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Sample records for activator inhibitor-1 drive

  1. Does plasminogen activator inhibitor-1 drive lymphangiogenesis?

    Bruyère, Françoise; Melen-Lamalle, Laurence; Blacher, Silvia; Detry, Benoît; Masset, Anne; Lecomte, Julie; Lambert, Vincent; Maillard, Catherine; Høyer-Hansen, Gunilla; Lund, Leif R; Foidart, Jean-Michel; Noël, Agnès

    2010-01-01

    by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To...... induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by...

  2. Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

    Gils, Ann; Pedersen, Katrine Egelund; Skottrup, Peter; Christensen, Anni; Naessens, Dominik; Deinum, Johanna; Enghild, Jan Johannes; Declerck, Paul; Andreasen, Peter

    2003-01-01

    The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous......-inactivating compounds of potential clinical importance....

  3. Plasminogen activator inhibitor-1 in sputum and nasal fluids increases in asthmatics during common colds

    Cho, Seong H.; Hong, Seung J.; Chen, Haimei; Habib, Ali; Cho, David; Lee, Sun H.; Kang, Joseph; Ward, Theresa; Boushey, Homer A.; Schleimer, Robert P.; Avila, Pedro C.

    2014-01-01

    Capsule Summary This study showed that sputum and nasal lavage levels of plasminogen activator inhibitor-1 (PAI-1) rise during a common cold in asthmatic patients. This rise may contribute to the progression of airway remodeling. PMID:24373352

  4. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice.

    Samad, F; Loskutoff, D J

    1996-01-01

    BACKGROUND: Although elevated plasminogen activator inhibitor-1 (PAI-1) is associated with obesity and may be a risk factor for cardiovascular disease, the mechanism(s) that lead to this elevation, and the tissue/cellular origins of this increase, remain to be defined. In this report, we have addressed these questions using genetically obese mice (ob/ob) and their lean counterparts (+/?). MATERIALS AND METHODS: PAI-1 activity and antigen levels were determined using a tissue-type plasminogen ...

  5. Regulation of Plasminogen Activator Inhibitor-1 Expression in Endothelial Cells with Exposure to Metal Nanoparticles

    Yu, Min; Mo, Yiqun; Wan, Rong; Chien, Sufan; Zhang, Xing; Zhang, Qunwei

    2010-01-01

    Recent studies demonstrated that exposure to nanoparticles could enhance the adhesion of endothelial cells and modify the membrane structure of vascular endothelium. The endothelium plays an important role in the regulation of fibrinolysis, and imbalance of the fibrinolysis system potential contributes to the development of thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is the most potent endogenous inhibitor of fibrinolysis and is involved in the pathogenesis of several cardiovascular...

  6. Tryptophan Properties in Fluorescence and Functional Stability of Plasminogen Activator Inhibitor 1

    Verheyden, Stefan; Sillen, Alain; Gils, Ann; Paul J Declerck; Engelborghs, Yves

    2003-01-01

    Plasminogen activator inhibitor 1 harbors four tryptophan residues at positions 86, 139, 175, and 262. To investigate the contribution of each tryptophan residue to the total fluorescence and to reveal the mutual interactions of the tryptophan residues and interactions with the other amino acids, 15 mutants in which tryptophan residues have been replaced by phenylalanines were constructed, purified, and characterized. Conformational distribution analysis revealed that the tryptophan mutants h...

  7. Regulation of Plasminogen Activator Inhibitor-1 Expression by Tumor Suppressor Protein p53*

    Shetty, Sreerama; Shetty, Praveenkumar; Idell, Steven; Velusamy, Thirunavukkarasu; Bhandary, Yashodhar P.; Shetty, Rashmi S.

    2008-01-01

    H1299 lung carcinoma cells lacking p53 (p53-/-) express minimal amounts of plasminogen activator inhibitor-1 (PAI-1) protein as well as mRNA. p53-/- cells express highly unstable PAI-1 mRNA. Transfection of p53 in p53-/- cells enhanced PAI-1 expression and stabilized PAI-1 mRNA. On the contrary, inhibition of p53 expression by RNA silencing in non-malignant human lung epithelial (Beas2B) cells decreased basal as well as urokinase-type plasminogen activator-induced PAI-...

