220 earth radii. Also found are strong bidirectional electron anisotropies throughout much of the distant plasma sheet, boundary layer, and magnetosheath.

  20. The case for regime-based water quality standards

    USGS Publications Warehouse

    Poole, Geoffrey C.; Dunham, J.B.; Keenan, D.M.; Sauter, S.T.; McCullough, D.A.; Mebane, Christopher; Lockwood, Jeffrey C.; Essig, Don A.; Hicks, Mark P.; Sturdevant, Debra J.; Materna, E.J.; Spalding, M.; Risley, John; Deppman, Marianne

    2004-01-01

    Conventional water quality standards have been successful in reducing the concentration of toxic substances in US waters. However, conventional standards are based on simple thresholds and are therefore poorly structured to address human-caused imbalances in dynamic, natural water quality parameters, such as nutrients, sediment, and temperature. A more applicable type of water quality standarda??a a??regime standarda??a??would describe desirable distributions of conditions over space and time within a stream network. By mandating the protection and restoration of the aquatic ecosystem dynamics that are required to support beneficial uses in streams, well-designed regime standards would facilitate more effective strategies for management of natural water quality parameters.

  1. Modeling of drop breakup in the bag breakup regime

    NASA Astrophysics Data System (ADS)

    Wang, C.; Chang, S.; Wu, H.; Xu, J.

    2014-04-01

    Several analytic models for predicting the drop deformation and breakup have been developed over the last three decades, but modeling drop breakup in the bag-type regime is less reported. In this Letter, a breakup model has been proposed to predict the drop deformation length and breakup time in the bag-type breakup regime in a more accurate manner. In the present model, the drop deformation which is approximately as the displacement of the centre of mass (c. m.) along the axis located at the centre of the drop, and the movement of c. m. is obtained by solving the pressure balance equation. The effects of the drop deformation on the drop external aerodynamic force are considered in this model. Drop breakup occurs when the deformation length reaches the maximum value and the maximum deformation length is a function of Weber number. The performance and applicability of the proposed breakup model are tested against the published experimental data.

  2. Scalable quantum memory in the ultrastrong coupling regime.

    PubMed

    Kyaw, T H; Felicetti, S; Romero, G; Solano, E; Kwek, L-C

    2015-03-02

    Circuit quantum electrodynamics, consisting of superconducting artificial atoms coupled to on-chip resonators, represents a prime candidate to implement the scalable quantum computing architecture because of the presence of good tunability and controllability. Furthermore, recent advances have pushed the technology towards the ultrastrong coupling regime of light-matter interaction, where the qubit-resonator coupling strength reaches a considerable fraction of the resonator frequency. Here, we propose a qubit-resonator system operating in that regime, as a quantum memory device and study the storage and retrieval of quantum information in and from the Z2 parity-protected quantum memory, within experimentally feasible schemes. We are also convinced that our proposal might pave a way to realize a scalable quantum random-access memory due to its fast storage and readout performances.

  3. Disorder-assisted quantum transport in suboptimal decoherence regimes

    NASA Astrophysics Data System (ADS)

    Novo, Leonardo; Mohseni, Masoud; Omar, Yasser

    2016-01-01

    We investigate quantum transport in binary tree structures and in hypercubes for the disordered Frenkel-exciton Hamiltonian under pure dephasing noise. We compute the energy transport efficiency as a function of disorder and dephasing rates. We demonstrate that dephasing improves transport efficiency not only in the disordered case, but also in the ordered one. The maximal transport efficiency is obtained when the dephasing timescale matches the hopping timescale, which represent new examples of the Goldilocks principle at the quantum scale. Remarkably, we find that in weak dephasing regimes, away from optimal levels of environmental fluctuations, the average effect of increasing disorder is to improve the transport efficiency until an optimal value for disorder is reached. Our results suggest that rational design of the site energies statistical distributions could lead to better performances in transport systems at nanoscale when their natural environments are far from the optimal dephasing regime.

  4. Couette flow regimes with heat transfer in rarefied gas

    SciTech Connect

    Abramov, A. A. Butkovskii, A. V.

    2013-06-15

    Based on numerical solution of the Boltzmann equation by direct statistic simulation, the Couette flow with heat transfer is studied in a broad range of ratios of plate temperatures and Mach numbers of a moving plate. Flow regime classification by the form of the dependences of the energy flux and friction stress on the Knudsen number Kn is proposed. These dependences can be simultaneously monotonic and nonmonotonic and have maxima. Situations are possible in which the dependence of the energy flux transferred to a plate on Kn has a minimum, while the dependence of the friction stress is monotonic or even has a maximum. Also, regimes exist in which the dependence of the energy flux on Kn has a maximum, while the dependence of the friction stress is monotonic, and vice versa.

  5. A new plasma regime in the distant geomagnetic tail

    NASA Technical Reports Server (NTRS)

    Hardy, D. A.; Hills, H. K.; Freeman, J. W.

