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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. 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.

  4. 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.

  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. Regulatory Effects of Urokinase on Mesenchymal Stromal Cell Migration, Proliferation, and Matrix Metalloproteinase Secretion.

    PubMed

    Beloglazova, I B; Zubkova, E S; Tsokolaeva, Z I; Stafeev, Yu S; Dergilev, K V; Ratner, E I; Shestakova, M V; Sukhareva, O Yu; Parfenova, E V; Men'shikov, M Yu

    2016-10-01

    We studied the effect of urokinase, its recombinant forms, and domain fragments on migration and proliferation of adipose tissue mesenchymal stromal cells (MSCs) and MMP secretion by these cells. Urokinase, but not its recombinant forms, slightly induced directed migration of MSCs. Spontaneous migration of MSCs increased under the action of urokinase or its isolated kringle domain. Migration induced by platelet-derived growth factor was inhibited by proteolytically inactive form of urokinase, the kringle domain, and blocking antibody to urokinase receptor. Urokinase, its proteolytically inactive form, and kringle domain produced no effect on MSC proliferation. In contrast to platelet-derived growth factor, all urokinase forms induced secretion of MMP-9 by MSCs.

  7. Regulation of urokinase by cellular receptors and inhibitors

    SciTech Connect

    Hebert, C.A.

    1989-01-01

    Several cell types display binding sites for {sup 125}I-urokinase 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. Using immunofluorescence double labeling, the author shows that the receptor-bound urokinase present on human foreskin fibroblasts and HT1080 human fibrosarcoma cells is colocalized with 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. He furthermore reports that neither EGF, TGF{beta} or PDGF significantly altered the shape or intensity of the receptor-bound urokinase clusters but that thrombin, at mitogenic doses, caused a disappearance of the urokinase strands and a loss or gross alteration of the underlying focal adhesion plaques, as indicated by immunofluorescence staining for vinculin and talin, and by interference reflection microscopy. These observations suggest that thrombin may be a unique effector of cell adhesion, shape and movement. He used a quantitative in vitro invasion assay to study the role of plasminogen activator inhibitors type 1 and 2 (PAI-1, PAI-2) and protease nexin (PN1) in basement membrane (BM) invasion by {sup 125}I-iododeoxyuridine-labeled HT 1080 cells. The results obtained showed that 5 {mu}g/ml of PAI-1, PAI-2 and PN1 preadsorbed to the BM completely blocked HT1080 invasion. On the contrary an anti-PAI-1 monoclonal antibody induced an approximately two-fold increase in invasion. {sup 125}I-fibrinogen was polymerized on the amnion BM and the fibrinolytic activity of the cells was measured under the invasion assay conditions by measuring the radioactivity in the culture medium at different time points.

  8. 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.

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

    PubMed

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

    1993-01-01

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

  10. 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.

  11. Reprogramming urokinase into an antibody-recruiting anticancer agent.

    PubMed

    Jakobsche, Charles E; McEnaney, Patrick J; Zhang, Andrew X; Spiegel, David A

    2012-02-17

    Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR). Urokinase-type plasminogen activator (uPA) and uPAR are overexpressed on the surfaces of a wide range of invasive cancer cells and are believed to contribute substantially to the migratory propensities of these cells. The key component of our approach is an antibody-recruiting molecule that targets the urokinase receptor (ARM-U). This bifunctional construct is formed by selectively, covalently attaching an antibody-binding small molecule to the active site of the urokinase enzyme. We demonstrate that ARM-U is capable of directing antibodies to the surfaces of target cancer cells and mediating both antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) against multiple human cancer cell lines. We believe that the reported strategy has the potential to inform novel treatment options for a variety of deadly, invasive cancers.

  12. Soluble Urokinase Receptor and Chronic Kidney Disease

    PubMed Central

    Hayek, Salim S.; Sever, Sanja; Ko, Yi-An; Trachtman, Howard; Awad, Mosaab; Wadhwani, Shikha; Altintas, Mehmet M.; Wei, Changli; Hotton, Anna L.; French, Audrey L.; Sperling, Laurence S.; Lerakis, Stamatios; Quyyumi, Arshed A.; Reiser, Jochen

    2015-01-01

    BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation

  13. Urokinase has direct catalytic activity against fibrinogen and renders it less clottable by thrombin.

    PubMed Central

    Weitz, J I; Leslie, B

    1990-01-01

    Recently, we demonstrated that tissue plasminogen activator directly releases fibrinopeptides A and B (FPA and FPB) from fibrinogen. The purpose of this study was to determine whether urokinase has similar activity. Incubation of urokinase with fibrinogen or heparinized plasma results in concentration-dependent FPB release unaccompanied by FPA cleavage. For equivalent amidolytic activity, high molecular weight urokinase releases twofold more FPB than the low molecular weight species. In contrast, prourokinase does not release FPB until activated to urokinase. Contaminating thrombin or plasma is not responsible for urokinase-mediated FPB release because this activity is unaccompanied by FPA or B beta 1-42 cleavage, and is unaffected by heparin, hirudin, a monospecific antibody against thrombin, aprotinin, or alpha 2-antiplasmin. FPB release reflects a direct action of urokinase on fibrinogen because release is completely inhibited by a monospecific antibody against the enzyme. Further, urokinase releases FPB from the FPB-containing substrate B beta 1-42, thus confirming its specificity for the B beta 14 (Arg)-B beta 15 (Gly) bond. In addition to FPB release, SDS-PAGE analysis of the time course of urokinase-mediated fibrinogenolysis indicates progressive proteolysis of both the A alpha- and B beta-chains of fibrinogen that occurs after FPB release is completed. As a consequence of urokinase-mediated fibrinogenolysis, there is progressive prolongation of the thrombin clotting time. These studies indicate that urokinase has direct catalytic activity against fibrinogen. By releasing FPB, a potent chemoattractant, and by rendering fibrinogen less clottable by thrombin, urokinase may participate in processes extending beyond fibrinolysis. Images PMID:2365816

  14. Human urokinase gene is located on the long arm of chromosome 10.

    PubMed Central

    Tripputi, P; Blasi, F; Verde, P; Cannizzaro, L A; Emanuel, B S; Croce, C M

    1985-01-01

    Urokinase is one of the two plasminogen activators that catalyze the conversion of inactive plasminogen to plasmin. By combining somatic cell genetics, in situ hybridization, and Southern hybridization, we localized the human urokinase gene on the distal third of the long arm (q24-qter) of chromosome 10. Images PMID:2989821

  15. How Biomechanical Improvements in Running Economy Could Break the 2-hour Marathon Barrier.

    PubMed

    Hoogkamer, Wouter; Kram, Rodger; Arellano, Christopher J

    2017-03-03

    A sub-2-hour marathon requires an average velocity (5.86 m/s) that is 2.5% faster than the current world record of 02:02:57 (5.72 m/s) and could be accomplished with a 2.7% reduction in the metabolic cost of running. Although supporting body weight comprises the majority of the metabolic cost of running, targeting the costs of forward propulsion and leg swing are the most promising strategies for reducing the metabolic cost of running and thus improving marathon running performance. Here, we calculate how much time could be saved by taking advantage of unconventional drafting strategies, a consistent tailwind, a downhill course, and specific running shoe design features while staying within the current International Association of Athletic Federations regulations for record purposes. Specifically, running in shoes that are 100 g lighter along with second-half scenarios of four runners alternately leading and drafting, or a tailwind of 6.0 m/s, combined with a 42-m elevation drop could result in a time well below the 2-hour marathon barrier.

  16. Intrapleural low-molecular-weight urokinase or tissue plasminogen activator versus single-chain urokinase in tetracycline-induced pleural loculation in rabbits.

    PubMed

    Idell, Steven; Azghani, Ali; Chen, Shande; Koenig, Kathy; Mazar, Andrew; Kodandapani, Lalitha; Bdeir, Khalil; Cines, Douglas; Kulikovskaya, Irina; Allen, Timothy

    2007-01-01

    The authors compared the ability of a single dose of the proenzyme single-chain urokinase (scuPA), low-molecular-weight urokinase, tissue plasminogen activator (tPA), or a mutant site-inactive scuPA to resolve intrapleural loculations at 72 to 96 hours after tetracycline-induced pleural injury in rabbits. Both scuPA and tPA reversed loculations at 96 hours after injury P < or = .001, whereas low-molecular-weight urokinase and the scuPA mutant were ineffective. scuPA and tPA generated inhibitor complexes, induced fibrinolytic activity, and quenched plasminogen activator-1 activity in pleural fluids. The authors conclude that scuPA reverses loculations as effectively as tPA at clinically applied intrapleural doses, whereas low-molecular-weight urokinase was ineffective.

  17. Urokinase immobilized on medical polymeric materials: fundamental and clinical studies.

    PubMed

    Ohshiro, T; Kosaki, G

    1980-02-01

    One of the methods of preparing an antithrombogenic material is to immobilize a fibrinolytic enzyme on the surface of a carrier. The clinical trial of such a material must be subject to not only a basic study on the quality of a carrier, the technique of immobilization, and the method of disinfection, but also an in vivo study on its antithrombotic effect. Reported herein is the evaluation of the fibrinolytic ability, at fundamental and clinical levels, of the urokinase that was immobilized on the surface of various polymeric materials. The results were favorable.

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

    PubMed

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

    1984-01-01

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

  19. Urokinase type plasminogen activator receptor expression in colorectal neoplasms

    PubMed Central

    Suzuki, S; Hayashi, Y; Wang, Y; Nakamura, T; Morita, Y; Kawasaki, K; Ohta, K; Aoyama, N; Kim, S; Itoh, H; Kuroda, Y; Doe, W

    1998-01-01

    Background—The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis. 
Aims—To study the involvement of uPAR in colorectal carcinogenesis. 
Methods—The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses. 
Results—uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes' stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes' stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver. 
Conclusions—Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer. 

 Keywords: urokinase type plasminogen activator receptor; colorectal adenoma; colorectal cancer; adenoma-carcinoma sequence PMID:9824607

  20. "An Imminent Sub 2-Hours Marathon is Unlikely: historical Trends of the Gender Gap in Running Events".

    PubMed

    Tucker, Ross; Santos-Concejero, Jordan

    2016-12-14

    The aim of the present study was to analyse men's and women's world records across the full range of running disciplines to contextualise the recent debate about the possibility of a sub-2 hour marathon. The average male-female gap is currently 11.2 ± 1.0% for all running events. However, reducing the marathon time to below two hours would produce a performance 12.9% (+1.7 SD) faster than the women's marathon record. This gap would be greater than all current World Record differences, and would also require a reversal of medium and long-term historical trends in the men's and women's record differences. We therefore conclude that on the basis of historical trends and known differences between men's and women's performances, the current women's World Record is not yet the equivalent of a sub-2 hour marathon and therefore, that an imminent sub-2 hour marathon is implausible.

  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. Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration.

    PubMed

    Kapustin, Alexander; Stepanova, Victoria; Aniol, Natalia; Cines, Douglas B; Poliakov, Alexei; Yarovoi, Serge; Lebedeva, Tatiana; Wait, Robin; Ryzhakov, Grigory; Parfyonova, Yelena; Gursky, Yaroslav; Yanagisawa, Hiromi; Minashkin, Mikhail; Beabealashvilli, Robert; Vorotnikov, Alexander; Bobik, Alex; Tkachuk, Vsevolod

    2012-04-15

    uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5-/-) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (Fbln(RGE/RGE) MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility.

  3. Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration

    PubMed Central

    Kapustin, Alexander; Stepanova, Victoria; Aniol, Natalia; Cines, Douglas B.; Poliakov, Alexei; Yarovoi, Serge; Lebedeva, Tatiana; Wait, Robin; Ryzhakov, Grigory; Parfyonova, Yelena; Gursky, Yaroslav; Yanagisawa, Hiromi; Minashkin, Mikhail; Beabealashvilli, Robert; Vorotnikov, Alexander; Bobik, Alex; Tkachuk, Vsevolod

    2015-01-01

    uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5−/−) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (FblnRGE/RGE MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+ -binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility. PMID:22280367

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

    PubMed Central

    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

  5. Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage.

    PubMed

    Tan, Qiang; Chen, Qianwei; Niu, Yin; Feng, Zhou; Li, Lin; Tao, Yihao; Tang, Jun; Yang, Liming; Guo, Jing; Feng, Hua; Zhu, Gang; Chen, Zhi

    2017-02-01

    OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor-κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH. CONCLUSIONS This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

  6. The Urokinase/Urokinase Receptor System in Mast Cells: Effects of its Functional Interaction with fMLF Receptors

    PubMed Central

    Rossi, Francesca Wanda; Prevete, Nella; Rivellese, Felice; Napolitano, Filomena; Montuori, Nunzia; Postiglione, Loredana; Selleri, Carmine; de Paulis, Amato

    2016-01-01

    Mast cell and basophils express the high affinity receptor for IgE (FcɛRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs). We investigated the expression of the uPA-uPAR system and its functional interaction with FPRs in human mast cells (MCs). Differently from basophils, MCs produced uPA that was able to induce their chemotaxis. Indeed, MCs also expressed uPAR, both in the intact and in a cleaved form (DII-DIII-uPAR) that can expose, at the N-terminus, the SRSRY sequence, able to interact with FPRs and to mediate cell chemotaxis. MCs also expressed mRNAs for FPRs that were functionally active; indeed, uPA and a soluble peptide (uPAR84–95), containing the SRSRY chemotactic sequence of uPAR and able to interact with FPRs, were able to induce MCs chemotaxis. Thus, uPA is a potent chemoattractant for MCs acting through the exposure of the chemotactic epitope of uPAR, that is an endogenous ligand for FPRs. The same mechanism could be involved in VEGF-A secretion by human MCs, also induced by uPA and uPAR84–95 stimulation. PMID:27896225

  7. Urokinase receptor modulates cellular and angiogenic responses in obstructive nephropathy.

    PubMed

    Zhang, Guoqiang; Kim, Heungsoo; Cai, Xiaohe; Lopez-Guisa, Jesus M; Carmeliet, Peter; Eddy, Allison A

    2003-05-01

    Interstitial cells have been implicated in the pathogenesis of renal fibrosis. Given that the urokinase receptor (uPAR) is known to play a role in cell adhesion, migration, and angiogenesis, the present study was designed to evaluate the role of uPAR in the regulation of the phenotypic composition of interstitial cells (macrophages, myofibroblasts, capillaries) in response to chronic renal injury. Groups of uPAR wild-type (+/+) and knockout (-/-) mice were investigated between 3 and 14 d after unilateral ureteral obstruction (UUO) or sham surgery (n = 8 mice per group). The density of F4/80+ interstitial macrophages (Mphi) was significantly lower in the -/- mice (3.3 +/- 0.4 versus 6.9 +/- 1.7% area at day 3 UUO; 10.8 +/- 1.6 versus 15.7 +/- 1.0% at day 14 UUO; -/- versus +/+). In contrast, in the -/- mice there were significantly more alpha smooth muscle actin (alphaSMA)-positive cells (12.9 +/- 3.2 versus 7.8 +/- 1.5% area at day 3 UUO; 21.0 +/- 4.7 versus 9.7 +/- 1.9% at day 14 UUO) and CD34-positive endothelial cells (8.4 +/- 1.9 versus 4.0 +/- 1.1% area at day 14 UUO). These differences were associated with significantly more interstitial fibrosis in the -/- mice based on Sirius red staining (4.6 +/- 0.9 versus 2.3 +/- 0.9% area at 14 d UUO). Absence of the uPAR scavenger receptor was associated with significantly greater accumulation of plasminogen activator inhibitor-1 protein (PAI-1) (20.5 +/- 3.5 versus 9.1 +/- 2.9% area, day 14 UUO) and vitronectin protein (2.4 +/- 1.1 versus 0.9 +/- 0.4% area, day 14 UUO). By immunostaining alphaSMA+ cells, CD34+ cells, vitronectin and PAI-1 co-localized to the same tubulointerstitial area. The number of apoptotic cells increased in response to UUO but was significantly higher in the -/- mice (2.0 +/- 0.2 versus 1.2 +/- 0.2 per 100 tubulointerstitial cells, day 14 UUO) while the number of proliferating cells was significantly lower in the uPAR-/- mice. These data suggest that uPAR deficiency suppresses renal Mphi

  8. Activity of urokinase diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored in glass or plastic syringes.

    PubMed

    Patel, J P; Tran, L T; Sinai, W J; Carr, L J

    1991-07-01

    The effects of the diluent, the container, the i.v. set, and the drug concentration on the adsorption of urokinase to i.v. administration systems were studied, along with the compatibility of urokinase with plastic and glass syringes. Solutions of urokinase 1500 and 5000 IU/mL in 0.9% sodium chloride injection and 5% dextrose injection in glass and polyvinyl chloride (PVC) containers were sampled at 2 and 30 minutes. Administration sets were attached to PVC containers containing the urokinase-5% dextrose injection solutions, and samples were collected at 90 and 150 minutes. Glass and polypropylene syringes containing urokinase 5000 IU/mL in 0.9% sodium chloride injection or 5% dextrose injection were sampled at 0, 4, 8, and 24 hours. Urokinase activity was measured by an in vitro clot lysis assay. No urokinase diluted in 0.9% sodium chloride injection adsorbed to glass or PVC containers. For urokinase 1500 IU/mL in 5% dextrose injection, a loss of 15% to 20% occurred almost instantaneously in PVC containers; additional losses to the infusion sets were minimal. However, for urokinase 5000 IU/mL in 5% dextrose injection, no losses were observed in the PVC systems. No drug loss to glass bottles was seen for urokinase 1500 or 5000 IU/mL in 5% dextrose injection. Urokinase potency remained constant in polypropylene and glass syringes for 24 hours. To minimize urokinase sorption to PVC containers, higher concentrations of urokinase diluted in 5% dextrose injection should be used, provided that clinical safety and efficacy are not compromised. The use of 0.9% sodium chloride injection as a diluent also prevents sorption losses.

  9. 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

  10. 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%.

  11. 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

  12. Induction of Brain Microvascular Endothelial Cell Urokinase Expression by Cryptococcus neoformans Facilitates Blood-Brain Barrier Invasion

    PubMed Central

    Stie, Jamal; Fox, Deborah

    2012-01-01

    The invasive ability of the blood-borne fungal pathogen Cryptococcus neoformans can be enhanced through interactions with host plasma components, such as plasminogen. Previously we showed by in vitro studies that plasminogen coats the surface of C. neoformans and is converted to the active serine protease, plasmin, by host plasminogen activators. Viable, but not formaldehyde- or sodium azide-killed, cryptococcal strains undergo brain microvascular endothelial cell-dependent plasminogen-to-plasmin activation, which results in enhanced, plasmin-dependent cryptococcal invasion of primary bovine brain microvascular endothelial cells and fungal ability to degrade plasmin substrates. In the present work, brain microvascular endothelial cells cultured with viable, but not killed, cryptococcal strains led to significant increases in both urokinase mRNA transcription and cell-associated urokinase protein expression. Soluble urokinase was also detected in conditioned medium from brain microvascular endothelial cells cultured with viable, but not killed, C. neoformans. Exposure of plasminogen pre-coated viable C. neoformans to conditioned medium from strain-matched brain microvascular endothelial cell-fungal co-cultures resulted in plasminogen-to-plasmin activation and plasmin-dependent cryptococcal invasion. siRNA-mediated silencing of urokinase gene expression or the use of specific inhibitors of urokinase activity abrogated both plasminogen-to-plasmin activation on C. neoformans and cryptococcal-brain microvascular endothelial cell invasion. Our results suggest that pathogen exploitation of the host urokinase-plasmin(ogen) system may contribute to C. neoformans virulence during invasive cryptococcosis. PMID:23145170

  13. Prophylaxis with urokinase in pediatric oncology patients with central venous catheters.

    PubMed

    Kalmanti, Maria; Germanakis, John; Stiakaki, Eftichia; Syfridaki, Cathrin; Christidou, Athanasia; Tsetis, Dimitris; Vardas, Panagiotis; Charisis, George

    2002-01-01

    This study evaluated the effects of urokinase in the prevention of central venous catheter (CVC)-related complications in children with malignancy. Fifteen patients with 16 CVCs (study group A) received an intraluminal application of urokinase (10,000 IU in each catheter lumen for 4 h) once a week. They were monitored prospectively with quantitative blood cultures and ultrasonography (color Doppler ultrasound of the great veins and echocardiography). The rate of complications was compared with that of 15 children with 19 CVCs without thromboprophylaxis, treated the previous significantly lower incidence of CVC dysfunction year (control group B). The authors found a wer incidence of CVC dysfunction (3/16 versus 13/19), no major thrombosis, fewer CVC-related bacteremias (2/16 versus 8/19), and a higher salvage of CVCs (1/16 versus 5/19 CVC removals due to persistent bacteremia) in the thromboprophylaxis group. Asymptomatic thrombosis rate was also lower (7/16 cases in group A versus 9/11 in group B when sonography was performed). No hemorrhagic complications were noted. Thromboprophylaxis with urokinase seems a safe and effective measure for reducing the rate of CVC-related complications.

  14. A cleavage-resistant urokinase plasminogen activator receptor exhibits dysregulated cell-surface clearance.

    PubMed

    Nieves, Evelyn C; Manchanda, Naveen

    2010-04-23

    Urokinase plasminogen activator receptor (u-PAR) binds urokinase plasminogen activator (u-PA) and participates in plasminogen activation in addition to modulating several cellular processes such as adhesion, proliferation, and migration. u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases. To elucidate the biological significance of receptor cleavage by u-PA, we engineered and expressed a two-chain urokinase plasminogen activator (tcu-PA) cleavage-resistant u-PAR (cr-u-PAR). This mutated receptor was similar to wild-type u-PAR in binding u-PA and initiating plasminogen activation. However, cr-u-PAR exhibited accelerated internalization and resurfacing due to direct association with the endocytic receptor alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein in the absence of the enzyme x inhibitor complex of tcu-PA and plasminogen activator inhibitor-1 (tcu-PA.PAI-1). cr-u-PAR-expressing cells had enhanced migration compared with wild-type u-PAR-expressing cells, and cr-u-PAR was less sensitive to chymotrypsin cleavage as compared with wt u-PAR. Our studies suggest that these mutations in the linker region result in a rearrangement within the cr-u-PAR structure that makes it resemble its ligand-bound form. This constitutively active variant may mimic highly glycosylated cleavage-resistant u-PAR expressed in certain highly malignant cancer-cells.

  15. 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.

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

    PubMed Central

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

    2013-01-01

    We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis. PMID:23730603

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

    PubMed

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

    2013-05-01

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

  18. 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

  19. 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

  20. Combined Low-Frequency Ultrasound and Urokinase-Containing Microbubbles in Treatment of Femoral Artery Thrombosis in a Rabbit Model

    PubMed Central

    Mu, Yuming

    2016-01-01

    This paper aims to study the thrombolytic effect of low-frequency ultrasound combined with targeted urokinase-containing microbubble contrast agents on treatment of thrombosis in rabbit femoral artery; and to determine the optimal combination of parameters for achieving thrombolysis in this model. A biotinylated-avidin method was used to prepare microbubble contrast agents carrying urokinase and Arg-Gly-Asp-Ser (RGDS) peptides. Following femoral artery thrombosis in New Zealand white rabbits, microbubble contrast agents were injected intravenously, and ultrasonic exposure was applied. A 3 × 2 × 2 factorial table was applied to categorize the experimental animals based on different levels of combination of ultrasonic frequencies (Factor A: 1.6 MHz, 2.2 MHz, 2.8 MHz), doses of urokinase (Factor B: 90,000 IU/Kg, 180,000 IU/Kg) and ultrasound exposure time (Factor C: 30 min, 60 min). A total of 72 experimental animals were randomly divided into 12 groups (n = 6/group). Doppler techniques were used to assess blood flow in the distal end of the thrombotic femoral artery during the 120 minutes thrombolysis experiment. The rate of recanalization following thrombolysis was calculated, and thrombolytic efficacy was evaluated and compared. The thrombolytic recanalization rate for all experimental subjects after thrombolytic therapy was 68.1%. The optimal parameters for thrombolysis were determined to be 1) an ultrasound frequency of 2.2 MHz and 2) a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 min vs. 60 min) had no significant effect on the thrombolytic effects. The combination of local low-frequency ultrasound radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2 MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 min or 60 min of ultrasound exposure had similar effects. PMID:28033371

  1. Intra-arterial urokinase for treatment of retrograde thrombosis following resection of an arteriovenous malformation. Case report.

    PubMed

    Sipos, E P; Kirsch, J R; Nauta, H J; Debrun, G; Ulatowski, J A; Bell, W R

    1992-06-01

    Retrograde thrombosis of feeding arteries is a potentially catastrophic complication occasionally reported following resection of arteriovenous malformations (AVM's). No successful therapy for this condition, which causes postoperative stroke, has previously been reported. A case of retrograde thrombosis of the left middle cerebral artery immediately following resection of a parietal AVM is reported in a patient with a retained intra-arterial catheter from preoperative embolization. The administration of urokinase within 4 hours of surgery resulted in dramatic clinical and angiographic improvement without hemorrhagic complications. While urokinase is considered highly experimental in this setting, this case demonstrates that thrombolytic agents should be viewed as therapeutic options worthy of further investigation.

  2. Geometry of GPPE binding to picrate and to the urokinase type plasminogen activator.

    PubMed

    Zesławska, Ewa; Stürzebecher, Jörg; Oleksyn, Barbara J

    2007-11-15

    Crystal structure of 2-(4-guanidynephenyl)-1-phenyl-ethanone (GPPE) in two different environments was determined in order to compare the binding geometry of these compound to a simple picrate anion and to protein, urokinase-type plasminogen activator (uPA), which may be treated as a target for anti-cancer drugs. It was shown that the conformation and the hydrogen-bonding formation by GPPE molecule are similar in both environments, but several important differences were discovered and described.

  3. Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer

    PubMed Central

    Montuori, Nunzia; Pesapane, Ada; Rossi, Francesca W; Giudice, Valentina; De Paulis, Amato; Selleri, Carmine; Ragno, Pia

    2016-01-01

    The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials. PMID:27896223

  4. 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.

  5. Intrapleural activation, processing, efficacy, and duration of protection of single-chain urokinase in evolving tetracycline-induced pleural injury in rabbits.

    PubMed

    Idell, Steven; Allen, Timothy; Chen, Shande; Koenig, Kathy; Mazar, Andrew; Azghani, Ali

    2007-01-01

    Intrapleural fibrinolysins have been used to treat pleural loculations. However, the efficacy of clinically available agents has recently been questioned, providing a rationale for investigation of new interventions. Single-chain urokinase plasminogen activator resists inhibition by serpins, and repeated, daily intrapleural administration of this agent prevents intrapleural loculation more effectively than complexes of this proenzyme with its receptor (Idell S, Mazar A, Cines D, Kuo A, Parry G, Gawlak S, Juarez J, Koenig K, Azghani A, Hadden W, McLarty J, Miller E. Am J Respir Crit Care Med 166: 920-926, 2002). Understanding of the protective mechanism and intrapleural processing remains unclear. We speculated that single-chain urokinase could induce sustained local fibrinolysis and protection by selective administration either before, during, or following loculation after pleural injury induced by tetracycline in rabbits. Enzymography, immunoassays, histology, immunohistochemistry, morphology, and morphometry were used to test the efficacy, duration of protective effect, and processing of single-chain urokinase. Intrapleural single chain urokinase prevented loculation at 72 h after injury (P < 0.01) if given either before or during adhesion formation and was converted to two-chain high-molecular-weight urokinase, which remained active for at least 24 h within pleural fluids. The effect was dose dependent, and established loculations at 72 h after tetracycline-induced injury were reversed at 96 h by single-dose treatment. Single-chain urokinase bound and saturated intrapleural plasminogen activator inhibitory (PAI)-1-like activity and urokinase-related immunoreactivity of the mesothelium was comparable in treatment or vehicle-control groups. Adhesions recurred by 2 wk after treatment with recurrence of excess local PAI activity. Single-chain urokinase induces sustained local fibrinolysis and reversibly prevents pleural loculation for up to 48 h after intrapleural

  6. Imaging of Prostate Cancer Using Urokinase-Type Plasminogen Activator Receptor PET.

    PubMed

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2017-04-01

    Urokinase-type plasminogen activator receptor (uPAR) overexpression is an important biomarker for aggressiveness in cancer including prostate cancer (PC) and provides independent clinical information in addition to prostate-specific antigen and Gleason score. This article focuses on uPAR PET as a new diagnostic and prognostic imaging biomarker in PC. Many preclinical uPAR-targeted PET imaging studies using AE105 in cancer models have been undertaken with promising results. A major breakthrough was obtained with the recent human translation of uPAR PET in using (64)Cu- and (68)Ga-labelled versions of AE105, respectively. Clinical results from patients with PC included in these studies are encouraging and support continuation with large-scale clinical trials.

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

    PubMed

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

    1990-01-01

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

  8. Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells

    PubMed Central

    1987-01-01

    Cellular migration is an essential component of invasive biological processes, many of which have been correlated with an increase in plasminogen activator production. Endothelial cell migration occurs in vivo during repair of vascular lesions and angiogenesis, and can be induced in vitro by wounding a confluent monolayer of cells. By combining the wounded monolayer model with a substrate overlay technique, we show that cells migrating from the edges of an experimental wound display an increase in urokinase-type plasminogen activator (uPA) activity, and that this activity reverts to background levels upon cessation of movement, when the wound has closed. Our results demonstrate a direct temporal relationship between endothelial cell migration and uPA activity, and suggest that induction of uPA activity is a component of the migratory process. PMID:3121633

  9. Monocyte-expressed urokinase inhibits vascular smooth muscle cell growth by activating Stat1.

    PubMed

    Kunigal, Sateesh; Kusch, Angelika; Tkachuk, Natalia; Tkachuk, Sergey; Jerke, Uwe; Haller, Hermann; Dumler, Inna

    2003-12-15

    After vascular injury, a remodeling process occurs that features leukocyte migration and infiltration. Loss of endothelial integrity allows the leukocytes to interact with vascular smooth muscle cells (VSMCs) and to elicit "marching orders"; however, the signaling processes are poorly understood. We found that human monocytes inhibit VSMC proliferation and induce a migratory potential. The monocytes signal the VSMCs through the urokinase-type plasminogen activator (uPA). The VSMC uPA receptor (uPAR) receives the signal and activates the transcription factor Stat1 that, in turn, mediates the antiproliferative effects. These results provide the first evidence that monocytes signal VSMCs by mechanisms involving the fibrinolytic system, and they imply an important link between the uPA/uPAR-related signaling machinery and human vascular disease.

  10. 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

  11. The urokinase receptor is required for human monocyte chemotaxis in vitro.

    PubMed Central

    Gyetko, M R; Todd, R F; Wilkinson, C C; Sitrin, R G

    1994-01-01

    Mononuclear phagocytes (Mphi) produce urokinase-type plasminogen activator (uPA) and also express a specific cell-surface receptor for urokinase, uPAR. The concomitant expression of these proteins provides a mechanism by which Mphi can degrade extracellular matrix proteins during directed cell migration. In this study, we sought to determine if uPAR plays a role in Mphi chemotaxis that is distinct from its role in matrix proteolysis. Exposing adherent monocytes to a chemotactic gradient causes plasma membrane uPAR to localize strongly to the leading edge of cell migration. Adherence alone or exposure to FMLP had no effect on uPAR expression. Using Boyden chamber chemotaxis assays, we demonstrate that treating mononuclear cells with an anti-uPAR mAb (either as an intact mAb or F[ab']2) ablates chemotaxis induced by FMLP and monocyte chemotactic peptide-1 (P < 0.001). Inactivating the catalytic activity of uPAR-bound uPA had no effect on chemotaxis. Similarly, blocking uPAR expression with an antisense oligonucleotide to uPAR completely ablates chemotaxis, but blocking uPA expression with an antisense oligonucleotide to uPA has a minimal effect. We therefore demonstrate that expression and unimpeded function of uPAR plays an obligate role in M phi chemotaxis by mechanisms that are largely independent of its ligand, uPA. Combined with its known role in mediating pericellular proteolysis, these observations demonstrate that uPAR is essential for both locomotion and traversing tissue barriers during M phi migration. Images PMID:8163642

  12. Intraventricular administration of urokinase as a novel therapeutic approach for communicating hydrocephalus.

    PubMed

    Feng, Zhou; Tan, Qiang; Tang, Jun; Li, Lin; Tao, Yihao; Chen, Yujie; Yang, Yunfeng; Luo, Chunxia; Feng, Hua; Zhu, Gang; Chen, Qianwei; Chen, Zhi

    2017-02-01

    Fibrosis of the subarachnoid space (SAS) after infection, inflammation, or hemorrhage can impair cerebrospinal fluid absorption and circulation, causing diffuse ventricular dilatation. In the present study, we tested the hypothesis that urokinase (also known as urokinase-type plasminogen activator [uPA]), a fibrinolytic agent, attenuates fibrosis and ventriculomegaly in a rat model of kaolin-induced communicating hydrocephalus and thus may have potential as a therapy for these conditions. Thirty microliters of sterile 25% kaolin suspension was injected into the basal cisterns of adult Sprague-Dawley rats to induce hydrocephalus, and 2 intraventricular injections of either uPA or vehicle (saline) were administered immediately and 3 days thereafter. Ventricular volumes were measured by magnetic resonance imaging (MRI) on days 3, 14, and 28 after kaolin injection. Fibrosis and reactive astrogliosis were evaluated on day 28 by immunofluorescence and Western blotting. Neurocognitive features were tested using the Morris water maze from days 23 to 28. MRI analysis demonstrated that kaolin administration successfully induced hydrocephalus in rats and that uPA treatment significantly attenuated ventricular enlargement. In addition, uPA inhibited the deposition of laminin and fibronectin, extracellular matrix molecules, in the SAS, attenuated gliosis, and improved learning and memory in kaolin-treated rats. Therefore, we concluded that uPA prevents the development of kaolin-induced communicating hydrocephalus by preventing the development of subarachnoid fibrosis and by eliciting improvements in neurocognition. The results of this study indicate that uPA may be a novel clinical therapy for communicating hydrocephalus.

  13. 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

  14. Participation of the urokinase-type plasminogen activator receptor (uPAR) in neutrophil transendothelial migration.

    PubMed

    Pliyev, Boris K; Antonova, Olga A; Menshikov, Mikhail

    2011-05-01

    The mechanisms underlying migration of neutrophils across endothelium are not completely understood. The urokinase-type plasminogen activator receptor (uPAR) plays a key role in neutrophil adhesion and migration. In the present study, we addressed whether uPAR regulates neutrophil transendothelial migration. We first showed that siRNA-mediated knockdown of uPAR in human umbilical vein endothelial cells (HUVECs) did not affect neutrophil migration across HUVEC monolayers indicating that endothelial uPAR does not regulate neutrophil transmigration. In contrast, the transmigration was significantly inhibited by Fab' fragment of anti-uPAR monoclonal antibody and proteolytically inactive urokinase (uPA), whereas inhibition of proteolytical activity of endogenous uPA (with amiloride or plasminogen activator inhibitor-1) did not affect the transmigration. Both the anti-uPAR Fab' fragment and proteolytically inactive uPA did not exert significant effects upon the transmigration conducted in the presence of F(ab')(2) fragment of blocking antibody to integrin Mac-1 indicating that uPAR regulates Mac-1-dependent transmigration. Mac-1-dependent, but not Mac-1-independent, transmigration was significantly reduced in the presence of N-acetyl-d-glucosamine and d-mannose, the saccharides that disrupt uPAR/Mac-1 association, but was unaffected in the presence of control saccharides (d-sorbitol and sucrose). We conclude that physical association of uPAR with Mac-1 mediates the regulatory effect of uPAR over the transmigration. Finally, we provide evidence that the functional cooperation between uPAR and Mac-1 is essential at both adhesion and diapedesis steps of neutrophil migration across endothelium. Thus, uPAR expressed on neutrophil plasma membrane regulates transendothelial migration independently of uPA proteolytical activity and acting as a cofactor for integrin Mac-1.