  8. Triglyceride concentration and waist circumference influence alcohol-related plasminogen activator inhibitor-1 activity increase in black South Africans

    Pieters, Marlien; de Lange, Zelda; Hoekstra, Tiny; Ellis, Suria M.; Kruger, Annamarie

    2010-01-01

    We investigated the association between alcohol consumption and plasminogen activator inhibitor-1 activity (PAI-1(act)) and fibrinogen concentration in a black South African population presenting with lower PAI-1(act) and higher fibrinogen than what is typically observed in white populations. We, fu

  9. Plasminogen Activator Inhibitor-1 and Susceptibility to Lung Cancer: A Population Genetics Perspective

    Bayramoglu, Aysegul; Gunes, Hasan Veysi; Metintas, Muzaffer; Degirmenci, Irfan; Guler, Halil Ibrahim; Ustuner, Cengiz; Musmul, Ahmet

    2014-01-01

    Aim: The aim of this study was to investigate the polymorphism frequency of plasminogen activator inhibitor-1 (PAI-1) (rs1799889) 4G/5G in patients with lung cancer. Methods: In this study, 286 genomic DNAs (154 lung cancer patients+132 subjects without lung cancer) were analyzed. Polymorphisms were determined by using the polymerase chain reaction (PCR) method, with 4G and 5G allele-specific primers. PCR products were assessed by a charge-coupled device camera and exposed to 2% agarose gel e...

  10. Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice

    Almholt, Kasper; Nielsen, Boye Schnack; Frandsen, Thomas Leth; Brunner, Nils; Danø, Keld; Johnsen, M.

    2003-01-01

    The plasminogen activator inhibitor-1 (PAI-1) blocks the activation of plasmin(ogen), an extracellular protease vital to cancer invasion. PAI-1 is like the corresponding plasminogen activator uPA (urokinase-type plasminogen activator) consistently expressed in human breast cancer. Paradoxically......, high levels of PAI-1 as well as uPA are equally associated with poor prognosis in cancer patients. PAI-1 is thought to play a vital role for the controlled extracellular proteolysis during tumor neovascularization. We have studied the effect of PAI-1 deficiency in a transgenic mouse model of...... metastasizing breast cancer. In these tumors, the expression pattern of uPA and PAI-1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis. In a cohort of 63 transgenic mice that were either PAI-1-deficient or wild-type sibling controls, primary tumor growth and...

  11. Plasminogen activator inhibitor-1: physiologic role, regulation, and the influence of common pharmacologic agents.

    Tsikouris, James P; Suarez, Jose A; Meyerrose, Gary E

    2002-11-01

    Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of endogenous thrombolysis, thereby promoting thrombosis. PAI-1 is also a primary contributor to the development and recurrence of acute myocardial infarction. The renin angiotensin system, hypertriglyceridemia, hyperglycemia and hyperinsulinemia, and estrogen all influence the fibrinolytic system and PAI-1 in particular. Available data strongly suggest that angiotensin-converting enzyme (ACE) inhibitors and hormone replacement therapy with estrogen beneficially reduce PAI-1 production. Metformin, an agent commonly used for non-insulin-dependent diabetes mellitus (NIDDM), appears to favorably decrease PAI-1 production in NIDDM patients but not nondiabetic patients. Among the cholesterol-lowering statins, clinical literature evaluating pravastatin provides the most compelling data to support this agent's favorable effect on PAI-1. Other available statins either have not displayed an effect on PAI-1 or do not have clear data to conclusively define their effects on the fibrinolytic system. PMID:12412817

  12. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  13. Abrogation of Plasminogen Activator Inhibitor-1-Vitronectin Interaction Ameliorates Acute Kidney Injury in Murine Endotoxemia

    Gupta, Kamlesh K.; Donahue, Deborah L.; Sandoval-Cooper, Mayra J.; Castellino, Francis J.; Ploplis, Victoria A.