    1975-01-01

    Observations are reported of an extensive region of low-energy plasma particles (LEP) flowing antisunward along the ordered field lines in the lobes of the geomagnetic tail at lunar distances. The flow was detected by three suprathermal ion detectors deployed on the lunar surface during the Apollo 12, 14, and 15 missions. This particle regime is found to be similar to the 'boundary layer' and 'plasma mantle' observed at smaller geocentric distances and to an interior flow region parallel to the magnetopause in the dayside magnetosphere. It is located exterior to the plasma sheet across essentially the entire tail and adjacent to the magnetopause on both the dawn and dusk sides of the magnetosphere. Variations in the integral flux, temperature, and number density are described. It is suggested that this flow and the three similar regimes are simply connected along the inner surface of the magnetopause and are, in fact, the same phenomenon.

  6. Disorder-assisted quantum transport in suboptimal decoherence regimes

    PubMed Central

    Novo, Leonardo; Mohseni, Masoud; Omar, Yasser

    2016-01-01

    We investigate quantum transport in binary tree structures and in hypercubes for the disordered Frenkel-exciton Hamiltonian under pure dephasing noise. We compute the energy transport efficiency as a function of disorder and dephasing rates. We demonstrate that dephasing improves transport efficiency not only in the disordered case, but also in the ordered one. The maximal transport efficiency is obtained when the dephasing timescale matches the hopping timescale, which represent new examples of the Goldilocks principle at the quantum scale. Remarkably, we find that in weak dephasing regimes, away from optimal levels of environmental fluctuations, the average effect of increasing disorder is to improve the transport efficiency until an optimal value for disorder is reached. Our results suggest that rational design of the site energies statistical distributions could lead to better performances in transport systems at nanoscale when their natural environments are far from the optimal dephasing regime. PMID:26726133

  7. When do jammed sphere packings have a valid linear regime?

    NASA Astrophysics Data System (ADS)

    Goodrich, Carl; Liu, Andrea; Nagel, Sidney

    2014-03-01

    The physics of jamming can be studied in its purest form in packings of soft spheres at zero temperature. One of the successes of this approach is that bulk material properties, such as the elastic moduli or density of normal modes, can be predicted solely from the distance of the system to the jamming transition. Such properties are both defined and measured in the linear-response regime. It is thus tacitly assumed that the harmonic approximation to the local energy landscape can capture the meaningful physics, and it is therefore essential to delineate when this assumption is valid. We will examine the regime of validity of the harmonic approximation in jammed sphere packings as a function of system size and density. We will also discuss the crossover from linear response of the zero-temperature jammed solid to thermal behavior at nonzero temperatures.

  8. Computer Language Choices in Arms Control and Nonproliferation Regimes

    SciTech Connect

    White, G K

    2005-06-10

    The U.S. and Russian Federation continue to make substantive progress in the arms control and nonproliferation transparency regimes. We are moving toward an implementation choice for creating radiation measurement systems that are transparent in both their design and in their implementation. In particular, the choice of a programming language to write software for such regimes can decrease or significantly increase the costs of authentication. In this paper, we compare procedural languages with object-oriented languages. In particular, we examine the C and C++ languages; we compare language features, code generation, implementation details, and executable size and demonstrate how these attributes aid or hinder authentication and backdoor threats. We show that programs in lower level, procedural languages are more easily authenticated than are object-oriented ones. Potential tools and methods for authentication are covered. Possible mitigations are suggested for using object-oriented programming languages.

  9. Nondiffusive transport regimes for suprathermal ions in turbulent plasmas

    NASA Astrophysics Data System (ADS)

    Bovet, A.; Fasoli, A.; Ricci, P.; Furno, I.; Gustafson, K.

    2015-04-01

    The understanding of the transport of suprathermal ions in the presence of turbulence is important for fusion plasmas in the burning regime that will characterize reactors, and for space plasmas to understand the physics of particle acceleration. Here, three-dimensional measurements of a suprathermal ion beam in the toroidal plasma device TORPEX are presented. These measurements demonstrate, in a turbulent plasma, the existence of subdiffusive and superdiffusive transport of suprathermal ions, depending on their energy. This result stems from the unprecedented combination of uniquely resolved measurements and first-principles numerical simulations that reveal the mechanisms responsible for the nondiffusive transport. The transport regime is determined by the interaction of the suprathermal ion orbits with the turbulent plasma dynamics, and is strongly affected by the ratio of the suprathermal ion energy to the background plasma temperature.

  10. On the heat capacity of elements in WMD regime

    NASA Astrophysics Data System (ADS)

    Hamel, Sebatien

    2014-03-01

    Once thought to get simpler with increasing pressure, elemental systems have been discovered to exhibit complex structures and multiple phases at high pressure. For carbon, QMD/PIMC simulations have been performed and the results are guiding alternative modelling methodologies for constructing a carbon equation-of-state covering the warm dense matter regime. One of the main results of our new QMD/PIMC carbon equation of state is that the decay of the ion-thermal specific heat with temperature is much faster than previously expected. An important question is whether this is only found in carbon and not other element. In this presentation, based on QMD calculations for several elements, we explore trends in the transition from condensed matter to warm dense matter regime.