  15. The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

    PubMed Central

    Schuliga, Michael; Jaffar, Jade; Harris, Trudi; Knight, Darryl A; Westall, Glen; Stewart, Alastair G

    2017-01-01

    The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5–15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5–6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung fibrosis. PMID:28139758

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

    PubMed Central

    2012-01-01

    Background Corneal ulceration leading to perforation is associated with infectious and non-infectious destructive conditions in the cornea. The fibrinolytic (plasminogen/plasmin) system is considered to contribute to tissue remodeling in the wound healing process and it is believed to play an important role in proteolysis and fibrosis. To determine the localization of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR) and α2-antiplasmin (α2AP) in the tissue of a corneal perforation, we investigated immunohistochemical expressions of u-PA, u-PAR, α2AP, CD68, and α-smooth muscle actin (α-SMA) in a patient with corneal perforation that developed from an ulcer of no clear cause. Case presentation The patient was a 77-year-old woman who presented with a perforated corneal ulcer in her right eye. The cause of her corneal ulcer was unknown. Double immunohistochemistry was performed for the combinations of u-PA with u-PAR, CD68 or α-SMA and α2AP with CD68 or α-SMA to detect the localization of u-PA and α2AP. u-PA and u-PAR co-localization was seen in the corneal ulceration area. u-PA was mainly observed in CD68-positive cells and in some α-SMA positive cells. On the other hand, α2AP was not expressed in CD68-positive cells, but was expressed in α-SMA positive cells. Conclusion We identified expression of the u-PA/u-PAR complex and α2AP in a patient with a corneal ulcer. These two molecules are believed to play a crucial role in inflammatory cell recruitment, ECM synthesis and degradation during corneal wound healing. PMID:23190581

  17. Urokinase Lysis for Acute Left Subclavian Artery Thrombosis after Placement of Infusion Catheter: Report of Two Cases

    SciTech Connect

    Seki, Hiroshi; Kimura, Motomasa; Yoshimura, Norihiko; Takano, Tooru; Takaki, Satoshi; Awaji, Masanori; Sakai, Kunio

    2002-03-15

    We present two cases of acute subclavian and/or axillary arterial occlusion after transaxillary catheterization with an implantable port for hepatic arterial infusion chemotherapy. They were successfully treated with thrombolytic therapy using intraarterial administration of urokinase without removal of the infusion catheter system. We consider that this treatment is suitable for managing acute thrombosis of the conduit artery after catheterization for hepatic arterial infusion chemotherapy.

  18. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    SciTech Connect

    Takahashi, K.; Gojobori, T.; Tanifuji, M. )

    1991-02-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate.

  19. Steady States and Dynamics of Urokinase-Mediated Plasmin Activation In Silico and In Vitro

    PubMed Central

    Venkatraman, Lakshmi; Li, Huipeng; Dewey, C. Forbes; White, Jacob K.; Bhowmick, Sourav S.; Yu, Hanry; Tucker-Kellogg, Lisa

    2011-01-01

    Plasmin (PLS) and urokinase-type plasminogen activator (UPA) are ubiquitous proteases that regulate the extracellular environment. Although they are secreted in inactive forms, they can activate each other through proteolytic cleavage. This mutual interplay creates the potential for complex dynamics, which we investigated using mathematical modeling and in vitro experiments. We constructed ordinary differential equations to model the conversion of precursor plasminogen into active PLS, and precursor urokinase (scUPA) into active urokinase (tcUPA). Although neither PLS nor UPA exhibits allosteric cooperativity, modeling showed that cooperativity occurred at the system level because of substrate competition. Computational simulations and bifurcation analysis predicted that the system would be bistable over a range of parameters for cooperativity and positive feedback. Cell-free experiments with recombinant proteins tested key predictions of the model. PLS activation in response to scUPA stimulus was found to be cooperative in vitro. Finally, bistability was demonstrated in vitro by the presence of two significantly different steady-state levels of PLS activation for the same levels of stimulus. We conclude that ultrasensitive, bistable activation of UPA-PLS is possible in the presence of substrate competition. An ultrasensitive threshold for activation of PLS and UPA would have ramifications for normal and disease processes, including angiogenesis, metastasis, wound healing, and fibrosis. PMID:22004735

  20. 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.

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  3. [The effect of hypoxia on the urokinase and adenylate cyclase systems in the culture of endothelial cells of the human umbilical vein].

    PubMed

    Kapustin, A N; Tishchenko, E P; Torosian, N A; Panina, O B; Tsokolaeva, Z I; Ratner, E I; Savel'eva, G M; Parfenova, E V

    2005-06-01

    Hypoxia induces angiogenesis in ischemized tissues by means of pro-angiogenic factor expression. The key role in the growth processes and blood vessel functioning belongs to the matrix metalloproteinases, plasminogen, and its activator systems. Effect of hypoxia on expression of the urokinase activating agent plasminogen and its receptor in endothelium was studied in human umbilical vein endothelial cell model. Incubation of the endothelial cells under the conditions of hypoxia proved to reduce both urokinase formation in these cells and its secreting into the culture medium. The hypoxia-induced reduction of urokinase contents was accompanied by enhancement of expression of the urokinase receptor. The hypoxia also entailed reduction of the adenylate cyclase activity and cAMP contents in the endothelial cells. The data obtained suggest that reduction of the adenylate cyclase activity and cAMP contents under the conditions of hypoxia provide basis for suppression of the urokinase expression by the endothelial cells and, consequently, inhibition of blood vessel formation in the ischemized tissue.

  4. Urokinase Receptor Promotes Skin Tumor Formation by Preventing Epithelial Cell Activation of Notch1.

    PubMed

    Mazzieri, Roberta; Pietrogrande, Giovanni; Gerasi, Laura; Gandelli, Alessandro; Colombo, Piergiuseppe; Moi, Davide; Brombin, Chiara; Ambrosi, Alessandro; Danese, Silvio; Mignatti, Paolo; Blasi, Francesco; D'Alessio, Silvia

    2015-11-15

    The urokinase-type plasminogen activator receptor (uPAR) has a well-established role in cancer progression, but it has been little studied at earlier stages of cancer initiation. Here, we show that uPAR deficiency in the mouse dramatically reduces susceptibility to the classical two-stage protocol of inflammatory skin carcinogenesis. uPAR genetic deficiency decreased papilloma formation and accelerated keratinocyte differentiation, effects mediated by Notch1 hyperactivation. Notably, Notch1 inhibition in uPAR-deficient mice rescued their susceptibility to skin carcinogenesis. Clinically, we found that human differentiated keratoacanthomas expressed low levels of uPAR and high levels of activated Notch1, with opposite effects in proliferating tumors, confirming the relevance of the observations in mice. Furthermore, we found that TACE-dependent activation of Notch1 in basal kerantinocytes was modulated by uPAR. Mechanistically, uPAR sequestered TACE within lipid rafts to prevent Notch1 activation, thereby promoting cell proliferation and tumor formation. Given that uPAR signaling is nonessential for normal epidermal homeostasis, our results argue that uPAR may present a promising disease-specific target for preventing skin cancer development.

  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. 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.

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

    PubMed

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

    2012-04-01

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

  8. 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

  9. Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

    PubMed Central

    Udomsinprasert, Wanvisa; Honsawek, Sittisak; Jirathanathornnukul, Napaphat; Chongsrisawat, Voranush; Poovorawan, Yong

    2016-01-01

    AIM To investigate serum urokinase-type plasminogen activator receptor (uPAR) and liver stiffness in biliary atresia (BA) and examine the correlation of circulating uPAR, liver stiffness, and clinical outcomes in postoperative BA children. METHODS Eighty-five postKasai BA children and 24 control subjects were registered. Circulating uPAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography. RESULTS BA children had significantly greater circulating uPAR and liver stiffness scores than control subjects (P < 0.001). Circulating uPAR and liver stiffness were substantially higher in jaundiced BA children than non-jaundiced BA children (P < 0.001). In addition, circulating uPAR was positively associated with serum aspartate aminotransferase (r = 0.507, P < 0.001), alanine aminotransferase (r = 0.364, P < 0.001), total bilirubin (r = 0.559, P < 0.001), alkaline phosphatase (r = 0.325, P < 0.001), and liver stiffness scores (r = 0.508, P < 0.001). CONCLUSION Circulating uPAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating uPAR was associated with liver dysfunction in BA. As a consequence, serum uPAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in postKasai BA. PMID:27957246

  10. 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.

  11. Urokinase-type plasminogen activator: a new target for male contraception?

    PubMed Central

    Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

    2015-01-01

    Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P < 0.05) when compared with control groups. However, the mating capacity and reproductive organ weights had no obvious change, and histological analysis of the testes and epididymides also showed normal morphology for immunized male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P < 0.05). Together, these observations indicated that subcutaneous injection human uPA to the male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development. PMID:25578931

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

    PubMed

    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

    2015-03-01

    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 h. 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 multicenter 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 with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS.

  13. Expression and localization of urokinase-type plasminogen activator receptor in bovine cumulus-oocyte complexes.

    PubMed

    García, Daniela C; Miceli, Dora C; Rizo, Gabriela; García, Elina V; Valdecantos, Pablo A; Roldán-Olarte, Mariela

    2016-04-01

    Urokinase-type plasminogen activator (uPA) is a serine protease involved in extracellular matrix remodeling through plasmin generation. uPA usually binds to its receptor, uPAR, which is anchored to the plasma membrane through a glycosylphosphatidylinositol anchor. uPA/uPAR binding increases proteolytic activity in the neighborhood of the cells containing uPAR and activates intracellular signaling pathways involved in extracellular matrix remodeling, cell migration and proliferation. The aim of this work was to study the expression of uPA, uPAR and plasminogen activator inhibitor-1 (PAI-1) in immature and in vitro matured bovine cumulus-oocyte complexes (COCs). uPA is only expressed in the cumulus cells of immature and in vitro matured COCs, while uPAR and PAI-1 are expressed in both the cumulus cells and the immature and in vitro matured oocytes. In addition, uPAR protein was localized by confocal microscopy in the plasma membrane of oocytes and cumulus cells of immature COCs. Results from this research led us to hypothesize that the uPA/uPAR interaction could cause the local production of uPA-mediated plasmin over oocyte and cumulus cell surface; plasmin formation could also be regulated by PAI-1.

  14. Urokinase gene transfer augments angiogenesis in ischemic skeletal and myocardial muscle.

    PubMed

    Traktuev, Dmitry O; Tsokolaeva, Zoya I; Shevelev, Alexander A; Talitskiy, Konstantin A; Stepanova, Victoria V; Johnstone, Brian H; Rahmat-Zade, Tahmina M; Kapustin, Alexander N; Tkachuk, Vsevolod A; March, Keith L; Parfyonova, Yelena V

    2007-11-01

    Urokinase plasminogen activator (uPA) is required for both endogenous and vascular endothelial growth factor (VEGF)-augmented angiogenesis in normal tissues, leading us to hypothesize that uPA augmentation by gene transfer might promote angiogenesis in ischemic tissues. Overexpression of uPA was studied in rat myocardial infarction (MI) and mouse hind limb ischemia models and compared with VEGF overexpression effects. Animals were divided into control and three experimental groups (n = 6), receiving intramuscular injections of plasmids as follows: (i) control (empty vector or expressing beta-galactosidase); (ii) uPA; (iii) VEGF(165); (iv) a 1:1 mixture of uPA and VEGF(165). The capillary densities in both ischemic models were greater (P < 0.05) in tissues treated with uPA, VEGF, or a combination of both than in controls. Infarct size was reduced in hearts from uPA and VEGF experimental groups compared with controls (P < 0.05). Local overexpression of uPA induced a marked increase in the number of macrophages and myofibroblasts present within infarcts. Hind limb blood flow was greater in all experimental groups by day 10 (P < 0.05). Overall, the effects of uPA and VEGF were uniformly comparable. Additional analysis revealed association of local edema with VEGF but not with uPA treatment. This study established that uPA gene therapy effectively induces functionally significant angiogenesis in models of acute MI and hind limb ischemia.

  15. Pyelonephritis: renal urokinase activity in rats on essential fatty acid diets.

    PubMed

    du Toit, P J; van Aswegen, C H; Nel, J D; Strasheim, B; Becker, P J; du Plessis, D J

    1994-01-01

    This study was undertaken to assess whether additions of different oils to the diets of male rats would affect the renal urokinase (UK) activity of healthy and pyelonephritic kidneys. Four groups of fatty acid diets were studied: fat-free, coconut oil, fish oil and evening primrose oil (EPO). Pyelonephritis was obtained by unilateral extrarenal urinary obstruction and subcutaneous injection of Escherichia coli. The UK activity of the non-obstructed kidneys did not differ statistically between rats infected and not infected with bacteria (P > 0.056), except within the coconut oil group. A statistically decreased UK activity was obtained with bacteria injected animals on a coconut oil diet (P < 0.0001). This phenomenon, namely a decrease in UK activity, was also seen with pyelonephritic kidneys of rats on fat-free, coconut and fish oil diets (P < 0.0065). However, the UK activity of the obstructed kidneys with and without infection in the EPO group remained similar (P = 0.8477). These results suggest that the UK activity in infection-induced renal stones may be restored by EPO containing diets and may be of high relevance in the prevention and treatment of infection-induced renal stones. This revelation now needs to be more fully investigated.

  16. Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression.

    PubMed Central

    de Vries, T. J.; Quax, P. H.; Denijn, M.; Verrijp, K. N.; Verheijen, J. H.; Verspaget, H. W.; Weidle, U. H.; Ruiter, D. J.; van Muijen, G. N.

    1994-01-01

    Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis. Recently, we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here we report on the occurrence of components of the PA system in the various stages of human melanoma tumor progression in situ. We studied the protein distribution on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (= atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present in endothelial cells in all lesions, whereas in metastases it could be detected in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI-2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells. Localization of the corresponding messenger RNAs and enzyme activities revealed a similar distribution. We conclude that plasminogen activation is a late event in melanoma tumor progression. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8291613

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

    PubMed

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

    2002-01-01

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

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

    PubMed

    Patecki, Margret; von Schaewen, Markus; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika

    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.

  19. 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

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

    PubMed Central

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

    2017-01-01

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

  1. Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors.

    PubMed

    Hiendlmeyer, Elke; Regus, Susanne; Wassermann, Stella; Hlubek, Falk; Haynl, Angela; Dimmler, Arno; Koch, Claudia; Knoll, Claudia; van Beest, Moniek; Reuning, Ute; Brabletz, Thomas; Kirchner, Thomas; Jung, Andreas

    2004-02-15

    Expression of the urokinase plasminogen activator (uPA) increases during the progression of colorectal tumors from adenomas to carcinomas. The highest amounts of uPA are found at the invasion front of carcinomas, which also displays a strong expression of nuclear beta-catenin and is therefore a region expressing beta-catenin target genes at high levels. Here we show that beta-catenin contributes to the transactivation of uPA. Therefore, beta-catenin might have an impact on the capacity of colorectal tumors for invasion and metastasis, as well as dormancy, which are hallmarks of cancer.

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

    PubMed

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

    2013-11-01

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

  3. 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

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

    PubMed Central

    Chen, Yushu; Gong, Li; Gao, Ning; Liao, Jichun; Sun, Jiayu; Wang, Yuqing; Wang, Lei; Zhu, Pengjin; Fan, Qing; Wang, Yongqiang Andrew; Zeng, Wen; Mao, Hui; Yang, Lily; Gao, Fabao

    2015-01-01

    Purpose To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys. Methods We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating. Results The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study. Conclusion All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of

  5. Binding site of amiloride to urokinase plasminogen activator depends on species.

    PubMed

    Jankun, J; Skrzypczak-Jankun, E

    2001-10-01

    A novel drug candidate is checked on its potency on animal models before it can advance to human phase of the research. Usually negative results on animal phase disqualify it. Targeting specific enzymes by small chemicals raises the question about the appropriateness of this approach. As an example, the urokinase (uPA) is recognized as an important enzyme responsible for cancer metastasis and angiogenesis. It is therefore important to ask the question if a small chemical will inhibit uPA of different species with the same or different potency. Using DNA sequence and known structure of uPA we have modeled 3D structures of uPAs for several different species. By theoretical calculations we have determined most probable structure of amiloride/uPAs complexes. Catalytic triad (B57, B102, B195) and specificity pocket (B187-B197, B212-B229) are highly conserved in all cases, and are the regions responsible for proteolytic activity and recognition of the substrate. Significant differences were observed in a different region (loop B93-B101), that we identified as binding site of amiloride to the tissue plasminogen activator (tPA). Although tPA shares the same function of activating plasminogen and it is structurally similar to uPA. Amiloride is a specific inhibitor of uPA but does not inhibit tPA. Our study shows that predicted position of amiloride depends on species and in some cases was located, as expected, in the specificity pocket, but in the other cases close to the loop B93-B101. This location could weaken affinity of binding or prevent inhibition of uPA. Therefore, drug screening and elimination process based solely on animal study, without careful structural analysis, could lead to the elimination of potential drugs for humans.

  6. 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

  7. Hepatic Microenvironment Affects Oval Cell Localization in Albumin-Urokinase-Type Plasminogen Activator Transgenic Mice

    PubMed Central

    Braun, Kristin M.; Thompson, Anne W.; Sandgren, Eric P.

    2003-01-01

    Mice carrying an albumin-urokinase type plasminogen activator transgene (AL-uPA) develop liver disease secondary to uPA expression in hepatocytes. Transgene-expressing parenchyma is replaced gradually by clones of cells that have deleted transgene DNA and therefore are not subject to uPA-mediated damage. Diseased liver displays several abnormalities, including hepatocyte vacuolation and changes in nonparenchymal tissue. The latter includes increases in laminin protein within parenchyma and the appearance of cytokeratin 19-positive bile ductule-like cells (oval cells) both in portal regions and extending into the hepatic parenchyma. In this study, we subjected AL-uPA mice to two-thirds partial hepatectomy to identify the response of these livers to additional growth stimulation. We observed several changes in hepatic morphology. First, the oval cells increased in number and often formed ductules in the parenchyma. Second, this cellular change was accompanied by a further increase in laminin associated with single or clusters of oval cells. Third, desmin-positive Ito cells increased in number and maintained close association with oval cells. Fourth, these changes were localized precisely to uPA-expressing areas of liver. Regenerating clones of uPA-deficient cells appeared to be unaffected both by stromal and cellular alterations. Thus, additional growth stimulation of diseased uPA-expressing liver induces an oval cell-like response, as observed in other models of severe hepatic injury, but the localization of this response seems to be highly regulated by the hepatic microenvironment. PMID:12507902

  8. Regulation of urokinase receptor proteolytic function by the tetraspanin CD82.

    PubMed

    Bass, Rosemary; Werner, Finn; Odintsova, Elena; Sugiura, Tsuyoshi; Berditchevski, Fedor; Ellis, Vincent

    2005-04-15

    The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored cellular receptor (uPAR) promotes plasminogen activation and the efficient generation of pericellular proteolytic activity. We demonstrate here that expression of the tetraspanin CD82/KAI1 (a tumor metastasis suppressor) leads to a profound effect on uPAR function. Pericellular plasminogen activation was reduced by approximately 50-fold in the presence of CD82, although levels of components of the plasminogen activation system were unchanged. uPAR was present on the cell surface and molecularly intact, but radioligand binding analysis with uPA and anti-uPAR antibodies revealed that it was in a previously undetected cryptic form unable to bind uPA. This was not due to direct interactions between uPAR and CD82, as they neither co-localized on the cell surface nor could be co-immunoprecipitated. However, expression of CD82 led to a redistribution of uPAR to focal adhesions, where it was shown by double immunofluorescence labeling to co-localize with the integrin alpha(5)beta(1), which was also redistributed in the presence of CD82. Co-immunoprecipitation experiments showed that, in the presence of CD82, uPAR preferentially formed stable associations with alpha(5)beta(1), but not with a variety of other integrins, including alpha(3)beta(1). These data suggest that CD82 inhibits the proteolytic function of uPAR indirectly, directing uPAR and alpha(5)beta(1) to focal adhesions and promoting their association with a resultant loss of uPA binding. This represents a novel mechanism whereby tetraspanins, integrins, and uPAR, systems involved in cell adhesion and migration, cooperate to regulate pericellular proteolytic activity and may suggest a mechanism for the tumor-suppressive effects of CD82/KAI1.

  9. Cell associated urokinase activity and colonic epithelial cells in health and disease.

    PubMed Central

    Gibson, P R; van de Pol, E; Doe, W F

    1991-01-01

    It is not known if urokinase-type plasminogen activator (uPA) is associated with normal colonic epithelial cells. The aims of this study were to determine if normal colonic epithelial cells have uPA activity and whether this is concentrated at the cell membrane. In addition, the contribution of colonic epithelial cell associated uPA activity to disease related pertubations of mucosal uPA activity were examined. A highly enriched population of colonic epithelial cells was isolated from resected colon or biopsy specimens by an enzymatic technique. uPA activity was measured in cell homogenates by a specific and sensitive colorimetric method and expressed relative to cellular DNA. In two experiments subcellular fractionation of colonic epithelial cells was performed by nitrogen cavitation followed by ultracentrifugation over a linear sucrose gradient. The fractions collected were analysed for uPA and organelle-specific enzyme activities. Normal colonic epithelial cells have cell associated uPA activity (mean (SEM) 5.6 (1.1) IU/mg, n = 18). This colocalised with fractions enriched for leucine-beta-naphthylamidase and 5'-nucleotidase, markers of plasma membrane. uPA activities in epithelial cells from cancerous colons (9.8 (3.1) n = 7) or from mucosa affected by inflammatory bowel disease (3.8 (0.7) n = 15) were not significantly different from normal (paired t test), while that in epithelial cells from greatly inflamed mucosa was similar to that from autologous normal or mildly inflamed areas (4.4 (1.2) v 5.9 (3.6), n = 9). Thus normal colonic epithelial cells have cell associated uPA activity which is concentrated on the plasma membranes, suggesting the presence of uPA receptors. Increased mucosal levels of uPA previously reported in patients with inflammatory bowel disease are not due to increased colonic epithelial cell associated uPA. PMID:1650741

  10. Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population

    PubMed Central

    Yee, Jaeyong; Kim, Yongkang; Park, Taesung

    2016-01-01

    Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait. PMID:28154509

  11. 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.

  12. 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.

  13. Design, Synthesis, Biochemical Studies, Cellular Characterization, and Structure-Based Computational Studies of Small Molecules Targeting the Urokinase Receptor

    PubMed Central

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

    2012-01-01

    The urokinase receptor (uPAR) serves as a docking site to the serine protease urokinase-type plasminogen activator (uPA) to promote extracellular matrix (ECM) degradation and tumor invasion and metastasis. Previously, we had reported a small molecule inhibitor of the uPAR•uPA interaction that emerged from structure-based virtual screening. Here, we measure the affinity of a large number of derivatives from commercial sources. Synthesis of additional compounds was carried out to probe the role of various groups on the parent compound. Extensive structure-based computational studies suggested a binding mode for these compounds that led to a structure-activity relationship study. Cellular studies in non-small cell lung cancer (NSCLC) cell lines that include A549, H460 and H1299 showed that compounds blocked invasion, migration and adhesion. The effects on invasion of active compounds were consistent with their inhibition of uPA and MMP proteolytic activity. These compounds showed weak cytotoxicity consistent with the confined role of uPAR to metastasis. PMID:22771232

  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. Characterization of the murine plasminogen/urokinase-type plasminogen-activator system.

    PubMed

    Lijnen, H R; Van Hoef, B; Collen, D

    1996-11-01

    The murine plasminogen/urokinase-type plasminogen-activator (u-PA) system was studied using purified proteins, plasma and endothelioma cells. Recombinant murine u-PA was obtained as a single-chain molecule of 45 kDa which was converted to two-chain u-PA with plasmin by cleavage of the Lys159-Ile160 peptide bond. Murine plasminogen, purified from plasma as a single-chain protein of 95 kDa, was resistant to quantitative activation with murine recombinant two-chain u-PA: only 15% activation within 1 h at 37 degrees C was obtained in mixtures of 1 microM plasminogen and 5 nM recombinant two-chain u-PA, whereas quantitative activation was observed in the autologous human system. Addition of 6-aminohexanoic acid to native murine plasminogen resulted in quantitative activation within 1 h. In murine plasma in vitro, plasminogen was also resistant to quantitative activation with u-PA (50% activation within 1 h at 37 degrees C with 50 nM recombinant two-chain u-PA, whereas in the human system nearly quantitative activation was obtained). Murine plasma clots submerged in murine plasma were resistant to lysis with u-PA; < or = 2% clot lysis in 2 h was obtained with 80 nM recombinant two-chain u-PA in the autologous murine system whereas 50% clot lysis in 2 h required only 15 nM recombinant two-chain u-PA in the autologous human system. Saturable binding of murine recombinant two-chain u-PA was observed to murine endothelioma cells that are genetically deficient in u-PA (u-PA-/- End cells). Binding was characterized by a Kd of 5.5 nM and 800000 binding sites/cell. However, u-PA-/- End cells did not significantly stimulate the activation rate of murine plasminogen by murine recombinant two-chain u-PA and did not enhance the plasmin-mediated conversion rate of murine recombinant single-chain u-PA to its two-chain derivative. Murine recombinant two-chain u-PA bound to murine endothelioma cells was quantitatively inhibited by murine plasminogen-activator inhibitor-1 (PAI-1). Thus

  16. Cytoplasmic-nuclear shuttling of the urokinase mRNA binding protein regulates message stability.

    PubMed

    Shetty, Sreerama

    2002-08-01

    Treatment of small airway epithelial (SAEC) cells or lung epithelial (Beas2B) cells with TNF-alpha or PMA induces urokinase-type plasminogen activator (uPA) expression. Treatment of these cells with TNF-alpha, PMA or cycloheximide but not TGF-beta increased steady-state expression of uPAmRNA. TNF-alpha, PMA or cycloheximide caused 8-10 fold extensions of the uPAmRNA half-life in SAEC or Beas2B cells treated with DRB, a transcriptional inhibitor. These findings suggest that uPA gene expression involves a post-transcriptional regulatory mechanism. Using gel mobility shift and UV cross-linking assays, we identified a 30 kDa uPA mRNA binding protein (uPA mRNABp) that selectively binds to a 66 nt protein binding fragment of uPA mRNA containing regulatory information for message stabilization. Binding of cytoplasmic uPA mRNABp to uPA mRNA was abolished after treatment with TNF-alpha but not TGF-beta. In addition, we found the accumulation of 30 kDa uPAmRNABp in the nuclear extracts of TNF-alpha but not TGF-beta treated cells. The uPA mRNABp starts moving to the nucleus from the cytoplasmic compartment as early as three hours after TNF-alpha treatment. Complete translocation is achieved between 12-24 h, which coincides with the maximal expression of uPA protein effected by cytokine stimulation. Treatment of Beas2B cells with NaF inhibited TNF-alpha-mediated translocation of uPA mRNABp from the cytoplasm to the nucleus and concomitant inhibition of uPA expression. TNF-alpha stabilizes uPA mRNA by translocating the uPA mRNABp from the cytoplasm to the nucleus. Our results demonstrate a novel mechanism governing uPA mRNA stability through shuttling of uPA mRNABp between the nucleus and cytoplasm. This newly identified pathway may have evolved to regulate uPA-mediated functions of the lung epithelium in inflamation or neoplasia.

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

    PubMed

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

    1998-01-01

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

  18. 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.

  19. Comparison of dose regimens for the administration of recombinant pro-urokinase in a canine thrombosis model.

    PubMed

    Burke, S E; Lubbers, N L; Nelson, R A; Henkin, J

    1997-05-01

    Pro-urokinase represents an important addition to the array of thrombolytic drugs currently available for clinical use because of its high clot specificity but distinctly different mechanism compared with that of t-PA. Recombinant pro-urokinase (r-proUK) is a single-chain precursor of high molecular weight urokinase which has been expressed in a mouse myeloma cell line. The present study was conducted to determine the dosing regimen which would produce optimal clot lysis and restoration of blood flow 2 h after treatment with r-proUK, using a dog model of arterial thrombosis. Efficacy was indicated by lysis of a radio-labelled clot which was formed in the heat-damaged femoral arteries of 39 male beagle dogs. The animals were divided into six heparinized treatment groups, each receiving one of five dosing regimens or the vehicle for r-proUK. The total dose (80,000 U/kg) was divided into an initial loading bolus, followed by either a second bolus or by infusions for various time periods, as shown below: Group Treatment Regimen % Lysis 1 r-proUK Bolus/bolus, 50%/50% at 0 and 15 min 52 +/- 7 2 r-proUK Bolus/bolus, 50%/50% at 0 and 30 min 62 +/- 7 3 r-proUK Bolus/infusion, 20%/80% infused to 30 min 41 +/- 8 4 r-proUK Bolus/infusion, 20%/80% infused to 60 min 66 +/- 5 5 r-proUK Bolus/infusion, 50%/50% infused to 30 min 73 +/- 4 6 Vehicle Bolus/infusion, 50%/50% infused to 30 min 12 +/- 6 It was concluded that optimal clot lysis and restoration of femoral flow was accomplished using a regimen in which 50% of the dose was given as a bolus, followed immediately by the remaining 50% given as a 30 min intravenous infusion (Group 5). At the dose used in this study, r-proUK did not produce degradation of fibrinolytic or hemostatic plasma proteins.

  20. The crystal structures of 3-TAPAP in complexes with the urokinase-type plasminogen activator and picrate.

    PubMed

    Zesławska, Ewa; Jacob, Uwe; Stürzebecher, Jörg; Oleksyn, Barbara J

    2006-01-01

    The urokinase-type plasminogen activator (uPA) is a protein involved in tissue remodeling and other biological processes. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly this enzyme is widely accepted as a promising anticancer target. In this work, we have investigated the conformation of the uPA inhibitor 3-TAPAP in two different crystalline environments of a picrate and a uPA complex. These structures were compared to the known structure of the 3-TAPAP in the complex with trypsin. In the complexes with the proteins, trypsin, and uPA, the binding mode of 3-TAPAP is similar. A larger difference in the conformation, in the comparison to these structures, has been observed by us in the 3-TAPAP picrate crystal. This observation contradicts the hypothesis that 3-TAPAP derivatives inhibit serine proteinases in preformed stable conformations.

  1. Association of calcium urolithiasis with urokinase P141L and 3'-UTR C>T polymorphisms in a Japanese population.

    PubMed

    Hagikura, Shoichi; Wakai, Kenji; Kawai, Sayo; Goto, Yasuyuki; Naito, Mariko; Hagikura, Minako; Gotoh, Momokazu; Hamajima, Nobuyuki

    2013-02-01

    This was a case-control study to analyze the associations between calcium urolithiasis and the urokinase polymorphisms, P141L (rs2227564) and 3'-UTR C>T (rs4065), in a Japanese population. Cases consisted of 232 patients with urinary calcium stones (174 men and 58 women) who presented to a general hospital between April 2009 and June 2011. Among these cases, 115 (49.6 %) patients had calcium oxalate stones alone, and 113 (48.7 %) patients had calcium oxalate stones mixed with calcium phosphate stones. Controls consisted of 454 subjects who had a routine health check-up in the same prefecture. The two polymorphisms were genotyped via polymerase chain reaction with confronting two-pair primers. In the control group, the genotype frequencies of P141L were 0.573 for PP, 0.375 for PL, and 0.052 for LL, and those of 3'-UTR C>T were 0.835 for CC, 0.165 for CT, and TT was not identified. Neither of the polymorphisms was significantly associated with urolithiasis. The age- and sex-adjusted odds ratios of urolithiasis were 0.96 [95 % confidence interval (CI), 0.66-1.41] for PL and 1.22 (0.58-2.57) for LL as compared with PP genotype of P141L, and 1.01 (0.62-1.64) for CT as compared with CC genotype of 3'-UTR C>T. When compared with the PP genotype of P141L, the frequency of PL was significantly lower in female cases with a family history of urolithiasis than in females without such family history (p = 0.028). P141L and 3'-UTR polymorphisms of the urokinase gene are not associated with urolithiasis in a Japanese population.

  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. Detecting spatial regimes in ecosystems

    EPA Science Inventory

    Research on early warning indicators has generally focused on assessing temporal transitions with limited application of these methods to detecting spatial regimes. Traditional spatial boundary detection procedures that result in ecoregion maps are typically based on ecological ...

  4. Feasibility of continuous, catheter-directed thrombolysis using low-dose urokinase in combination with low molecular-weight heparin for acute iliofemoral venous thrombosis in patients at risk of bleeding

    PubMed Central

    Chen, Guoping; Shi, Wangyin; He, Xu; Lou, Wensheng; Chen, Liang; Gu, Jianping

    2017-01-01

    The present study aimed to examine the feasibility of catheter-directed thrombolysis (CDT) using continuous infusion of low-dose urokinase in combination with low molecular weight heparin (LMWH) for acute iliofemoral venous thrombosis. This retrospective analysis included patients with symptomatic acute iliofemoral venous thrombosis who received CDT using continuous infusion of low-dose urokinase in combination with LMWH within the past four years. Urokinase was administered at 1×104 U/h and 2×104 U/h in patients at high-risk and low-risk of bleeding, respectively. Measurements included urokinase dosage, duration, clinical outcomes and CDT-related complications. A total of 46 patients were included (high-risk, n=17; low-risk, n=29). In the high-risk patients, 64.7% experienced dissolution of ≥50% thrombi after a median CDT duration of 8 days (range, 6–10 days) and median total urokinase dose of 1.92×106 units (range, 1.44–2.4×106 units). In the low-risk patients, 82.8% achieved dissolution of ≥50% thrombi after a median CDT duration of 7 days (range, 4–10 days) and a median total urokinase dose of 3.36×106 units (range, 1.92–4.80×106 units). Remission of clinical symptoms after CDT was achieved in 15 (88.2%) and 28 (96.6%) cases in high-risk and low-risk patients, respectively. No treatment-associated pulmonary embolism or major bleeding was observed. Three (6.5%) subjects (high-risk, n=1; low-risk, n=2) experienced minor bleeding. In conclusion, continuous infusion of low-dose urokinase via CDT in combination with LMWH is effective and safe for acute iliofemoral venous thrombosis in patients with one or more risk factor for bleeding. PMID:28352362

  5. Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer

    PubMed Central

    Asuthkar, Swapna; Stepanova, Victoria; Lebedeva, Tatiana; Holterman, AiXuan L.; Estes, Norman; Cines, Douglas B.; Rao, Jasti S.; Gondi, Christopher S.

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the underlying reasons for this lethality is believed to be the presence of cancer stem cells (CSC), which impart chemoresistance and promote recurrence, but the mechanisms responsible are unclear. Recently the poor prognosis of PDAC has been correlated with increased expression of urokinase plasminogen activator (uPA). In the present study we examine the role of uPA in the generation of PDAC CSC. We observe a subset of cells identifiable as a side population (SP) when sorted by flow cytometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possess the properties of CSC. A large fraction of these SP cells are CD44 and CD24 positive, are gemcitabine resistant, possess sphere-forming ability, and exhibit increased tumorigenicity, known characteristics of cancer stemness. Increased tumorigenicity and gemcitabine resistance decrease after suppression of uPA. We observe that uPA interacts directly with transcription factors LIM homeobox-2 (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote cancer stemness. uPA regulates Lhx2 expression by suppressing expression of miR-124 and p53 expression by repressing its promoter by inactivating HOXA5. These results demonstrate that regulation of gene transcription by uPA contributes to cancer stemness and clinical lethality. PMID:23864708

  6. 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

  7. Proximity oscillations of complement type 4 (alphaX beta2) and urokinase receptors on migrating neutrophils.

    PubMed Central

    Kindzelskii, A L; Eszes, M M; Todd, R F; Petty, H R

    1997-01-01

    Migrating neutrophils utilize beta2 integrins for substrate attachment and urokinase receptors (uPAR) to focus pericellular proteolysis. Our studies show that CR3 associates with uPAR on resting cells, whereas uPAR associates with CR4 at lamellipodia of migrating cells. Using resonance energy transfer (RET) microscopy, we show that the molecular proximity between CR4 and uPAR oscillates on migrating cells, thus suggesting that CR4 molecules periodically bind/release uPAR. Cell contact with fibrinogen, endothelial cells, chemotactic factors and indomethacin, and treatment with sub-optimal doses of signal transduction inhibitors, affect the oscillations' period, amplitude, and/or waveform. The oscillations were indistinguishable in period and 180 degrees out-of-phase with cytosolic NAD(P)H autofluorescence oscillations. Thus, CR4 and CR3 identify a neutrophil's axis of migration and CR4 may restrain uPAR at lamellipodia. Oscillations in signal transduction and energy metabolism may coordinate cell adherence, local proteolysis, oxidant release, actin assembly, and cell extension. Images FIGURE 1 PMID:9336173

  8. 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

  9. Transforming Growth Factor-Beta and Urokinase-Type Plasminogen Activator: Dangerous Partners in Tumorigenesis—Implications in Skin Cancer

    PubMed Central

    Santibanez, Juan F.