    2015-01-01

    Sepsis-induced acute kidney injury (AKI) contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1) and vitronectin (Vn) are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1−/−) or expressing a PAI-1-mutant (PAI-1R101A/Q123K) in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1−/− and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT) mice after LPS challenge. Also, PAI-1−/− mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC) in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity. PMID:25799354

  14. PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts.

    Kassem, Kamal M; Clevenger, Margarette H; Szandzik, David L; Peterson, Edward; Harding, Pamela

    2014-10-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  15. Host Plasminogen Activator Inhibitor-1 Promotes Human Skin Carcinoma Progression in a Stage-Dependent Manner

    Catherine Maillard

    2005-01-01

    Full Text Available Angiogenesis and tumor expansion are associated with extracellular matrix remodeling and involve various proteases such as the plasminogen (Pig/plasminogen activator (PA system. Recently, several experimental data have implicated the plasminogen activator inhibitor-1 (PAI-1 in tumor angiogenesis in murine systems. However, little is known about PAI-1 functions in human skin carcinoma progression. By generating immunodeficient mice (in Rag-1-/- or nude background deleted for PAI-1 gene (PAI-1-/- , we have evaluated the impact of host PAI-1 deficiency on the tumorigenicity of two malignant human skin keratinocyte cell lines HaCaT II-4 and HaCaT A5-RT3 forming low-grade and high-grade carcinomas, respectively. When using the surface transplantation model, angiogenesis and tumor invasion of these two cell lines are strongly reduced in PAI-1-deficient mice as compared to the wild-type control animals. After subcutaneous injection in PAI-1-/- mice, the tumor incidence is reduced for HaCaT II-4 cells, but not for those formed by HaCaT A5-RT3 cells. These data indicate that PAI-1 produced by host cells is an important contributor to earlier stages of human skin carcinoma progression. It exerts its tumor-promoting effect in a tumor stage-dependent manner, but PAI-1 deficiency is not sufficient to prevent neoplastic growth of aggressive tumors of the human skin.

  16. Plasminogen Activator Inhibitor-1 in depression: Results from Animal and Clinical Studies.

    Jiang, Haitang; Li, Xiaoli; Chen, Suzhen; Lu, Na; Yue, Yingying; Liang, Jinfeng; Zhang, Zhijun; Yuan, Yonggui

    2016-01-01

    Evidence suggests that plasminogen activator inhibitor-1 (PAI-1) is a stress-related factor, and serum PAI-1 levels are increased in patients with major depressive disorders (MDD). Herein, we analysed PAI-1 protein levels in the brain, cerebrospinal fluid (CSF) and serum of rodents exposed to chronic unpredictable mild stress or treated with escitalopram. In addition, we examined PAI-1 concentrations in serum obtained from 17 drug-free depressed patients before and after escitalopram treatment. We found that PAI-1 expression was increased in area 1 of the cingulate cortex and prelimbic cortex of the medial prefrontal cortex as well as in the hippocampal cornu ammonis 3 and dentate gyrus in stressed rats. A downregulation of PAI-1 following chronic escitalopram treatment was also found. PAI-1 levels were higher in the CSF and serum in stressed rats than in controls, although the difference did not reach statistical significance in the serum. Escitalopram treatment significantly decreased PAI-1 levels in the serum, but not in the CSF. MDD patients had significantly greater serum PAI-1 concentrations than controls. Our results suggest that PAI-1 is implicated in the pathophysiology of depression. PMID:27456456