  11. Supercontinuum pulse shaping in the few-cycle regime.

    PubMed

    Hagemann, Franz; Gause, Oliver; Wöste, Ludger; Siebert, Torsten

    2013-03-11

    The synthesis of nearly arbitrary supercontinuum pulse forms is demonstrated with sub-pulse structures that maintain a temporal resolution in the few-cycle regime. Spectral broadening of the 35 fs input pulses to supercontinuum bandwidths is attained in a controlled two-stage sequential filamentation in air at atmospheric pressure, facilitating a homogeneous power density over the full spectral envelope in the visible to near infrared spectral range. Only standard optics and a liquid crystal spatial light modulator (LC-SLM) are employed for achieving pulse compression to the sub 5 fs regime with pulse energies of up to 60 μJ and a peak power of 12 GW. This constitutes the starting point for further pulse form synthesis via phase modulation within the sampling limit of the pulse shaper. Transient grating frequency-resolved optical gating (TG-FROG) allows for the characterization of pulse forms that extend over several hundred femtoseconds with few-cycle substructures. PMID:23482125

  12. Giant magnetoresistance in the variable-range hopping regime

    SciTech Connect

    Ioffe, L. B.; Spivak, B. Z.

    2013-09-15

    We predict the universal power-law dependence of the localization length on the magnetic field in the strongly localized regime. This effect is due to the orbital quantum interference. Physically, this dependence shows up in an anomalously large negative magnetoresistance in the hopping regime. The reason for the universality is that the problem of the electron tunneling in a random media belongs to the same universality class as the directed polymer problem even in the case of wave functions of random sign. We present numerical simulations that prove this conjecture. We discuss the existing experiments that show anomalously large magnetoresistance. We also discuss the role of localized spins in real materials and the spin polarizing effect of the magnetic field.

  13. The single-channel regime of transport through random media

    PubMed Central

    Peña, A.; Girschik, A.; Libisch, F.; Rotter, S.; Chabanov, A. A.

    2014-01-01

    The propagation of light through samples with random inhomogeneities can be described by way of transmission eigenchannels, which connect incoming and outgoing external propagating modes. Although the detailed structure of a disordered sample can generally not be fully specified, these transmission eigenchannels can nonetheless be successfully controlled and used for focusing and imaging light through random media. Here we demonstrate that in deeply localized quasi-1D systems, the single dominant transmission eigenchannel is formed by an individual Anderson-localized mode or by a ‘necklace state’. In this single-channel regime, the disordered sample can be treated as an effective 1D system with a renormalized localization length, coupled through all the external modes to its surroundings. Using statistical criteria of the single-channel regime and pulsed excitations of the disordered samples allows us to identify long-lived localized modes and short-lived necklace states at long and short time delays, respectively. PMID:24663028

  14. Quantum Theory as a Critical Regime of Language Dynamics

    NASA Astrophysics Data System (ADS)

    Grinbaum, Alexei

    2015-10-01

    Some mathematical theories in physics justify their explanatory superiority over earlier formalisms by the clarity of their postulates. In particular, axiomatic reconstructions drive home the importance of the composition rule and the continuity assumption as two pillars of quantum theory. Our approach sits on these pillars and combines new mathematics with a testable prediction. If the observer is defined by a limit on string complexity, information dynamics leads to an emergent continuous model in the critical regime. Restricting it to a family of binary codes describing `bipartite systems,' we find strong evidence of an upper bound on bipartite correlations equal to 2.82537. This is measurably different from the Tsirelson bound. The Hilbert space formalism emerges from this mathematical investigation as an effective description of a fundamental discrete theory in the critical regime.

  15. Steady state plasma operation in RF dominated regimes on EAST

    SciTech Connect

    Zhang, X. J.; Zhao, Y. P.; Gong, X. Z.; Hu, C. D.; Liu, F. K.; Hu, L. Q.; Wan, B. N. Li, J. G.

    2015-12-10

    Significant progress has recently been made on EAST in the 2014 campaign, including the enhanced CW H&CD system over 20MW heating power (LHCD, ICRH and NBI), more than 70 diagnostics, ITER-like W-monoblock on upper divertor, two inner cryo-pumps and RMP coils, enabling EAST to investigate long pulse H mode operation with dominant electron heating and low torque to address the critical issues for ITER. H-mode plasmas were achieved by new H&CD system or 4.6GHz LHCD alone for the first time. Long pulse high performance H mode has been obtained by LHCD alone up to 28s at H{sub 98}∼1.2 or by combing of ICRH and LHCD, no or small ELM was found in RF plasmas, which is essential for steady state operation in the future Tokamak. Plasma operation in low collision regimes were implemented by new 4.6GHz LHCD with core Te∼4.5keV. The non-inductive scenarios with high performance at high bootstrap current fraction have been demonstrated in RF dominated regimes for long pulse operation. Near full non-inductive CD discharges have been achieved. In addition, effective heating and decoupling method under multi-transmitter for ICRF system were developed in this campaign, etc. EAST could be in operation with over 30MW CW heating and current drive power (LHCD ICRH NBI and ECRH), enhanced diagnostic capabilities and full actively-cooled metal wall from 2015. It will therefore allow to access new confinement regimes and to extend these regimes towards to steady state operation.