    2013-01-01

    Transforming growth factor-beta (TGF-β) is a pleiotropic factor, with several different roles in health and disease. TGF-β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF-β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF-β, thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF-β and uPA system in cancer cells and their implication in skin cancer. PMID:23984088

  10. 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

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

    PubMed Central

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

    2017-01-01

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

  12. The influence of opioid peptides on matrix metalloproteinase-9 and urokinase plasminogen activator expression in three cancer cell lines.

    PubMed

    Gach, K; Wyrebska, A; Szemraj, J; Janecka, A

    2012-01-01

    Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) regulate proteolysis of the extracellular matrix (ECM) and as a consequence are involved in a number of physiological and pathological states, including cancer. A crucial feature of cancer progression and metastasis is the disruption of the ECM and spreading of proliferating cancer cells. Over-expression of MMPs and uPA is common for most types of cancers and correlates well with the adverse prognosis. Compounds able to modulate the activity of these proteolytic enzymes may become important agents in cancer therapy. In the present study, we examined the effect of the mu-opioid receptor selective peptide, morphiceptin, and its two synthetic analogs on mRNA and protein levels of MMP-9 and uPA in three human cancer cell lines: MCF-7, HT-29, and SH-SY5Y. Our findings indicate that in all three cell lines morphiceptin and its analogs attenuated MMP-9 expression and secretion and that this effect is not mediated by opioid receptors but is under control of the nitric oxide system. On the other hand, tested opioids up-regulated uPA levels through a mechanism that involved opioid-receptors. Different pathways by which opioid peptides exert their actionin cancer cells can explain their contradictory influence on the level of cancer markers.

  13. Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer.

    PubMed

    Asuthkar, Swapna; Stepanova, Victoria; Lebedeva, Tatiana; Holterman, Aixuan L; Estes, Norman; Cines, Douglas B; Rao, Jasti S; Gondi, Christopher S

    2013-09-01

    Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the underlying reasons for this lethality is believed to be the presence of cancer stem cells (CSC), which impart chemoresistance and promote recurrence, but the mechanisms responsible are unclear. Recently the poor prognosis of PDAC has been correlated with increased expression of urokinase plasminogen activator (uPA). In the present study we examine the role of uPA in the generation of PDAC CSC. We observe a subset of cells identifiable as a side population (SP) when sorted by flow cytometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possess the properties of CSC. A large fraction of these SP cells are CD44 and CD24 positive, are gemcitabine resistant, possess sphere-forming ability, and exhibit increased tumorigenicity, known characteristics of cancer stemness. Increased tumorigenicity and gemcitabine resistance decrease after suppression of uPA. We observe that uPA interacts directly with transcription factors LIM homeobox-2 (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote cancer stemness. uPA regulates Lhx2 expression by suppressing expression of miR-124 and p53 expression by repressing its promoter by inactivating HOXA5. These results demonstrate that regulation of gene transcription by uPA contributes to cancer stemness and clinical lethality.

  14. 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.

  15. Urokinase type plasminogen activator mediates Interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration.

    PubMed

    Krstić, Jelena; Obradović, Hristina; Jauković, Aleksandra; Okić-Đorđević, Ivana; Trivanović, Drenka; Kukolj, Tamara; Mojsilović, Slavko; Ilić, Vesna; Santibañez, Juan F; Bugarski, Diana

    2015-02-01

    Mesenchymal stem cells (MSCs) have the potential to migrate toward damaged tissues increasing tissue regeneration. Interleukin-17 (IL-17) is a proinflammatory cytokine with pleiotropic effects associated with many inflammatory diseases. Although IL-17 can modulate MSC functions, its capacity to regulate MSC migration is not well elucidated so far. Here, we studied the role of IL-17 on peripheral blood (PB) derived MSC migration and transmigration across endothelial cells. IL-17 increased PB-MSC migration in a wound healing assay as well as cell mobilization from collagen gel. Concomitantly IL-17 induced the expression of urokinase type plasminogen activator (uPA) without affecting matrix metalloproteinase expression. The incremented uPA expression mediated the capacity of IL-17 to enhance PB-MSC migration in a ERK1,2 MAPK dependent way. Also, IL-17 induced PB-MSC migration alongside with changes in cell polarization and uPA localization in cell protrusions. Moreover, IL-17 increased PB-MSC adhesion to endothelial cells and transendothelial migration, as well as increased the capacity of PB-MSC adhesion to fibronectin, in an uPA-dependent fashion. Therefore, our data suggested that IL-17 may act as chemotropic factor for PB-MSCs by incrementing cell motility and uPA expression during inflammation development.

  16. 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

  17. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target: potential clinical applications

    PubMed Central

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) has been shown to be of special importance during cancer invasion and metastasis. However, currently, tissue samples are needed for measurement of uPAR expression limiting the potential as a clinical routine. Therefore, non-invasive methods are needed. In line with this, uPAR has recently been identified as a very promising imaging target candidate. uPAR consists of three domains attached to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor and binds it natural ligand uPA with high affinity to localize plasminogen activation at the cell surface. Due to the importance of uPAR in cancer invasion and metastasis, a number of high-affinity ligands have been identified during the last decades. These ligands have recently been used as starting point for the development of a number of ligands for imaging of uPAR using various imaging modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker. PMID:23701192

  18. In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase

    PubMed Central

    1988-01-01

    The ability of the chick embryo chorioallantoic membrane (CAM) to withstand invasion by tumor cells can be intentionally compromised by altering its morphological integrity. Using a newly developed quantitative assay of invasion we showed that intact CAMs were completely resistant to invasion by tumor cells, wounded CAMs did not pose a barrier to penetration, and CAMs that were wounded and then allowed to reseal displayed partial susceptibility to invasion. The invasion of resealed CAMs required catalytically active plasminogen activator (PA) of the urokinase type (uPA); the invasive efficiency of tumor cells was reduced by 75% when tumor uPA activity or tumor uPA production was inhibited. The invasive ability of human tumor cells, which have surface uPA receptors but which do not produce the enzyme, could be augmented by saturating their receptors with exogenous uPA. The mere stimulation of either uPA or tissue plasminogen activator production, in absence of binding to cell receptors, did not result in an enhancement of invasiveness. These findings suggest that the increased invasive potential of tumor cells is correlated with cell surface-associated proteolytic activity stemming from the interaction between uPA and its surface receptor. PMID:2848851

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

    PubMed Central

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

    2016-01-01

    The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88–92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR88–92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro, the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream. PMID:27323409

  20. Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec

    PubMed Central

    Ilkovitch, Dan

    2009-01-01

    The transmembrane isoform of mucin 1 (MUC1/TM) is a well-recognized tumor antigen, contributing to tumorigenesis and immune evasion. Although MUC1/TM has been correlated with malignancy, we have previously reported on antitumor properties and prevention of tumor development by a secreted splice variant of MUC1 (MUC1/sec). Because myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-induced immunosuppression, we investigated their recruitment by tumor cells expressing either MUC1/TM or MUC1/sec. DA-3 tumor cells expressing MUC1/sec recruit dramatically lower levels of MDSCs, relative to MUC1/TM-expressing DA-3 cells. Because MUC1/sec was previously shown to down-regulate tumor expression of urokinase plasminogen activator (uPA), a protease linked to tumor aggressiveness and metastasis, the potential role of uPA in MDSC recruitment was investigated. Tumor-derived uPA is capable of recruiting MDSCs, and correlates with tumor development. In addition to diminishing recruitment of MDSCs, the effect of MUC1/sec on MDSC-suppressive mechanisms was investigated. MUC1/sec, or its unique immunoenhancing peptide, is capable of blocking expression of arginase 1 and production of reactive oxygen species in MDSCs, implicated in the suppression of T cells. These findings demonstrate a new mechanism of MDSC recruitment, and provide evidence that MUC1/sec has antitumor properties affecting MDSCs. PMID:19196663

  1. Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec.

    PubMed

    Ilkovitch, Dan; Lopez, Diana M

    2009-05-07

    The transmembrane isoform of mucin 1 (MUC1/TM) is a well-recognized tumor antigen, contributing to tumorigenesis and immune evasion. Although MUC1/TM has been correlated with malignancy, we have previously reported on antitumor properties and prevention of tumor development by a secreted splice variant of MUC1 (MUC1/sec). Because myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-induced immunosuppression, we investigated their recruitment by tumor cells expressing either MUC1/TM or MUC1/sec. DA-3 tumor cells expressing MUC1/sec recruit dramatically lower levels of MDSCs, relative to MUC1/TM-expressing DA-3 cells. Because MUC1/sec was previously shown to down-regulate tumor expression of urokinase plasminogen activator (uPA), a protease linked to tumor aggressiveness and metastasis, the potential role of uPA in MDSC recruitment was investigated. Tumor-derived uPA is capable of recruiting MDSCs, and correlates with tumor development. In addition to diminishing recruitment of MDSCs, the effect of MUC1/sec on MDSC-suppressive mechanisms was investigated. MUC1/sec, or its unique immunoenhancing peptide, is capable of blocking expression of arginase 1 and production of reactive oxygen species in MDSCs, implicated in the suppression of T cells. These findings demonstrate a new mechanism of MDSC recruitment, and provide evidence that MUC1/sec has antitumor properties affecting MDSCs.

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

    PubMed

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

    2017-01-16

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

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

    PubMed

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

    1986-04-15

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

  4. 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.

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

    PubMed Central

    Salvati, Annamaria; Serio, Bianca; Pesapane, Ada; Ricci, Patrizia; Gorrasi, Anna; Santi, Anna Li; Hoyer-Hansen, Gunilla; Ragno, Pia

    2016-01-01

    Hematopoietic stem cells (HSCs) reside in bone marrow (BM) and can be induced to mobilize into the circulation for transplantation. Homing and lodgement into BM of transplanted HSCs are the first critical steps in their engraftment and involve multiple interactions between HSCs and the BM microenvironment. uPAR is a three domain receptor (DIDIIDIII) which binds urokinase, vitronectin, integrins. uPAR can be cleaved and shed from the cell surface generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR). DIIDIII-suPAR can bind fMLF receptors through the SRSRY sequence (residues 88-92). We previously reported the involvement of soluble uPAR in HSC mobilization. We now investigate its possible role in HSC homing and engraftment. We show similar levels of circulating full-length suPAR in healthy donors and in acute myeloid leukemia (AML) patients before and after the pre-transplant conditioning regimen. By contrast, levels of circulating DIIDIII-suPAR in AML patients are higher as compared to controls and significantly decrease after the conditioning. We found that suPAR and uPAR84-95, a uPAR-derived peptide which mimics active DIIDIII-suPAR, induce a significant increase in Long Term Culture (LTC)-Initiating Cells (ICs) and in the release of clonogenic progenitors from LTCs of CD34+ HSCs. Further, suPAR increases adhesion and survival of CD34+ KG1 AML cells, whereas uPAR84-95 increases their proliferation. Thus, circulating DIIDIII-suPAR, strongly increased in HSC mobilization, is indeed down-regulated by pre-transplant conditioning, probably to favour HSC homing. BM full-length suPAR and DIIDIII-suPAR may be involved in HSC lodgement within the BM by contributing to a suitable microenvironment. PMID:27517491

  6. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives.

    PubMed

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer (64)Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome.

  7. Discovery of new small molecules targeting the vitronectin-binding site of the urokinase receptor that block cancer cell invasion.

    PubMed

    Rea, Vincenza Elena Anna; Lavecchia, Antonio; Di Giovanni, Carmen; Rossi, Francesca Wanda; Gorrasi, Anna; Pesapane, Ada; de Paulis, Amato; Ragno, Pia; Montuori, Nunzia

    2013-08-01

    Besides focusing urokinase (uPA) proteolytic activity on the cell membrane, the uPA receptor (uPAR) is able to bind vitronectin, via a direct binding site. Furthermore, uPAR interacts with other cell surface receptors, such as integrins, receptor tyrosine kinases, and chemotaxis receptors, triggering cell-signaling pathways that promote tumor progression. The ability of uPAR to coordinate binding and degradation of extracellular matrix (ECM) and cell signaling makes it an attractive therapeutic target in cancer. We used structure-based virtual screening (SB-VS) to search for small molecules targeting the uPAR-binding site for vitronectin. Forty-one compounds were identified and tested on uPAR-negative HEK-293 epithelial cells transfected with uPAR (uPAR-293 cells), using the parental cell line transfected with the empty vector (V-293 cells) as a control. Compounds 6 and 37 selectively inhibited uPAR-293 cell adhesion to vitronectin and the resulting changes in cell morphology and signal transduction, without exerting any effect on V-293 cells. Compounds 6 and 37 inhibited uPAR-293 cell binding to vitronectin with IC50 values of 3.6 and 1.2 μmol/L, respectively. Compounds 6 and 37 targeted S88 and R91, key residues for uPAR binding to vitronectin but also for uPAR interaction with the fMLF family of chemotaxis receptors (fMLF-Rs). As a consequence, compounds 6 and 37 impaired uPAR-293 cell migration toward fetal calf serum (FCS), uPA, and fMLF, likely by inhibiting the interaction between uPAR and FPR1, the high affinity fMLF-R. Both compounds blocked in vitro ECM invasion of several cancer cell types, thus representing new promising leads for pharmaceuticals in cancer.

  8. 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

  9. Involvement of the serine protease inhibitor, SERPINE2, and the urokinase plasminogen activator in cumulus expansion and oocyte maturation.

    PubMed

    Lu, Chung-Hao; Lee, Robert Kuo-Kuang; Hwu, Yuh-Ming; Lin, Ming-Huei; Yeh, Ling-Yu; Chen, Ying-Jie; Lin, Shau-Ping; Li, Sheng-Hsiang

    2013-01-01

    The serpin peptidase inhibitor, clade E, member 2 (SERPINE2) inhibits urokinase-type plasminogen activator (PLAU) and tissue-type plasminogen activator. Higher SERPINE2 expression levels were detected in cumulus cells of human immature oocytes than in those of mature oocytes. The objective of this study was to evaluate whether high SERPINE2 levels in cumulus cells are associated with oocyte immaturity. Using the mouse cumulus-oocyte complex as an experimental model, the effects of elimination and overexpression of SERPINE2 in cumulus cells on cumulus expansion and oocyte maturation were assayed by in vitro maturation. Serpine2 and PLAU transcripts were the most highly expressed serpins and plasminogen activators, respectively. Their expression was coordinately regulated in cumulus cells during gonadotropin-induced oocyte maturation. Silencing of Serpine2 expression using small interfering RNAs or blockage of SERPINE2 protein using a specific antibody had no effect on oocyte maturation. However, overexpression of Serpine2 or exogenous supplementation with high levels of SERPINE2 impaired cumulus expansion and oocyte maturation, probably by decreasing hyaluronan synthase 2 (Has2) and versican (Vcan) mRNA expression. Amiloride, a specific PLAU inhibitor, also suppressed these processes. PLAU supplementation of the oocyte in vitro maturation medium caused earlier and more extensive expansion of cumulus cells and oocyte maturation that may be mediated by increased Has2 mRNA expression. However, these effects were neutralized by coincubation with SERPINE2 or amiloride and PLAU. In conclusion, SERPINE2 and PLAU are involved in cumulus expansion and oocyte maturation. High SERPINE2 levels impair these processes, probably by decreasing cumulus matrix gene expression as well as reducing cumulus hyaluronan contents and inhibiting PLAU activity. These findings may explain why cumulus cells surrounding immature human oocytes express high SERPINE2 levels.

  10. Urokinase-Targeted Fusion by Oncolytic Sendai Virus Eradicates Orthotopic Glioblastomas by Pronounced Synergy With Interferon-β Gene

    PubMed Central

    Hasegawa, Yuzo; Kinoh, Hiroaki; Iwadate, Yasuo; Onimaru, Mitsuho; Ueda, Yasuji; Harada, Yui; Saito, Satoru; Furuya, Aki; Saegusa, Takashi; Morodomi, Yosuke; Hasegawa, Mamoru; Saito, Shigeyoshi; Aoki, Ichio; Saeki, Naokatsu; Yonemitsu, Yoshikazu

    2010-01-01

    Glioblastoma multiforme (GM), the most frequent primary malignant brain tumor, is highly invasive due to the expression of proteases, including urokinase-type plasminogen activator (uPA). Here, we show the potential of our new and powerful recombinant Sendai virus (rSeV) showing uPA-specific cell-to-cell fusion activity [rSeV/dMFct14 (uPA2), named “BioKnife”] for GM treatment, an effect that was synergistically enhanced by arming BioKnife with the interferon-β (IFN-β) gene. BioKnife killed human GM cell lines efficiently in a uPA-dependent fashion, and this killing was prevented by PA inhibitor-1. Rat gliosarcoma 9L cells expressing both uPA and its functional receptor uPAR (9L-L/R) exhibited high uPA activity on the cellular surface and were highly susceptible to BioKnife. Although parent 9L cells (9L-P) were resistant to BioKnife and to BioKnife expressing IFN-β (BioKnife-IFNβ), cell–cell fusion of 9L-L/R strongly facilitated the expression of IFN-β, and in turn, IFN-β significantly accelerated the fusion activity of BioKnife. A similar synergy was seen in a rat orthotopic brain GM model with 9L-L/R in vivo; therefore, these results suggest that BioKnife-IFNβ may have significant potential to improve the survival of GM patients in a clinical setting. PMID:20606645

  11. Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma(△).

    PubMed

    Shou, Li-Hong; Cao, Dan; Dong, Xiao-Hui; Fang, Qiu; Xu, Bao-Lian; Fei, Ju-Ping

    2016-09-20

    Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. Methods uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. Results uPAR level in bone marrow fluid of MM patients (1.52±0.32 μg/ml) was found to be higher than that in the control group (0.98±0.15 μg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. Conclusion Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

  12. Expression of urokinase-type plasminogen activator, stromelysin 1, stromelysin 3, and matrilysin genes in lung carcinomas.

    PubMed Central

    Bolon, I.; Devouassoux, M.; Robert, C.; Moro, D.; Brambilla, C.; Brambilla, E.

    1997-01-01

    We have previously shown that the extracellular-matrix-degrading enzymes, urokinase-type plasminogen activator (u-PA), stromelysin 1, stromelysin 3, and matrilysin, may play an important role in the transition from lung preneoplasia to invasive carcinoma. Using in situ hybridization and immunohistochemistry, we analyzed serial frozen sections for the expression of these enzymes in 89 lung carcinomas including 25 neuroendocrine (NE) carcinomas (10 small-cell lung carcinomas, 7 large-cell NE carcinomas, 1 atypical, and 7 typical carcinoids) and 64 non-small-cell, non-NE carcinomas (29 squamous and 7 basaloid carcinomas, 23 adenocarcinomas, and 5 large-cell carcinomas). Proteases, except matrilysin, were more often expressed in stromal than cancer cells. In non-small-cell, non-NE carcinomas, stromal co-expression of u-PA and stromelysin 3 was seen in 80 to 90% of the tumors and was highly correlated (P < 0.0001). Stromal u-PA and stromelysin 3 expression was linked to tumor size (P = 0.01 and 0.03, respectively) and lymph node involvement (P = 0.001 and 0.02, respectively). Epithelial expression of u-PA was correlated to tumor size (P = 0.04). Epithelial expression of stromelysin 3 predominated in squamous and basaloid carcinomas (P = 0.0005) and was inversely correlated to squamous differentiation (P = 0.018). Epithelial expression of matrilysin predominated in adenocarcinomas and large-cell carcinomas (P = 0.07). In NE carcinomas including small-cell lung carcinomas, stromal expression of u-PA was correlated to lymph node metastasis (P = 0.017). Epithelial expression of all enzymes were significantly less frequent in NE than in non-NE tumors. We conclude that 1) epithelial expression of matrix proteases in lung cancer is linked to cell phenotype (NE versus non-NE, squamous versus glandular) and 2) their stromal, rather than epithelial, expression influences local metastasis. Images Figure 1 PMID:9137088

  13. Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children: A Single-Center Report

    PubMed Central

    Price, Heather E.; Gallon, Lorenzo; Langman, Craig B.

    2013-01-01

    Summary Background and objectives FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children. Design, setting, participants, & measurements This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases. Results This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1–21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P>0.05). However, suPAR levels (median [25%–75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml [2695–4392]) versus FSGS (2487 pg/ml [2191–3351]; P<0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr >2) had lower suPAR levels than those without proteinuria (2380 pg/ml [2116–2571] versus 3125 pg/ml [2516–4198], respectively; P<0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P>0.05). Conclusions On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS. PMID:23620441

  14. Hall effect in hopping regime

    NASA Astrophysics Data System (ADS)

    Avdonin, A.; Skupiński, P.; Grasza, K.

    2016-02-01

    A simple description of the Hall effect in the hopping regime of conductivity in semiconductors is presented. Expressions for the Hall coefficient and Hall mobility are derived by considering averaged equilibrium electron transport in a single triangle of localization sites in a magnetic field. Dependence of the Hall coefficient is analyzed in a wide range of temperature and magnetic field values. Our theoretical result is applied to our experimental data on temperature dependence of Hall effect and Hall mobility in ZnO.

  15. Detecting spatial regimes in ecosystems

    USGS Publications Warehouse

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

    2017-01-01

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

  16. 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.

  17. Flow regimes during immiscible displacement

    DOE PAGES

    Armstrong, Ryan T.; Mcclure, James; Berrill, Mark A.; ...

    2017-02-01

    Fractional ow of immiscible phases occurs at the pore scale where grain surfaces and phases interfaces obstruct phase mobility. However, the larger scale behavior is described by a saturation-dependent phenomenological relationship called relative permeability. As a consequence, pore-scale parameters, such as phase topology and/ or geometry, and details of the flow regime cannot be directly related to Darcy-scale flow parameters. It is well understood that relative permeability is not a unique relationship of wetting-phase saturation and rather depends on the experimental conditions at which it is measured. Herein we use fast X-ray microcomputed tomography to image pore-scale phase arrangements duringmore » fractional flow and then forward simulate the flow regimes using the lattice-Boltzmann method to better understand the underlying pore-scale flow regimes and their influence on Darcy-scale parameters. We find that relative permeability is highly dependent on capillary number and that the Corey model fits the observed trends. At the pore scale, while phase topologies are continuously changing on the scale of individual pores, the Euler characteristic of the nonwetting phase (NWP) averaged over a sufficiently large field of view can describe the bulk topological characteristics; the Euler characteristic decreases with increasing capillary number resulting in an increase in relative permeability. Lastly, we quantify the fraction of NWP that flows through disconnected ganglion dynamics and demonstrate that this can be a significant fraction of the NWP flux for intermediate wetting-phase saturation. Furthermore, rate dependencies occur in our homogenous sample (without capillary end effect) and the underlying cause is attributed to ganglion flow that can significantly influence phase topology during the fractional flow of immiscible phases.« less

  18. Overview of the regimes: CWC

    SciTech Connect

    1995-12-31

    The Chemical Weapons Convention`s (CWC) seeks to eradicate an entire category of catastrophic weapons and to ensure their continued non-production. Unlike the Non-Proliferation Treaty`s (NPT), the CWC requires disarmament. States Parties having chemical weapons (CW) must destroy them. The CWC has not adopted the NPT distinction between weapons and non-weapons states; the CWC`s prohibitions and obligations will apply identically to all States parties. In most other respects, the two treaties establish similar regimes with similar approaches. Included are objectives and primary obligations, legal bases, institutional oversight, trade restrictions, protection of information, penal consequences, and role of the United Nations.

  19. 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…

  20. 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.

  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. 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

  3. Tissue and urokinase plasminogen activators instigate the degeneration of retinal ganglion cells in a mouse model of glaucoma

    PubMed Central

    Chintala, Shravan K

    2015-01-01

    Elevated intraocular pressure (IOP) promotes the degeneration of retinal ganglion cells (RGCs) during the progression of Primary Open-Angle Glaucoma (POAG). However, the molecular mechanisms underpinning IOP-mediated degeneration of RGCs remain unclear. Therefore, by employing a mouse model of POAG, this study examined whether elevated IOP promotes the degeneration of RGCs by up-regulating tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) in the retina. IOP was elevated in mouse eyes by injecting fluorescent-microbeads into the anterior chamber. Once a week, for eight weeks, IOP in mouse eyes was measured by using Tono-Pen XL. At various time periods after injecting microbeads, proteolytic activity of tPA and uPA in retinal protein extracts was determined by fibrinogen/plasminogen zymography assays. Localization of tPA and uPA, and their receptor LRP-1 (low-density receptor-related protein-1) in the retina was determined by immunohistochemistry. RGCs’ degeneration was assessed by immunostaining with antibodies against Brn3a. Injection of microbeads into the anterior chamber led to a progressive elevation in IOP, increased the proteolytic activity of tPA and uPA in the retina, activated plasminogen into plasmin, and promoted a significant degeneration of RGCs. Elevated IOP up-regulated tPA and LRP-1 in RGCs, and uPA in astrocytes. At four weeks after injecting microbeads, RAP (receptor associated protein; 0.5 and 1.0 μM) or tPA-Stop (1.0 and 4.0 μM) was injected into the vitreous humor. Treatment of IOP-elevated eyes with RAP led to a significant decrease in proteolytic activity of both tPA and uPA, and a significant decrease in IOP-mediated degeneration of RGCs. Also, treatment of IOP-elevated eyes with tPA-Stop decreased the proteolytic activity of both tPA and uPA, and, in turn, significantly attenuated IOP-mediated degeneration of RGCs. Results presented in this study provide evidence that elevated IOP promotes the degeneration of

  4. 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

  5. Fire regime in Mediterranean ecosystem

    NASA Astrophysics Data System (ADS)

    Biondi, Guido; Casula, Paolo; D'Andrea, Mirko; Fiorucci, Paolo

    2010-05-01

    The analysis of burnt areas time series in Mediterranean regions suggests that ecosystems characterising this area consist primarily of species highly vulnerable to the fire but highly resilient, as characterized by a significant regenerative capacity after the fire spreading. In a few years the area burnt may once again be covered by the same vegetation present before the fire. Similarly, Mediterranean conifer forests, which often refers to plantations made in order to reforest the areas most severely degraded with high erosion risk, regenerate from seed after the fire resulting in high resilience to the fire as well. Only rarely, and usually with negligible damages, fire affects the areas covered by climax species in relation with altitude and soil types (i.e, quercus, fagus, abies). On the basis of these results, this paper shows how the simple Drossel-Schwabl forest fire model is able to reproduce the forest fire regime in terms of number of fires and burned area, describing whit good accuracy the actual fire perimeters. The original Drossel-Schwabl model has been slightly modified in this work by introducing two parameters (probability of propagation and regrowth) specific for each different class of vegetation cover. Using model selection methods based on AIC, the model with the optimal number of classes with different fire behaviour was selected. Two different case studies are presented in this work: Regione Liguria and Regione Sardegna (Italy). Both regions are situated in the center of the Mediterranean and are characterized by a high number of fires and burned area. However, the two regions have very different fire regimes. Sardinia is affected by the fire phenomenon only in summer whilst Liguria is affected by fires also in winter, with higher number of fires and larger burned area. In addition, the two region are very different in vegetation cover. The presence of Mediterranean conifers, (Pinus Pinaster, Pinus Nigra, Pinus halepensis) is quite spread in

  6. 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.

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

    PubMed

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

    2006-09-01

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

  8. 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

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

    PubMed

    Boutaud, A; Castellino, F J

    1993-06-01

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

  10. 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).

  11. 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...

  12. Three regimes of relativistic beam - plasma interaction

    SciTech Connect

    Muggli, P.; Allen, B.; Fang, Y.; Yakimenko, V.; Babzien, M.; Kusche, K.; Fedurin, M.; Vieira, J.; Martins, J.; Silva, L.

    2012-12-21

    Three regimes of relativistic beam - plasma interaction can in principle be reached at the ATF depending on the relative transverse and longitudinal size of the electron bunch when compared to the cold plasma collisionless skin depth c?{omega}{sub pe}: the plasma wakefield accelerator (PWFA), the self-modulation instability (SMI), and the current filamentation instability (CFI) regime. In addition, by choosing the bunch density, the linear, quasi-nonlinear and non linear regime of the PWFA can be reached. In the case of the two instabilities, the bunch density determines the growth rate and therefore the occurrence or not of the instability. We briefly describe these three regimes and outline results demonstrating that all these regime have or will be reached experimentally. We also outline planned and possible follow-on experiments.

  13. 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.

  14. Distinct Turbulence Saturation Regimes in Stellarators

    NASA Astrophysics Data System (ADS)

    Plunk, G. G.; Xanthopoulos, P.; Helander, P.

    2017-03-01

    In the complex 3D magnetic fields of stellarators, ion-temperature-gradient turbulence is shown to have two distinct saturation regimes, as revealed by petascale numerical simulations and explained by a simple turbulence theory. The first regime is marked by strong zonal flows and matches previous observations in tokamaks. The newly observed second regime, in contrast, exhibits small-scale quasi-two-dimensional turbulence, negligible zonal flows, and, surprisingly, a weaker heat flux scaling. Our findings suggest that key details of the magnetic geometry control turbulence in stellarators.

  15. Photosynthesis, Carbohydrate Metabolism, and Export in Beta vulgaris L. and Phaseolus vulgaris L. during Square and Sinusoidal Light Regimes.

    PubMed

    Fondy, B R; Geiger, D R; Servaites, J C

    1989-02-01

    Rates of photosynthesis, sucrose synthesis, starch accumulation and degradation were measured in sugar beet (Beta vulgaris L.) and bean (Phaseolus vulgaris L.) plants under a square-wave light regime and under a sinusoidal regime that simulated the natural daylight period. Photosynthesis rate increased in a measured manner in direct proportion to the increasing light level. In contrast to this close correspondence between photosynthesis and light, a lag in photosynthesis rate was seen during the initial hour under square-wave illumination. The leaf appeared to be responding to limits set by carbon metabolism rather than by gas exchange or light reactions. Under the sinusoidal regime starch degradation occurred during the first and last 2 hours of the photoperiod, likely in response to photosynthesis rate rather than directly to light level. Starch broke down when photosynthesis was below a threshold rate and accumulated above this rate. Under square-wave illumination, accumulation of starch did not begin until irradiance was at full level for an hour or more and photosynthesis was at or near its maximum. Under a sinusoidal light regime, sucrose synthesis rate comprised carbon that was newly fixed throughout the day plus that from starch degradation at the beginning and end of the day. Synthesis of sucrose from recently fixed carbon increased with increasing net carbon fixation rate while its formation from degradation of starch decreased correspondingly. The complementary sources of carbon maintained a relatively steady rate of sucrose synthesis under the changing daytime irradiance.

  16. 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).

  17. Prolonged instability prior to a regime shift.

    PubMed

    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.

  18. 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.}

  19. Iranian Regime Reform: Opportunities and Consequences

    DTIC Science & Technology

    2010-12-01

    formal political access to mitigate the adverse effects of . . . the deterioration of quality of life .”70 Three broad sets of factors outlined by...demanding changes in the Iranian regime that mesh with U.S.. national interests. However, the Green Movement may not be successful in effecting change...viable threat to the Iranian regime. This thesis used game theory as a tool because game theory outcomes very often reflect real- life outcomes

  20. Greenland Meltwater and Arctic Circulation Regimes

    NASA Astrophysics Data System (ADS)

    Dukhovskoy, D. S.; Proshutinsky, A. Y.; Timmermans, M. L.; Myers, P. G.; Platov, G.

    2015-12-01

    Between 1948 and 1996, wind-driven components of ice drift and surface ocean currents experienced a well-pronounced decadal variability alternating between anticyclonic and cyclonic circulation regimes. During cyclonic regimes, low sea level atmospheric pressure dominated over the Arctic Ocean driving sea ice and the upper ocean clockwise; the Arctic atmosphere was relatively warm and humid and freshwater flux from the Arctic Ocean toward the sub-Arctic seas was intensified. During anticylonic circulation regimes, high sea level pressure dominated over the Arctic driving sea ice and ocean counter-clockwise; the atmosphere was cold and dry and the freshwater flux from the Arctic to the sub-Arctic seas was reduced. Since 1997, however, the Arctic system has been dominated by an anticyclonic circulation regime with a set of environmental parameters that are atypical for these regimes. Of essential importance is to discern the causes and consequences of the apparent break-down in the natural decadal variability of the Arctic climate system, and specifically: Why has the well-pronounced decadal variability observed in the 20th century been replaced by relatively weak interannual changes under anticyclonic circulation regime conditions in the 21st century? 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 Greenland impact environmental conditions and interrupt their decadal variability. In order to test this hypothesis, numerical experiments with several FAMOS (Forum for Arctic Modeling & Observational Synthesis) ice-ocean coupled models have been conducted. In these experiments, Greenland melt freshwater is tracked by passive tracers being constantly released along the Greenland coast. Propagation pathways and time scales of Greenland meltwater within the sub-Arctic seas are discussed.

  1. 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.

  2. 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.

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

    PubMed Central

    Siahanidou, Tania; Margeli, Alexandra; Charoni, Stavroula; Giannaki, Maria; Vavourakis, Eustathios; Charisiadou, Athina; Papassotiriou, Ioannis

    2014-01-01

    Background. suPAR, the soluble form of the urokinase-type plasminogen activator receptor, has been identified as a biomarker of infection in adults but its properties in neonatal infection are not known. Methods. Plasma suPAR levels were determined by ELISA in 47 term neonates with infection (19 bacterial and 28 viral) and in 18 healthy neonates as controls. Thirteen out of 47 infected neonates were septic. In all infected neonates, suPAR levels were repeated at 24 hours, 48 hours, 3–5 days, and 7–10 days following admission. Results. Plasma suPAR levels were significantly increased in infected neonates upon admission, whereas they were highest in septic neonates, in comparison with controls (P < 0.001) and correlated positively with serum CRP levels (P = 0.001). At infection subsidence, suPAR concentrations decreased significantly in comparison with baseline (P < 0.001) but remained higher than in controls (P = 0.01). Receiver operating characteristic analysis resulted in significant areas under the curve for detecting either infected or septic neonates, but not for discriminating between bacterial and viral cause of infection. Conclusions. suPAR is a diagnostic biomarker of infection or sepsis in term neonates; however, it cannot discriminate bacterial from viral infections and also its utility for monitoring the response to treatment is questioned. PMID:24882949

  4. 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

  5. Fluorescence Correlation Spectroscopy and Photon Counting Histogram on membrane proteins: Functional dynamics of the GPI-anchored Urokinase Plasminogen Activator Receptor

    PubMed Central

    Malengo, Gabriele; Andolfo, Annapaola; Sidenius, Nicolai; Gratton, Enrico; Zamai, Moreno; Caiolfa, Valeria R

    2009-01-01

    The oligomerization of GPI-anchored proteins is thought to regulate their association with membrane microdomains, sub-cellular sorting and activity. However, these mechanisms need to be comprehensively explored in living, unperturbed cells, without artificial clustering agents, and using fluorescent protein-tagged chimeras that are fully biologically active. We expressed in HEK293 cells a biologically active chimera of the urokinase plasminogen activator receptor (uPAR), the uPAR-mEGFP-GPI. We also produced HEK293/D2D3-mEGFP-GPI cells expressing the truncated form of the receptor, lacking biological activity. We studied the dynamics and oligomerization of the two proteins, combining FCS and PCH analyses, and using subclones with homogenously low expression levels. Overall, the mobile fractions of the two proteins, constituted by monomers and dimers, had comparable diffusion coefficients. However, only for the active receptor the diffusion coefficient decreased in monomer-enriched fractions, suggesting that uPAR monomers might be preferentially engaged in multi-protein transmembrane signaling complexes. Our approach helps in limiting the alteration of the data due to out-of-focus, and minimizing the overestimation of the molecular brightness. Joint to a careful design of the cellular model, it gives reliable estimates of diffusion coefficients and oligomerization of GPI-anchored proteins, in steady state conditions, at low expression levels, and in live, unperturbed cells. PMID:18601539

  6. Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

    PubMed Central

    Amos, Samson; Mut, Melike; diPierro, Charles G.; Carpenter, Joan E.; Xiao, Aizhen; Kohutek, Zachary A.; Redpath, Gerard T.; Zhao, Yunge; Wang, Jiahu; Shaffrey, Mark E.; Hussaini, Isa M.