  17. Plasminogen Activator Inhibitor-1 Controls Vascular Integrity by Regulating VE-Cadherin Trafficking.

    Anna E Daniel

    Full Text Available Plasminogen activator inhibitor-1 (PAI-1, a serine protease inhibitor, is expressed and secreted by endothelial cells. Patients with PAI-1 deficiency show a mild to moderate bleeding diathesis, which has been exclusively ascribed to the function of PAI-1 in down-regulating fibrinolysis. We tested the hypothesis that PAI-1 function plays a direct role in controlling vascular integrity and permeability by keeping endothelial cell-cell junctions intact.We utilized PAI-039, a specific small molecule inhibitor of PAI-1, to investigate the role of PAI-1 in protecting endothelial integrity. In vivo inhibition of PAI-1 resulted in vascular leakage from intersegmental vessels and in the hindbrain of zebrafish embryos. In addition PAI-1 inhibition in human umbilical vein endothelial cell (HUVEC monolayers leads to a marked decrease of transendothelial resistance and disrupted endothelial junctions. The total level of the endothelial junction regulator VE-cadherin was reduced, whereas surface VE-cadherin expression was unaltered. Moreover, PAI-1 inhibition reduced the shedding of VE-cadherin. Finally, we detected an accumulation of VE-cadherin at the Golgi apparatus.Our findings indicate that PAI-1 function is important for the maintenance of endothelial monolayer and vascular integrity by controlling VE-cadherin trafficking to and from the plasma membrane. Our data further suggest that therapies using PAI-1 antagonists like PAI-039 ought to be used with caution to avoid disruption of the vessel wall.

  18. Increased concentration of plasminogen activator inhibitor-1 and fibrinogen in individuals with metabolic syndrome.

    Palomo, Iván G; Gutiérrez, César L; Alarcón, Marcelo L; Jaramillo, Julio C; Segovia, Fabián M; Leiva, Elba M; Mujica, Verónica E; Icaza, Gloria N; Díaz, Nora S; Moore-Carrasco, Rodrigo

    2009-01-01

    Metabolic syndrome (MS) is closely linked to a generalized metabolic disorder referred to as insulin resistance. Disturbances in the hemostasis and fibrinolytic systems are a feature of MS. The aim of this study was to determine the concentration levels of fibrinogen and plasminogen activator inhibitor-1 (PAI-1) in a group of patients with MS with respect to a non-MS group, and to evaluate their possible relation with other risk factors in MS. The study was carried out in a total of 186 male and female non-smoking individuals aged 45-64 years, 93 with MS (ATP III criteria) and 93 without MS. Plasmatic levels of PAI-1 were measured by ELISA, and those of fibrinogen by the Claus method. The plasmatic levels of PAI-1 (men 49.2±19.8 vs. 35.0±12.2 ng/ml and women 42.0±19.7 vs. 31.6±14.6 ng/ml; p=0.0026) and fibrinogen (274.0±82.1 vs. 232.7±66.6 ng/ml; p=0.0002) were significantly higher in the MS group than in the non-MS group. PAI-1 was significantly associated with diastolic blood pressure, triglycerides and waist circumference. Fibrinogen was negatively associated with HDL-c. High plasmatic levels of PAI-1 and fibrinogen contribute to the cardiovascular risk that characterizes individuals with MS. PMID:21475821

  19. Enhancing the function of CD34(+ cells by targeting plasminogen activator inhibitor-1.

    Sugata Hazra

    Full Text Available Previously, we showed that transient inhibition of TGF- β1 resulted in correction of key aspects of diabetes-induced CD34(+ cell dysfunction. In this report, we examine the effect of transient inhibition of plasminogen activator inhibitor-1 (PAI-1, a major gene target of TGF-β1 activation. Using gene array studies, we examined CD34(+ cells isolated from a cohort of longstanding diabetic individuals, free of microvascular complications despite suboptimal glycemic control, and found that the cells exhibited reduced transcripts of both TGF-β1 and PAI-1 compared to age, sex, and degree of glycemic control-matched diabetic individuals with microvascular complications. CD34(+ cells from diabetic subjects with microvascular complications consistently exhibited higher PAI-1 mRNA than age-matched non-diabetic controls. TGF- β1 phosphorodiamidate morpholino oligo (PMO reduced PAI-1 mRNA in diabetic (p<0.01 and non-diabetic (p=0.05 CD34(+ cells. To reduce PAI-1 in human CD34(+ cells, we utilized PAI-1 siRNA, lentivirus expressing PAI-1 shRNA or PAI-1 PMO. We found that inhibition of PAI-1 promoted CD34(+ cell proliferation and migration in vitro, likely through increased PI3(K activity and increased cGMP production. Using a retinal ischemia reperfusion injury model in mice, we observed that recruitment of diabetic CD34(+ cells to injured acellular retinal capillaries was greater after PAI-1-PMO treatment compared with control PMO-treated cells. Targeting PAI-1 offers a promising therapeutic strategy for restoring vascular reparative function in defective diabetic progenitors.