  16. Signature candidate of quantum chaos far from the semiclassical regime

    SciTech Connect

    Li, Shang-Bin Xu, Zhengyuan

    2014-03-15

    We numerically investigated the entanglement product in the simplest coupled kicked top model with the spin j = 1. Different from the dynamical pattern of entanglement in the semiclassical regime, two similar initial states may have discordant entanglement oscillations. A candidate of the quantum signature of this classical chaotic system was proposed. The potential antimonotonic relation between the rank correlation coefficient qualifying the concordant of two entanglement evolutions and the stationary entanglement was preliminarily revealed.

  17. Determination of flow-regime boundaries for cohesive particles

    SciTech Connect

    Knowlton, T.M.; Findlay, J.G.

    1992-01-01

    The overall objective of this program is the development of a hydrodynamic model to predict the choking/non-choking flow regime boundary of fine, cohesive (i.e., Geldart Group C) powders. Specific objectives are to: (1) Develop a two-dimensional hydrodynamic model that can be applied to cohesive solids. (2) Generate large-scale solids-flows data that will be used to verify the model.

  18. Cosmological probes of modified gravity: the nonlinear regime.

    PubMed

    Schmidt, Fabian

    2011-12-28

    We review the effects of modified gravity on large-scale structure in the nonlinear regime, focusing on f(R) gravity and the Dvali-Gabadadze-Porrati model, for which full N-body simulations have been performed. In particular, we discuss the abundance of massive halos, the nonlinear matter power spectrum and the dynamics within clusters and galaxies, with particular emphasis on the screening mechanisms present in these models. PMID:22084294

  19. The Thermal Regime Around Buried Submarine High-Voltage Cables

    NASA Astrophysics Data System (ADS)

    Emeana, C. J.; Dix, J.; Henstock, T.; Gernon, T.; Thompson, C.; Pilgrim, J.

    2015-12-01

    The expansion of offshore renewable energy infrastructure and the desire for "trans-continental shelf" power transmission, all require the use of submarine High Voltage (HV) cables. These cables have maximum operating surface temperatures of up to 70oC and are typically buried at depths of 1-2 m beneath the seabed, within the wide range of substrates found on the continental shelf. However, the thermal properties of near surface shelf sediments are poorly understood and this increases the uncertainty in determining the required cable current ratings, cable reliability and the potential effects on the sedimentary environments. We present temperature measurements from a 2D laboratory experiment, designed to represent a buried, submarine HV cable. We used a large (2.5 m-high) tank, filled with water-saturated ballotini and instrumented with 120 thermocouples, which measured the time-dependent 2D temperature distributions around the heat source. The experiments use a buried heat source to represent a series of realistic cable surface temperatures with the aim for identifying the thermal regimes generated within typical non-cohesive shelf sediments: coarse silt, fine sand and very coarse sand. The steady state heat flow regimes, and normalised and radial temperature distributions were assessed. Our results show that at temperatures up to 60°C above ambient, the thermal regimes are conductive for the coarse silt sediments and convective for the very coarse sand sediments even at 7°C above ambient. However, the heat flow pattern through the fine sand sediment shows a transition from conductive to convective heat flow at a temperature of approximately 20°C above ambient. These findings offer an important new understanding of the thermal regimes associated with submarine HV cables buried in different substrates and has huge impacts on cable ratings as the IEC 60287 standard only considers conductive heat flow as well as other potential near surface impacts.

  20. Idealized Simulations of Precipitation Regimes over Small Tropical Islands

    NASA Astrophysics Data System (ADS)

    Wang, S.; Sobel, A. H.

    2014-12-01

    Tropical islands are global focal points of convection. Observational studies have shown that precipitation over tropical islands is strongly regulated by their size and elevation, and by the large scale prevailing wind. To further develop physical understanding of convection over tropical islands, we perform a set of highly idealized simulations with uniform sea surface temperature to explore flow regimes around an idealized small island (~120 km wide) as a function of large scale wind speed and island elevation. In our simulations the domain as a whole is in radiative-convective equilibrium (RCE), which constrains the domain average precipitation. The island occupies a small part of the domain, so that significant precipitation variations over the island can occur, compensated by smaller anomalies over the larger surrounding area. Over flat islands, as we vary prevailing wind speed, the island experiences three distinct flow regimes: rainfall is greatly enhanced and a local symmetric circulation is formed in the time mean around the island when the prevailing large scale wind speed is small (0 m/s); but there is little rainfall enhancement when the wind speed is increased to a moderate value (~5 m/s). We interpret these two regimes as the shift of triggering mechanism of convection: thermally forced convection due to surface solar heating dominates when large scale wind is very weak, while mechanically forced convection is favored when the impinging wind is moderate. Further increase of the prevailing wind speed to large values leads to strong asymmetry in the windward and leeward side of island and its coastal area, likely due to gravity waves from flow passing over elevated diurnal heating. Topography has a quantitative impact, but does not alter the qualitative shift of flow regimes as a function of wind speed.