    2008-01-01

    Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor–related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-α (PKC-α) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-α small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate–induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRP-deficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-α/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-α and PI3K could provide a new treatment paradigm for glioblastomas. PMID:17974965

  7. Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis

    PubMed Central

    Ni, Wentao; Han, Yuliang; Zhao, Jin; Cui, Junchang; Wang, Kai; Wang, Rui; Liu, Youning

    2016-01-01

    The serum concentration of soluble urokinase-type plasminogen activator receptor (suPAR) reflects immune activation. We performed a meta-analysis to evaluate the usefulness of suPAR for the diagnosis and prognosis of bacterial infections. PubMed, Embase and Cochrane Library databases were searched for studies reporting the detection of suPAR in adult patients with bacterial infections. Seventeen studies were selected from 671 studies. The pooled sensitivity and specificity of suPAR for diagnosing infection were 0.73 and 0.79, respectively, and the area under the summary receiver operating characteristic curve (AUC) was 0.82. Subgroup analyses revealed suPAR showed similar AUC values for diagnosing sepsis and bacteremia, but the AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was only 0.68. Elevated suPAR levels were significantly associated with a high risk of death, with a pooled risk ratio of 3.37 (95% confidence interval, 2.60–4.38). The pooled sensitivity and specificity for predicting mortality were 0.70 and 0.72, respectivfely, with an AUC of 0.77. Serum suPAR could be a biomarker for the diagnosis and prognosis of bacterial infection, but it is relatively ineffective for differentiating sepsis from SIRS. Further investigation is required to evaluate whether using of suPAR in combination with other biomarkers can improve diagnostic efficacy. PMID:27991579

  8. Regulation of proteinases during mouse peri-implantation development: urokinase-type plasminogen activator expression and cross talk with matrix metalloproteinase 9.

    PubMed

    Martínez-Hernández, M G; Baiza-Gutman, L A; Castillo-Trápala, A; Armant, D Randall

    2011-02-01

    Trophoblast cells express urokinase-type plasminogen activator (PLAU) and may depend on its activity for endometrial invasion and tissue remodeling during peri-implantation development. However, the developmental regulation, tissue distribution, and function of PLAU are not completely understood. In this study, the expression of PLAU and its regulation by extracellular matrix proteins was examined by RT-PCR, immunocytochemistry, and plasminogen-casein zymography in cultured mouse embryos. There was a progressive increase in Plau mRNA expression in blastocysts cultured on gestation days 4-8. Tissue-type plasminogen activator (55 kDa) and PLAU (a triplet of 40, 37, and 31 kDa) were present in conditioned medium and embryo lysates, and were adsorbed to the culture plate surface. The temporal expression pattern of PLAU, according to semi-quantitative gel zymography, was similar in non-adhering embryos and embryos cultured on fibronectin, laminin, or type IV collagen, although type IV collagen and laminin upregulated Plau mRNA expression. Immunofluorescence revealed PLAU on the surface of the mural trophectoderm and in non-spreading giant trophoblast cells. Exogenous human plasminogen was transformed to plasmin by cultured embryos and activated endogenous matrix metalloproteinase 9 (MMP9). Indeed, the developmental expression profile of MMP9 was similar to that of PLAU. Our data suggest that the intrinsic developmental program predominantly regulates PLAU expression during implantation, and that PLAU could be responsible for activation of MMP9, leading to localized matrix proteolysis as trophoblast invasion commences.

  9. Urokinase-type Plasminogen Activator Resulting from Endometrial Carcinogenesis Enhances Tumor Invasion and Correlates with Poor Outcome of Endometrial Carcinoma Patients

    PubMed Central

    Huang, Chia-Yen; Chang, Ming-Cheng; Huang, Wei-Yun; Huang, Ching-Ting; Tang, Yu-Chien; Huang, Hsien-Da; Kuo, Kuan-Ting; Chen, Chi-An; Cheng, Wen-Fang

    2015-01-01

    The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC), and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia, and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis, and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC. PMID:26033187

  10. Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA-MB231 Breast Cancer Cells.

    PubMed

    Longo, Alessandra; Librizzi, Mariangela; Chuckowree, Irina S; Baltus, Christine B; Spencer, John; Luparello, Claudio

    2015-05-28

    BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding; and (ii) the co-presence of the EGFR inhibitor PD153035 potentiates BC-11's cytotoxicity. Exposure of cells to a higher concentration of BC-11 corresponding to its ED75 at 72 h (250 μM) caused additional impairment of mitochondrial activity, the production of reactive oxygen species and promotion of apoptosis. Therefore, BC-11 treatment appears to show potential for the development of this class of compounds in the prevention and/or therapy of "aggressive" breast carcinoma.

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

    PubMed

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

    2009-01-01

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

  12. Dynamic treatment regimes: technical challenges and applications

    PubMed Central

    Lizotte, Daniel J.; Qian, Min; Pelham, William E.; Murphy, Susan A.

    2014-01-01

    Dynamic treatment regimes are of growing interest across the clinical sciences because these regimes provide one way to operationalize and thus inform sequential personalized clinical decision making. Formally, a dynamic treatment regime is a sequence of decision rules, one per stage of clinical intervention. Each decision rule maps up-to-date patient information to a recommended treatment. We briefly review a variety of approaches for using data to construct the decision rules. We then review a critical inferential challenge that results from nonregularity, which often arises in this area. In particular, nonregularity arises in inference for parameters in the optimal dynamic treatment regime; the asymptotic, limiting, distribution of estimators are sensitive to local perturbations. We propose and evaluate a locally consistent Adaptive Confidence Interval (ACI) for the parameters of the optimal dynamic treatment regime. We use data from the Adaptive Pharmacological and Behavioral Treatments for Children with ADHD Trial as an illustrative example. We conclude by highlighting and discussing emerging theoretical problems in this area. PMID:25356091

  13. 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

  14. 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.

  15. Gradual regime shifts in fairy circles.

    PubMed

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

    2015-10-06

    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.

  16. Multiscale regime shifts and planetary boundaries.

    PubMed

    Hughes, Terry P; Carpenter, Stephen; Rockström, Johan; Scheffer, Marten; Walker, Brian

    2013-07-01

    Life on Earth has repeatedly displayed abrupt and massive changes in the past, and there is no reason to expect that comparable planetary-scale regime shifts will not continue in the future. Different lines of evidence indicate that regime shifts occur when the climate or biosphere transgresses a tipping point. Whether human activities will trigger such a global event in the near future is uncertain, due to critical knowledge gaps. In particular, we lack understanding of how regime shifts propagate across scales, and whether local or regional tipping points can lead to global transitions. The ongoing disruption of ecosystems and climate, combined with unprecedented breakdown of isolation by human migration and trade, highlights the need to operate within safe planetary boundaries.

  17. On the regimes of charge reversal.

    PubMed

    Jiménez-Angeles, Felipe; Lozada-Cassou, Marcelo

    2008-05-07

    Charge reversal of the planar electrical double layer is studied by means of a well known integral equation theory. By a numerical analysis, a diagram is constructed with the onset points of charge reversal in the space of the fundamental variables of the system. Within this diagram, two regimes of charge reversal are identified, which are referred to as oscillatory and nonoscillatory. We found that these two regimes can be distinguished through a simple formula. Furthermore, a symmetry between electrostatic and size correlations in charge reversal is exhibited. Agreement of our results with other theories and molecular simulations data is discussed.

  18. 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.

  19. 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.

  20. Light focusing in the Anderson regime

    NASA Astrophysics Data System (ADS)

    Leonetti, Marco; Karbasi, Salman; Mafi, Arash; Conti, Claudio

    2014-07-01

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

  1. 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

  2. Atmospheric weather regimes over tropical South America

    NASA Technical Reports Server (NTRS)

    Connors, Vickie S.; Garstang, Michael; Nolf, Scott R.

    1991-01-01

    Infrared radiance measurements by the GOES-6 satellite during April 1986 through April 1987 were used to characterize and identify distinct regimes of persistent large-scale cloudiness patterns over the Amazon Basin. It is suggested that the energetics of the tropical troposphere over the Amazon Basin can be directly related to the GOES large-scale cloudiness patterns. The geometry and persistence of the cloud patterns are influenced by shifts in general circulation features and are likely modulated by 4- to 5-day and 40- to 60-day waves. Diurnal forcing effects are more pronounced during weather regimes characterized by prominently clear skies over land areas.

  3. Markovian quantum master equation beyond adiabatic regime.

    PubMed

    Yamaguchi, Makoto; Yuge, Tatsuro; Ogawa, Tetsuo

    2017-01-01

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

  4. Markovian quantum master equation beyond adiabatic regime

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Makoto; Yuge, Tatsuro; Ogawa, Tetsuo

    2017-01-01

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

  5. 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.

  6. 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

  7. Regimes of turbulence without an energy cascade

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    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.

  8. 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

  9. 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.

  10. Climatic regimes of tropical convection and rainfall

    SciTech Connect

    Wang, Bin )

    1994-07-01

    Annual distribution and phase propagation of tropical convection are delineated using harmonic and amplitude-phase characteristics analysis of climatological pentad mean outgoing longwave radiation and monthly frequencies of highly reflective cloud. An annual eastward propagation of peak rainy season along the equator from the central Indian Ocean (60[degrees]E) to Arafura Sea (130[degrees]E) is revealed. This indicates a transition from the withdrawal of the Indian summer monsoon to the onset of the Australian summer monsoon. Significant bimodal variations are found around major summer monsoon regions. These variations originate from the interference of two adjacent regimes. The convergence zones over the eastern North Pacific, the South Pacific, and the southwest Indian Ocean are identified as a marine monsoon regime that is characterized by a unimodal variation with a concentrated summer rainfall associated with the development of surface westerlies equatorward of a monsoon trough. Conversely, the central North Pacific and North Atlantic convergence zones between persistent northeast and southeast trades are classified as trade-wind convergence zones; which differ from the marine monsoon regime by their persistent rainy season and characteristic bimodal variation with peak rainy seasons occurring in late spring and fall. The roles of the annual march of sea surface temperature in the phase propagation and formation of various climatic regimes of tropical convection are also discussed. 34 refs., 8 figs., 1 tab.

  11. 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…

  12. Impacts of different hydrodynamic regimes on flocculation

    NASA Astrophysics Data System (ADS)

    Ramirez-Mendoza, Rafael; Souza, Alejandro; Amoudry, Laurent

    2014-05-01

    A number of activities carried out in coastal zones and estuaries are affected by sediment transport. Therefore, good knowledge of the processes involved is necessary to adequately manage these areas. Flocculation is a key process on fine sediment dynamics, which affects the effective particle size and settling velocity. The process is further complicated under the combined effect of currents and waves. This research seeks to improve our understanding of the flocculation process under the combined effect of currents and waves. The study site is the Dee Estuary located in Liverpool Bay, United Kingdom. Measurements of volume concentration, grain size and current velocities near the sea bed were obtained from a mooring deployed between 12 February 2008 and 9 March 2008. Turbulent properties could also be calculated because of the fast sampling rate used for current velocities. Water samples were taken from a research vessel during the first two days of the study in order to calibrate moored instruments and convert volume to mass concentration. The observations almost covered two fortnightly periods and three different dynamic regimes can be distinguished: currents-only, combined waves and currents, and wave dominated. During the currents-only regime, floc aggregation and breakup coincide with periods of low and high turbulent stress respectively. The combination of waves and spring tide currents makes the second regime and the floc breakup is most dominant when waves are higher than one meter and small flocs are found even with low turbulent stress from both waves and currents. The third regime is identified as wave-dominant during neap tides with current speed less than 0.25 m/s and waves of 1-2 meters height. In this regime the wave effect takes large sediment into suspension at the same time as small particle sizes from floc breakup. In this case the median particle size is strongly related to the wave height which means that a slight particle aggregation is still

  13. Regime Dependant Microphysical Variability in Darwin, Australia

    NASA Astrophysics Data System (ADS)

    Dolan, B.; Rutledge, S. A.; Lang, T. J.

    2010-12-01

    Of utmost importance for global precipitation estimates from satellites such as TRMM and the upcoming Global Precipitation Measurement (GPM) is to understand processes that lead to variability in precipitation on sub-seasonal, seasonal, and climatological scales. Many studies have linked differences in rainfall characteristics such as mean diameter (D0) to sub-seasonal regime variability forced by large scale wind shifts, topography, and continental and maritime convection, across various regions of the globe. Several analyses have tied differences between regimes to differing microphysical processes that drive changes in the drop-size distributions occurring in convective rainfall. For example, decreased ice mass aloft and smaller mean diameters are indicative of warm rain processes, while vigorous ice formation leads to large, melting ice to create large drops. If the microphysical variability in different regimes is characterized and understood, the results could be used to improve satellite precipitation algorithms. The polarimetric, Doppler C-band radar, CPOL, located near Darwin, Australia provides a unique platform to study differences in microphysics between land and ocean, as well as variability between monsoon and break periods. The focus of this study is to examine the microphysical processes occurring in four distinct regimes around Darwin (monsoon-land, monsoon-ocean, break-land, break-ocean), using polarimetric data from CPOL. Analyses such as contoured frequency by altitude (CFADs) diagrams, cumulative distribution functions, and mean profiles of precipitation water mass, precipitation ice mass, reflectivity, differential reflectivity and specific differential phase will aide in understanding the physics of precipitation in these regimes. The formation of precipitation ice aloft, warm rain processes, and the contributions of warm rain and cold cloud processes including melting of ice into large drops, will be linked to differences in D0, rain

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

    PubMed Central

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

    2017-01-01

    Background Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events. Purpose We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients. Methods and Results In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P<0.001), LVMI (R = 0.16, P = 0.014) and BNP (R = 0.46, P<0.001). In logistic regression analysis, the highest suPAR tertile (> 3236 pg/mL) was associated with low LVEF (< 50%) and elevated BNP (> 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22–12.1) and 5.36 (95% CI, 1.32–21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029). Conclusions suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis. PMID:28135310

  15. The ultrasound contrast imaging properties of lipid microbubbles loaded with urokinase in dog livers and their thrombolytic effects when combined with low-frequency ultrasound in vitro.

    PubMed

    Ren, Shu-Ting; Kang, Xiao-Ning; Liao, Yi-Ran; Wang, Wei; Ai, Hong; Chen, Li-Na; Luo, Hui-Ting; Fu, Rong-Guo; Tan, Li-Fang; Shen, Xin-Liang; Wang, Bing

    2014-04-01

    A new microbubble loaded with urokinase (uPA-MB) was explored in a previous study. However, its zeta potential and ultrasound contrast imaging properties and its thrombolytic effects when combined with low-frequency ultrasound (LFUS) were unclear. The zeta potential and ultrasound contrast imaging property of 5 uPA-MBs loading with 50,000 IU uPA was respectively detected using a Malvern laser particle analyzer and a Logiq 9 digital premium ultrasound system. Its ultrasound contrast imaging property was performed on the livers of two healthy dogs to compare with SonoVue. And the clot mass loss rate, D-dimer concentration and surface morphology of the clot residues were measured to evaluate the thrombolytic effect after treatment with three doses of 5 uPA-MBs combined with LFUS in vitro. The zeta potential of 5 uPA-MBs (-27.0 ± 2.40 mV) was higher than that of normal microbubbles (-36.95 ± 1.77 mV). Contrast-enhanced imaging of the hepatic vessels using 5 uPA-MBs was similar to SonoVue, while the imaging duration of 5 uPA-MBs (10 min) was longer than SonoVue (6 min). The thrombolytic effect of three doses of uPA-MBs combined with LFUS was significantly better than that of the control group and showed dose dependence. The 5 uPA-MBs have a negative charge on their surface and good echogenicity as ultrasound contrast agents. The 5 uPA-MBs combined with LFUS can promote thrombolysis in a dose-dependent manner.

  16. The preparation of a new self-made microbubble-loading urokinase and its thrombolysis combined with low-frequency ultrasound in vitro.

    PubMed

    Ren, Shu-Ting; Zhang, Hui; Wang, Ya-Wen; Jing, Bo-Bin; Li, Ying-Xue; Liao, Yi-Ran; Kang, Xiao-Ning; Zang, Wei-Jin; Wang, Bing

    2011-11-01

    Urokinase (uPA) is used widely for thrombosis therapy in the clinic. However, ways to minimize its adverse effect of hemorrhage are still being studied. As a new technique for the local delivery of genes and drugs, ultrasound (US) contrast agents, microbubbles (MBs), have been mentioned. The purpose of this study is to explore a more efficacious and safer thrombolytic method by preparing three groups of self-made microbubble-loading uPA (uPA-MBs) (1 uPA-MBs, 5 uPA-MBs and 10 uPA-MBs) using freeze-drying methods and measuring their thrombolysis when combined in vitro with low-frequency US. The results showed the mean concentration, mean diameter, pH value and encapsulation efficiency of uPA of the three groups of uPA-MBs were approximately 2.08-2.82 × 10(8)/mL, ∼3.13 μm, 6.89-6.99 and from (78.08% ± 0.57%) to (57.23% ± 0.94%), respectively. Under US exposure, the loaded uPA demonstrated bioactivity by agarose fibrin plate and in vitro thrombolysis of the three uPA-MBs also showed higher effects than in the group of those who received uPA-MBs alone, the control group or the US group. In conclusion, the physiochemical properties of these self-made uPA-MBs are suitable for intravenous administration but 1 uPA-MB and 5 uPA-MBs are better than 10 uPA-MBs. uPA-MBs combined with US can decrease the in vitro dosage of uPA for thrombolysis.

  17. 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

  18. Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study

    PubMed Central

    Rasmussen, Line Jee Hartmann; Ladelund, Steen; Haupt, Thomas Huneck; Ellekilde, Gertrude; Poulsen, Jørgen Hjelm; Iversen, Kasper; Eugen-Olsen, Jesper; Andersen, Ove

    2016-01-01

    Objective Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker associated with presence and progression of disease and with increased risk of mortality. We aimed to evaluate the unspecific biomarker suPAR as a prognostic marker in patients admitted to acute care. Methods This registry-based retrospective cohort study included 4343 consecutively admitted patients from the Acute Medical Unit at a large Danish university hospital. Time to readmission and death were analysed by multiple Cox regression. Results were reported as HRs for 30-day and 90-day follow-up. Results During 30-day follow-up, 782 patients (18.0%) were readmitted and 224 patients (5.2%) died. Comparing 30-day readmission and mortality between patients in the highest and lowest suPAR quartiles yielded HRs of 2.11 (95% CI 1.70 to 2.62) and 4.11 (95% CI 2.46 to 6.85), respectively, when adjusting for age, sex, Charlson score and C reactive protein. Area under the curve for receiver operating characteristics curve analysis of suPAR for 30-day mortality was 0.84 (95% CI 0.81 to 0.86). Furthermore, in the entire cohort, women had slightly higher suPAR compared with men, and suPAR was associated with age, admission time, admission to intensive care unit and Charlson score. Conclusions In this large unselected population of acute medical patients, suPAR is strongly associated with disease severity, readmission and mortality after adjusting for all other risk factors, indicating that suPAR adds information to established prognostic indicators. While patients with low suPAR levels have low risk of readmission and mortality, patients with high suPAR levels have a high risk of adverse events. PMID:27590986

  19. 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

  20. Mouse ovarian granulosa cells produce urokinase-type plasminogen activator, whereas the corresponding rat cells produce tissue-type plasminogen activator

    PubMed Central

    1987-01-01

    It is well established that rat ovarian granulosa cells produce tissue plasminogen activator (tPA). The synthesis and secretion of the enzyme are induced by gonadotropins, and correlate well with the time of follicular rupture in vivo. We have found that in contrast, mouse granulosa cells produce a different form of plasminogen activator, the urokinase-type (uPA). As with tPA synthesis in the rat, uPA production by mouse granulosa cells is induced by gonadotropins, dibutyryl cAMP, and prostaglandin E2. However, dexamethasone, a drug which has no effect on tPA synthesis in rat cells inhibits uPA synthesis in the mouse. Results of these determinations made in cell culture were corroborated by examining follicular fluid, which is secreted in vivo predominantly by granulosa cells, from stimulated rat and mouse ovarian follicles. Rat follicular fluid contained only tPA, and mouse follicular fluid only uPA, indicating that in vivo, granulosa cells from the two species are secreting different enzymes. The difference in the type of plasminogen activator produced by the rat and mouse granulosa cells was confirmed at the messenger RNA level. After hormone stimulation, only tPA mRNA was present in rat cells, whereas only uPA mRNA was found in mouse cells. Furthermore, the regulation of uPA levels in mouse cells occurs via transient modulation of steady-state levels of mRNA, a pattern similar to that seen with tPA in rat cells. PMID:3040774

  1. Cyclization of the Urokinase Receptor-Derived Ser-Arg-Ser-Arg-Tyr Peptide Generates a Potent Inhibitor of Trans-Endothelial Migration of Monocytes

    PubMed Central

    Bifulco, Katia; Ingangi, Vincenzo; Di Carluccio, Gioconda; Merlino, Francesco; Motti, Maria Letizia; Grieco, Paolo; Carriero, Maria Vincenza

    2015-01-01

    The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88-92 is the minimal sequence required to induce cell motility. We and others have previously documented that the uPAR88-92 sequence, even in the form of synthetic linear peptide (SRSRY), interacts with the formyl peptide receptor type 1 (FPR1), henceforth inducing cell migration of several cell lines, including monocytes. FPR1 is mainly expressed by mammalian phagocytic leukocytes and plays a crucial role in chemotaxis. In this study, we present evidence that the cyclization of the SRSRY sequence generates a new potent and stable inhibitor of monocyte trafficking. In rat basophilic leukaemia RBL-2H3/ETFR cells expressing high levels of constitutively activated FPR1, the cyclic SRSRY peptide ([SRSRY]) blocks FPR1 mediated cell migration by interfering with both internalization and ligand-uptake of FPR1. Similarly to RBL-2H3/ETFR cells, [SRSRY] competes with fMLF for binding to FPR1 and prevents agonist-induced FPR1 internalization in human monocyte THP-1 cells. Unlike scramble [RSSYR], [SRSRY] inhibits fMLF-directed migration of monocytes in a dose-dependent manner, with IC50 value of 0.01 nM. PMA-differentiated THP-1 cell exposure to fMLF gradient causes a marked cytoskeletal re-organization with the formation of F-actin rich pseudopodia that are prevented by the addition of [SRSRY]. Furthermore, [SRSRY] prevents migration of human primary monocytes and trans-endothelial migration of monocytes. Our findings indicate that [SRSRY] is a new FPR1 inhibitor which may suggest the development of new drugs for treating pathological conditions sustained by increased motility of monocytes, such as chronic inflammatory diseases. PMID:25938482

  2. Tissue-specific inhibition of urokinase-type plasminogen activator expression in the testes of mice by inducible lentiviral RNA interference causes male infertility.

    PubMed

    Zhao, Kai; Liu, Yan; Xiong, Zhe; Hu, Lian; Xiong, Cheng-Liang

    2017-03-16

    Urokinase-type plasminogen activator (uPA) is involved in many physiological processes, including male infertility. To explore the effects of uPA in male reproduction, we constructed an inducible uPA short hairpin RNA (shRNA) system expressed by lentiviral vectors. After proving inhibition of uPA expression in the mouse Sertoli cell line TM4 by 1μgmL-1 doxycycline (Dox), two lentivirus (pLenti4-shRNA and pLenti6/TR) were co-microinjected into mouse testes to produce TetR&shuPA mice model. Though oral gavage by 0.75mgmL-1 Dox each day for 1 week, the Plau mRNA expression, uPA protein level and uPA enzyme activity in mice testis decreased significantly in TetR&shuPA mice model. After Dox induction of 1 week, the TetR&shuPA mice mated with female mice. Our results show that the pregnancy rate was reduced by approximately 40% and the sperm motility also decreased significantly. These data indicated that downregulation of uPA could decrease the fertility of male mice, which may be caused by a reduction in sperm motility. To investigate the reversible effect and safety of the inducible uPA shRNA system, we withdraw Dox and found the mating rate and sperm motility gradually recovered after 2 weeks. The histopathology structure of the testis, epididymis, and main organs was not altered significantly. The results of the present study indicating that uPA may be regarded as a novel target for the regulation of male fertility.

  3. A distinct basic fibroblast growth factor (FGF-2)/FGF receptor interaction distinguishes urokinase-type plasminogen activator induction from mitogenicity in endothelial cells.

    PubMed Central

    Rusnati, M; Dell'Era, P; Urbinati, C; Tanghetti, E; Massardi, M L; Nagamine, Y; Monti, E; Presta, M

    1996-01-01

    Basic fibroblast growth factor (FGF-2) induces cell proliferation and urokinase-type plasminogen activator (uPA) production in fetal bovine aortic endothelial GM 7373 cells. In the present paper we investigated the role of the interaction of FGF-2 with tyrosine-kinase (TK) FGF receptors (FGFRs) in mediating uPA up-regulation in these cells. The results show that FGF-2 antagonists suramin, protamine, heparin, the synthetic peptide FGF-2(112-155), and a soluble form of FGFR-1 do not inhibit FGF-2-mediated uPA up-regulation at concentrations that affect growth factor binding to cell surface receptors and mitogenic activity. In contrast, tyrosine phosphorylation inhibitors and overexpression of a dominant negative TK- mutant of FGFR-1 abolish the uPA-inducing activity of FGF-2, indicating that FGFR and its TK activity are essential in mediating uPA induction. Accordingly, FGF-2 induces uPA up-regulation in Chinese hamster ovary cells transfected with wild-type FGFR-1, -2, -3, or -4 but not with TK- FGFR-1 mutant. Small unilamellar phosphatidyl choline:cholesterol vesicles loaded with FGF-2 increased uPA production in GM 7373 cells in the absence of a mitogenic response. Liposome-encapsulated FGF-2 showed a limited but significant capacity, relative to free FGF-2, to interact with FGFR both at 4 degrees C and 37 degrees C and to be internalized within the cell. uPA up-regulation by liposome-encapsulated FGF-2 was quenched by neutralizing anti-FGF-2 antibodies, indicating that the activity of liposome-delivered FGF-2 is mediated by an extracellular action of the growth factor. Taken together, the data indicate that a distinct interaction of FGF-2 with FGFR, quantitatively and/or qualitatively different from the one that leads to mitogenicity, is responsible for the uPA-inducing activity of the growth factor. Images PMID:8868466

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Flamelet Regime Diagram for Turbulent Combustion Simulations

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  9. Photoelectron circular dichroism in different ionization regimes

    NASA Astrophysics Data System (ADS)

    Wollenhaupt, Matthias

    2016-12-01

    Photoelectron circular dichroism (PECD) describes an asymmetry in the photoelectron angular distribution (PAD) from photoionization of randomly oriented enantiomers with circularly polarized light. Baulieu et al present a comprehensive set of measured PADs from multiphoton ionization of limonene and fenchone in different ionization regimes (multiphoton and tunneling) and analyze the resulting PECD (Baulieu et al 2016 New J. Phys. 18 102002). From their observations the authors conclude that the PECD is universal in the sense that the molecular chirality is encoded in the PAD independent of the ionization regime. The analysis is supplemented by a classical model based on electron scattering in a chiral potential. The paper presents beautiful data and is an important step towards a more complete physical picture of PECD. The results and their interpretation stimulate the ongoing vivid debate on the role of resonances in multiphoton PECD.

  10. 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.

  11. Economic Performance and North Korean Regime Legitimacy

    DTIC Science & Technology

    2014-06-01

    PERFORMANCE AND NORTH KOREAN REGIME LEGITIMACY by Patrick J. Moore June 2014 Thesis Advisor: Naazneen Barma Second Reader: Robert Weiner THIS...Advisor Dr. Robert Weiner Second Reader Dr. Mohammed Hafez Chair, Department of National Security Affairs iv THIS PAGE...offers a view of success, the country outside the capital is a much different situation. Victor Cha writes that even in Kaesong, the second -largest city

  12. A Regime Legitimacy Explanation of African Peacekeeping

    DTIC Science & Technology

    2011-09-01

    peacekeeping in a U-shaped curve, meaning that states attempting to increase their legitimacy participate at a higher-than-expected level. Likewise, the...distribution is unlimited A REGIME LEGITIMACY EXPLANATION OF AFRICAN PEACEKEEPING Matthew Ross Second Lieutenant, United States Air Force...B.S., Political Science, United States Air Force Academy, 2010 Submitted in partial fulfillment of the requirements for the degree of

  13. Maxwellian distribution in non-classical regime

    NASA Astrophysics Data System (ADS)

    Mohazzabi, Pirooz; L. Helvey, Shannon; McCumber, Jeremy

    2002-12-01

    A molecular dynamics investigation shows that the assumption of molecular chaos remains valid in the non-classical regime. Consequently, the velocity distribution function of an extremely dense system of spinless particles relaxes into Maxwellian, even in the presence of arbitrary interactions between the particles of the system. Systems with densities exceeding 30 times solid densities are investigated using a soft Lennard-Jones interparticle potential energy function.

  14. The nuclear non-proliferation treaty regime

    SciTech Connect

    1995-12-31

    The Non-Proliferation Treaty (NPT) regime, including national safeguards agreements and the International Atomic Energy Agency (IAEA) Statute, embodies the international effort to ban illicit transfers of nuclear material and acquisition or transfer of nuclear weaponry. Included are objectives and primary obligations, legal bases, institutional oversight, trade restrictions, protection of information, penal consequences, and role of the United Nations. Regional agreements supplement the NPT.

  15. Proliferation Control Regimes: Background and Status

    DTIC Science & Technology

    2012-10-25

    the further spread of nuclear weapons, several challenges to the regime have arisen in recent years: India and Pakistan tested nuclear weapons in 1998...States and other countries to India , a non-party to the NPT with nuclear weapons, has raised questions about what benefits still exist for non... India , Pakistan, North Korea, and Israel are not members of the NPT. Apart from diplomatic questions about how to treat their status as states with

  16. 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.

  17. Utilizing Surface Sensors to Identify Wake Regimes

    NASA Astrophysics Data System (ADS)

    Wang, Mengying; Hemati, Maziar S.

    2016-11-01

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

  18. Partial accretion regime of accreting millisecond pulsars

    NASA Astrophysics Data System (ADS)

    Eksi, Kazim

    2016-07-01

    The inner parts of the disks around neutron stars in low mass X-ray binaries may become geometrically thick due to inhibition of accretion at the disk mid-plane when the central object is rotating rapidly. In such a case matter inflowing through the disk may keep accreting onto the poles of the neutron star from the parts of the disk away from the disk mid-plane while the matter is propelled at the disk mid-plane. An important ingredient of the evolution of millisecond pulsars is then the fraction of the inflowing matter that can accrete onto the poles in the fast rotation regime depending on the fastness parameter. This ``soft'' propeller regime may be associated with the rapid decay stage observed in the light curves of several accreting millisecond pulsars. To date only a few studies considered the partial accretion regime. By using geometrical arguments we improve the existing studies and test the model by reproducing the lightcurves of millisecond X-ray pulsars via time dependent simulations of disk evolution. We also present analytical solutions that represent disks with partial accretion.

  19. Dynamical Response of Continuum Regime Langmuir Probe

    NASA Astrophysics Data System (ADS)

    Rappaport, H. L.

    2009-11-01

    Probe dynamic response is sometimes used as a way to increase the amount of information obtained from Langmuir probes [1]. In this poster, the effects of frequency dependent probe capacitance and coupling of probe fields to damped Langmuir waves and damped ion acoustic waves are considered. In the continuum regime, with small Debye length to spherical probe radius ratio, the probe DC current vs. voltage characteristic displays a hard saturation at sufficiently large probe potential [2]. In this regime, the sheath thickness varies little with the applied voltage although the plasma response can still be measured. A goal of the present investigation is to show that the probe dynamical response is richer as a result of modulation of sheath thickness or shielding particularly in the larger Debye length to probe radius ratio regime. Inertia inhibits ion response at sufficiently high frequency and deviation from the DC characteristic is shown.[4pt] [1] D. N. Walker, R.F. Fernsler, D.D. Blackwell, and W.E. Amatucci, Phys. Plasmas 15, 123506 (2008).[0pt] [2] E. Baum and R.L. Chapkis, AIAA J. 8, 1073 (1970).

  20. 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.

  1. 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.

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

    EPA Pesticide Factsheets

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

  3. 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...

  4. Toward a dynamical understanding of planetary-scale flow regimes.

    NASA Astrophysics Data System (ADS)

    Marshall, J.; Molteni, F.

    1993-06-01

    A strategy for diagnosing and interpreting flow regimes that is firmly rooted in dynamical theory is presented and applied to the study of observed and modeled planetary-scale regimes of the wintertime circulation in the Northern Hemisphere.

  5. 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 ...

  6. 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

  7. Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc.

    PubMed

    Kuhn, W; Schmalfeldt, B; Reuning, U; Pache, L; Berger, U; Ulm, K; Harbeck, N; Späthe, K; Dettmar, P; Höfler, H; Jänicke, F; Schmitt, M; Graeff, H

    1999-04-01

    Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low- and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from

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

    PubMed

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

    2012-07-01

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

  9. 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

  10. Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids

    PubMed Central

    Florova, Galina; Azghani, Ali; Karandashova, Sophia; Kurdowska, Anna K.; Idell, Steven

    2013-01-01

    Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0–80 min and 24 h after IPFT with scuPA (0–0.5 mg/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with α-macroglobulin (αM) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. The peak of uPA activity (5–40 min) reciprocally correlated with the dose of intrapleural scuPA. Endogenous active PAI-1 (10–20 nM) decreased the rate of intrapleural scuPA activation. The slow step of intrapleural inactivation of free uPA (t1/2β = 40 ± 10 min) was dose independent and 6.7-fold slower than in blood. Up to 260 ± 70 nM of αM/uPA formed in vivo [second order association rate (kass) = 580 ± 60 M−1·s−1]. αM/uPA and products of its degradation contributed to durable intrapleural plasminogen activation up to 24 h after IPFT. Active PAI-1, active α2M, and α2M/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of αM/uPA; and 3) slow intrapleural degradation of αM/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications. PMID:23997178

  11. CD44 stimulation by fragmented hyaluronic acid induces upregulation of urokinase-type plasminogen activator and its receptor and subsequently facilitates invasion of human chondrosarcoma cells.

    PubMed

    Kobayashi, Hiroshi; Suzuki, Mika; Kanayama, Naohiro; Nishida, Takashi; Takigawa, Masaharu; Terao, Toshihiko

    2002-12-01

    It has been established that fragmented hyaluronic acid (HA), but not native high molecular weight HA, can induce angiogenesis, cell proliferation and migration. We have studied the outside-in signal transduction pathways responsible for fragmented HA-mediated cancer cell invasion. In our study, we have studied the effects of CD44 stimulation by ligation with HA upon the expression of matrix metalloproteinases (MMPs)-2 and -9 as well as urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) and the subsequent induction of invasion of human chondrosarcoma cell line HCS-2/8. Our study indicates that (i) CD44 stimulation by fragmented HA upregulates expression of uPA and uPAR mRNA and protein but does not affect MMPs secretion or PAI-1 mRNA expression; (ii) the effects of HA fragments are critically HA size dependent: high molecular weight HA is inactive, but lower molecular weight fragmented HA (Mr 3.5 kDa) is active; (iii) cells can bind avidly Mr 3.5 kDa fragmented HA through a CD44 molecule, whereas cells do not effectively bind higher Mr HA; (iv) a fragmented HA induces phosphorylation of MAP kinase proteins (MEK1/2, ERK1/2 and c-Jun) within 30 min; (v) CD44 is critical for the response (activation of MAP kinase and upregulation of uPA and uPAR expression); and (vi) cell invasion induced by CD44 stimulation with a fragmented HA is inhibited by anti-CD44 mAb, MAP kinase inhibitors, neutralizing anti-uPAR pAb, anti-catalytic anti-uPA mAb or amiloride. Therefore, our study represents the first report that CD44 stimulation induced by a fragmented HA results in activation of MAP kinase and, subsequently, enhances uPA and uPAR expression and facilitates invasion of human chondrosarcoma cells.