  20. Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Svendsen, M N;

    2002-01-01

    months. METHODS: Vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA methods in plasma collected from the patients before treatment and after 1, 3 and 6 months. Vessel counts were performed in biopsies from affected skin areas taken before...

  1. Plasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis.

    Maher, Vincent M G

    2009-08-01

    Patients with high plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels are prone to develop thrombosis. Lowering PAI-1 levels may offer a therapeutic option and help to better understand PAI-1 metabolism. We examined the effect on plasma PAI-1 levels of LDL-apheresis using dextran sulphate (DS) columns in 12 patients (9 male, 3 female, 49 +\\/- 10 years) with heterozygous familial hypercholesterolaemia and coronary artery disease. One plasma volume equivalent (2.3-4.0 l) was treated during each procedure (at flow rates of 23 +\\/- 2 ml\\/min). Lipids and PAI-1 antigen levels were measured in plasma before and immediately after 19 aphereses (once in 7 patients, twice in 3 patients and three times in 2 patients) and also at 3 and 7 days post apheresis in five of these patients and in the column eluates from 8 of these patients. DS-apheresis reduced plasma cholesterol (50 +\\/- 8%), triglyceride (45 +\\/- 27%), apolipoprotein B (59 +\\/- 10%) and PAI-1 antigen levels from 10.2 +\\/- 5.2 to 6.0 +\\/- 3.1 ng\\/ml (P = 0.005). The PAI-I changes were independent of circadian variation. PAI-I bound to the DS-columns (3.51 +\\/- 1.03 ng\\/ml filtered plasma) and the percent of filtered PAI-1 that was bound correlated inversely (r = -0.81, P < 0.02) with basal PAI-1 levels indicating a high affinity saturable binding process. In four patients, plasma PAI-1 levels post-apheresis were higher than expected based on the amount of PAI-removed by the DS columns. The difference between the expected and actual PAI-1 level post apheresis, reflecting PAI-1 secretion or extracellular redistribution, correlated inversely with basal PAI-1 levels (r = -0.83, P = 0.01). PAI-1 levels returned to baseline pre-apheresis values 7 days post apheresis. PAI-1 antigen may be removed from plasma without adverse effect, resulting temporarily in its extracellular redistribution and restoration to baseline levels over one week. PAI-1 redistribution particularly when baseline pre

  2. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis

    Zhang Tengyue; Pang Chong; Li Ningdong; Zhou Elaine; Zhao Kanxing

    2013-01-01

    Abstract Background Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods Data were retrieved in a systematic manner a...

  3. Temporal changes in circulating P-selectin, plasminogen activator inhibitor-1, magnesium, and creatine kinase after percutaneous coronary intervention*

    Ying, Shu-qin; Xiang, Mei-xiang; Fang, Lu; Wang, Jian-an

    2010-01-01

    Objective: This study aims to determine the mechanisms underlying restenosis and ischemia-reperfusion injury of the myocardium after percutaneous coronary intervention (PCI). Methods: The present study examined serial changes (5 min, 30 min, 2 h, 6 h, and 24 h after PCI) in circulating P-selectin, plasminogen activator inhibitor-1 (PAI-1), magnesium (Mg), and creatine kinase-myocardial band fraction (CK-MB) levels, which may be associated with restenosis and myocardial injury in patients unde...

  4. An In Silico Approach towards the Prediction of Druglikeness Properties of Inhibitors of Plasminogen Activator Inhibitor1

    Umadevi Subramanian; Ashok Sivapunniyam; Ayyasamy Pudukadu Munusamy; Rajakumar Sundaram

    2014-01-01

    Diabetic retinopathy is the leading cause of blindness worldwide. It is caused by the abnormal growth of the retinal blood vessels. Plasminogen activator inhibitor1 (PAI1) is the key growth factor and the inhibition of PAI1 can reduce the angiogenesis. In this study, currently available inhibitors are taken and tested for the toxicity, binding affinity, and bioactivities of the compounds by in silico approach. Five toxic free inhibitors were identified, among which N-acetyl-D-glucosamine show...