  1. 2D Melting of Plasma Crystals: Equilibrium and Nonequilibrium Regimes

    SciTech Connect

    Nosenko, V.; Zhdanov, S. K.; Ivlev, A. V.; Knapek, C. A.; Morfill, G. E.

    2009-07-03

    Comprehensive experimental investigations of melting in two-dimensional complex plasmas were carried out. Different experiments were performed in steady and unsteady heating regimes. We demonstrate an Arrhenius dependence of the defect concentration on the kinetic temperature in steady-state experiments, and show the evidence of metastable quenching in unsteady experiments, where the defect concentration follows a power-law temperature scaling. In all experiments, independent indicators suggest a grain-boundary-induced melting scenario.

  2. Optimal Ranking Regime analysis of TreeFlow dendrohydrological reconstructions

    NASA Astrophysics Data System (ADS)

    Mauget, S. A.

    2015-03-01

    The Optimal Ranking Regime (ORR) method was used to identify 6-100 year time windows containing significant ranking sequences in 55 western US streamflow reconstructions, and reconstructions of the level of the Great Salt Lake and San Francisco Bay salinity during 1500-2007. The method's ability to identify optimally significant and non-overlapping runs of low and high rankings allows it to re-express a reconstruction time series as a simplified sequence of regime segments marking intra- to multi-decadal (IMD) periods of low or high streamflow, lake level, or salinity. Those ORR sequences, referred to here as Z lines, can be plotted to identify consistent regime patterns in the analysis of numerous reconstructions. The Z lines for the 57 reconstructions evaluated here show a common pattern of IMD cycles of drought and pluvial periods during the late 16th and 17th centuries, a relatively dormant period during the 18th century, and the reappearance of alternating dry and wet IMD periods during the 19th and early 20th centuries. Although this pattern suggests the possibility of similarly active and inactive oceanic modes in the North Pacific and North Atlantic, such centennial-scale patterns are not evident in the ORR analyses of reconstructed Pacific Decadal Oscillation (PDO), El Niño-Southern Oscillation, and North Atlantic seas-surface temperature variation. But given the inconsistency in the analyses of four PDO reconstructions the possible role of centennial-scale oceanic mechanisms is uncertain. In future research the ORR method might be applied to climate reconstructions around the Pacific Basin to try to resolve this uncertainty. Given its ability to compare regime patterns in climate reconstructions derived using different methods and proxies, the method may also be used in future research to evaluate long-term regional temperature reconstructions.

  3. Optimal ranking regime analysis of TreeFlow dendrohydrological reconstructions

    NASA Astrophysics Data System (ADS)

    Mauget, S. A.

    2015-08-01

    The optimal ranking regime (ORR) method was used to identify 6-100-year time windows containing significant ranking sequences in 55 western US streamflow reconstructions, and reconstructions of the level of the Great Salt Lake and San Francisco Bay salinity during 1500-2007. The method's ability to identify optimally significant and non-overlapping runs of low- and high-rankings allows it to re-express a reconstruction time series as a simplified sequence of regime segments marking intra- to multi-decadal (IMD) periods of low or high streamflow, lake level, and salinity. Those ORR sequences, referred to here as Z-lines, can be plotted to identify consistent regime patterns in the analysis of numerous reconstructions. The Z-lines for the 57 reconstructions evaluated here show a common pattern of IMD cycles of drought and pluvial periods during the late 16th and 17th centuries, a relatively dormant period during the 18th century, and the reappearance of alternating dry and wet IMD periods during the 19th and early 20th centuries. Although this pattern suggests the possibility of similarly active and inactive oceanic modes in the North Pacific and North Atlantic, such centennial-scale patterns are not evident in the ORR analyses of reconstructed Pacific Decadal Oscillation (PDO), El Niño-Southern Oscillation, and North Atlantic sea-surface temperature variation. However, given the inconsistency in the analyses of four PDO reconstructions, the possible role of centennial-scale oceanic mechanisms is uncertain. In future research the ORR method might be applied to climate reconstructions around the Pacific Basin to try to resolve this uncertainty. Given its ability to compare regime patterns in climate reconstructions derived using different methods and proxies, the method may also be used in future research to evaluate long-term regional temperature reconstructions.

  4. Plasma regimes in high power pulsed magnetron sputtering

    NASA Astrophysics Data System (ADS)