  12. Expression of tissue type and urokinase type plasminogen activators as well as plasminogen activator inhibitor type-1 and type-2 in human and rhesus monkey placenta

    PubMed Central

    HU, ZHAO-YUAN; LIU, YI-XUN; LIU, KUI; BYRNE, SIMON; NY, TOR; FENG, QIANG; OCKLEFORD, COLIN D.

    1999-01-01

    The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears

  13. Production of a urokinase plasminogen activator-IgG fusion protein (uPA-IgG) in the baculovirus expression system.

    PubMed

    Kost, T A; Ignar, D M; Clay, W C; Andrews, J; Leray, J D; Overton, L; Hoffman, C R; Kilpatrick, K E; Ellis, B; Emerson, D L

    1997-04-29

    Numerous studies have demonstrated the importance of urokinase plasminogen activator (uPA) and its receptor, uPAR, in the processes of tumor progression and metastasis. Thus, the uPA/uPAR interaction may represent an important target for inhibiting metastatic disease. The baculovirus expression system was used to produce high levels of a secreted uPA-Immunoglobulin G fusion protein (uPA-IgG) which could then be used for displacing uPA from the surface of tumor cells. The recombinant uPA-IgG fusion protein was placed under the control of either the viral polyhedrin promoter or a copy of the viral basic protein promoter. Recombinant viruses were then used to infect Sf9 and BTI-Tn-5B1-4 cells. Infection of both cell types resulted in the production of secreted uPA-IgG. The molecular mass of the secreted protein as determined by SDS-PAGE was approximately 40 kDa. The highest level of secreted uPA-IgG, 444 microg/ml, was found in the culture medium of BTI-Tn-5B1-4 cells 72 h post-infection with the basic protein promoter-uPA-IgG virus. In the case of Sf9 cells, the highest level of secreted protein was 195 microg/ml. The amount of cell-associated uPA-IgG in infected BTI-Tn-5B1-4 cells was significantly less than that of infected Sf9 cells, reflecting the superior secretory capability of the BTI-Tn-5B1-4 cells. The uPA-IgG was readily purified using a combination of zinc chelate and sephacryl S-100 column chromatography. Routinely, greater than 100 mg of greater than 95% pure protein could be obtained per liter of culture medium collected at 72 h post-infection of BTI-Tn-5B1-4 cells with the basic protein promoter virus. BIAcore analysis and competition binding assays using LOX human malignant melanoma cells expressing uPAR indicated that the purified recombinant protein possessed similar ligand binding characteristics to that of human uPA.

  14. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    SciTech Connect

    Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. Black-Right-Pointing-Pointer Staurosporine mediates uPA activation during RGC differentiation in vitro. Black-Right-Pointing-Pointer Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. Black-Right-Pointing-Pointer Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that

  15. 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.

  16. 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

  17. Laboratory Exploration of Multiple Zonal Jet Regimes

    NASA Astrophysics Data System (ADS)

    Smith, C. A.; Speer, K. G.; Griffiths, R. W.

    2012-12-01

    The differentially heated, rotating annulus has classically been used to study wave interactions within a single, baroclinic jet. At high rotation rates, the baroclinic instability of the flow leads to a transition to a turbulent, eddy-dominated regime. In the presence of a topographic beta effect, the flow has been observed to produce multiple, meandering zonal jets that are qualitatively similar to those found in planetary atmospheres and in the Antarctic Circumpolar Current (ACC). Our study builds on previous annulus experiments [1] by making observations further within this new regime. We observe with PIV and other techniques how the structure of the flow responds to changes in various parameters such as tank geometry, gradient in the Coriolis parameter, rotation rate, and differential thermal forcing. By not employing the more typical direct forcing of small scales, but by applying a large scale forcing over the annulus gap width, this study allows the varying effects of eddy scale selection, enstrophy cascade, etc. to naturally generate flow that more closely resembles planetary atmospheres and the ACC. We seek nondimensional parameters that significantly control zonation in a real fluid. These observations will provide a metric for the comparison of various theoretical models for multiple zonal jet formation. Other properties of the jets, such as their migration, meandering, bifurcation, and merging, can also be observed in an idealized situation and compared to numerical simulations. Ultimately, this will aid the testing and development of sub-grid-scale parameterizations for the multiple zonal jet regime that remain robust in the face of multiple forcing parameters. [1] Wordsworth, R. D., Read, P. L., & Yamazaki, Y. H. (2008). Turbulence, waves, and jets in a differentially heated rotating annulus experiment Physics of Fluids, 20(12), 126602.Streak photograph of suspended particles visualizing the flow representative of multiple zonal jets

  18. Potential vorticity regimes over East Asia during winter

    NASA Astrophysics Data System (ADS)

    Huang, Wenyu; Chen, Ruyan; Wang, Bin; Wright, Jonathon S.; Yang, Zifan; Ma, Wenqian

    2017-02-01

    Nine potential vorticity (PV) regimes over East Asia are identified by applying a Self-Organizing Map and Hierarchical Ascendant Classification regime analysis to the daily PV reanalysis fields on the 300 K isentropic surface for December-March 1948-2014. According to the surface temperature anomalies over East Asia, these nine regimes are further classified into three classes, i.e., cold class (three regimes), warm class (four regimes), and neutral class (two regimes). The PV-based East Asian winter monsoon index (EAWMI) is used to study the relationship between PV distributions and the temperature anomalies. The magnitude of cold (warm) anomalies over the land areas of East Asia increases (decreases) quasi-linearly with the EAWMI. Regression analysis reveals that cold temperature anomalies preferentially occur when the EAWMI exceeds a threshold at ˜0.2 PVU (where 1 PVU ≡ 10-6 m2 K kg-1 s-1). PV inversion uncovers the mechanisms behind the relationships between the PV regimes and surface temperature anomalies and reveals that cold (warm) PV regimes are associated with significant warming (cooling) in the upper troposphere and lower stratosphere. On average, cold regimes have longer durations than warm regimes. Interclass transition probabilities are much higher for paths from warm/neutral regimes to cold regimes than for paths from cold regimes to warm/neutral regimes. Besides, intraclass transitions are rare within the warm or neutral regimes. The PV regime analysis provides insight into the causes of severe cold spells over East Asia, with blocking circulation patterns identified as the primary factor in initiating and maintaining these cold spells.

  19. 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.

  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. Ultracold Molecules: Physics in the Quantum Regime

    SciTech Connect

    Doyle, John

    2014-11-17

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

  3. Global oscillation regime change by gated inhibition.

    PubMed

    Romeo, August; Supèr, Hans

    2016-10-01

    The role of sensory inputs in the modelling of synchrony regimes is exhibited by means of networks of spiking cells where the relative strength of the inhibitory interaction is controlled by the activation of a linear unit working as a gating variable. Adaptation to stimulus size is determined by the value of a changing length scale, modelled by the time-varying radius of a circular receptive field. In this set-up, 'consolidation' time intervals relevant to attentional effects are shown to depend on the dynamics governing the evolution of the introduced length scale.

  4. 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.

  5. 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...

  6. 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...

  7. Pulse regime in formation of fractal fibers

    NASA Astrophysics Data System (ADS)

    Smirnov, B. M.

    2016-11-01

    The pulse regime of vaporization of a bulk metal located in a buffer gas is analyzed as a method of generation of metal atoms under the action of a plasma torch or a laser beam. Subsequently these atoms are transformed into solid nanoclusters, fractal aggregates and then into fractal fibers if the growth process proceeds in an external electric field. We are guided by metals in which transitions between s and d-electrons of their atoms are possible, since these metals are used as catalysts and filters in interaction with gas flows. The resistance of metal fractal structures to a gas flow is evaluated that allows one to find optimal parameters of a fractal structure for gas flow propagation through it. The thermal regime of interaction between a plasma pulse or a laser beam and a metal surface is analyzed. It is shown that the basic energy from an external source is consumed on a bulk metal heating, and the efficiency of atom evaporation from the metal surface, that is the ratio of energy fluxes for vaporization and heating, is 10-3-10-4 for transient metals under consideration. A typical energy flux ( 106 W/cm2), a typical surface temperature ( 3000 K), and a typical pulse duration ( 1 μs) provide a sufficient amount of evaporated atoms to generate fractal fibers such that each molecule of a gas flow collides with the skeleton of fractal fibers many times.

  8. Variety of synchronous regimes in neuronal ensembles.

    PubMed

    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.

  9. Distinct transport regimes for two elastically coupled molecular motors.

    PubMed

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

    2012-05-18

    Cooperative cargo transport by two molecular motors involves an elastic motor-motor coupling, which can reduce the motors' velocity and/or enhance their unbinding from the filament. We show theoretically that these interference effects lead, in general, to four distinct transport regimes. In addition to a weak coupling regime, kinesin and dynein motors are found to exhibit a strong coupling and an enhanced unbinding regime, whereas myosin motors are predicted to attain a reduced velocity regime. All of these regimes, which we derive by explicit calculations and general time scale arguments, can be explored experimentally by varying the elastic coupling strength.

  10. 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.

  11. Cointegration and causal linkages in fertilizer markets across different regimes

    NASA Astrophysics Data System (ADS)

    Lahmiri, Salim

    2017-04-01

    Cointegration and causal linkages among five different fertilizer markets are investigated during low and high market regimes. The database includes prices of rock phosphate (RP), triple super phosphate (TSP), diammonium phosphate (DAP), urea, and potassium chloride (PC). It is found that fertilizer markets are closely linked to each other during low and high regimes; and, particularly during high regime (after 2007 international financial crisis). In addition, there is no evidence of bidirectional linear relationship between markets during low and high regime time periods. Furthermore, all significant linkages are only unidirectional. Moreover, some causality effects have emerged during high regime. Finally, the effect of an impulse during high regime time period persists longer and is stronger than the effect of an impulse during low regime time period (before 2007 international financial crisis).

  12. 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.

  13. Dynamic Recrystallization: The Dynamic Deformation Regime

    NASA Astrophysics Data System (ADS)

    Murr, L. E.; Pizaña, C.

    2007-11-01

    Severe plastic deformation (PD), especially involving high strain rates (>103 s 1), occurs through solid-state flow, which is accommodated by dynamic recrystallization (DRX), either in a continuous or discontinuous mode. This flow can be localized in shear instability zones (or adiabatic shear bands (ASBs)) with dimensions smaller than 5 μ, or can include large volumes with flow zone dimensions exceeding centimeters. This article illustrates these microstructural features using optical and electron metallography to examine a host of dynamic deformation examples: shaped charge jet formation, high-velocity and hypervelocity impact crater formation, rod penetration into thick targets (which includes rod and target DRX flow and mixing), large projectile-induced target plug formation and failure, explosive welding, and friction-stir welding and processing. The DRX is shown to be a universal mechanism that accommodates solid-state flow in extreme (or severe) PD regimes.

  14. Diffusive Transport Properties Across Coupling Regimes

    NASA Astrophysics Data System (ADS)

    Dharuman, G.; Murillo, M. S.; Verboncoeur, J.; Christlieb, A.

    2014-10-01

    Transport properties are poorly known across coupling regimes, therefore understanding them is of importance for theoretical and practical reasons. A useful tool is an ultracold plasma system because of the experimental capability to tune the system to attain Coulomb coupling Γ ranging from 0.1 to 1 to 10 with the screening parameter κ ranging from 0 to 4 to 8, spanning the regions of the phase diagram from weak to moderate to strongly coupled and screened systems. Strong coupling is possible if Disorder Induced Heating is mitigated which requires a correlated initial ion state. Of particular interest is Rydberg blockaded gas of ultracold atoms where the local blockade effect results in correlations. Predictions of higher coupling in ultracold plasma created from a Rydberg blockaded gas have been reported. In this work we examine the diffusive transport properties of ultracold plasma system using molecular dynamics simulations for experimentally realizable values of Γ and κ as discussed above.

  15. 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.

  16. Capillary underwater discharges in repetitive pulse regime

    NASA Astrophysics Data System (ADS)

    de Baerdemaeker, F.; Monte, M.; Leys, C.

    2004-03-01

    In this study a capillary underwater discharge, that is sustained with AC (50 Hz) voltages up to 7.5 kV, is investigated. In a capillary discharge scheme, the current is, at some point along its path between two submerged electrodes, flowing through a narrow elongated bore in a dielectric material. When the current density is sufficiently high, local boiling and subsequent vapour breakdown results in the formation of a plasma within this capillary. At the same time the capillary emits an intense jet of vapour bubbles. Time-dependent electrical current, voltage and light emission curves are recorded for discharges in solutions of NaCl in distilled water and reveal different discharge regimes, depending on the conductivity and the excitation voltage, ranging from repetitive microsecond discharge pulses to a quasi-continuous discharge with a glow-like voltage-current characteristic.

  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. Multimode optomechanical system in the quantum regime.

    PubMed

    Nielsen, William Hvidtfelt Padkær; Tsaturyan, Yeghishe; Møller, Christoffer Bo; Polzik, Eugene S; Schliesser, Albert

    2017-01-03

    We realize a simple and robust optomechanical system with a multitude of long-lived (Q > 10(7)) mechanical modes in a phononic-bandgap shielded membrane resonator. An optical mode of a compact Fabry-Perot resonator detects these modes' motion with a measurement rate (96 kHz) that exceeds the mechanical decoherence rates already at moderate cryogenic temperatures (10 K). Reaching this quantum regime entails, inter alia, quantum measurement backaction exceeding thermal forces and thus strong optomechanical quantum correlations. In particular, we observe ponderomotive squeezing of the output light mediated by a multitude of mechanical resonator modes, with quantum noise suppression up to -2.4 dB (-3.6 dB if corrected for detection losses) and bandwidths ≲90 kHz. The multimode nature of the membrane and Fabry-Perot resonators will allow multimode entanglement involving electromagnetic, mechanical, and spin degrees of freedom.

  19. Multimode optomechanical system in the quantum regime

    NASA Astrophysics Data System (ADS)

    Hvidtfelt Padkær Nielsen, William; Tsaturyan, Yeghishe; Møller, Christoffer Bo; Polzik, Eugene S.; Schliesser, Albert

    2017-01-01

    We realize a simple and robust optomechanical system with a multitude of long-lived (Q > 107) mechanical modes in a phononic-bandgap shielded membrane resonator. An optical mode of a compact Fabry–Perot resonator detects these modes’ motion with a measurement rate (96 kHz) that exceeds the mechanical decoherence rates already at moderate cryogenic temperatures (10 K). Reaching this quantum regime entails, inter alia, quantum measurement backaction exceeding thermal forces and thus strong optomechanical quantum correlations. In particular, we observe ponderomotive squeezing of the output light mediated by a multitude of mechanical resonator modes, with quantum noise suppression up to ‑2.4 dB (‑3.6 dB if corrected for detection losses) and bandwidths ≲90 kHz. The multimode nature of the membrane and Fabry–Perot resonators will allow multimode entanglement involving electromagnetic, mechanical, and spin degrees of freedom.

  20. The Great Lakes' regional climate regimes

    NASA Astrophysics Data System (ADS)

    Sugiyama, Noriyuki

    For the last couple of decades, the Great Lakes have undergone rapid surface warming. In particular, the magnitude of the summer surface-warming trends of the Great Lakes have been much greater than those of surrounding land (Austin and Colman, 2007). Among the Great Lakes, the deepest Lake Superior exhibited the strongest warming trend in its annual, as well as summer surface water temperature. We find that many aspects of this behavior can be explained in terms of the tendency of deep lakes to exhibit multiple regimes characterized, under the same seasonally varying forcing, by the warmer and colder seasonal cycles exhibiting different amounts of wintertime lake-ice cover and corresponding changes in the summertime lake-surface temperatures. In this thesis, we address the problem of the Great Lakes' warming using one-dimensional lake modeling to interpret diverse observations of the recent lake behavior. (Abstract shortened by ProQuest.).

  1. 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.

  2. 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.

  3. Anomalous Transport in the Superfluid Fluctuation Regime

    NASA Astrophysics Data System (ADS)

    Uchino, Shun; Ueda, Masahito

    2017-03-01

    Motivated by a recent experiment in ultracold atoms [S. Krinner et al., Proc. Natl. Acad. Sci. U.S.A. 113, 8144 (2016), 10.1073/pnas.1601812113], we analyze transport of attractively interacting fermions through a one-dimensional wire near the superfluid transition. We show that in a ballistic regime where the conductance is quantized in the absence of interaction, the conductance is renormalized by superfluid fluctuations in reservoirs. In particular, the particle conductance is strongly enhanced, and the conductance plateau is blurred by emergent bosonic pair transport. For spin transport, in addition to the contact resistance, the wire itself is resistive, leading to a suppression of the measured spin conductance. Our results are qualitatively consistent with the experimental observations.

  4. 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.

  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. Antecedents of Teachers Fostering Effort within Two Different Management Regimes: An Assessment-Based Accountability Regime and Regime without External Pressure on Results

    ERIC Educational Resources Information Center

    Christophersen, Knut-Andreas; Elstad, Eyvind; Turmo, Are

    2012-01-01

    This article focuses on the comparison of organizational antecedents of teachers' fostering of students' effort in two quite different accountability regimes: one management regime with an external-accountability system and one with no external accountability devices. The methodology involves cross-sectional surveys from two different management…

  7. 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

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... paragraphs (a)(1), (2) and (3) of this section. The employer may round up hours at the end of a computation... each hour for which back pay, irrespective of mitigation of damages, is either awarded or agreed to by... receives a back pay award following a determination that he or she was paid at an unlawful rate for...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... paragraphs (a)(1), (2) and (3) of this section. The employer may round up hours at the end of a computation... each hour for which back pay, irrespective of mitigation of damages, is either awarded or agreed to by... receives a back pay award following a determination that he or she was paid at an unlawful rate for...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... paid on a bi-weekly basis. The amount of salary payments attributable to be paid vacation was... employer maintaining a plan pays employees on a bi-weekly basis. The plan designates the calendar year as... performance of duties during a bi-weekly payroll period to the vesting computation period in which the...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... paid on a bi-weekly basis. The amount of salary payments attributable to be paid vacation was... employer maintaining a plan pays employees on a bi-weekly basis. The plan designates the calendar year as... performance of duties during a bi-weekly payroll period to the vesting computation period in which the...

  12. 29 CFR 2530.200b-2 - Hour of service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... paid on a bi-weekly basis. The amount of salary payments attributable to be paid vacation was... employer maintaining a plan pays employees on a bi-weekly basis. The plan designates the calendar year as... performance of duties during a bi-weekly payroll period to the vesting computation period in which the...

  13. 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.

  14. Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

    PubMed Central

    Bujanda, Luis; Sarasqueta, Cristina; Cosme, Angel; Hijona, Elizabeth; Enríquez-Navascués, José M.; Placer, Carlos; Villarreal, Eloisa; Herreros-Villanueva, Marta; Giraldez, María D.; Gironella, Meritxell; Balaguer, Francesc; Castells, Antoni

    2013-01-01

    Background Colorectal cancer (CRC) is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool. Aim Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC. Methods In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7), urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF), cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2), and CD44) and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA) and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results. Results Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79±0.25 in the CRC group vs 1.27±0.25 in the control group, P<0.0005). The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79–0.96). The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81) and tetranectin (0.80), COX-2 (0.78), uPAR (0.78) and carbonic anhydrase (0.77). The markers which identified early stage CRC (Stages I and II) were alpha 1-antitrypsin, uPAR, COX-2 and MMP7. Conclusions Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages. PMID:23300952

  15. Urokinase plasminogen activator receptor induced non-small cell lung cancer invasion and metastasis requires NHE1 transporter expression and transport activity.

    PubMed

    Provost, J J; Rastedt, D; Canine, J; Ngyuen, T; Haak, A; Kutz, C; Berthelsen, N; Slusser, A; Anderson, K; Dorsam, G; Wallert, M A

    2012-04-01

    BACKGROUND: Non-small cell lung cancers (NSLC) are aggressive cancers that are insensitive to chemotherapies and accounts for nearly 33% of all cancer deaths in the United States. Two hallmarks of cancer that allow cells to invade and metastasize are sustained proliferation and enhanced motility. In this study we investigate the relationship between urokinase plasminogen activator (uPA)/uPA receptor (uPAR) signaling and Na(+)/H(+) exchanger isoform 1 (NHE1) expression and activity. METHODS AND RESULTS: The addition of 10nM uPA increased the carcinogenic potential of three NSCLC cell lines, NCI-H358, NCI-H460, and NCI-H1299. This included an increase in the rate of cell proliferation 1.6 to 1.9 fold; an increase in the percentage of cells displaying stress fibers 3.05 to 3.17 fold; and an increase in anchorage-independent growth from 1.64 to 2.0 fold. In each of these cases the increase was blocked when the experiments were performed with NHE1 inhibited by 10 μM EIPA (ethylisopropyl amiloride). To further evaluate the role of uPA/uPAR and NHE1 in tumor progression we assessed signaling events using full-length uPA compared to the uPA amino terminal fragment (ATF). Comparing uPA and ATF signaling in H460 cells, we found that both uPA and ATF increased stress fiber formation approximately 2 fold, while uPA increased matrix metalloproteinase 9 (MMP9) activity 5.44 fold compared to 2.81 fold for ATF. To expand this signaling study, two new cell lines were generated, one with reduced NHE1 expression (H460 NHE1 K/D) and one with reduced uPAR expression (H460 uPAR K/D). Using the K/D cell lines we found that neither uPA nor ATF could stimulate stress fiber formation or MMP9 activity in cells with dramatically decreased NHE1 or uPAR expression. Finally, using in vivo tumor formation studies in athymic mice we found that when mice were injected with H460 cells 80% of mice formed tumors with an average volume of 390 mm(3). This was compared to 20% of H460 uPAR K/D injected

  16. TGF-β2 promotes RPE cell invasion into a collagen gel by mediating urokinase-type plasminogen activator (uPA) expression.

    PubMed

    Sugioka, Koji; Kodama, Aya; Okada, Kiyotaka; Iwata, Mihoko; Yoshida, Koji; Kusaka, Shunji; Matsumoto, Chota; Kaji, Hiroshi; Shimomura, Yoshikazu

    2013-10-01

    Transforming growth factor-beta (TGF-β) is one of the main epithelial-mesenchymal transition (EMT)-inducing factors. In general, TGF-β-induced EMT promotes cell migration and invasion. TGF-β also acts as a potent regulator of pericellular proteolysis by regulating the expression and secretion of plasminogen activators. Urokinase-type plasminogen activator (uPA) is a serine protease that binds to its cell surface receptor (uPAR) with high affinity. uPA binding to uPAR stimulates uPAR's interaction with transmembrane proteins, such as integrins, to regulate cytoskeletal reorganization and cell migration, differentiation and proliferation. However, the influence of TGF-β and the uPA/uPAR system on EMT in retinal pigment epithelial (RPE) cells is still unclear. The purpose of this study was to determine the effect of TGF-β2, which is the predominant isoform in the retina, and the uPA/uPAR system on RPE cells. In this study, we first examined the effect of TGF-β2 and/or the inhibitor of uPA (u-PA-STOP(®)) on the proliferation of a human retinal pigment epithelial cell line (ARPE-19 cells). Treatment with TGF-β2 or u-PA-STOP(®) suppressed cell proliferation. Combination treatment of TGF-β2 and u-PA-STOP(®) enhanced cell growth suppression. Furthermore, western blot analysis, fibrin zymography and real-time reverse transcription PCR showed that that TGF-β2 induced EMT in ARPE-19 cells and that the expression of uPA and uPAR expression was up-regulated during EMT. The TGF-β inhibitor SB431542 suppressed TGF-β2-stimulated uPA expression and secretion but did not suppress uPAR expression. Furthermore, we seeded ARPE-19 cells onto Transwell chambers and allowed them to invade the collagen matrix in the presence of TGF-β2 alone or with TGF-β2 and u-PA-STOP(®). TGF-β2 treatment induced ARPE-19 cell invasion into the collagen gel. Treatment with a combination of TGF-β2 and the uPA inhibitor strongly inhibited ARPE-19 cell invasion compared with treatment with

  17. 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

  18. Evaluating temperature regimes for protection of brown trout

    USGS Publications Warehouse

    Armour, Carl L.

    1994-01-01

    Geographic distribution and population success of brown trout (Salmo trutta) are affected by temperature regimes. Concepts are presented for evaluating alternative temperature regimes for brown trout based on published temperature information and professional judgment. Temperature information from the literature is included for spawning runs, spawning, egg and larval development, growth, and other subjects. The objective is to aid biologists in evaluating alternative temperature regimes so as to select those that will protect and enhance environmental quality for brown trout.

  19. Shearing box simulations in the Rayleigh unstable regime

    NASA Astrophysics Data System (ADS)

    Nauman, Farrukh; Blackman, Eric G.

    2017-01-01

    We study the stability properties of Rayleigh unstable flows both in the purely hydrodynamic and magnetohydrodynamic (MHD) regimes for two different values of the shear q = 2.1, 4.2 (q = -dln Ω/dln r) and compare it with the Keplerian case q = 1.5. We find that the q > 2 regime is unstable both in the hydrodynamic and in the MHD limit (with an initially weak magnetic field). In this regime, the velocity fluctuations dominate the magnetic fluctuations. In contrast, in the q < 2 (magnetorotational instability (MRI)) regime the magnetic fluctuations dominate. This highlights two different paths to MHD turbulence implied by the two regimes, suggesting that in the q > 2 regime the instability produces primarily velocity fluctuations that cause magnetic fluctuations, with the causality reversed for the q < 2 MRI unstable regime. We also find that the magnetic field correlation is increasingly localized as the shear is increased in the Rayleigh unstable regime. In calculating the time evolution of spatial averages of different terms in the MHD equations, we find that the q > 2 regime is dominated by terms which are nonlinear in the fluctuations, whereas for q < 2, the linear terms play a more significant role.

  20. Film thickness for different regimes of fluid-film lubrication

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.

    1980-01-01

    Film thickness equations are provided for four fluid-film lubrication regimes found in elliptical contacts. These regimes are isoviscous-rigid; viscous-rigid; elastohydrodynamic lubrication of low-elastic-modulus materials (soft EHL), or isoviscous-elastic; and elastohydrodynamic lubrication of high-elastic-modulus materials (hard EHL), or viscous-elastic. The influence or lack of influence of elastic and viscous effects is the factor that distinguishes these regimes. The results are presented as a map of the lubrication regimes, with film thickness contours on a log-log grid of the viscosity and elasticity for three values of the ellipticity parameter.

  1. Varying Inundation Regimes Differentially Affect Natural and ...

    EPA Pesticide Factsheets

    Climate change is altering sea-level rise rates and precipitation patterns worldwide. Coastal wetlands are vulnerable to these changes. System responses to stressors are important for resource managers and environmental stewards to understand in order to best manage them. Thin layer sand or sediment application to drowning and eroding marshes is one approach to build elevation and resilience. The above- and below-ground structure, soil carbon dioxide emissions, and pore water constituents in vegetated natural marsh sediments and sand-amended sediments were examined at varying inundation regimes between mean sea level and mean high water (0.82 m NAVD88 to 1.49 m NAVD88) in a field experiment at Laws Point, part of the Plum Island Sound Estuary (MA). Significantly lower salinities, pH, sulfides, phosphates, and ammonium were measured in the sand-amended sediments than in the natural sediments. In natural sediments there was a pattern of increasing salinity with increasing elevation while in the sand-amended sediments the trend was reversed, showing decreasing salinity with increasing elevation. Sulfide concentrations generally increased from low to high inundation with highest concentrations at the highest inundation (i.e., at the lowest elevations). High pore water phosphate concentrations were measured at low elevations in the natural sediments, but the sand-amended treatments had mostly low concentrations of phosphate and no consistent pattern with elevation. A

  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. On spinfoam models in large spin regime

    NASA Astrophysics Data System (ADS)

    Han, Muxin

    2014-01-01

    We study the semiclassical behavior of Lorentzian Engle-Pereira-Rovelli-Livine (EPRL) spinfoam model, by taking into account the sum over spins in the large spin regime. We also employ the method of stationary phase analysis with parameters and the so-called, almost analytic machinery, in order to find the asymptotic behavior of the contributions from all possible large spin configurations in the spinfoam model. The spins contributing the sum are written as Jf = λjf, where λ is a large parameter resulting in an asymptotic expansion via stationary phase approximation. The analysis shows that at least for the simplicial Lorentzian geometries (as spinfoam critical configurations), they contribute the leading order approximation of spinfoam amplitude only when their deficit angles satisfy \\gamma \\mathring{\\Theta }_f\\le \\lambda ^{-1/2} mod 4\\pi {Z}. Our analysis results in a curvature expansion of the semiclassical low energy effective action from the spinfoam model, where the UV modifications of Einstein gravity appear as subleading high-curvature corrections.

  4. 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.

  5. TBT causes regime shift in shallow lakes.

    PubMed

    Sayer, Carl D; Hoare, Daniel J; Simpson, Gavin L; Henderson, Andrew C G; Liptrot, Eleanor R; Jackson, Michael J; Appleby, Peter G; Boyle, John F; Jones, I Iwan; Waldock, Mike J

    2006-09-01

    Tributyltin (TBT) is an organotin compound used since the early 1960s as a biocide in boat antifouling paints. Its use has been linked to a host of negative effects in marine ecosystems including malformations and imposex in Mollusca and acute toxicity in many other aquatic animals. Yet, the consequences of TBT use in freshwaters are largely unknown. Here, for the first time we reveal that TBT may have caused hitherto unsuspected damage to freshwater ecosystems. Through an analysis of dated sediment cores collected from a system of recreationally boated, shallow lakes, we show that first evidence of TBT is associated with a dramatic loss of submerged vegetation and associated diverse animal communities. Cause and effect are difficult to unravel in our study. However, we hypothesize that TBT, through reducing populations of grazing organisms in lakes already affected by eutrophication, promoted the replacement of macrophytes by phytoplankton, ultimately leading to a regime shift in the ecosystem. Our findings may have parallels in freshwater ecosystems all over the world.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. 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…

  12. 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…

  13. 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 ...

  14. 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...

  15. 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.

  16. 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.

  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. 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-...

  19. 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 ...

  20. Conditional heteroscedasticity as a leading indicator of ecological regime shifts.

    PubMed

    Seekell, David A; Carpenter, Stephen R; Pace, Michael L

    2011-10-01

    Regime shifts are massive, often irreversible, rearrangements of nonlinear ecological processes that occur when systems pass critical transition points. Ecological regime shifts sometimes have severe consequences for human well-being, including eutrophication in lakes, desertification, and species extinctions. Theoretical and laboratory evidence suggests that statistical anomalies may be detectable leading indicators of regime shifts in ecological time series, making it possible to foresee and potentially avert incipient regime shifts. Conditional heteroscedasticity is persistent variance characteristic of time series with clustered volatility. Here, we analyze conditional heteroscedasticity as a potential leading indicator of regime shifts in ecological time series. We evaluate conditional heteroscedasticity by using ecological models with and without four types of critical transition. On approaching transition points, all time series contain significant conditional heteroscedasticity. This signal is detected hundreds of time steps in advance of the regime shift. Time series without regime shifts do not have significant conditional heteroscedasticity. Because probability values are easily associated with tests for conditional heteroscedasticity, detection of false positives in time series without regime shifts is minimized. This property reduces the need for a reference system to compare with the perturbed system.

  1. 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.

  2. Transition from column to micropinch regime in Z-pinches

    SciTech Connect

    Engel, A.; Lebert, R.; Koshelev, K. N.; Sidelnikov, Yu. V.; Gavrilescu, C.; Neff, W.

    1997-05-05

    Plasma focus and Z-pinches are known to be intensive sources of K-ion radiation. This radiation is observed in two different regimes of compression: column and micropinch. Appearance of these regimes depends on combination of discharge circuit parameter and element composition of plasma. Column regime is typical for low current discharges operating in low Z gases. Micropinch regime, which represents a development of ''neck'' type instabilities in a presence of strong radiation losses, is typical for heavy ion plasma, i.e. vacuum spark or plasma focus with admixture of heavy gases. Transition from column to micropinch mode has been investigated experimentally. It was found that appearance of either regime can be quantitatively described by a distinction parameter depending on pinch current, particle density and used element.

  3. Investigation of the regimes of mixing of superconducting tunneling structures

    NASA Astrophysics Data System (ADS)

    Kalashnikov, K. V.; Artanov, A. A.; Filippenko, L. V.; Koshelets, V. P.

    2016-11-01

    The regimes of operation of a superconductor-insulator-superconductor tunnel junction based on three-layer structures Nb/AlOx/Nb and Nb/AlN/NbN as a harmonic mixer (for frequencies of the order of 600 and 20 GHz, respectively) and a frequency up-converter (in the frequency range from 0.1 to 5.0 GHz) have been investigated experimentally. The quasiparticle and Josephson mixing regimes have been compared. It has been shown that, in some practical applications, such as the use of the superconductor-insulator-superconductor junction as a cryogenic harmonic phase detector, the Josephson mixing regime is more preferable, because it can provide a higher signal and a greater signal-to-noise ratio as compared to the quasiparticle mixing regime. It has also been demonstrated that the Josephson mixing regime is promising for the use in signal multiplexing systems for superconducting detectors.

  4. 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

  5. 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

  6. Constraints on flow regimes in wide-aperture fractures

    SciTech Connect

    Ghezzehei, Teamrat A.

    2004-02-28

    In recent years, significant advances have been made in our understanding of the complex flow processes in individual fractures, aided by flow visualization experiments and conceptual modeling efforts. These advances have led to the recognition of several flow regimes in individual fractures subjected to different initial and boundary conditions. Of these, the most important regimes are film flow, rivulet flow, and sliding of droplets. The existence of such significantly dissimilar flow regimes has been a major hindrance in the development of self-consistent conceptual models of flow for single fractures that encompass all the flow regimes. The objective of this study is to delineate the existence of the different flow regimes in individual fractures. For steady-state flow conditions, we developed physical constraints on the different flow regimes that satisfy minimum energy configurations, which enabled us to segregate the wide range of fracture transmissivity (volumetric flow rate per fracture width) into several flow regimes. These are, in increasing order of flow rate, flow of adsorbed films, flow of sliding drops, rivulet flow, stable film flow, and unstable (turbulent) film flow. The scope of this study is limited to wide-aperture fractures with the flow on the opposing sides of fracture being independent.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  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. 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.

  14. 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.

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

    DOE PAGES

    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

  16. 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.

  17. Spacetime-noncommutativity regime of loop quantum gravity

    NASA Astrophysics Data System (ADS)

    Amelino-Camelia, Giovanni; Da Silva, Malú Maira; Ronco, Michele; Cesarini, Lorenzo; Lecian, Orchidea Maria

    2017-01-01

    A recent study by Bojowald and Paily [M. Bojowald and G. M. Paily, Phys. Rev. D 87, 044044 (2013)., 10.1103/PhysRevD.87.044044] provided a path toward the identification of an effective quantum-spacetime picture of loop quantum gravity, applicable in the "Minkowski regime," the regime where the large-scale (coarse-grained) spacetime metric is flat. A pivotal role in the analysis is played by loop-quantum-gravity-based modifications to the hypersurface deformation algebra, which leave a trace in the Minkowski regime. We here show that the symmetry-algebra results reported by Bojowald and Paily are consistent with a description of spacetime in the Minkowski regime given in terms of the κ -Minkowski noncommutative spacetime, whose relevance for the study of the quantum-gravity problem had already been proposed for independent reasons.

  18. 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.

  19. Analysis of light regime in continuous light distributions in photobioreactors.

    PubMed

    Brindley, Celeste; Fernández, F G Acién; Fernández-Sevilla, J M

    2011-02-01

    Maximum photobioreactor (PBR) efficiency is a must in applications such as the obtention of microalgae-derived fuels. Improving PBR performance requires a better understanding of the "light regime", the varying irradiance that microalgal cells moving in a dense culture are exposed to. We propose a definition of light regime that can be used consistently to describe the continuously varying light patterns in PBRs as well as in light/dark cycles. Equivalent continuous and light/dark regimes have been experimentally compared and the results show that continuous variations are not well represented by light/dark cycles, as had been widely accepted. It has been shown that a correct light regime allows obtaining photosynthetic rates higher than the corresponding to continuous light, the so-called "flashing light effect" and that this is possible in commercial PBRs. A correct PBR operation could result in photosynthetic efficiency close to the optimum eight quanta per O(2).