  5. Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

    Zaid Al-Hamodi

    2012-01-01

    Full Text Available Elevated activity of plasminogen activator inhibitor-1 (PAI-1 and decreased tissue plasminogen activator (tPA activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM and metabolic syndrome (MetS. The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35, P=0.045; OR=1.67, P=0.058. On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32, P=0.013 whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

  6. Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Svendsen, M N; Hansen, Ulla; Werther, K; Brünner, N; Petersen, L J; Kristensen, J K

    2002-01-01

    OBJECTIVE AND DESIGN: An evaluation of angiogenesis related molecules during open treatment of psoriasis. MATERIALS AND SUBJECTS: Plasma samples and skin biopsies from 16 patients with psoriasis and plasma samples from 13 healthy controls. TREATMENT: Ranitidine 300 mg orally twice daily for 6...... months. METHODS: Vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA methods in plasma collected from the patients before treatment and after 1, 3 and 6 months. Vessel counts were performed in biopsies from affected skin areas taken before...... treatment and after 3 and 6 months. The results were compared to simultaneous PASI scores. RESULTS: Pre-treatment plasma levels of VEGF and PAI-1 were significantly elevated in patients compared with levels in healthy persons (p = 0.02 and p = 0.04, respectively). The plasma levels decreased significantly...

  7. An In Silico Approach towards the Prediction of Druglikeness Properties of Inhibitors of Plasminogen Activator Inhibitor1

    Umadevi Subramanian

    2014-01-01

    Full Text Available Diabetic retinopathy is the leading cause of blindness worldwide. It is caused by the abnormal growth of the retinal blood vessels. Plasminogen activator inhibitor1 (PAI1 is the key growth factor and the inhibition of PAI1 can reduce the angiogenesis. In this study, currently available inhibitors are taken and tested for the toxicity, binding affinity, and bioactivities of the compounds by in silico approach. Five toxic free inhibitors were identified, among which N-acetyl-D-glucosamine shows the significant binding affinity and two of the molecules are having the better bioactivity properties. The molecular optimization of 2-(acetylamino-2-deoxy-A-D-glucopyranose and alpha-L-fucose can be used for the treatment of diabetic retinopathy.

  8. Plasminogen activator inhibitor-1 polymers, induced by inactivating amphipathic organochemical ligands

    Pedersen, Katrine E; Einholm, Anja P; Christensen, Anni;

    2003-01-01

    compared with native PAI-1, the polymers exhibited an increased resistance to temperature-induced unfolding. Polymerization was associated with specific changes in patterns of digestion with non-target proteases. During incubation with urokinase-type plasminogen activator, the polymers were slowly...

  9. A plasminogen activator inhibitor-1 inhibitor reduces airway remodeling in a murine model of chronic asthma.

    Lee, Sun H; Eren, Mesut; Vaughan, Douglas E; Schleimer, Robert P; Cho, Seong H

    2012-06-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  10. Plasminogen activator inhibitor 1: Mechanisms of its synergistic regulation by growth factors

    Song, Xiaoling [Iowa State Univ., Ames, IA (United States)

    2010-01-01

    My research is on the synergistic regulation of PAI-1 by EGF and TGF-β. The mechanism of synergistic regulation of PAI-1 by EGF and TGF-β are addressed. Methods are described for effective identification of RNA accessible sites for antisense oligodexoxynucleotides (ODNs) and siRNA. In this study effective AS-ODN sequences for both Lcn2 and Bcl2 were identified by in vitro tiled microarray studies. Our results suggest that hybridization of ODN arrays to a target mRNA under physiological conditions might be used as a rapid and reliable in vitro method to accurately identify targets on mRNA molecules for effective antisense and potential siRNA activity in vivo.