    de Los Arcos, Teresa

    2013-09-01

    High Power Pulsed Magnetron Sputtering (HPPMS) is a relatively recent variation of magnetron sputtering where high power is applied to the magnetron in short pulses. The result is the formation of dense transient plasmas with a high fraction of ionized species, ideally leading to better control of film growth through substrate bias. However, the broad range of experimental conditions accessible in pulsed discharges results in bewildering variations in current and voltage pulse shapes, pulse power densities, etc, which represent different discharge behaviors, making it difficult to identify relevant deposition conditions. The complexity of the plasma dynamics is evident. Within each pulse, plasma characteristics such as plasma composition, density, gas rarefaction, spatial distribution, degree of self-sputtering, etc. vary with time. A recent development has been the discovery that the plasma emission can self-organize into well-defined regions of high and low plasma emissivity above the racetrack (spokes), which rotate in the direction given by the E ×B drift and that significantly influence the transport mechanisms in HPPMS. One seemingly universal characteristic of HPPMS plasmas is the existence of well defined plasma regimes for different power ranges. These regimes are clearly differentiated in terms of plasma conductivity, plasma composition and spatial plasma self-organization. We will discuss the global characteristics of these regimes in terms of current-voltage characteristics, energy-resolved QMS and OES analysis, and fast imaging. In particular we will discuss how the reorganization of the plasma emission into spokes is associated only to specific regimes of high plasma conductivity. We will also briefly discuss the role of the target in shaping the characteristics of the HPPMS plasma, since sputtering is a surface-driven process. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) within the framework of the SFB-TR87.

  5. Analytic expression for poloidal flow velocity in the banana regime

    SciTech Connect

    Taguchi, M.

    2013-01-15

    The poloidal flow velocity in the banana regime is calculated by improving the l = 1 approximation for the Fokker-Planck collision operator [M. Taguchi, Plasma Phys. Controlled Fusion 30, 1897 (1988)]. The obtained analytic expression for this flow, which can be used for general axisymmetric toroidal plasmas, agrees quite well with the recently calculated numerical results by Parker and Catto [Plasma Phys. Controlled Fusion 54, 085011 (2012)] in the full range of aspect ratio.

  6. MCNP/X TRANSPORT IN THE TABULAR REGIME

    SciTech Connect

    HUGHES, H. GRADY

    2007-01-08

    The authors review the transport capabilities of the MCNP and MCNPX Monte Carlo codes in the energy regimes in which tabular transport data are available. Giving special attention to neutron tables, they emphasize the measures taken to improve the treatment of a variety of difficult aspects of the transport problem, including unresolved resonances, thermal issues, and the availability of suitable cross sections sets. They also briefly touch on the current situation in regard to photon, electron, and proton transport tables.

  7. Far-from-equilibrium superconductor in fluctuational regime

    NASA Astrophysics Data System (ADS)

    Petković, A.; Chtchelkatchev, N. M.; Vinokur, V. M.

    2011-08-01

    We derive Ginzburg-Landau-type action for a two-dimensional disordered superconductor under far-from-equilibrium conditions in a fluctuational regime. Then, utilizing it, we calculate fluctuation-induced density of states and Maki-Thomson- and Aslamazov-Larkin-type contributions to the in-plane electrical conductivity. We apply our approach to a thin superconducting film sandwiched between a gate and a substrate, which have different temperatures and different electrochemical potentials.

  8. Nano-plasmonic antennas in the near infrared regime.

    PubMed

    Berkovitch, N; Ginzburg, P; Orenstein, M

    2012-02-22

    Plasmonic nano-antennas constitute a central research topic in current science and engineering with an enormous variety of potential applications. Here we review the recent progress in the niche of plasmonic nano-antennas operating in the near infrared part of the spectrum which is important for a variety of applications. Tuning of the resonance into the near infrared regime is emphasized in the perspectives of fabrication, measurement, modeling, and analytical treatments, concentrating on the vast recent achievements in these areas.

  9. Cascade frequency generation regime in an optical parametric oscillator

    SciTech Connect

    Kolker, D B; Dmitriev, Aleksandr K; Gorelik, P; Vong, Franko; Zondy, J J

    2009-05-31

    In a parametric oscillator of a special two-sectional design based on a lithium niobate periodic structure, a cascade frequency generation regime was observed in which a signal wave pumped a secondary parametric oscillator, producing secondary signal and idler waves. The secondary parametric oscillator can be tuned in a broad range of {approx}200 nm with respect to a fixed wavelength of the primary idler wave. (nonlinear optical phenomena)

  10. Simulated natural hydrologic regime of an intermountain playa conservation site

    USGS Publications Warehouse

    Sanderson, J.S.; Kotliar, N.B.; Steingraeber, D.A.; Browne, C.

    2008-01-01

    An intermountain playa wetland preserve in Colorado's San Luis Valley was studied to assess how its current hydrologic function compares to its natural hydrologic regime. Current hydrologic conditions were quantified, and on-site effects of off-site water use were assessed. A water-budget model was developed to simulate an unaltered (i.e., natural) hydrologic regime, and simulated natural conditions were compared to observed conditions. From 1998-2002, observed stream inflows accounted for ??? 80% of total annual water inputs. No ground water discharged to the wetland. Evapotranspiration (ET) accounted for ??? 69% of total annual water loss. Simulated natural conditions differed substantially from current altered conditions with respect to depth, variability, and frequency of flooding. During 1998-2002, observed monthly mean surface-water depth was 65% lower than under simulated natural conditions. Observed monthly variability in water depth range from 129% greater (May) to 100% less (September and October) than simulated. As observed, the wetland dried completely (i.e., was ephemeral) in all years; as simulated, the wetland was ephemeral in two of five years. For the period 1915-2002, the simulated wetland was inundated continuously for as long as 16 years and nine months. The large differences in observed and simulated surface-water dynamics resulted from differences between altered and simulated unaltered stream inflows. The maximum and minimum annual total stream inflows observed from 1998-2005 were 3.1 ?? 106 m3 and 0 m3, respectively, versus 15.5 ?? 106 m3 and 3.2 ?? 106 m3 under simulated natural conditions from 1915-2002. The maximum simulated inflow was 484% greater than observed. These data indicate that the current hydrologic regime of this intermountain playa differs significantly from its natural hydrologic regime, which has important implications for planning and assessing conservation success. ?? 2008, The Society of Wetland Scientists.