  20. Regime change and oscillation thresholds in recorder-like instruments.

    PubMed

    Auvray, Roman; Fabre, Benoît; Lagrée, Pierre-Yves

    2012-02-01

    Based on results from the literature, a description of sound generation in a recorder is developed. Linear and non-linear analysis are performed to study the dependence of the frequency on the jet velocity. The linear analysis predicts that the frequency is a function of the jet velocity. The non-linear resolution provides information about limit cycle oscillation and hysteretic regime change thresholds. A comparison of the frequency between linear theory and experiments on a modified recorder shows good agreement except at very low jet velocities. Although the predicted threshold for the onset of the first regime shows an important deviation from experiments, the hysteresis of threshold to higher regimes is accurately estimated. Furthermore, a qualitative analysis of the influence of different parameters in the model on the sound generation and regime changes is presented.

  1. 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...

  2. Plasma confinement regimes and collective modes characterizing them

    SciTech Connect

    Coppi, B.; Zhou, T.

    2012-10-15

    A unified theory is presented for the modes that are excited at the edge of the plasma column and are important signatures of the advanced confinement regimes into which magnetically confined plasmas can be driven. In particular, the so-called EDA H-Regime, the Elmy H-Regime, and the I-Regime are considered. The modes that are identified theoretically have characteristics that are consistent with or have anticipated those of the modes observed experimentally for each of the investigated regimes. The phase velocities, the produced transport processes, the frequencies, the wavelengths, and the consistency with the direction of spontaneous rotation are the factors considered for comparison with the relevant experiments. The quasi-coherent mode [I. Cziegler, Ph.D. dissertation, Massachusetts Institute of Technology, Cambridge, MA, 2011] that is present in the EDA H-Regime has a phase velocity in the direction of the ion diamagnetic velocity in the plasma reference frame. Consequently, this is identified as a ballooning mode near finite Larmor radius marginal stability involving the effects of transverse ion viscosity and other dissipative effects. In this regime, impurities are driven outward by the combined effects of the local temperature gradients of the impurities and their thermal conductivity, while in the Elmy H-Regime impurities are driven toward the center of the plasma column. In the I-Regimes, the excited 'Heavy Particle' modes [B. Coppi and T. Zhou, Phys. Plasmas 19, 012302 (2012); Phys. Lett. A 375, 2916 (2011)] are not of the ballooning kind and are shown to expel the impurities toward the plasma edge in the presence of significant fluctuations. These modes can have a finite frequency of oscillation with a phase velocity in the direction of the electron diamagnetic velocity or they can be nearly purely growing, explaining why there are I-Regimes where fluctuations are not observed. Instead, the modes considered for the Elmy H-Regime are of the ballooning

  3. 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.

  4. Distributed Low Temperature Combustion: Fundamental Understanding of Combustion Regime Transitions

    DTIC Science & Technology

    2016-09-07

    study is to bring fundamental understanding of the impact of the chemical (Tau_c) and flow (Tau_f) timescales on combustion regime transitions in...reaction zone regime. The choice of DME is partly due to the potential practical relevance, but also due to the fundamentally different chemical ... chemical mechanisms for the considered fuels (e.g. DME) to establish their ability to reproduce laminar flame and auto-ignition properties. The

  5. 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.

  6. Evaluation of interregional variability in MODIS cloud regimes

    NASA Astrophysics Data System (ADS)

    Leinonen, J. S.; Lebsock, M. D.; Oreopoulos, L.; Cho, N.

    2015-12-01

    Clustering techniques have been used in the last few decades to classify cloud types automatically from satellite observations, most commonly using cloud top pressure and cloud optical depth. The underlying assumption is that the resulting clusters, called "cloud regimes" or "weather states", represent some type of basic states of the atmosphere, and thus that their occurrence can be used as a proxy for related variables such as radiative balance or precipitation. We have examined the validity of these assumptions by using independent measurements from the CloudSat and CALIPSO satellites. The CloudSat radar yields a reflectivity product that is sensitive to many aspects of the physics of the clouds, while CloudSat together with the CALIPSO lidar can retrieve the vertical structure of the cloud column, including multi-layer clouds. These observations have been separated into groups according to the recently published cloud regimes based on data from the MODIS instrument, deployed on the Aqua satellite orbiting in the same constellation with CloudSat and CALIPSO. The distributions of these observations have been constructed both globally and in a number of regions in different parts of the Earth. By analyzing the differences in the distributions between these regions, we can evaluate the usefulness of the cloud regimes as a proxy for the measured variables. Some cloud regimes have been found to be rather stable between regions, while others display considerable variability. Moreover, some cloud regimes appear much more similar to each other in CloudSat observations than they do using the MODIS regimes. We analyze the implications of these differences for the usability of the cloud regimes as climate indicators. We also explore various filtering techniques and different clustering methods that can potentially be used to reduce these differences, and thus to improve the universality of the cloud regimes.

  7. 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.

  8. 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.

  9. 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.

  10. O-regime dynamics and modeling in Tore Supra

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

    The regime of nonlinear temperature oscillations (O-regime), characteristic of noninductive discharges on Tore Supra [Équipe Tore Supra, Proceedings of the 12th International Conference on Plasma Physics and Controlled Nuclear Fusion Research, Nice, France, 1988 (International Atomic Energy Agency, Vienna, 1989), Vol. 1, p. 9], is investigated in its triggering and suppressing mechanism. This regime can be described by two nonlinearly coupled equations for the current density j(r ) and the electron temperature Te(r) where the equation coefficients are functions of j and Te themselves. Both the integrated modeling code CRONOS [V. Basiuk et al., Nucl. Fusion 43, 822 (2003)] and a two-patch predator-prey system with diffusion and noise have been used and results have been compared to the experimental observations of the O-regime. A database of discharges is analyzed which features monotonic, flat, and reversed safety factor (q) profiles in order to characterize the action of external actuators on the regime dynamics with the widest generality. Electron cyclotron current drive and neutral beam injections have been used in order to induce localized perturbations in the total current profile j(r ) as well as to change the plasma confinement conditions in the central region. Magnetic shear perturbations and modifications of the heat transport turn out to be the central parameters governing the dynamics of the O-regime.

  11. 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.

  12. 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

  13. 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.

  14. Regime-Switching Bivariate Dual Change Score Model.

    PubMed

    Chow, Sy-Miin; Grimm, Kevin J; Filteau, Guillaume; Dolan, Conor V; McArdle, John J

    2013-07-01

    Mixture structural equation model with regime switching (MSEM-RS) provides one possible way of representing over-time heterogeneities in dynamic processes by allowing a system to manifest qualitatively or quantitatively distinct change processes conditional on the latent "regime" the system is in at a particular time point. Unlike standard mixture structural equation models such as growth mixture models, MSEM-RS allows individuals to transition between latent classes over time. This class of models, often referred to as regime-switching models in the time series and econometric applications, can be specified as regime-switching mixture structural equation models when the number of repeated measures involved is not large. We illustrate the empirical utility of such models using one special case-a regime-switching bivariate dual change score model in which two growth processes are allowed to manifest regime-dependent coupling relations with one another. The proposed model is illustrated using a set of longitudinal reading and arithmetic performance data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99 study (ECLS-K; U.S. Department of Education, National Center for Education Statistics, 2010).

  15. 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.

  16. Dynamic Regime Marginal Structural Mean Models for Estimation of Optimal Dynamic Treatment Regimes, Part II: Proofs of Results*

    PubMed Central

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

    2010-01-01

    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. PMID:20405047

  17. 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

  18. 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 ...

  19. 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...

  20. 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).

  1. 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.

  2. Liquid drop spreading on surfaces: Initial regimes revisited

    NASA Astrophysics Data System (ADS)

    Mitra, Surjyasish; Mitra, Sushanta

    2016-11-01

    Liquid drop spreading on a given surface is fundamental towards technological processes like coating and paints, inkjet printing, surface characterization, etc. Though, the underlying dynamics is well understood, we have revisited this problem through experiments conducted on surfaces kept in air as well as immersed in water. It was found that the two key parameters that dictated the spreading process were drop-surrounding medium viscosity ratio and the characteristic viscous length scale. It was observed that irrespective of the drop liquid and surrounding liquid medium (air and water in this case), spreading always began in a regime dominated by drop viscosity, where the spreading radius scales as r t . However, the prefactor of the scaling observed was different for air (of the order of unity) and under-water (much less than unity). Following this initial regime, a second intermediate regime dominated by drop inertia (typically found for water drops spreading in air) was observed only when the characteristic viscous length scale favored such a transition. In this regime as well, a non-universal prefactor was noted for the scaling law, i.e., r t1/2. In all cases considered, the spreading process terminated in the Tanner's regime where the spreading radius scaled as r t1/10.

  3. Differentially Rotating White Dwarfs I: Regimes of Internal Rotation

    NASA Astrophysics Data System (ADS)

    Ghosh, Pranab; Wheeler, J. Craig

    2017-01-01

    Most viable models of Type Ia supernovae (SNe Ia) require the thermonuclear explosion of a carbon/oxygen white dwarf that has evolved in a binary system. Rotation could be an important aspect of any model for SNe Ia, whether single or double degenerate, with the white dwarf mass at, below, or above the Chandrasekhar limit. Differential rotation is specifically invoked in attempts to account for the apparent excess mass in the super-Chandrasekhar events. Some earlier work has suggested that only uniform rotation is consistent with the expected mechanisms of angular momentum transport in white dwarfs, while others have found pronounced differential rotation. We show that if the baroclinic instability is active in degenerate matter and the effects of magnetic fields are neglected, both nearly uniform rotation and strongly differential rotation are possible. We classify rotation regimes in terms of the Richardson number, Ri. At small values of Ri ≤slant 0.1, we find both the low-viscosity Zahn regime with a nonmonotonic angular velocity profile and a new differential rotation regime for which the viscosity is high and scales linearly with the shear, σ. Employment of Kelvin–Helmholtz viscosity alone yields differential rotation. Large values of Ri ≫ 1 produce a regime of nearly uniform rotation for which the baroclinic viscosity is of intermediate value and scales as {σ }3. We discuss the gap in understanding of the behavior at intermediate values of Ri and how observations may constrain the rotation regimes attained by nature.

  4. Regimes of Internal Rotation in Differentially Rotating White Dwarfs

    NASA Astrophysics Data System (ADS)

    Wheeler, J. Craig; Ghosh, Pranab

    2017-01-01

    Most viable models of Type Ia supernovae (SN Ia) require the thermonuclear explosion of a carbon/oxygen white dwarf that has evolved in a binary system. Rotation could be an important aspect of any model for SN Ia, whether single or double degenerate, with the white dwarf mass at, below, or above the Chandrasekhar limit. Differential rotation is specifically invoked in attempts to account for the apparent excess mass in the super--Chandrasekhar events. Some earlier work has suggested that only uniform rotation is consistent with the expected mechanisms of angular momentum transport in white dwarfs, while others have found pronounced differential rotation. We show that if the baroclinic instability is active in degenerate matter and the effects of magnetic fields are neglected, both nearly-uniform and strongly-differential rotation are possible. We classify rotation regimes in terms of the Richardson number, Ri. At small values of Ri < 0.1, we find both the low-viscosity Zahn regime with a non-monotonic angular velocity profile and a new differential rotation regime for which the viscosity is high and scales linearly with the shear, σ. Employment of Kelvin-Helmholtz viscosity alone yields differential rotation. Large values of Ri >> 1 produce a regime of nearly-uniform rotation for which the baroclinic viscosity is of intermediate value and scales as σ3. We discuss the gap in understanding of the behavior at intermediate values of Ri and how observations may constrain the rotation regimes attained by nature.

  5. 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.

  6. 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.

  7. Similarity in Neuronal Firing Regimes across Mammalian Species

    PubMed Central

    Mochizuki, Yasuhiro; Onaga, Tomokatsu; Shimazaki, Hideaki; Shimokawa, Takeaki; Tsubo, Yasuhiro; Kimura, Rie; Saiki, Akiko; Sakai, Yutaka; Isomura, Yoshikazu; Fujisawa, Shigeyoshi; Shibata, Ken-ichi; Hirai, Daichi; Furuta, Takahiro; Kaneko, Takeshi; Takahashi, Susumu; Nakazono, Tomoaki; Ishino, Seiya; Sakurai, Yoshio; Kitsukawa, Takashi; Lee, Jong Won; Lee, Hyunjung; Jung, Min Whan; Babul, Cecilia; Maldonado, Pedro E.; Takahashi, Kazutaka; Arce-McShane, Fritzie I.; Ross, Callum F.; Sessle, Barry J.; Hatsopoulos, Nicholas G.; Brochier, Thomas; Riehle, Alexa; Chorley, Paul; Grün, Sonja; Nishijo, Hisao; Ichihara-Takeda, Satoe; Funahashi, Shintaro; Shima, Keisetsu; Mushiake, Hajime; Yamane, Yukako; Tamura, Hiroshi; Fujita, Ichiro; Inaba, Naoko; Kawano, Kenji; Kurkin, Sergei; Fukushima, Kikuro; Kurata, Kiyoshi; Taira, Masato; Tsutsui, Ken-Ichiro; Ogawa, Tadashi; Komatsu, Hidehiko; Koida, Kowa; Toyama, Keisuke; Richmond, Barry J.

    2016-01-01

    The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities. PMID:27225764

  8. Weather Regimes: The Challenge in Extended-Range Forecasting

    NASA Astrophysics Data System (ADS)

    Reinhold, Brian

    1987-01-01

    A hypothesis to explain the low-frequency (10- to 90-day) variance of the mid-latitude atmosphere is presented. In this hypothesis it is proposed that the planetary-scale waves forced by topography or other zonal inhomogeneities and the day-to-day weather disturbances (synoptic scales) influence each other to generate weather regimes. These quasi-stable flow configurations are responsible for short-range climate anomalies such as droughts, heat waves, deep freezes, and excessive precipitation, as the weather-producing disturbances are organized into storm tracks. Onset and disruption of the weather regimes may be induced by the anomalous development of perhaps a single cyclonic disturbance, which can throw the quasi equilibrium out of balance. Thus, rapid changes in flow regimes can occur almost at random. The development and transition of weather regimes may then be purely internal (that is, depending only upon the properties of the fluid motions themselves) to the atmospheric dynamics. This internal quality suggests that the chaotic, abrupt short-range climatic behavior of the mid-latitudes is a natural behavior of the system that requires no assistance from the outside. The weather regime concept presents a different view of the extended-range atmospheric behavior than the stimulus-response model, such as the atmospheric response to the El Nino.

  9. 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.

  10. Nonlinear regime-switching state-space (RSSS) models.

    PubMed

    Chow, Sy-Miin; Zhang, Guangjian

    2013-10-01

    Nonlinear dynamic factor analysis models extend standard linear dynamic factor analysis models by allowing time series processes to be nonlinear at the latent level (e.g., involving interaction between two latent processes). In practice, it is often of interest to identify the phases--namely, latent "regimes" or classes--during which a system is characterized by distinctly different dynamics. We propose a new class of models, termed nonlinear regime-switching state-space (RSSS) models, which subsumes regime-switching nonlinear dynamic factor analysis models as a special case. In nonlinear RSSS models, the change processes within regimes, represented using a state-space model, are allowed to be nonlinear. An estimation procedure obtained by combining the extended Kalman filter and the Kim filter is proposed as a way to estimate nonlinear RSSS models. We illustrate the utility of nonlinear RSSS models by fitting a nonlinear dynamic factor analysis model with regime-specific cross-regression parameters to a set of experience sampling affect data. The parallels between nonlinear RSSS models and other well-known discrete change models in the literature are discussed briefly.

  11. 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.

  12. 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.

  13. The history of research into improved confinement regimes

    NASA Astrophysics Data System (ADS)

    Wagner, F.

    2017-01-01

    Increasing the pressure by additional heating of magnetically confined plasmas had the consequence that turbulent processes became more violent and plasma confinement degraded. Since this experience from the early 1980ies, fusion research was dominated by the search for confinement regimes with improved properties. It was a gratifying experience that toroidally confined plasmas are able to self-organise in such a way that turbulence diminishes, resulting in a confinement with good prospects to reach the objectives of fusion R&D. The understanding of improved confinement regimes revolutionized the understanding of turbulent transport in high-temperature plasmas. In this paper the story of research into improved confinement regimes will be narrated starting with 1980.

  14. Suspended-sediment concentration regimes in Tennessee biological reference streams

    USGS Publications Warehouse

    Diehl, Timothy H.; Wolfe, William J.

    2010-01-01

    Suspended-sediment-concentration (SSC) regimes of five biological reference streams in Tennessee were characterized from 15-minute SSC records spanning 1 to 4 water years (October 1 through September 30) between 2004 and 2008. These streams represent least disturbed conditions for their respective ecoregions and have exceptional biodiversity in terms of fish or aquatic invertebrates. SSC regimes in streams, when plotted in terms of duration above a given SSC at a given annual frequency such as the annual maximum or the annual tenth longest duration, can be compared directly to published biological impairment thresholds derived from experimental trials. Based on such comparison, the SSC regimes of all five reference streams reached published impairment thresholds at least 10 times per water year for all years of record. The results suggest that the published impairment thresholds are not directly applicable to streams in Tennessee and, by extension, the southeastern United States.

  15. Two-phase flow regime map predictions under microgravity

    SciTech Connect

    Karri, S.B.R.; Mathur, V.K.

    1988-01-01

    In this paper, the widely used models of Taitel-Dukler and Weisman et al. are extrapolated to microgravity levels to compare predicted flow pattern boundaries for horizontal and vertical flows. Efforts have been made to analyze how the two-phase flow models available in the literature predict flow regime transitions in microgravity. The models of Taitel-Dukler and Weisman et al. have been found to be more suitable for extrapolation to a wide range of system parameters than the other two-phase flow regime maps available in the literature. The original criteria for all cases are used to predict the transition lines, except for the transition to dispersed flow regime in case of the Weisman model for horizontal flow. The constant 0.97 on the righthand side of this correlation should be two times that value, i.e., 1.94, in order to match this transition line in their original paper.

  16. Adaptive management of ecosystem services across different land use regimes.

    PubMed

    Ruhl, J B

    2016-12-01

    Using adaptive management to manage desired flows of ecosystem services may seem on the surface to be a good fit, but many social, economic, environmental, legal, and political factors influence how good a fit. One strongly influential factor is the land use regime within which the profile of ecosystem services is being managed. Shaped largely by legal mandates, market forces, and social and cultural practices, different land use regimes present different opportunities for and constraints on goals for ecosystem services and pose different decision making environments. Even where all other conditions appear amenable to using adaptive management, therefore, it is essential to consider the constraining (or liberating) effects of different land use regimes when deciding whether to adopt adaptive management to achieve those goals and, if so, how to implement it.

  17. Hydrodynamic interaction of swimming organisms in an inertial regime

    NASA Astrophysics Data System (ADS)

    Li, Gaojin; Ostace, Anca; Ardekani, Arezoo M.

    2016-11-01

    We numerically investigate the hydrodynamic interaction of swimming organisms at small to intermediate Reynolds number regimes, i.e., Re˜O (0.1 -100 ) , where inertial effects are important. The hydrodynamic interaction of swimming organisms in this regime is significantly different from the Stokes regime for microorganisms, as well as the high Reynolds number flows for fish and birds, which involves strong flow separation and detached vortex structures. Using an archetypal swimmer model, called a "squirmer," we find that the inertial effects change the contact time and dispersion dynamics of a pair of pusher swimmers, and trigger hydrodynamic attraction for two pullers. These results are potentially important in investigating predator-prey interactions, sexual reproduction, and the encounter rate of marine organisms such as copepods, ctenophora, and larvae.

  18. 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.

  19. 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.

  20. 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.

  1. Hydrodynamic interaction of swimming organisms in an inertial regime.

    PubMed

    Li, Gaojin; Ostace, Anca; Ardekani, Arezoo M

    2016-11-01

    We numerically investigate the hydrodynamic interaction of swimming organisms at small to intermediate Reynolds number regimes, i.e., Re∼O(0.1-100), where inertial effects are important. The hydrodynamic interaction of swimming organisms in this regime is significantly different from the Stokes regime for microorganisms, as well as the high Reynolds number flows for fish and birds, which involves strong flow separation and detached vortex structures. Using an archetypal swimmer model, called a "squirmer," we find that the inertial effects change the contact time and dispersion dynamics of a pair of pusher swimmers, and trigger hydrodynamic attraction for two pullers. These results are potentially important in investigating predator-prey interactions, sexual reproduction, and the encounter rate of marine organisms such as copepods, ctenophora, and larvae.

  2. The Self-energy Of Growing Aggregates: "Strength Regime"

    NASA Astrophysics Data System (ADS)

    Guimaraes, Ana H. F.; Spahn, F.; Seiss, M.; Brilliantov, N. V.

    2009-09-01

    The vivid appearance of the outer regions of Saturn's rings points to a balance of ongoing fragmentation and coagulation processes. This idea finds support especially in the F-ring, where collisional processes occur on an almost daily basis stirred by perturbations of the satellites Prometheus and Pandora, and in addition due the presence of putative moonlets. In order to quantify this balance in a kinetic theory we propose to calculate the resistivity of small agglomerates ("dynamic ephemeral bodies") against rupture due collisional processes and tidal pull. Earlies studies have shown that the resistivity of an aggregate is divided into two phases: "strength regime" and "gravitational regime". Early in their formation, small agglomerates are supported basically by their "glue" between the particles (adhesion) - "strength regime". For larger agglomerates the "gravitational regime" takes over provided their sizes to be bigger than a threshold in which the self-gravitational energy exceeds the adhesive binding energy, in this case the cluster's constituents are held together gravitationally. We calculated the self-energy caused by adhesion and gravity of ring's aggregates which has been considered as the threshold of impact energy or of tidal work to disrupt the agglomerate. Using a Ballistic Particle Cluster Aggregate Model (BPCA) we varied the densities of the aggregates and the size distribution of their constituents (1-10cm), calculated their self-energy and identified the transition between the "strength" to "gravitational regime". The transition between the regimes occurs at house-size aggregates (diameter of approximately 20m), a fact, that fits to the cut-off on the dense rings' main population (cm - 5m in size). Acknowledgments: A.H.F.G. thanks Dr. E. Vieira-Neto for the discussions, and also the DAAD and Uni-Potsdam for the financial support of this project.

  3. The Isolated Bubble Regime in Pool Nucleate Boiling

    NASA Technical Reports Server (NTRS)

    Buyevich, Y. A.; Webbon, Bruce W.; Callaway, Robert (Technical Monitor)

    1995-01-01

    We consider an isolated bubble boiling regime in which vapour bubbles are intermittently produced at a prearranged set of nucleation site on an upward facing overheated wall plane. In this boiling regime, the bubbles depart from the wall and move as separate entities. Except in the matter of rise velocity, the bubbles do not interfere and are independent of one another. However, the rise velocity is dependent on bubble volume concentration in the bulk. Heat transfer properties specific to this regime cannot be described without bubble detachment size, and we apply our previously developed dynamic theory of vapour bubble growth and detachment to determine this size. Bubble growth is presumed to be thermally controlled. Two limiting cases of bubble evolution are considered: the one in which buoyancy prevails in promoting bubble detachment and the one in which surface tension prevails. We prove termination of the isolated regime of pool nucleate boiling to result from one of the four possible causes, depending on relevant parameters values. The first cause consists in the fact that the upward flow of rising bubbles hampers the downward liquid flow, and under certain conditions, prevents the liquid from coming to the wall in an amount that would be sufficient to compensate for vapour removal from the wall. The second cause is due to the lateral coalescence of growing bubbles that are attached to their corresponding nucleation sites, with ensuing generation of larger bubbles and extended vapour patches near the wall. The other two causes involve longitudinal coalescence either 1) immediately in the wall vicinity, accompanied by the establishment of the multiple bubble boiling regime, or 2) in the bulk, with the formation of vapour columns. The longitudinal coalescence in the bulk is shown to be the most important cause. The critical wall temperature and the heat flux density associated with isolated bubble regime termination are found to be functions of the physical and

  4. The legacy of large regime shifts in shallow lakes.

    PubMed

    Ramstack Hobbs, Joy M; Hobbs, William O; Edlund, Mark B; Zimmer, Kyle D; Theissen, Kevin M; Hoidal, Natalie; Domine, Leah M; Hanson, Mark A; Herwig, Brian R; Cotner, James B

    2016-12-01

    Ecological shifts in shallow lakes from clear-water macrophyte-dominated to turbid-water phytoplankton-dominated are generally thought of as rapid short-term transitions. Diatom remains in sediment records from shallow lakes in the Prairie Pothole Region of North America provide new evidence that the long-term ecological stability of these lakes is defined by the legacy of large regime shifts. We examine the modern and historical stability of 11 shallow lakes. Currently, four of the lakes are in a clear-water state, three are consistently turbid-water, and four have been observed to change state from year to year (transitional). Lake sediment records spanning the past 150-200 yr suggest that (1) the diatom assemblage is characteristic of either clear or turbid lakes, (2) prior to significant landscape alteration, all of the lakes existed in a regime of a stable clear-water state, (3) lakes that are currently classified as turbid or transitional have experienced one strong regime shift over the past 150-200 yr and have since remained in a regime where turbid-water predominates, and (4) top-down impacts to the lake food-web from fish introductions appear to be the dominant driver of strong regime shifts and not increased nutrient availability. Based on our findings we demonstrate a method that could be used by lake managers to identify lakes that have an ecological history close to the clear-turbid regime threshold; such lakes might more easily be returned to a clear-water state through biomanipulation. The unfortunate reality is that many of these lakes are now part of a managed landscape and will likely require continued intervention.

  5. 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.

  6. Thermal regime of ventilation shafts and its regulation

    SciTech Connect

    Petrov, N.N.; Timoshenko, N.I.

    1986-03-01

    This paper evaluates the regime of air flow through a ventilation shaft and the nondimensional heat-exchange criteria. It is shown that the air temperature in the shaft is affected more by the walls than by the reinforcement structure metal and that the heat released by internal combustion engines could be an alternative source for heating the air. High bypass aircraft turbojet engines decommissioned after their maximum surface life on planes could be used for this purpose. The study of the thermal regime in the shaft in the case of a sudden change of air temperature such as occurs during ventilation reversals has established the requirements for air heating equipment.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Ocean Wave Energy Regimes of the Circumpolar Coastal Zones

    NASA Astrophysics Data System (ADS)

    Atkinson, D. E.

    2004-12-01

    Ocean wave activity is a major enviromental forcing agent of the ice-rich sediments that comprise large sections of the arctic coastal margins. While it is instructive to possess information about the wind regimes in these regions, direct application to geomorphological and engineering needs requires knowledge of the resultant wave-energy regimes. Wave energy information has been calculated at the regional scale using adjusted reanalysis model windfield data. Calculations at this scale are not designed to account for local-scale coastline/bathymetric irregularities and variability. Results will be presented for the circumpolar zones specified by the Arctic Coastal Dynamics Project.

  12. 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

  13. 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.

  14. Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals.

    PubMed

    Shapiro, R L; Duquette, J G; Roses, D F; Nunes, I; Harris, M N; Kamino, H; Wilson, E L; Rifkin, D B

    1996-08-01

    Evidence suggests that the plasminogen activators (PAs), in particular urokinase-type PA (uPA), play a pivotal role in tumor invasion and metastasis. We studied the contribution of the PAs to the malignant phenotype through the chemical induction of melanocytic neoplasms in uPA-deficient mice. Primary tumors were induced and promoted concurrently in 35 uPA-/- deficient and 35 uPA+/+ wild-type mice using a single application of 7,12-dimethylbenz(a)anthracene followed by repetitive applications of croton oil. Animals were sacrificed at 60-day intervals for 1 year. At necropsy, the four largest pigmented lesions in each animal were excised, characterized histologically, and evaluated microscopically for evidence of invasion. The regional lymph nodes, lungs, and solid abdominal visceral organs were sectioned and examined microscopically for evidence of metastatic disease. Cellular blue nevi were induced in 100% of uPA-/- and uPA+/+ promoted animals. Although a reduction in the radial and vertical progression of these lesions was noted in the uPA-deficient mice compared with the wild-type group, more than 95% of cellular blue nevi induced in both groups of animals invaded the underlying tissues. These lesions did not metastasize to the regional lymph nodes. Malignant melanoma arose in 5 of 35 (14.3%) of promoted wild-type mice. These tumors were locally aggressive, produced tissue-type PA, but were not metastatic to the regional nodes, lungs, or abdominal viscera. These results indicate that the invasive capability of melanocytic lesions may depend more on tissue-type PA than uPA activity. No melanomas were induced in the uPA-/- mice. The resistance of the uPA -/- strain to melanoma induction suggests that uPA contributes to malignant progression. We propose that the absence of uPA negatively affects tumorigenesis by decreasing the liberation and availability of growth factors such as basic fibroblast growth factor.

  15. 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.

  16. 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.

  17. Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells.

    PubMed

    Mahanivong, C; Chen, H M; Yee, S W; Pan, Z K; Dong, Z; Huang, S

    2008-02-21

    We reported previously that a signaling pathway consisting of G(i)-Ras-NF-kappaB mediates lysophosphatidic acid (LPA)-induced urokinase plasminogen activator (uPA) upregulation in ovarian cancer cells. However, it is not clear what signaling components link Ras to nuclear factor (NF)-kappaB for this LPA-induced event. In the present study, we found that treatment of protein kinase C (PKC) inhibitors including conventional PKC (cPKC) inhibitor Gö6976 abolished LPA-induced uPA upregulation in ovarian cancer cell lines tested, indicating the importance of cPKC activity in this LPA-induced event. Indeed, LPA stimulation led to the activation of PKCalpha and Ras-PKCalpha interaction. Although constitutively active mutants of PKCalpha (a cPKC), PKCtheta (a novel PKC (nPKC)) and PKCzeta (an atypical PKC (aPKC)) were all able to activate NF-kappaB and upregulate uPA expression, only dominant-negative PKCalpha mutant attenuated LPA-induced NF-kappaB activation and uPA upregulation. These results suggest that PKCalpha, rather than PKC isoforms in other PKC classes, participates in LPA-induced NF-kappaB activation and uPA upregulation in ovarian cancer cells. To determine the signaling components downstream of PKCalpha mediating LPA-induced uPA upregulation, we showed that forced expression of dominant-negative CARMA3 or silencing CARMA3, Bcl10 and MALT1 with specific siRNAs diminished these LPA-induced events. Furthermore, we demonstrated that PKCalpha/CARMA3 signaling axis is important in LPA-induced ovarian cancer cell in vitro invasion.

  18. Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity - clinical relevance and prognostic value.

    PubMed

    Hundsdorfer, Brigitte; Zeilhofer, Hans-Florian; Bock, Klaus Peter; Dettmar, Peer; Schmitt, Manfred; Kolk, Andreas; Pautke, Christoph; Horch, Hans-Henning

    2005-06-01

    The central role of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor, the plasminogen activator-inhibitor-1 (PAI-1), in tumour invasion and metastasis becomes more and more evident. In several studies, uPA and PAI-1 proved to be of prognostic relevance as shown for different types of cancer (e.g. breast, stomach, lung). Elevated antigen levels of uPA and/or PAI-1 predict poor outcome (relapse-free survival) for patients afflicted with cancer. For oral squamous cell carcinomas, however, the prognostic relevance of the tumour-associated proteolytic factors uPA and PAI-1 has still to be evaluated. In the present study, using tissue extracts of 79 oral cancer cases, 58 specimens of normal oral cavity mucosa and of 16 tumour positive lymph nodes taken from the same patients, uPA and PAI-1 antigen were determined by highly sensitive enzyme-linked immunosorbent assays (ELISA). A correlation was found between uPA and PAI-1 in tumour tissue, when compared with the normal mucosa of the same oral cavity. Median levels showed significant elevations in cancer tissue and in tumour positive lymph nodes versus normal oral mucosa. In patients with high levels of uPA or PAI-1, there were significantly more tumour relapses. There was no significant correlation between pathological TNM categories, grading, residual tumour category, tumour site and patient age. In summary, tumour uPA/PAI-1 content (as determined by ELISA) appears to be a strong independent prognostic factor for relapse-free survival in squamous cell cancer of the oral cavity. These observations might help to select patients with poor prognosis for additional adjuvant therapy in conjunction with complete surgical resection.

  19. 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

  20. The soluble form of LR11 protein is a regulator of hypoxia-induced, urokinase-type plasminogen activator receptor (uPAR)-mediated adhesion of immature hematological cells.

    PubMed

    Nishii, Keigo; Nakaseko, Chiaki; Jiang, Meizi; Shimizu, Naomi; Takeuchi, Masahiro; Schneider, Wolfgang J; Bujo, Hideaki

    2013-04-26

    A key property of hematopoietic stem and progenitor cells (HSPCs) regarding differentiation from the self-renewing quiescent to the proliferating stage is their adhesion to the bone marrow (BM) niche. An important molecule involved in proliferation and pool size of HSPCs in the BM is the hypoxia-induced urokinase-type plasminogen activator receptor (uPAR). Here, we show that the soluble form (sLR11) of LR11 (also called SorLA or SORL1) modulates the uPAR-mediated attachment of HSPCs under hypoxic conditions. Immunohistochemical and mRNA expression analyses revealed that hypoxia increased LR11 expression in hematological c-Kit(+) Lin(-) cells. In U937 cells, hypoxia induced a transient rise in LR11 transcription, production of cellular protein, and release of sLR11. Attachment to stromal cells of c-Kit(+) Lin(-) cells of lr11(-/-) mice was reduced by hypoxia much more than of lr11(+/+) animals. sLR11 induced the adhesion of U937 and c-Kit(+) Lin(-) cells to stromal cells. Cell attachment was increased by sLR11 and reduced in the presence of anti-uPAR antibodies. Furthermore, the fraction of uPAR co-immunoprecipitated with LR11 in membrane extracts of U937 cells was increased by hypoxia. CoCl2, a chemical inducer of HIF-1α, enhanced the levels of LR11 and sLR11 in U937 cells. The decrease in hypoxia-induced attachment of HIF-1α-knockdown cells was largely prevented by exogenously added sLR11. Finally, hypoxia induced HIF-1α binding to a consensus binding site in the LR11 promoter. Thus, we conclude that sLR11 regulates the hypoxia-enhanced adhesion of HSPCs via an uPAR-mediated pathway that stabilizes the hematological pool size by controlling cell attachment to the BM niche.

  1. Dioscorea nipponica Attenuates Migration and Invasion by Inhibition of Urokinase-Type Plasminogen Activator through Involving PI3K/Akt and Transcriptional Inhibition of NF-[Formula: see text]B and SP-1 in Hepatocellular Carcinoma.

    PubMed

    Hsieh, Ming-Ju; Yeh, Chao-Bin; Chiou, Hui-Ling; Hsieh, Ming-Chang; Yang, Shun-Fa

    2016-01-01

    High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. In our previous studies, we have reported that Dioscorea nipponica Makino extract (DNE) has anti-metastasis effects on human oral cancer cells. However, the effect of DNE on hepatoma metastasis have not been thoroughly investigated and remains poorly understood. To determine the effects of DNE on the migration and invasion in HCC cells we used a wound healing model, Boyden chamber assays, gelatin/casein zymography and Western blotting. Transcriptional levels of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA) were detected by real-time PCR and promoter assays. In this study, DNE treatment significantly inhibited the migration/invasion capacities of Huh7 cell lines. The results of gelatin/casein zymography and Western blotting revealed that the activities and protein levels of the MMP-9 and u-PA were inhibited by DNE. Tests of the mRNA levels, real-time PCR, and promoter assays evaluated the inhibitory effects of DNE on u-PA expression in human hepatoma cells. A chromatin immunoprecipitation (ChIP) assay showed not only that DNE inhibits u-PA expression, but also the inhibitory effects were associated with the down-regulation of the transcription factors of NF-[Formula: see text]B and SP-1 signaling pathways. Western blot analysis also showed that DNE inhibits PI3K and phosphorylation of Akt. In conclusion, these results show that u-PA expression may be a potent therapeutic target in the DNE-mediated suppression of HCC invasion/migration. DNE may have potential use as a chemo-preventive agent against liver cancer metastasis.