  11. Evaluation of 12-Lipoxygenase (12-LOX and Plasminogen Activator Inhibitor 1 (PAI-1 as Prognostic Markers in Prostate Cancer

    Tomasz Gondek

    2014-01-01

    Full Text Available In carcinoma of prostate, a causative role of platelet 12-lipoxygenase (12-LOX and plasminogen activator inhibitor 1 (PAI-1 for tumor progression has been firmly established in tumor and/or adjacent tissue. Our goal was to investigate if 12-LOX and/or PAI-1 in patient’s plasma could be used to predict outcome of the disease. The study comprised 149 patients (age 70±9 divided into two groups: a study group with carcinoma confirmed by positive biopsy of prostate (n=116 and a reference group (n=33 with benign prostatic hyperplasia (BPH. The following parameters were determined by the laboratory test in plasma or platelet-rich plasma: protein level of 12-LOX, PAI-1, thromboglobulin (TGB, prostate specific antigen (PSA, C-reactive protein (CRP, hemoglobin (HGB, and hematocrit (HCT, as well as red (RBC and white blood cells (WBC, number of platelets (PLT, international normalized ratio of blood clotting (INR, and activated partial thromboplastin time (APTT. The only difference of significance was noticed in the concentration of 12-LOX in platelet rich plasma, which was lower in cancer than in BPH group. Standardization to TGB and platelet count increases the sensitivity of the test that might be used as a biomarker to assess risk for prostate cancer in periodically monitored patients.

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

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

    2009-01-01

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

  13. Hydrogen/Deuterium Exchange Mass Spectrometry Reveals Specific Changes in the Local Flexibility of Plasminogen Activator Inhibitor 1 upon Binding to the Somatomedin B Domain of Vitronectin

    Trelle, Morten Beck; Hirschberg, Daniel; Jansson, Anna; Ploug, Michael; Roepstorff, Peter; Andreasen, Peter; Jørgensen, Thomas

    2012-01-01

    The native fold of plasminogen activator inhibitor 1 (PAI-1) represents an active metastable conformation that spontaneously converts to an inactive latent form. Binding of the somatomedin B domain (SMB) of the endogenous cofactor vitronectin to PAI-1 delays the transition to the latent state and...

  14. Plasminogen activator inhibitor-1 4G/5G gene polymorphism in patients with myocardial or cerebrovascular infarction in Tianjin, China

    战梅; 周玉玲; 韩忠朝

    2003-01-01

    Objective To investigate the association between the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and the occurrence of myocardial and cerebrovascular infarctions in individuals from Tianjin, China.Methods The PAI-1 genotype was determined using allele-specific polymerase chain reaction (AS-PCR) in 56 myocardial infarction (MI) patients, 54 cerebrovascular infarction(CI) patients and 83 unrelated healthy controls. All subjects ' clinical features and plasma PAI-1 activity levels were determined.Results The PAI-1 genotype distribution frequency of the single guanine deletion/insertion 4G/5G polymorphism (located -675 bp upstream from the start of transcription) significantly differed between the patients and healthy controls. In the MI group, the 4G/4G-genotype frequency was increased, but the 4G/5G-genotype is decreased when compared to the control group. In the CI group, both the 4G/4G- and 4G/5G -genotypes occurred at a lower frequency than those in the control group (P<0.001). The plasma PAI-1 activity level in the MI group was lowered as the presence of the 4G allele decreases. In the CI group, the frequency of 5G/5G was much higher than that of the control group (P<0.001). The plasma PAI-1 activity level in the CI group was elevated as the presence of the 5G allele increased. Furthermore, positive correlation between triglyceride, glucose levels and PAI-1 activity were found in all three groups (P<0.001).Conclusions The PAI-1 4G/5G gene polymorphism is associated with a higher risk of MI and CI in individuals in Tianjin, China. The deletion/insertion polymorphism is probably an important hereditary risk factor for heart diseases. Moreover, triglyceride and glucose levels of plasma have functional importance in regulating PAI-1 activity.

  15. Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice

    We investigated the effects of plasminogen activator inhibitor-1 (PAI-1) deficiency on spontaneous metastasis of Lewis lung carcinoma (LLC) in PAI-1 deficient (PAI-1-/-) and wildtype mice (C57BL/6J background) fed the AIN93G diet or that diet modified with 45% calories from fat. The high-fat diet i...