  11. Improving entanglement of two atoms in strong coupling regime

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Yang, Qing; Yang, Ming; Cao, Zhuoliang

    2016-03-01

    We consider a model of two identical atoms coupled to a single-mode cavity. When in atom-field strong coupling regime, the entanglement of the two atoms with spontaneous emission should be investigated beyond rotating-wave approximation (RWA). In order to improve the entanglement of the two atoms, some typical feedback based on quantum-jump are attempted to impose on the atoms. The result of numerical simulations shows that an appropriate feedback control can improve the entanglement.

  12. Investigations of the temperature regimes of the selective laser melting

    NASA Astrophysics Data System (ADS)

    Chivel, Yu.

    2012-06-01

    The principles of measuring the surface temperature of powder bed in the focal spot of the laser radiation while scanning the surface using galvoscanner with F-teta lens have been elaborated. Investigation of the melting of overhang layers has been conducted under full temperature monitoring. Temperature regimes of the selective laser melting process of the 3D object from steel 316L powder have been investigated.

  13. Statistical instability of barrier microdischarges operating in townsend regime

    SciTech Connect

    Nagorny, V. P.

    2007-01-15

    The dynamics of barrier microdischarges operating in a Townsend regime is studied analytically and via kinetic particle-in-cell/Monte Carlo simulations. It is shown that statistical fluctuations of the number of charged particles in the discharge gap strongly influence the dynamics of natural oscillations of the discharge current and may even lead to a disruption of the discharge. Analysis of the statistical effects based on a simple model is suggested. The role of external sources in stabilizing microdischarges is clarified.

  14. Supersonic regime of the Hall-magnetohydrodynamics resistive tearing instability

    SciTech Connect

    Ahedo, Eduardo; Ramos, Jesus J.

    2012-07-15

    An earlier analysis of the Hall-magnetohydrodynamics (MHD) tearing instability [E. Ahedo and J. J. Ramos, Plasma Phys. Controlled Fusion 51, 055018 (2009)] is extended to cover the regime where the growth rate becomes comparable or exceeds the sound frequency. Like in the previous subsonic work, a resistive, two-fluid Hall-MHD model with massless electrons and zero-Larmor-radius ions is adopted and a linear stability analysis about a force-free equilibrium in slab geometry is carried out. A salient feature of this supersonic regime is that the mode eigenfunctions become intrinsically complex, but the growth rate remains purely real. Even more interestingly, the dispersion relation remains of the same form as in the subsonic regime for any value of the instability Mach number, provided only that the ion skin depth is sufficiently small for the mode ion inertial layer width to be smaller than the macroscopic lengths, a generous bound that scales like a positive power of the Lundquist number.

  15. Idiosyncratic responses of high Arctic plants to changing snow regimes.

    PubMed

    Rumpf, Sabine B; Semenchuk, Philipp R; Dullinger, Stefan; Cooper, Elisabeth J

    2014-01-01

    The Arctic is one of the ecosystems most affected by climate change; in particular, winter temperatures and precipitation are predicted to increase with consequent changes to snow cover depth and duration. Whether the snow-free period will be shortened or prolonged depends on the extent and temporal patterns of the temperature and precipitation rise; resulting changes will likely affect plant growth with cascading effects throughout the ecosystem. We experimentally manipulated snow regimes using snow fences and shoveling and assessed aboveground size of eight common high arctic plant species weekly throughout the summer. We demonstrated that plant growth responded to snow regime, and that air temperature sum during the snow free period was the best predictor for plant size. The majority of our studied species showed periodic growth; increases in plant size stopped after certain cumulative temperatures were obtained. Plants in early snow-free treatments without additional spring warming were smaller than controls. Response to deeper snow with later melt-out varied between species and categorizing responses by growth forms or habitat associations did not reveal generic trends. We therefore stress the importance of examining responses at the species level, since generalized predictions of aboveground growth responses to changing snow regimes cannot be made.