  2. Improving Mesoscale Prediction of Shallow Convection and Cloud Regime Transitions in NRL COAMPS

    DTIC Science & Technology

    2013-09-30

    continuum of cloud regimes from stratocumulus to trade cumulus , with particular emphasis on cloud regime transitions. OBJECTIVES Accurate prediction...of cloud -topped marine boundary layers regional forecast models is currently hindered the ability of the models to represent shallow cumulus ... cloud regime transitions, exist in between stratocumulus and trade cumulus . These cloud regimes are typically characterized by one of the following

  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. Production regimes for Self-Interacting Dark Matter

    SciTech Connect

    Bernal, Nicolás; Chu, Xiaoyong; Garcia-Cely, Camilo; Hambye, Thomas; Zaldivar, Bryan E-mail: xchu@ictp.it E-mail: thambye@ulb.ac.be

    2016-03-01

    In the context of Self-Interacting Dark Matter as a solution for the small-scale structure problems, we consider the possibility that Dark Matter could have been produced without being in thermal equilibrium with the Standard Model bath. We discuss one by one the following various dark matter production regimes of this kind: freeze-in, reannihilation and dark freeze-out. We exemplify how these mechanisms work in the context of the particularly simple Hidden Vector Dark Matter model. In contrast to scenarios where there is thermal equilibrium with the Standard Model bath, we find two regimes which can easily satisfy all the laboratory and cosmological constraints. These are dark freeze-out with 3-to-2 annihilations and freeze-in via a light mediator. In the first regime, different temperatures in the visible and the Dark Matter sectors allow us to avoid the constraints coming from cosmic structure formation as well as the use of non-perturbative couplings to reproduce the observed relic density. For the second regime, different couplings are responsible for Dark Matter relic density and self-interactions, permitting to surpass BBN, X-ray, CMB and direct detection constraints.

  5. 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 Section 120.29 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND... amendments thereto. (c) List of all items on the MTCR Annex. Section 71(a) of the Arms Export Control Act...

  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 Section 120.29 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND... thereto; (c) List of all items on the MTCR Annex. Section 71(a) of the Arms Export Control Act (22...

  7. 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 Section 120.29 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND... thereto; (c) List of all items on the MTCR Annex. Section 71(a) of the Arms Export Control Act (22...

  8. 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

  9. Optimal ranking regime analysis of TreeFlow dendrohydrological reconstructions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Optimal Ranking Regime (ORR) method was used to identify 6-100 year time windows containing significant ranking sequences in 55 western U.S. streamflow reconstructions, and reconstructions of the level of the Great Salt Lake and San Francisco Bay salinity during 1500-2007. The method’s ability t...

  10. 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…

  11. 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…

  12. ECOLOGICALLY-RELEVANT QUANTIFICATION OF STREAMFLOW REGIMES IN WESTERN STREAMS

    EPA Science Inventory

    This report describes the rationale for and application of a protocol for estimation of ecologically-relevant streamflow metrics that quantify streamflow regime for ungaged sites subject to a range of human impact. The analysis presented here is focused on sites sampled by the U....

  13. Welfare Regimes and Educational Inequality: A Cross-National Exploration

    ERIC Educational Resources Information Center

    Peter, Tracey; Edgerton, Jason D.; Roberts, Lance W.

    2010-01-01

    Research on welfare state regimes and research on educational policy share a common concern for the reduction of social inequality. On one hand, welfare state research is typically designed within a comparative approach where scholars investigate similarities and differences in social institutions across selected countries. On the other hand, the…

  14. 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.

  15. 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.

  16. 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...

  17. Regime Change the Old Fashioned Way: US Support to Insurgencies

    DTIC Science & Technology

    2008-04-23

    attributed the failure to poor direction and coordination, and created a special structure to oversee Operation MONGOOSE , a second covert program...against the Castro regime in Cuba. To ensure unity of effort, Kennedy designated Brigadier General Edward Lansdale in writing as the 7 MONGOOSE

  18. The rainfall regime and its uncertainty in Valencia and Larnaca

    NASA Astrophysics Data System (ADS)

    Reiser, H.; Kutiel, H.

    2007-08-01

    The Most Expected Rainfall Regime - MERR in a certain region is composed of various parameters regarding the annual rainfall regime in that region. The present study examines several parameters of the MERR, such as: the rainfall TOTAL, the Date of Accumulated Percentage-DAP, the Rainy Season Length-RSL, the Number of Rain-Spells-NRS, the Rain-Spell Yield-RSY, the ratio between Average and Median rainfall-AMED, the relationship between accumulated precipitation and the number of rain-spells and the Dry-Spell Distribution-DSD. Two stations at the two sides of the Mediterranean basin, Valencia and Larnaca, have been used to illustrate the distribution of the above parameters across the Mediterranean. The main conclusion of the study is that the rainfall regime at Larnaca is less uncertain as compared with the regime in Valencia. This is probably due to the fact that rainfalls are completely absent during the summer in Larnaca, which better suits the definition of a Mediterranean climate than that of Valencia.

  19. Multi-Fluid Modeling of Low-Recycling Divertor Regimes

    SciTech Connect

    Smirnov, R. D.; Pigarov, A. Y.; Krasheninnikov, S. I.; Rognlien, T. D.; Soukhanovskii, V. A.; Rensink, M. E.; Maingi, Rajesh; Skinner, C. H.; Stotler, D. P.; Bell, R. E.; Kugel, H. W.

    2010-01-01

    The low-recycling regimes of divertor operation in a single-null NSTX magnetic configuration are studied using computer simulations with the edge plasma transport code UEDGE. The edge plasma transport properties pertinent to the low-recycling regimes are demonstrated. These include the flux-limited character of the parallel heat transport and the high plasma temperatures with the flattened profiles in the scrape-off-layer. It is shown that to maintain the balance of particle fluxes at the core interface the deuterium gas puffing rate should increase as the divertor recycling coefficient decreases. The radial profiles of the heat load to the outer divertor plate, the upstream radial plasma profiles, and the effects of the cross-field plasma transport in the low-recycling regimes are discussed. It is also shown that recycling of lithium impurities evaporating from the divertor plate at high surface temperatures can reverse the low-recycling divertor operational regime to the high-recycling one and may cause thermal instability of the divertor plate. (C) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  20. Institutional Regimes and Induced Dependency in Homes for the Aged.

    ERIC Educational Resources Information Center

    Booth, Tim

    1986-01-01

    Reports effects of institutional regimes on levels of dependency among residents of public homes for the elderly in England. Differences in management practices and caring routines did not affect the creation or reduction of dependency among residents. Questions the rationale that informs some current notions of good practice in residential work.…

  1. 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.

  2. 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.

  3. 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 led…

  4. Notion of time and the semiclassical regime of quantum gravity

    SciTech Connect

    Castagnino, M.A.; Mazzitelli, F.D. Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab 1, 1428 Buenos Aires )

    1990-07-15

    Using the notion of {ital probabilistic} {ital time} introduced in a previous work, we analyze the perturbed minisuperspace models of quantum gravity. For Robertson-Walker minisuperspace we show that it is possible to derive the so-called self-consistent cosmology in the semiclassical regime. The generalization to models with several semiclassical variables is also discussed.

  5. Observed trends in the hydrologic regime of Alpine catchments

    NASA Astrophysics Data System (ADS)

    Bard, Antoine; Renard, Benjamin; Lang, Michel

    2010-05-01

    A European trans-national project, AdaptAlp, has been set up since 2008 in order to study the impacts of climate change in the Alps and to assess adaptation strategies. One of the objectives of this project is to study past and present changes in the hydrologic regime of Alpine rivers. This poster presents preliminary results of a trend analysis over the whole Alpine area. A new dataset of more than two hundred discharge time series has been collected over the six countries of the alpine space: Switzerland, Italy, Germany, Austria, Slovenia and France. These series are made up of at least forty years of daily record and are related to undisturbed catchments. This dataset covers the whole spectrum of hydrological regimes existing in the Alps (from glacier- to mixed rainfall/snow regimes). In a second step, a set of hydrologic indices has been defined to characterize the hydrologic regime in terms of low, medium and high flows. In particular, these indices describe the drought severity (in terms of duration, intensity and volume deficit) and seasonality, the volume and timing of snowmelt, floods intensity and seasonality. A statistical trend test is finally applied for each hydrologic indice at each site. Consistent trends affecting the timing of snowmelt-dominated streamflow are found all over the Alps. Spring floods appear earlier in the season and tend to be longer in duration. Winter droughts tend to be shorter and less severe in terms of volume deficit.

  6. 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)

  7. 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.

  8. 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…

  9. Regime-based analysis of aerosol-cloud interactions

    NASA Astrophysics Data System (ADS)

    Gryspeerdt, Edward; Stier, Philip

    2012-11-01

    Previous global satellite studies into the indirect aerosol effect have relied on determining the sensitivity of derived Cloud Droplet Number Concentration (Nd) to co-located Aerosol Optical Depth (AOD). These studies generally find a positive Nd sensitivity to AOD changes over ocean, but some find a negative sensitivity over land, in contrast to that predicted by models and theory. Here we investigate the Nd sensitivity to AOD in different cloud regimes, determined using a k-means clustering process on retrieved cloud properties. We find the strongest positive Nd sensitivity in the stratiform regimes over both land and ocean, providing the majority of the total sensitivity. The negative sensitivity previously observed over land is generated by the low cloud fraction regimes, suggesting that it is due to the difficulty of retrieving Nd at low cloud fractions. When considering a mean sensitivity, weighted by liquid cloud fraction to account for sampling biases, we find an increased sensitivity over land, in some regions becoming positive. This highlights the importance of regime based analysis when studying aerosol indirect effects.

  10. 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…

  11. Nonlinear transport processes in tokamak plasmas. I. The collisional regimes

    NASA Astrophysics Data System (ADS)

    Sonnino, Giorgio; Peeters, Philippe

    2008-06-01

    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-Schlüter (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 102. 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 102 when the nonlinear contributions are duly taken into account but, there is still a factor of 102 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.

  12. 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.

  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. 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

  15. TRMM Observations of Convective Regimes in the Amazon

    NASA Technical Reports Server (NTRS)

    Petersen, W. A.; Nesbitt, S. W.; Blakeslee, Robert J.; Hein, P.; Cifelli, R.; Rutledge, S. A.; Arnold, James E. (Technical Monitor)

    2001-01-01

    This study utilizes TRMM satellite precipitation radar, lightning imaging sensor, and passive microwave imager data together with ground-based lightning data to investigate the vertical structure, lightning, and rainfall characteristics of Amazonian and central South American convection for three separate wet-seasons. These characteristics are partitioned as a function of 850 mb zonal wind direction, motivated by observations collected during the six-week TRMM-LBA field campaign. The TRMM-LBA field campaign observations suggest that systematic variations in Amazonian convective vertical structure, lightning, and rainfall are all linked to bimodal variations in the low-level zonal wind (e.g., easterly and westerly regimes). The more spatially and temporally comprehensive TRMM dataset used in this study extends the TRMM-LBA observations by examining regime variability in Amazonian and South American convective structure over a continental scale domain. On a continental-scale, patterns of east and west regime 850 mb winds combined with LIS lightning flash densities suggest the presence of synoptic-scale controls (e.g., intrusion of extratropical frontal systems and interaction with the SACZ) on regional-scale variability in convective vertical structure. TRMM PR, TMI and ground-based lightning data suggest that regional variability in wet-season convective structure is most evident over the southern Amazon, Mato Grosso, Altiplano, southern Brazil, and eastern coastal regions of central and southern South America. Convective vertical structure, rain fall rates, and lightning activity are all more pronounced during easterly (westerly) regimes over the southern Amazon and Mato Grosso (Altiplano, and southern Brazil). Importantly, when considered with case-study results from TRMM-LBA, the systematic differences in convective structure that occur as a function of regime suggest that associated regime-differences may exist in the vertical distribution of diabatic heating

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Nondiffusive transport regimes for suprathermal ions in turbulent plasmas.

    PubMed

    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.

  6. Disorder-assisted quantum transport in suboptimal decoherence regimes.

    PubMed

    Novo, Leonardo; Mohseni, Masoud; Omar, Yasser

    2016-01-04

    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.

  7. 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.

  8. 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.

  9. Spectator effects during Leptogenesis in the strong washout regime

    SciTech Connect

    Garbrecht, Björn; Schwaller, Pedro E-mail: pedro.schwaller@cern.ch

    2014-10-01

    By including spectator fields into the Boltzmann equations for Leptogenesis, we show that partially equilibrated spectator interactions can have a significant impact on the freeze-out value of the asymmetry in the strong washout regime. The final asymmetry is typically increased, since partially equilibrated spectators ''hide'' a part of the asymmetry from washout. We study examples with leptonic and non-leptonic spectator processes, assuming thermal initial conditions, and find up to 50% enhanced asymmetries compared to the limit of fully equilibrated spectators. Together with a comprehensive overview of the equilibration temperatures for various Standard Model processes, the numerical results indicate the ranges when the limiting cases of either fully equilibrated or negligible spectator fields are applicable and when they are not. Our findings also indicate an increased sensitivity to initial conditions and finite density corrections even in the strong washout regime.

  10. Regimes of strong light-matter coupling under incoherent excitation

    SciTech Connect

    Valle, E. del; Laussy, F. P.

    2011-10-15

    We study a two-level system (atom, superconducting qubit, or quantum dot) strongly coupled to a single photonic mode of a cavity, in the presence of incoherent pumping and including detuning and dephasing. This system displays a striking quantum-to-classical transition. On the grounds of several approximations that reproduce to various degrees exact results obtained numerically, we separate five regimes of operations, that we term ''linear,''''quantum,''''lasing,''''quenching,'' and ''thermal.'' In the fully quantized picture, the lasing regime arises as a condensation of dressed states and manifests itself as a Mollow triplet structure in the direct emitter photoluminescence spectrum, which embeds fundamental features of the full-field quantization description of light-matter interaction.

  11. 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.

  12. Multi-band metamaterial absorber topology for infrared frequency regime

    NASA Astrophysics Data System (ADS)

    Mulla, Batuhan; Sabah, Cumali

    2017-02-01

    In this paper, a new multiband metamaterial absorber design is proposed and the numerical characterization is carried out. The design is composed of three layers with differently sized quadruplets in which the interaction among them causes the multiband absorption response in the infrared frequency regime. In order to characterize the absorber and explain the multiband topology, some parametric studies with respect to the dimensions of the structure are carried out and the contributions of the quadruplets to the absorption spectrum are analyzed. According to the results, it is found that the proposed metamaterial absorber has five bands in the infrared frequency regime with the absorption levels of: 98.90%, 99.39%, 86.46%, 92.80% and 97.96%. Moreover, the polarization dependency of the structure is examined and it is found that the design operates well as a perfect absorber with polarization independency in the studied frequency range.

  13. 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.

  14. Optically Pumped NMR in the Fractional Quantum Hall Regime

    NASA Astrophysics Data System (ADS)

    Barrett, S. E.; Kuzma, N. N.; Khandelwal, P.; Pfeiffer, L. N.; West, K. W.

    1998-03-01

    Optically Pumped Nuclear Magnetic Resonance measurements are a local probe of the electron spin degree of freedom in n-type GaAs quantum wells.(S.E.Barrett et al.,Phys.Rev.Lett.72),1368(1994).^, footnote S. E. Barrett et al., Phys. Rev. Lett. 74, 5112 (1995)^, footnote R. Tycko et al., Science 268, 1460 (1995). We have recently shown that this OPNMR technique can be carried out in fields up to B=12 Tesla and temperatures down to T=0.3 K, making this technique a viable new probe of the Fractional Quantum Hall regime. We will discuss our latest measurements in these conditions, and compare our new results with previous measurements and the existing theoretical models for this regime.

  15. Scalable quantum memory in the ultrastrong coupling regime

    PubMed Central

    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

  16. Flow regimes and parameter dependence in nanochannel flows.

    PubMed

    Liu, Chong; Li, Zhigang

    2009-09-01

    Nanoscale fluid flow systems involve both microscopic and macroscopic parameters, which compete with each another and lead to different flow regimes. In this work, we investigate the interactions of four fundamental parameters, including the fluid-fluid, fluid-wall binding energies, temperature of the system, and driving force, and their effects on the flow motion in nanoscale Poiseuille flows. By illustrating the fluid flux as a function of a dimensionless number, which represents the effective surface effect on the fluid, we show that the fluid motion in nanochannels falls into different regimes, each of which is associated with a distinct mechanism. The mechanisms in different situations reveal the effects of the parameters on the fluid dynamics.

  17. 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.

  18. Ring-diffusion mediated homogeneous melting in the superheating regime

    NASA Astrophysics Data System (ADS)

    Bai, Xian-Ming; Li, Mo

    2008-04-01

    Homogeneous melting in the superheating regime is investigated by using molecular dynamics simulation of a Lennard-Jones model system. We show that the commonly observed catastrophic melting at the superheating limit is caused by fast heating rate. By keeping the system isothermally at temperatures below the superheating limit, we observe intense self-diffusion motions as the precursor of melting. The highly correlated atomic motions are related to the self-diffusion loops or rings. Two types of loops are observed, closed loop and open loop, where the latter is directly related to the homogeneous nucleation of the liquid phase. Homogeneous melting occurs when the number density of diffusion loops reaches a critical value. Our results suggest that homogeneous melting in the superheating regime is a first-order thermodynamic phase transition triggered by the self-diffusion loops when the kinetic constraint imposed by heating rate is lessened.

  19. 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

  20. 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.

  1. Study of a spur gear dynamic behavior in transient regime

    NASA Astrophysics Data System (ADS)

    Khabou, M. T.; Bouchaala, N.; Chaari, F.; Fakhfakh, T.; Haddar, M.

    2011-11-01

    In this paper the dynamic behavior of a single stage spur gear reducer in transient regime is studied. Dynamic response of the single stage spur gear reducer is investigated at different rotating velocities. First, gear excitation is induced by the motor torque and load variation in addition to the fluctuation of meshing stiffness due to the variation of input rotational speed. Then, the dynamic response is computed using the Newmark method. After that, a parameter study is made on spur gear powered in the first place by an electric motor and in the second place by four strokes four cylinders diesel engine. Dynamic responses come to confirm a significant influence of the transient regime on the dynamic behavior of a gear set, particularly in the case of engine acyclism condition.

  2. Impact of Export Control and Technology Transfer Regimes: International Perspectives

    DTIC Science & Technology

    2012-01-07

    Impact of Export Control and Technology Transfer Regimes: International Perspectives 7 January 2012 by BGen (Ret.) Raymond E. Franck ...contact: NPS Acquisition Research Program Attn: James B. Greene, RADM, USN, (Ret.) Acquisition Chair Graduate School of Business and Public Policy...k^s^i=mlpqdo^ar^qb=p`elli= About the Authors Raymond (Chip) Franck , PhD, Senior Lecturer, Graduate School of Business & Public Policy, Naval

  3. Far-from-equilibrium superconductor in fluctuational regime.

    SciTech Connect

    Petkovic, A.; Chtchelkatchev, N. M.; Vinokur, V. M.

    2011-08-19

    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.

  4. Study of the Transition Flow Regime using Monte Carlo Methods

    NASA Technical Reports Server (NTRS)

    Hassan, H. A.

    1999-01-01

    This NASA Cooperative Agreement presents a study of the Transition Flow Regime Using Monte Carlo Methods. The topics included in this final report are: 1) New Direct Simulation Monte Carlo (DSMC) procedures; 2) The DS3W and DS2A Programs; 3) Papers presented; 4) Miscellaneous Applications and Program Modifications; 5) Solution of Transitional Wake Flows at Mach 10; and 6) Turbulence Modeling of Shock-Dominated Fows with a k-Enstrophy Formulation.

  5. 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.

  6. Development of the Regimes of Semiautomatic Contact Soldering

    NASA Astrophysics Data System (ADS)

    Shtennikov, V. N.

    2015-01-01

    The influence of the soldering rod length on the contact soldering temperature has been studied. The results of investigations were taken as a basis for incorporating a high-speed semiautomatic regime of soldering integrated circuits with planar leads to multilayer printed circuit boards. It has been established that to ensure an optimum soldering temperature it is necessary to take account of the temperature of the soldering rod before soldering, its length and diameter, and the soldering time when the rod is short.

  7. An infrared spectral sequence into the brown dwarf regime

    NASA Astrophysics Data System (ADS)

    Jones, H. R. A.

    2000-05-01

    A spectral sequence from mid-type M dwarfs into the brown dwarf regime is presented. These spectra cover the wavelength range 0.8 to 2.4 microns and measure the peak of the spectral energy distribution for these extremely red objects. The spectra were taken with the Hubble Space Telescope and represent an infrared spectra of M dwarfs and brown dwarfs which are free from the problems of correcting for the terrestial atmospheric absorption.

  8. MCNP/X Transport in the Tabular Regime

    NASA Astrophysics Data System (ADS)

    Hughes, H. Grady

    2007-03-01

    We 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, we 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. We also briefly touch on the current situation in regard to photon, electron, and proton transport tables.

  9. 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.

  10. 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)

  11. 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.

  12. 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.

  13. Regime and Periphery in Northern Yemen: The Huthi Phenomenon

    DTIC Science & Technology

    2010-01-01

    for Primary Sa‘da Crops . . . . . . . . . . . . . . . . . . . . . 32 1.5. Weapons Estimates for Conflict Governorates, 2004...Huthi’s criti- cism of the Saleh regime began to target the latter’s readiness to close ranks with the United States. Husayn focused in particular on the...Huthi actions, and sympathetic Zaydis in the community—driven to greater affiliation with the Huthis? How do we inter- pret the readiness of groups

  14. 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.

  15. Vibration analysis of a hydro generator for different operating regimes

    NASA Astrophysics Data System (ADS)

    Haţiegan, C.; Pădureanu, I.; Jurcu, M.; Nedeloni, M. D.; Hamat, C. O.; Chioncel, C. P.; Trocaru, S.; Vasile, O.; Bădescu, O.; Micliuc, D.; (Filip Nedeloni, L.; Băra, A.; (Barboni Haţiegan, L.

    2017-01-01

    Based on experimental measurements, this paper presents the vibration analysis of a hydro generator that equips a Kaplan hydraulic turbine of a Hydropower plant in Romania. This analysis means vibrations measurement to different operating regimes of the hydro generator respectively before installing it and into operation, namely putting off load mode (unexcited and excited) respectively putting on load mode. By comparing, through the experimental results obtained before and after the operation of hydro aggregates are observed vibrations improvements.

  16. 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.

  17. 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.

  18. Maritime Security Regime Concept: A Global Approach to Regional Challenges

    DTIC Science & Technology

    2012-09-27

    issue-area.” Krasner , Stephen D . (ed.) 1983. International Regimes, Ithaca, NY: Cornell University Press. Page 1. 3 This Concept was developed...political will to address a specific problem. • Disputes and Legal Interpretations: the clash of interests between coastal states who aim for increased...S) AND ADDRESS (ES) JOINT STAFF-MN//ACT Integration 116 Lakeview Parkway Suffolk, VA 23435 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING

  19. 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.

  20. Steady state plasma operation in RF dominated regimes on EAST

    NASA Astrophysics Data System (ADS)

    Zhang, X. J.; Zhao, Y. P.; Gong, X. Z.; Hu, C. D.; Liu, F. K.; Hu, L. Q.; Wan, B. N.; Li, J. G.

    2015-12-01

    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 H98˜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.

  1. Non-gaussianity in the strong regime of warm inflation

    SciTech Connect

    Moss, Ian G.; Yeomans, Timothy E-mail: timothy.yeomans@ncl.ac.uk

    2011-08-01

    The bispectrum of scalar mode density perturbations is analysed for the strong regime of warm inflationary models. This analysis generalises previous results by allowing damping terms in the inflaton equation of motion that are dependent on temperature. A significant amount of non-gaussianity emerges with constant (or local) non-linearity parameter f{sub NL} ∼ 20, in addition to the terms with non-constant f{sub NL} which are characteristic of warm inflation.

  2. The effect of holidays on a token economy regime.

    PubMed

    Elliott, P A

    1977-05-01

    This preliminary study investigates the effect on patients' performance of a set time off, in the form of a short holiday, from a strict reinforcement (token economy) regime. Assessment was by the patients' mean token earnings before and after the holiday and their self-care and work performance throughout. The results suggest that a holiday from a token economy has beneficial effects for patients.

  3. Fishbone mode excitation in the ion kinetic regime

    SciTech Connect

    Shi, B.; Sui, G. |

    1997-08-01

    By solving the dispersion relation in the ion kinetic regime, it is found that the threshold of the plasma beta value for exciting the ion-fishbone mode is lowered. Thus, for most of the present-day tokamaks where the Bussac criterion [Bussac {ital et al.}, Phys. Rev. Lett. {bold 35}, 1638 (1975)] is not satisfied, it will still be possible to excite the ion-fishbone mode. {copyright} {ital 1997 American Institute of Physics.}

  4. Kolmogorov and scalar spectral regimes in numerical turbulence

    NASA Technical Reports Server (NTRS)

    Kerr, R. M.

    1985-01-01

    Velocity and passive-scalar spectra for turbulent fields generated by a forced three-dimensional simulation and Taylormicroscale Reynolds numbers up to 83 are shown to have distinct spectral regimes, including a Kolmogorov inertial subrange. Both one- and three-dimensional spectra are shown for comparison with experiment and theory, respectively. When normalized by the Kolmogorov dissipation scales velocity spectra collapse to a single curve and a high-wavenumber bulge is seen. The bulge leads to an artificially high Kolmogorov constant, but is consistent with recent measurements of the velocity spectrum in the dissipation regime and the velocity-derivative skewness. Scalar spectra, when normalized by the Oboukov-Corrsin scales, collapse to curves which depend only on Prandtl number and show a universal inertial-convective subrange, independent of Prandtl number. When normalized by the Batchelor scales, the scalar spectra show a universal dissipation regime which is independent of Prandtl numbers from 0.1 to 1.0. The time development of velocity spectra is illustrated by energy-transfer spectra in which distinct pulses propagate to high wavenumbers.

  5. Background and mass extinctions: the alternation of macroevolutionary regimes.

    PubMed

    Jablonski, D

    1986-01-10

    Comparison of evolutionary patterns among Late Cretaceous marine bivalves and gastropods during times of normal, background levels of extinction and during the end-Cretaceous mass extinction indicates that mass extinctions are neither an intensification of background patterns nor an entirely random culling of the biota. During background times, traits such as planktotrophic larval development, broad geographic range of constituent species, and high species richness enhanced survivorship of species and genera. In contrast, during the, end-Cretaceous and other mass extinctions these factors were ineffectual, but broad geographic deployment of an entire lineage, regardless of the ranges of its constituent species, enhanced survivorship. Large-scale evolutionary patterns are evidently shaped by the alternation of these two macroevolutionary regimes, with rare but important mass extinctions driving shifts in the composition of the biota that have little relation to success during the background regime. Lineages or adaptations can be lost during mass extinctions for reasons unrelated to their survival values for organisms or species during background times, and long-term success would require the chance occurrence within a single lineage of sets of traits conducive to survivorship under both regimes.

  6. Theoretical issues of gender in the transition from socialist regimes.

    PubMed

    Grapard, U

    1997-09-01

    This article applies a gender perspective to a consideration of the recent economic and political reforms in Eastern and Central Europe. After an introduction and a brief overview of recent empirical studies of the impact of women's economic, political, and social status, the paper explores the difficulties inherent in attempts to create an East-West dialogue on women's interests. The article proposes that these difficulties can be articulated by 1) identifying whether a political regime uses an essentialist (men and women have fundamentally different biological natures) or a social constructionist (most observed differences between men and women are socially created) view to define the nature of women; 2) identifying how these distinct views of gender relations are articulated in the philosophical underpinnings of the two political regimes (the liberal Western system that strictly separates the public and private spheres while assigning different activities for men and women and the socialistic/communistic system that subordinates social reproduction to the sphere of production); and 3) comparing how these views have been articulated in social and institutional arrangements of gender relations in the two regimes. The article then claims that an understanding of the interaction between gender relations, political theory, and social practices in both the West and the East is essential for understanding the problems involved in discussions of the political-economic transition and how it affects men and women.

  7. Identifying Biologically Relevant Cues in the Hydrologic Regime

    NASA Astrophysics Data System (ADS)

    Lovellford, R. M.; Flitcroft, R.; Santelmann, M. V.; Grant, G. E.; Safeeq, M.; Lewis, S.

    2012-12-01

    Seasonal variation in hydrologic discharge and temperature defines the availability, connectivity, and quality of lentic habitats. Native aquatic species are adapted to local hydrologic regimes , eg. magnitudes and rates of change . In recent decades, biologically relevant hydrologic conditions have been identified that are necessary to maintain habitat conditions for aquatic obligate species. Another element of hydrologic regimes important to aquatic species are the cues that inform individuals of seasonal changes that precipitate important physiological or behavioral alterations. There is a need for hydrologists, biologists, and ecologists, to define biologically significant cues within the hydrologic regime. Coho salmon (Onchorhynchus kisutch), an anadromous species of Pacific salmon, offers an example of sensitivity to environmental cues. Examinations of the run-timing of mature adult coho salmon on the North Umpqua River, OR, indicate that migration timing coincides with decreasing fall water temperatures prior to increasing winter discharge. For this species, adults leave the ocean ready to spawn. Adults need to spawn in small headwater streams prior to the onset of intense storm conditions that prohibit effective deposition or fertilization of eggs in redds (salmon nests).Therefore, the timing of spawning must be carefully executed. Understanding the cues that trigger specific behaviors gives insight to the processes that provide ecosystem stability and flexibility over time. Improved understanding of these cues may help us protect freshwater ecosystems and improve management for endangered species.

  8. Comparison of algorithms for determination of solar wind regimes

    NASA Astrophysics Data System (ADS)

    Neugebauer, Marcia; Reisenfeld, Daniel; Richardson, Ian G.

    2016-09-01

    This study compares the designation of different solar wind flow regimes (transient, coronal hole, and streamer belt) according to two algorithms derived from observations by the Solar Wind Ion Composition Spectrometer, the Solar Wind Electron Proton Alpha Monitor, and the Magnetometer on the ACE spacecraft, with a similar regime determination performed on board the Genesis spacecraft. The comparison is made for the interval from late 2001 to early 2004 when Genesis was collecting solar wind ions for return to Earth. The agreement between hourly regime assignments from any pair of algorithms was less than two thirds, while the simultaneous agreement between all three algorithms was only 49%. When the results of the algorithms were compared to a catalog of interplanetary coronal mass ejection events, it was found that almost all the events in the catalog were confirmed by the spacecraft algorithms. On the other hand, many short transient events, lasting 1 to 13 h, that were unanimously selected as transient like by the algorithms, were not included in the catalog.

  9. Osmotic adaptation in Ulva lactuca under fluctuating salinity regimes.

    PubMed

    Dickson, D M; Wyn Jones, R G; Davenport, J

    1982-09-01

    A study has been made of the osmotic responses of the green intertidal alga, Ulva lactuca, under two fluctuating salinity regimes; sinusoidal and square-wave fluctuations between 30 and 100% sea water in a 12 h cycle. These regimes closely resemble the tidal fluctuation of salinity encountered by the alga in its natural estuarine habitat. Data on changes in the inorganic ions, potassium, sodium, chloride and sulphate; in the organic solute, dimethylsulphoniopropionate; in the total sugar levels and estimated osmotic and turgor pressures under the two salinity regimes are reported. Significant differences in the solute responses under these different conditions were detected. In general, better control of ion fluxes appeared to be exercised under the sinusoidal conditions which also buffered changes in dimethylsulphoniopropionate levels. Influxes of potassium were highly light-dependent. Chloride levels conspicuously failed to reach the steady-state levels in the 6-h-hyper-osmotic part of either the abrupt or gradual cycle. The possible significance of these data, which may better reflect osmotic changes in the natural environment, and some of the problems encountered, particularly in accounting for charge balance under some conditions, are discussed.

  10. Unsustainable Groundwater Exploitation and Stochastic Regime Shifts: Converging Management Constraints

    NASA Astrophysics Data System (ADS)

    Rao, Suresh; Park, Jeryang

    2014-05-01

    Increasing water security concerns arise from projected increases in competing freshwater demands, resulting from rapid urbanization, growing affluent population, and the need for increased production of food and bio-energy. These global trends in concert with the convergence of three groups of threats are likely to exacerbate freshwater security issues: (1) increasing dependency on effectively non-renewable groundwater ("peak water"); (2) increasing groundwater quality impairment("land-use intensification") from larger contaminant loads delivered from the vadose zone and surface water; and (3) increasing uncertainties in groundwater demand/supply from climate change ("stochastic risks"). Here, we present a conceptual framework for exploring water security threats, with a consideration of aquifers as complex hydrological systems with two stable states. Regime shifts in groundwater pumping -- from "sufficient" to "insufficient" -- result from changes in both internal system dynamics and external forcing from stochastic divers (non-stationary demands, hydro-climatic patterns). Examples from recent related work, in groundwater and surface water systems and ecosystems, are briefly reviewed as a prelude to presentation of model simulations of hypothetical scenarios of regime-shifts (tipping points) involving groundwater quantity and quality constraints. In addition to three types of widely recognized tipping points, we introduce a new type, stochastic tipping, that contributes to unexpected, undesirable regime shifts, resulting in inability to meet groundwater pumping needs, even when the perceived precariousness is small and the system is far from bifurcation point (deterministic tipping). Implications to sustainable groundwater management are discussed.

  11. Analysis of thermionic bare tether operation regimes in passive mode

    NASA Astrophysics Data System (ADS)

    Sanmartín, J. R.; Chen, Xin; Sánchez-Arriaga, G.

    2017-01-01

    A thermionic bare tether (TBT) is a long conductor coated with a low work-function material. In drag mode, a tether segment extending from anodic end A to a zero-bias point B, with the standard Orbital-motion-limited current collection, is followed by a complex cathodic segment. In general, as bias becomes more negative in moving from B to cathodic end C, one first finds space-charge-limited (SCL) emission covering up to some intermediate point B*, then full Richardson-Dushman (RD) emission reaching from B* to end C. An approximate analytical study, which combines the current and voltage profile equations with results from asymptotic studies of the Vlasov-Poisson system for emissive probes, is carried out to determine the parameter domain covering two limit regimes, which are effectively controlled by just two dimensionless parameters involving ambient plasma and TBT material properties. In one such limit regime, no point B* is reached and thus no full RD emission develops. In an opposite regime, SCL segment BB* is too short to contribute significantly to the current balance.

  12. 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.

  13. Early regimes of water imbibition in nanoslit silica channels

    NASA Astrophysics Data System (ADS)

    Oyarzua, Elton; Zambrano, Harvey; Walther, Jens Honore; Mejia, Andres

    2014-11-01

    Capillarity is currently subject to a significant research interest. Attention is mainly paid to the late stage of the imbibition when a developed flow is reached and the Laplace pressure is balanced by the viscosity. Nevertheless, as the miniaturization of devices is reaching the nanoscale a thorough understanding of fluid flow in nanoconfinement is required. In nanofluidics, short timescales and surface characteristics dominate the flows. In this study, molecular simulations are conducted to investigate the early stage of water imbibition in silica nanochannels with heights of 4 to 10 nm. Results indicate that nanoscale imbibition is divided in three regimes. An initial regime with imbibition linearly dependent of time, where the capillary force is mainly balanced by inertia. Thereafter, a period, in which, the balance has contributions from both inertia and viscosity and, subsequently, a final regime, wherein, viscosity dominates the capillary force balance. Velocity profiles confirm the passage from an inviscid flow to a developed Poisseuille flow. The meniscus position as a function of time and air accumulation in front of the advancing meniscus are computed for different air pressures, the results reveal a systematic retarding effect of gas pressurization on the imbibition. We acknowledge support from Fondecyt Project No 11130559.

  14. Sustainability of Transient Kinetic Regimes and Origins of Death.

    PubMed

    Zubarev, Dmitry Yu; Pachón, Leonardo A

    2016-02-08

    It is generally recognized that a distinguishing feature of life is its peculiar capability to avoid equilibration. The origin of this capability and its evolution along the timeline of abiogenesis is not yet understood. We propose to study an analog of this phenomenon that could emerge in non-biological systems. To this end, we introduce the concept of sustainability of transient kinetic regimes. This concept is illustrated via investigation of cooperative effects in an extended system of compartmentalized chemical oscillators under batch and semi-batch conditions. The computational study of a model system shows robust enhancement of lifetimes of the decaying oscillations which translates into the evolution of the survival function of the transient non-equilibrium regime. This model does not rely on any form of replication. Rather, it explores the role of a structured effective environment as a contributor to the system-bath interactions that define non-equilibrium regimes. We implicate the noise produced by the effective environment of a compartmentalized oscillator as the cause of the lifetime extension.

  15. Models of warm and cold regimes of the winter stratosphere

    NASA Astrophysics Data System (ADS)

    Guryanov, Vladimir

    Research of fields of geopotential height, temperature, zonal and meridional wind in stratosphere was carried out using the Met Office data for winter seasons from 1991/1992 to 2006-2007. The above analyzes shows that change within season thermodynamic values at high latitudes during the winter is higher than seasonal or longitudinal change. Hence the average models of the cold periods of high latitudes and average monthly values have a limited applicability. In 1982 International Standard Organization (ISO) also acknowledged the necessity for creating of special models for "warm" and "cold" regimes of the high latitude winter stratosphere. Warm and cold stratosphere states were distinguished by the presence or absence of stratospheric warmings of variable intensity exceeding 10 hPa. Special maps and latitude-longitude cuts of mean values and mean square deviations of the geopotential height, temperature, zonal and meridional wind have been created for these regimes. Models of "warm" and "cold" regimes also included zonal harmonics with wave numbers 1 and 2 for all observed meteorological fields

  16. Sustainability of Transient Kinetic Regimes and Origins of Death

    PubMed Central

    Zubarev, Dmitry Yu.; Pachón, Leonardo A.

    2016-01-01

    It is generally recognized that a distinguishing feature of life is its peculiar capability to avoid equilibration. The origin of this capability and its evolution along the timeline of abiogenesis is not yet understood. We propose to study an analog of this phenomenon that could emerge in non-biological systems. To this end, we introduce the concept of sustainability of transient kinetic regimes. This concept is illustrated via investigation of cooperative effects in an extended system of compartmentalized chemical oscillators under batch and semi-batch conditions. The computational study of a model system shows robust enhancement of lifetimes of the decaying oscillations which translates into the evolution of the survival function of the transient non-equilibrium regime. This model does not rely on any form of replication. Rather, it explores the role of a structured effective environment as a contributor to the system-bath interactions that define non-equilibrium regimes. We implicate the noise produced by the effective environment of a compartmentalized oscillator as the cause of the lifetime extension. PMID:26853459

  17. Socioecological regime shifts in the setting of complex social interactions

    NASA Astrophysics Data System (ADS)

    Sugiarto, Hendrik Santoso; Chung, Ning Ning; Lai, Choy Heng; Chew, Lock Yue

    2015-06-01

    The coupling between social and ecological system has become more ubiquitous and predominant in the current era. The strong interaction between these systems can bring about regime shifts which in the extreme can lead to the collapse of social cooperation and the extinction of ecological resources. In this paper, we study the occurrence of such regime shifts in the context of a coupled social-ecological system where social cooperation is established by means of sanction that punishes local selfish act and promotes norms that prescribe nonexcessive resource extraction. In particular, we investigate the role of social networks on social-ecological regimes shift and the corresponding hysteresis effects caused by the local ostracism mechanism under different social and ecological parameters. Our results show that a lowering of network degree reduces the hysteresis effect and also alters the tipping point, which is duly verified by our numerical results and analytical estimation. Interestingly, the hysteresis effect is found to be stronger in scale-free network in comparison with random network even when both networks have the same average degree. These results provide deeper insights into the resilience of these systems, and can have important implications on the management of coupled social-ecological systems with complex social interactions.

  18. Sustainability of Transient Kinetic Regimes and Origins of Death

    NASA Astrophysics Data System (ADS)

    Zubarev, Dmitry Yu.; Pachón, Leonardo A.

    2016-02-01

    It is generally recognized that a distinguishing feature of life is its peculiar capability to avoid equilibration. The origin of this capability and its evolution along the timeline of abiogenesis is not yet understood. We propose to study an analog of this phenomenon that could emerge in non-biological systems. To this end, we introduce the concept of sustainability of transient kinetic regimes. This concept is illustrated via investigation of cooperative effects in an extended system of compartmentalized chemical oscillators under batch and semi-batch conditions. The computational study of a model system shows robust enhancement of lifetimes of the decaying oscillations which translates into the evolution of the survival function of the transient non-equilibrium regime. This model does not rely on any form of replication. Rather, it explores the role of a structured effective environment as a contributor to the system-bath interactions that define non-equilibrium regimes. We implicate the noise produced by the effective environment of a compartmentalized oscillator as the cause of the lifetime extension.

  19. Recovery of SINIS turnstile accuracy in a strongly nonequilibrium regime

    NASA Astrophysics Data System (ADS)

    Khaymovich, I. M.; Basko, D. M.

    2016-10-01

    We perform a theoretical study of nonequilibrium effects in charge transport through a hybrid single-electron transistor based on a small normal metal (N) island with the gate-controlled number of electrons, tunnel-coupled to voltage-biased superconducting (S) electrodes (SINIS). Focusing on the turnstile mode of the transistor operation with the gate voltage driven periodically, and electrons on the island being out of equilibrium, we find that the current quantization accuracy is a nonmonotonic function of the relaxation rate ΓF of the distribution function F (ɛ ) on the island due to tunneling, as compared to the drive frequency f , electron-electron 1 /τe e , and electron-phonon 1 /τe p h relaxation rates. Surprisingly, in the strongly nonequilibrium regime, f ≫ΓF≫τee -1,τep h -1 , the turnstile current plateau is recovered, similarly to the ideal equilibrium regime, τep h -1≫ΓF . The plateau is destroyed in the quasiequilibrium regime when the electron-electron relaxation is faster than tunneling.

  20. Global impacts of the 1980s regime shift.

    PubMed

    Reid, Philip C; Hari, Renata E; Beaugrand, Grégory; Livingstone, David M; Marty, Christoph; Straile, Dietmar; Barichivich, Jonathan; Goberville, Eric; Adrian, Rita; Aono, Yasuyuki; Brown, Ross; Foster, James; Groisman, Pavel; Hélaouët, Pierre; Hsu, Huang-Hsiung; Kirby, Richard; Knight, Jeff; Kraberg, Alexandra; Li, Jianping; Lo, Tzu-Ting; Myneni, Ranga B; North, Ryan P; Pounds, J Alan; Sparks, Tim; Stübi, René; Tian, Yongjun; Wiltshire, Karen H; Xiao, Dong; Zhu, Zaichun

    2016-02-01

    Despite evidence from a number of Earth systems that abrupt temporal changes known as regime shifts are important, their nature, scale and mechanisms remain poorly documented and understood. Applying principal component analysis, change-point analysis and a sequential t-test analysis of regime shifts to 72 time series, we confirm that the 1980s regime shift represented a major change in the Earth's biophysical systems from the upper atmosphere to the depths of the ocean and from the Arctic to the Antarctic, and occurred at slightly different times around the world. Using historical climate model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) and statistical modelling of historical temperatures, we then demonstrate that this event was triggered by rapid global warming from anthropogenic plus natural forcing, the latter associated with the recovery from the El Chichón volcanic eruption. The shift in temperature that occurred at this time is hypothesized as the main forcing for a cascade of abrupt environmental changes. Within the context of the last century or more, the 1980s event was unique in terms of its global scope and scale; our observed consequences imply that if unavoidable natural events such as major volcanic eruptions interact with anthropogenic warming unforeseen multiplier effects may occur.

  1. Environmental sampling: Issues for the cut-off regime

    SciTech Connect

    Fearey, B.L.

    1995-09-01

    The fissile material cut-off treaty (FMCT) initiative under the Conference on Disarmament mandate is envisioned to include certain aspects of environmental sampling and monitoring. One of the intents of this treaty is to bring certain non-NPT signatories (e.g., threshold states) under this treaty agreement along with the nuclear weapon states (NWSs). This paper provides a brief overview of some of the relevant issues that may be involved in the implementation and use of environmental monitoring for (1) verification of the cut-off regime declarations, (2) the detection of undeclared activities, and, (3) application in non-routine inspections. The intent is to provide backstopping information important for treaty negotiators. Specific issues addressed within this paper include signature sampling, differences in the proposed detection regime, potential signature integrators, specific examples and spoofing concerns. Many of these issues must be carefully considered and weighed in order to create a credibly verifiable inspection regime. Importantly, the cut-off treaty must enable nondiscriminatory implementation, while carefully assuring that nonproliferation treaty requirements are maintained (i.e., preventing unintentional release of critical weapons design information--potentially through environmental sampling and analysis).

  2. 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.

  3. Fire regime in a Mexican forest under indigenous resource management.

    PubMed

    Fulé, Peter Z; Ramos-Gómez, Mauro; Cortés-Montaño, Citlali; Miller, Andrew M

    2011-04-01

    The Rarámuri (Tarahumara) people live in the mountains and canyons of the Sierra Madre Occidental of Chihuahua, Mexico. They base their subsistence on multiple-use strategies of their natural resources, including agriculture, pastoralism, and harvesting of native plants and wildlife. Pino Gordo is a Rarámuri settlement in a remote location where the forest has not been commercially logged. We reconstructed the forest fire regime from fire-scarred trees, measured the structure of the never-logged forest, and interviewed community members about fire use. Fire occurrence was consistent throughout the 19th and 20th centuries up to our fire scar collection in 2004. This is the least interrupted surface-fire regime reported to date in North America. Studies from other relict sites such as nature reserves in Mexico or the USA have all shown some recent alterations associated with industrialized society. At Pino Gordo, fires recurred frequently at the three study sites, with a composite mean fire interval of 1.9 years (all fires) to 7.6 years (fires scarring 25% or more of samples). Per-sample fire intervals averaged 10-14 years at the three sites. Approximately two-thirds of fires burned in the season of cambial dormancy, probably during the pre-monsoonal drought. Forests were dominated by pines and contained many large living trees and snags, in contrast to two nearby similar forests that have been logged. Community residents reported using fire for many purposes, consistent with previous literature on fire use by indigenous people. Pino Gordo is a valuable example of a continuing frequent-fire regime in a never-harvested forest. The Rarámuri people have actively conserved this forest through their traditional livelihood and management techniques, as opposed to logging the forest, and have also facilitated the fire regime by burning. The data contribute to a better understanding of the interactions of humans who live in pine forests and the fire regimes of these

  4. The human dimension of fire regimes on Earth

    PubMed Central

    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

    2011-01-01

    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

  5. INTERFACIAL AREA TRANSPORT AND REGIME TRANSITION IN COMBINATORIAL CHANNELS

    SciTech Connect

    Seugjin Kim

    2011-01-28

    . This study investigates the geometric effects of 90-degree vertical elbows and flow configurations in two-phase flow. The study shows that the elbows make a significant effect on the transport characteristics of two-phase flow, which includes the changes in interfacial structures, bubble interaction mechanisms and flow regime transition. The effect of the elbows is characterized for global and local two-phase flow parameters. The global two-phase flow parameters include two-phase pressure, interfacial structures and flow regime transition. In order to characterize the frictional pressure drop and minor loss across the vertical elbows, pressure measurements are obtained across the test section over a wide range of flow conditions in both single-phase and two-phase flow conditions. A two-phase pressure drop correlation analogous to Lockhart-Martinelli correlation is proposed to predict the minor loss across the elbows. A high speed camera is employed to perform extensive flow visualization studies across the elbows in vertical upward, horizontal and vertical downward sections and modified flow regime maps are proposed. It is found that modified flow regime maps immediately downstream of the vertical upward elbow deviate significantly from the conventional flow regime map. A qualitative assessment of the counter-current flow limitation characteristics specific to the current experimental facility is performed. A multi-sensor conductivity probe is used to measure local two-phase flow parameters such as: void fraction, bubble velocity, interfacial area concentration and bubble frequency. The local measurements are obtained for six different flow conditions at ten measurement locations along axial direction of the test section. Both the vertical-upward and vertical-downward elbows have a significant impact on bubble distribution, resulting in, a bimodal distribution along the horizontal radius of the tube cross-section and migration of bubbles towards the inside of the

  6. Fire regimes of quaking aspen in the Mountain West

    USGS Publications Warehouse

    Shinneman, Douglas J.; Baker, William L.; Rogers, Paul C.; Kulakowski, Dominik

    2013-01-01

    Quaking aspen (Populus tremuloides Michx.) is the most widespread tree species in North America, and it is found throughout much of the Mountain West (MW) across a broad range of bioclimatic regions. Aspen typically regenerates asexually and prolifically after fire, and due to its seral status in many western conifer forests, aspen is often considered dependent upon disturbance for persistence. In many landscapes, historical evidence for post-fire aspen establishment is clear, and following extended fire-free periods senescing or declining aspen overstories sometimes lack adequate regeneration and are succeeding to conifers. However, aspen also forms relatively stable stands that contain little or no evidence of historical fire. In fact, aspen woodlands range from highly fire-dependent, seral communities to relatively stable, self-replacing, non-seral communities that do not require fire for persistence. Given the broad geographic distribution of aspen, fire regimes in these forests likely co-vary spatially with changing community composition, landscape setting, and climate, and temporally with land use and climate – but relatively few studies have explicitly focused on these important spatiotemporal variations. Here we reviewed the literature to summarize aspen fire regimes in the western US and highlight knowledge gaps. We found that only about one-fourth of the 46 research papers assessed for this review could be considered fire history studies (in which mean fire intervals were calculated), and all but one of these were based primarily on data from fire-scarred conifers. Nearly half of the studies reported at least some evidence of persistent aspen in the absence of fire. We also found that large portions of the MW have had little or no aspen fire history research. As a result of this review, we put forth a classification framework for aspen that is defined by key fire regime parameters (fire severity and probability), and that reflects underlying biophysical

  7. Hydrological regime modifications induced by climate change in Mediterranean area

    NASA Astrophysics Data System (ADS)

    Pumo, Dario; Caracciolo, Domenico; Viola, Francesco; Valerio Noto, Leonardo

    2015-04-01

    The knowledge of river flow regimes has a capital importance for a variety of practical applications, in water resource management, including optimal and sustainable use. Hydrological regime is highly dependent on climatic factors, among which the most important is surely the precipitation, in terms of frequency, seasonal distribution and intensity of rainfall events. The streamflow frequency regime of river basins are often summarized by flow duration curves (FDCs), that offer a simple and comprehensive graphical view of the overall historical variability associated with streamflow, and characterize the ability of the basin to provide flows of various magnitudes. Climate change is likely to lead shifts in the hydrological regime, and, consequently, in the FDCs. Staring from this premise, the primary objective of the present study is to explore the effects of potential climate changes on the hydrological regime of some small Mediterranean basins. To this aim it is here used a recent hydrological model, the ModABa model (MODel for Annual flow duration curves assessment in ephemeral small BAsins), for the probabilistic characterization of the daily streamflows in small catchments. The model has been calibrated and successively validated in a unique small catchment, where it has shown a satisfactory accuracy in reproducing the empirical FDC starting from easily derivable parameters arising from basic ecohydrological knowledge of the basin and commonly available climatic data such as daily precipitation and temperatures. Thus, this work also represents a first attempt to apply the ModABa to basins different from that used for its preliminary design in order to testing its generality. Different case studies are selected within the Sicily region; the model is first calibrated at the sites and then forced by future climatic scenarios, highlighting the principal differences emerging from the current scenario and future FDCs. The future climate scenarios are generated using

  8. SH2B1beta (SH2-Bbeta) enhances expression of a subset of nerve growth factor-regulated genes important for neuronal differentiation including genes encoding urokinase plasminogen activator receptor and matrix metalloproteinase 3/10.

    PubMed

    Chen, Linyi; Maures, Travis J; Jin, Hui; Huo, Jeffrey S; Rabbani, Shafaat A; Schwartz, Jessica; Carter-Su, Christin

    2008-02-01

    Previous work showed that the adapter protein SH2B adapter protein 1beta (SH2B1) (SH2-B) binds to the activated form of the nerve growth factor (NGF) receptor TrkA and is critical for both NGF-dependent neurite outgrowth and maintenance. To identify SH2B1beta-regulated genes critical for neurite outgrowth, we performed microarray analysis of control PC12 cells and PC12 cells stably overexpressing SH2B1beta (PC12-SH2B1beta) or the dominant-negative SH2B1beta(R555E) [PC12-SH2B1beta(R555E)]. NGF-induced microarray expression of Plaur and Mmp10 genes was greatly enhanced in PC12-SH2B1beta cells, whereas NGF-induced Plaur and Mmp3 expression was substantially depressed in PC12-SH2B1beta(R555E) cells. Plaur, Mmp3, and Mmp10 are among the 12 genes most highly up-regulated after 6 h of NGF. Their protein products [urokinase plasminogen activator receptor (uPAR), matrix metalloproteinase 3 (MMP3), and MMP10] lie in the same pathway of extracellular matrix degradation; uPAR has been shown previously to be critical for NGF-induced neurite outgrowth. Quantitative real-time PCR analysis revealed SH2B1beta enhancement of NGF induction of all three genes and the suppression of NGF induction of all three when endogenous SH2B1 was reduced using short hairpin RNA against SH2B1 and in PC12-SH2B1beta(R555E) cells. NGF-induced levels of uPAR and MMP3/10 and neurite outgrowth through Matrigel (MMP3-dependent) were also increased in PC12-SH2B1beta cells. These results suggest that SH2B1beta stimulates NGF-induced neuronal differentiation at least in part by enhancing expression of a specific subset of NGF-sensitive genes, including Plaur, Mmp3, and/or Mmp10, required for neurite outgrowth.

  9. Synergistic transcriptional activation of the mouse urokinase plasminogen activator (uPA) gene and of its enhancer activator protein 1 (AP1) site by cAMP and retinoic acid.

    PubMed Central

    Mira-Y-Lopez, R; Jaramillo, S; Jing, Y

    1998-01-01

    We have investigated the mechanism whereby all-trans retinoic acid (tRA) potentiates the 8-bromo-cAMP (8-BrcAMP)-dependent transcription of the urokinase plasminogen activator (uPA) gene in SC115 mouse mammary carcinoma cells. Photoaffinity labelling experiments showed that tRA did not alter the cellular content of cAMP-dependent protein kinase regulatory subunits I and II. In agreement with this, nuclear run-on analysis in the presence of the translational inhibitor puromycin demonstrated that the effect of 8-BrcAMP and its potentiation by tRA were independent of protein synthesis. A transiently transfected 6.6 kb uPA 5'-flanking region-chloramphenicol acetyltransferase (CAT) fusion gene mimicked the response of the endogenous uPA gene. Thus 1 mM 8-BrcAMP induced a 100-200% increase in CAT content, 100 nM tRA had no effect and 100 nM tRA+1 mM 8-BrcAMP induced a 300-500% increase in cells co-transfected with tRA receptor and/or 9-cis-RA receptor. Analysis of 5'-deleted constructs showed that the tRA effect required at least two cis regions: -2657 to -2186, encompassing the 100 bp uPA enhancer, and -709 to -324, which exhibited silencing activity. Neither region contained a tRA-response element-like motif. Because tRA receptor and 9-cis-RA receptor interact with activator protein 1 (AP1), we tested whether tRA regulated the uPA enhancer AP1 site in the presence of 8-BrcAMP. We found that a dimer of this site fused to a minimal uPA-CAT fusion gene was responsive to 1 mM 8-BrcAMP (100% CAT increase), not responsive to 100 nM tRA, and synergistically responsive to 100 nM tRA+1 mM 8-BrcAMP (240% CAT increase) in cells co-transfected with Fos and Jun. Synergistic activation of the same construct and of the 6.6 kb uPA-CAT fusion gene was also obtained using tRA and 100 nM PMA. We conclude that multiple cis elements, probably including the uPA enhancer AP1 site, mediate the tRA potentiation of uPA transcription. PMID:9560322

  10. The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells*

    PubMed Central

    Nishii, Keigo; Nakaseko, Chiaki; Jiang, Meizi; Shimizu, Naomi; Takeuchi, Masahiro; Schneider, Wolfgang J.; Bujo, Hideaki

    2013-01-01

    A key property of hematopoietic stem and progenitor cells (HSPCs) regarding differentiation from the self-renewing quiescent to the proliferating stage is their adhesion to the bone marrow (BM) niche. An important molecule involved in proliferation and pool size of HSPCs in the BM is the hypoxia-induced urokinase-type plasminogen activator receptor (uPAR). Here, we show that the soluble form (sLR11) of LR11 (also called SorLA or SORL1) modulates the uPAR-mediated attachment of HSPCs under hypoxic conditions. Immunohistochemical and mRNA expression analyses revealed that hypoxia increased LR11 expression in hematological c-Kit+ Lin− cells. In U937 cells, hypoxia induced a transient rise in LR11 transcription, production of cellular protein, and release of sLR11. Attachment to stromal cells of c-Kit+ Lin− cells of lr11−/− mice was reduced by hypoxia much more than of lr11+/+ animals. sLR11 induced the adhesion of U937 and c-Kit+ Lin− cells to stromal cells. Cell attachment was increased by sLR11 and reduced in the presence of anti-uPAR antibodies. Furthermore, the fraction of uPAR co-immunoprecipitated with LR11 in membrane extracts of U937 cells was increased by hypoxia. CoCl2, a chemical inducer of HIF-1α, enhanced the levels of LR11 and sLR11 in U937 cells. The decrease in hypoxia-induced attachment of HIF-1α-knockdown cells was largely prevented by exogenously added sLR11. Finally, hypoxia induced HIF-1α binding to a consensus binding site in the LR11 promoter. Thus, we conclude that sLR11 regulates the hypoxia-enhanced adhesion of HSPCs via an uPAR-mediated pathway that stabilizes the hematological pool size by controlling cell attachment to the BM niche. PMID:23486467

  11. Human impacts on river ice regime in the Carpathian Basin

    NASA Astrophysics Data System (ADS)

    Takács, Katalin; Nagy, Balázs; Kern, Zoltán

    2014-05-01

    River ice is a very important component of the cryosphere, and is especially sensitive to climatic variability. Historical records of appearance or disappearance and timing of ice phenomena are useful indicators for past climatic variations (Williams, 1970). Long-term observations of river ice freeze-up and break-up dates are available for many rivers in the temperate or cold region to detect and analyze the effects of climate change on river ice regime. The ice regime of natural rivers is influenced by climatic, hydrological and morphological factors. Regular ice phenomena observation mostly dates back to the 19th century. During this long-term observation period, the human interventions affecting the hydrological and morphological factors have become more and more intensive (Beltaos and Prowse, 2009). The anthropogenic effects, such as river regulation, hydropower use or water pollution causes different changes in river ice regime (Ashton, 1986). To decrease the occurrence of floods and control the water discharge, nowadays most of the rivers are regulated. River regulation changes the morphological parameters of the river bed: the aim is to create solid and equable bed size and stream gradient to prevent river ice congestion. For the satisfaction of increasing water demands hydropower is also used. River damming results a condition like a lake upstream to the barrage; the flow velocity and the turbulence are low, so this might be favourable for river ice appearance and freeze-up (Starosolsky, 1990). Water pollution affects ice regime in two ways; certain water contaminants change the physical characteristics of the water, e.g. lessens the freezing point of the water. Moreover the thermal stress effect of industrial cooling water and communal wastewater is also important; in winter these water sources are usually warmer, than the water body of the river. These interventions result different changes in the characteristic features of river ice regime. Selected

  12. Film thickness for different regimes of fluid-film lubrication. [elliptical contacts

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.; Dowson, D.

    1983-01-01

    Mathematical formulas are presented which express the dimensionless minimum film thickness for the four lubrication regimes found in elliptical contacts: isoviscous-rigid regime; piezoviscous-rigid regime; isoviscous-elastic regime; and piezoviscous-elastic regime. The relative importance of pressure on elastic distortion and lubricant viscosity is the factor that distinguishes these regimes for a given conjunction geometry. In addition, these equations were used to develop maps of the lubrication regimes by plotting film thickness contours on a log-log grid of the dimensionless viscosity and elasticity parameters for three values of the ellipticity parameter. These results present a complete theoretical film thickness parameter solution for elliptical constants in the four lubrication regimes. The results are particularly useful in initial investigations of many practical lubrication problems involving elliptical conjunctions.

  13. Rheology of cohesive granular materials across multiple dense-flow regimes.

    PubMed

    Gu, Yile; Chialvo, Sebastian; Sundaresan, Sankaran

    2014-09-01

    We investigate the dense-flow rheology of cohesive granular materials through discrete element simulations of homogeneous, simple shear flows of frictional, cohesive, spherical particles. Dense shear flows of noncohesive granular materials exhibit three regimes: quasistatic, inertial, and intermediate, which persist for cohesive materials as well. It is found that cohesion results in bifurcation of the inertial regime into two regimes: (a) a new rate-independent regime and (b) an inertial regime. Transition from rate-independent cohesive regime to inertial regime occurs when the kinetic energy supplied by shearing is sufficient to overcome the cohesive energy. Simulations reveal that inhomogeneous shear band forms in the vicinity of this transition, which is more pronounced at lower particle volume fractions. We propose a rheological model for cohesive systems that captures the simulation results across all four regimes.

  14. North Atlantic weather regimes: A synoptic study of phase space. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Orrhede, Anna Karin

    1990-01-01

    In the phase space of weather, low frequency variability (LFV) of the atmosphere can be captured in a large scale subspace, where a trajectory connects consecutive large scale weather maps, thus revealing flow changes and recurrences. Using this approach, Vautard applied the trajectory speed minimization method (Vautard and Legras) to atmospheric data. From 37 winters of 700 mb geopotential height anomalies over the North Atlantic and the adjacent land masses, four persistent and recurrent weather patterns, interpreted as weather regimes, were discernable: a blocking regime, a zonal regime, a Greenland anticyclone regime, and an Atlantic regime. These regimes are studied further in terms of maintenance and transitions. A regime survey unveils preferences regarding event durations and precursors for the onset or break of an event. The transition frequencies between regimes vary, and together with the transition times, suggest the existence of easier transition routes. These matters are more systematically studied using complete synoptic map sequences from a number of events.

  15. Characteristics of Whipple Shield Performance in the Shatter Regime

    NASA Technical Reports Server (NTRS)

    Ryan, Shannon; Bjorkman, Michael; Christiansen, Eric L.

    2009-01-01

    Between the onset of projectile fragmentation and the assumption of rear wall failure due to an impulsive load, multi-wall ballistic limit equations are linearly interpolated to provide reasonable yet conservative predictions of perforation thresholds with conveniently simple mathematics. Although low velocity and hypervelocity regime predictions are based on analytical expressions, there is no such scientific foundation for predictions in the intermediate (or shatter) regime. As the debris flux in low earth orbit (LEO) becomes increasingly dominated by manmade pollution, the profile of micrometeoroid and orbital debris (MMOD) risk shifts continually towards lower velocities. For the International Space Station (ISS), encounter velocities below 7 km/s now constitute approximately 50% of the penetration risk. Considering that the transition velocity from shatter to hypervelocity impact regimes described by common ballistic limit equations (e.g. new non-optimum Whipple shield equation [1]) occurs at 7 km/s, 50% of station risk is now calculated based on failure limit equations with little analytical foundation. To investigate projectile and shield behavior for impact conditions leading to projectile fragmentation and melt, a series of hypervelocity impact tests have been performed on aluminum Whipple shields. In the experiments projectile diameter, bumper thickness, and shield spacing were kept constant, while rear wall thickness was adjusted to determine spallation and perforation limits at various impact velocities and angles. The results, shown in Figure 1 for normal and 45 impacts, demonstrated behavior that was not sufficiently described by the simplified linear interpolation of the NNO equation (also shown in Figure 1). Hopkins et al. [2] investigated the performance of a nominally-identical aluminum Whipple shield, identifying the effects of phase change in the shatter regime. The results (conceptually represented in Figure 2) were found to agree well with

  16. Investigating Satellite Microwave observations of Precipitation in Different Climate Regimes

    NASA Astrophysics Data System (ADS)

    Wang, N.; Ferraro, R. R.

    2013-12-01

    Microwave satellite remote sensing of precipitation over land is a challenging problem due to the highly variable land surface emissivity, which, if not properly accounted for, can be much greater than the precipitation signal itself, especially in light rain/snow conditions. Additionally, surfaces such as arid land, deserts and snow cover have brightness temperature characteristics similar to precipitation Ongoing work by GPM microwave radiometer team is constructing databases through a variety of means, however, there is much uncertainty as to what is the optimal information needed for the wide array of sensors in the GPM constellation, including examination of regional conditions. The original data sets will focus on stratification by emissivity class, surface temperature and total perceptible water. We'll perform sensitivity studies to determine the potential role of ancillary data (e.g., land surface temperature, snow cover/water equivalent, etc.) to improve precipitation estimation over land in different climate regimes, including rain and snow. In other words, what information outside of the radiances can help describe the background and subsequent departures from it that are active precipitating regions? It is likely that this information will be a function of the various precipitation regimes. Statistical methods such as Principal Component Analysis (PCA) will be utilized in this task. Databases from a variety of sources are being constructed. They include existing satellite microwave measurements of precipitating and non-precipitating conditions, ground radar precipitation rate estimates, surface emissivity climatology from satellites, surface temperature and TPW from NWP reanalysis. Results from the analysis of these databases with respect to the microwave precipitation sensitivity to the variety of environmental conditions in different climate regimes will be discussed.

  17. Environmental controls on food web regimes: A fluvial perspective

    NASA Astrophysics Data System (ADS)

    Power, Mary E.

    2006-02-01

    Because food web regimes control the biomass of primary producers (e.g., plants or algae), intermediate consumers (e.g., invertebrates), and large top predators (tuna, killer whales), they are of societal as well as academic interest. Some controls over food web regimes may be internal, but many are mediated by conditions or fluxes over large spatial scales. To understand locally observed changes in food webs, we must learn more about how environmental gradients and boundaries affect the fluxes of energy, materials, or organisms through landscapes or seascapes that influence local species interactions. Marine biologists and oceanographers have overcome formidable challenges of fieldwork on the high seas to make remarkable progress towards this goal. In river drainage networks, we have opportunities to address similar questions at smaller spatial scales, in ecosystems with clear physical structure and organization. Despite these advantages, we still have much to learn about linkages between fluxes from watershed landscapes and local food webs in river networks. Longitudinal (downstream) gradients in productivity, disturbance regimes, and habitat structure exert strong effects on the organisms and energy sources of river food webs, but their effects on species interactions are just beginning to be explored. In fluid ecosystems with less obvious physical structure, like the open ocean, discerning features that control the movement of organisms and affect food web dynamics is even more challenging. In both habitats, new sensing, tracing and mapping technologies have revealed how landscape or seascape features (e.g., watershed divides, ocean fronts or circulation cells) channel, contain or concentrate organisms, energy and materials. Field experiments and direct in situ observations of basic natural history, however, remain as vital as ever in interpreting the responses of biota to these features. We need field data that quantify the many spatial and temporal scales of

  18. On the fast magnetic rotator regime of stellar winds

    NASA Astrophysics Data System (ADS)

    Johnstone, C. P.

    2017-01-01

    Aims: We study the acceleration of the stellar winds of rapidly rotating low mass stars and the transition between the slow magnetic rotator and fast magnetic rotator regimes. We aim to understand the properties of stellar winds in the fast magnetic rotator regime and the effects of magneto-centrifugal forces on wind speeds and mass loss rates. Methods: We extend a solar wind model to 1D magnetohydrodynamic simulations of the winds of rotating stars. We test two assumptions for how to scale the wind temperature to other stars and assume the mass loss rate scales as dot{M_star ∝ R_star2 Ω_star1.33 M_star-3.36}, in the unsaturated regime, as estimated from observed rotational evolution. Results: For 1.0 M⊙ stars, the winds can be accelerated to several thousand km s-1, and the effects of magneto-centrifugal forces are much weaker for lower mass stars. We find that the different assumptions for how to scale the wind temperature to other stars lead to significantly different mass loss rates for the rapid rotators. If we assume a constant temperature, the mass loss rates of solar mass stars do not saturate at rapid rotation, which we show to be inconsistent with observed rotational evolution. If we assume the wind temperatures scale positively with rotation, the mass loss rates are only influenced significantly at rotation rates above 75 Ω⊙. We suggest that models with increasing wind speed for more rapid rotators are preferable to those that assume a constant wind speed. If this conclusion is confirmed by more sophisticated wind modelling. it might provide an interesting observational constraint on the properties of stellar winds. All of the codes and output data used in this paper can be downloaded from http://https://zenodo.org/record/160052#.V_y6drWkVC1 or obtained by contacting the author.

  19. Petrologic Regime Diagrams: Parameterizing Kinetic Controls on Vesiculation and Crystallization

    NASA Astrophysics Data System (ADS)

    Cashman, K. V.

    2014-12-01

    Regime diagrams are commonly employed in geophysical fluid dynamics to classify experimental results and, ideally, to define non-dimensional parameters that allow those results to be applied to natural systems. Petrologic experiments, in contrast, are typically run to mimic a specific natural system, and to infer conditions of magma storage, cooling or decompression. This approach has produced important insight into specific volcanoes, but the results are difficult to generalize. Additionally, very few experimental studies evaluate the vesiculation, crystallization and degassing histories of the same sample suite, an omission that is understandable given the time-consuming nature of the experiments and analysis, but which leaves important gaps in our general understanding of the interplay between gas exsolution, crystal formation and eruption dynamics. One way to bridge these gaps is to construct a regime diagram for conditions of vesiculation and crystallization. As both are controlled by the effective supercooling experienced by the magma during cooling or decompression, one key parameter is supersaturation, although in practice, decompression rate (cooling rate) are commonly used as proxies for supersaturation. Vesiculation and crystallization are also modulated by diffusion (dependent on individual species and melt viscosity), which can be simply approximated by melt composition. Using these parameters and published data for water-saturated decompression experiments, the following fields can be (partially) defined: (1) non-equilibrium volatile exsolution, (2) equilibrium volatile exsolution, and (3) exsolution accompanied by crystallization. Melt compositions, volatile contents and crystal textures of natural samples can be measured, and thus related (crudely) to the regime diagram. Additional information required for fully linking experiments and volcanic pyroclasts includes phase proportions (crystallization efficiency), pyroclast textures (phase change

  20. Hydrodynamic Regimes Affect Coral Reef Resilience to Ocean Acidification

    NASA Astrophysics Data System (ADS)

    Teneva, L. T.; Dunbar, R. B.; Koseff, J. R.; Fleischfresser, J. D.; Koweek, D.

    2013-05-01

    Caribbean reefs hold tremendous value as sources of food, income, coastal protection, in addition to their cultural significance. Recently, studies showed that Caribbean reef growth has been surpassed in places by excessive rates of erosion due to climate change. The rates of coral reef response to ocean pH changes and warming and the implications for ecosystem resilience remain largely unknown. One way to investigate the potential structural resilience of reefs to climate change is to measure the physical oceanographic conditions in the area. Determining the hydrodynamic regimes and residence time of water in a particular reef environment is crucial to understanding the rates of future warming and acidification a reef site would experience. Our work on Pacific Islands' hydrodynamics - Central Equatorial Pacific, Great Barrier Reef, and Western Pacific -- would be of interest to Caribbean physical oceanographers and coral reef scientists. We use a combination of Acoustic Doppler Current Profilers, Acoustic Doppler Velocimeters, temperature and salinity sensors, and pressure sensors to characterize reef hydrodynamic regimes. Our work indicates that shallower, more protected reef habitats are characterized by longer residence times, their biological signals are strongly tidally modulated, essentially subjecting such habitats to higher rates of warming and acidification in the future. Reef crest environments and fore reef habitats, on the other hand, are well-mixed with open-ocean water. The hydrodynamic regimes there condition such reef sites to more attenuated temperature and pH ranges, conditions more typical of the open ocean. Our work suggests that investigating the geomorphology and resulting localized hydrodynamics in a reef area can provide insights into the relative rates at which a reef could resist or succumb to impacts of ocean acidification. Such information for different reef islands, in the Pacific or Caribbean basins, could provide helpful insights