  16. Warm inflation dynamics in the low temperature regime

    SciTech Connect

    Bastero-Gil, Mar; Berera, Arjun

    2007-08-15

    Warm inflation scenarios are studied with the dissipative coefficient computed in the equilibrium approximation. Use is made of the analytical expressions available in the low temperature regime with focus on the possibility of achieving strong dissipation within this approximation. Two different types of models are examined: monomial or equivalently chaotic type potentials, and hybrid like models where the energy density during inflation is dominated by the false vacuum. In both cases dissipation is shown to typically increase during inflation and bring the system into the strong dissipative regime. Observational consequences are explored for the amplitude of the primordial spectrum and the spectral index, which translate into constraints on the number of fields mediating the dissipative mechanism, and the number of light degrees of freedom produced during inflation. This paper furthers the foundational development of warm inflation dynamics from first principles quantum field theory by calculating conservative lower bound estimates on dissipative effects during inflation using the well established thermal equilibrium approximation. This approximation does not completely represent the actual physical system and earlier work has shown relaxing both the equilibrium and low temperature constraints can substantially enlarge the warm inflation regime, but these improvements still need further theoretical development.

  17. He-accreting white dwarfs: accretion regimes and final outcomes

    NASA Astrophysics Data System (ADS)

    Piersanti, L.; Tornambé, A.; Yungelson, L. R.

    2014-12-01

    The behaviour of carbon-oxygen (CO) white dwarfs (WDs) subject to direct helium accretion is extensively studied. We aim to analyse the thermal response of an accreting WD to mass deposition at different timescales. The analysis has been performed for initial WD masses and accretion rates in the range 0.60-1.02 M⊙ and 10-9-10-5 M⊙ yr-1, respectively. Thermal regimes in the parameter space MWD-dot{M}_He leading to formation of red-giant-like structures, steady burning of He, and mild, strong and dynamical flashes have been identified and the transition between these regimes has been studied in detail. In particular, the physical properties of WDs experiencing the He-flash accretion regime have been investigated to determine the mass retention efficiency as a function of the accretor total mass and accretion rate. We also discuss to what extent the building up of a He-rich layer via H burning could be described according to the behaviour of models accreting He-rich matter directly. Polynomial fits to the obtained results are provided for use in binary population synthesis computations. Several applications for close binary systems with He-rich donors and CO WD accretors are considered and the relevance of the results for interpreting He novae is discussed.

  18. Globalization, marine regime shifts and the Soviet Union

    PubMed Central

    Österblom, Henrik; Folke, Carl

    2015-01-01

    Regime shifts have been observed in marine ecosystems around the world, with climate and fishing suggested as major drivers of such shifts. The global and regional dynamics of the climate system have been studied in this context, and efforts to develop an analogous understanding of fishing activities are developing. Here, we investigate the timing of pelagic marine regime shifts in relation to the emergence of regional and global fishing activities of the Soviet Union. Our investigation of official catch statistics reflects that the Soviet Union was a major fishing actor in all large marine ecosystems where regime shifts have been documented, including in ecosystems where overfishing has been established as a key driver of these changes (in the Baltic and Black Seas and the Scotian Shelf). Globalization of Soviet Union fishing activities pushed exploitation to radically new levels and triggered regional and global governance responses for improved management. Since then, exploitation levels have remained and increased with new actors involved. Based on our exploratory work, we propose that a deeper understanding of the role of global fishing actors is central for improved management of marine ecosystems.

  19. Electron beam induced current in the high injection regime

    NASA Astrophysics Data System (ADS)

    Haney, Paul M.; Yoon, Heayoung P.; Koirala, Prakash; Collins, Robert W.; Zhitenev, Nikolai B.

    2015-07-01

    Electron beam induced current (EBIC) is a powerful technique which measures the charge collection efficiency of photovoltaics with sub-micron spatial resolution. The exciting electron beam results in a high generation rate density of electron-hole pairs, which may drive the system into nonlinear regimes. An analytic model is presented which describes the EBIC response when the total electron-hole pair generation rate exceeds the rate at which carriers are extracted by the photovoltaic cell, and charge accumulation and screening occur. The model provides a simple estimate of the onset of the high injection regime in terms of the material resistivity and thickness, and provides a straightforward way to predict the EBIC lineshape in the high injection regime. The model is verified by comparing its predictions to numerical simulations in one- and two-dimensions. Features of the experimental data, such as the magnitude and position of maximum collection efficiency versus electron beam current, are consistent with the three-dimensional model.

  20. Electron beam induced current in the high injection regime.

    PubMed

    Haney, Paul M; Yoon, Heayoung P; Koirala, Prakash; Collins, Robert W; Zhitenev, Nikolai B

    2015-07-24

    Electron beam induced current (EBIC) is a powerful technique which measures the charge collection efficiency of photovoltaics with sub-micron spatial resolution. The exciting electron beam results in a high generation rate density of electron-hole pairs, which may drive the system into nonlinear regimes. An analytic model is presented which describes the EBIC response when the total electron-hole pair generation rate exceeds the rate at which carriers are extracted by the photovoltaic cell, and charge accumulation and screening occur. The model provides a simple estimate of the onset of the high injection regime in terms of the material resistivity and thickness, and provides a straightforward way to predict the EBIC lineshape in the high injection regime. The model is verified by comparing its predictions to numerical simulations in one- and two-dimensions. Features of the experimental data, such as the magnitude and position of maximum collection efficiency versus electron beam current, are consistent with the three-dimensional model.