  16. Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis

    Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the

  17. Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to hypertension in Korean women

    Kyu-nam Kim; Kwang-min Kim; Bom-taeck Kim; Nam-seok Joo; Doo-yeoun Cho; Duck-joo Lee

    2012-01-01

    Background Hypertension (HTN) is a major determinant of various cardiovascular events.Plasma levels of plasminogen activator inhibitor 1 (PAl-1) modulate this risk.A deletion/insertion polymorphism within the PAl-1 loci (4G/4G,4G/5G,5G/5G) affects the expression of this gene.The present study investigated the association between PAl-1 loci polymorphisms and HTN in Korean women.@@Methods Korean women (n=1312) were enrolled in this study to evaluate the association between PAl-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk factors.PAl-1 loci polymorphisms were investigated using polymerase chain reaction amplification and single-strand conformation polymorphism analysis.@@Results The three genotype groups differed with respect to systolic blood pressure (P=0.043),and diastolic blood pressure (P=0.009) but not with respect to age,body mass index,total cholesterol,low or high density lipoprotein cholesterol,triglycerides,or fasting blood glucose.Carriers of the PAl-1 4G allele had more hypertension significantly (PAl-1 4G/5G vs.PAl-1 5G/5G,P=0.032; PAl-1 4G/4G vs.PAl-1 5G/5G,P=0.034).When stratified according to PAl-1 4G/5G polymorphism,there was no significant difference in all metabolic parameters among PAl-1 genotype groups in patients with HTN as well as subjects with normal blood pressure.The estimated odds ratio of the 4G/4G genotype and 4G/5G for HTN was 1.7 (P=0.005),and 1.6 (P=0.015),respectively.@@Conclusion These findings might indicate that PAl-1 loci polymorphisms independently contribute to HTN and that gene-environmental interaction may be not associated in Korean women.

  18. Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis.

    Nicolas Pelisch

    Full Text Available Multiple sclerosis (MS is characterized by inflammatory demyelination and deposition of fibrinogen in the central nervous system (CNS. Elevated levels of a critical inhibitor of the mammalian fibrinolitic system, plasminogen activator inhibitor 1 (PAI-1 have been demonstrated in human and animal models of MS. In experimental studies that resemble neuroinflammatory disease, PAI-1 deficient mice display preserved neurological structure and function compared to wild type mice, suggesting a link between the fibrinolytic pathway and MS. We previously identified a series of PAI-1 inhibitors on the basis of the 3-dimensional structure of PAI-1 and on virtual screening. These compounds have been reported to provide a number of in vitro and in vivo benefits but none was tested in CNS disease models because of their limited capacity to penetrate the blood-brain barrier (BBB. The existing candidates were therefore optimized to obtain CNS-penetrant compounds. We performed an in vitro screening using a model of BBB and were able to identify a novel, low molecular PAI-1 inhibitor, TM5484, with the highest penetration ratio among all other candidates. Next, we tested the effects on inflammation and demyelination in an experimental allergic encephalomyelitis mice model. Results were compared to either fingolimod or 6α-methylprednisolone. Oral administration of TM5484 from the onset of signs, ameliorates paralysis, attenuated demyelination, and axonal degeneration in the spinal cord of mice. Furthermore, it modulated the expression of brain-derived neurotrophic factor, which plays a protective role in neurons against various pathological insults, and choline acetyltransferase, a marker of neuronal density. Taken together, these results demonstrate the potential benefits of a novel PAI-1 inhibitor, TM5484, in the treatment of MS.

  19. Association of plasminogen activator inhibitor-1 and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women

    Fatemeh Shakarami

    2015-10-01

    Full Text Available Background: Recurrent pregnancy loss (RPL defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1 and angiotensin converting enzyme (ACE genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%, and 5 controls (5% (p=0.006 so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84. In addition, 7 patients (7 %, and no one from the control group, were homozygote (I/I for ACE polymorphism (p=0.034, suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

  20. Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis.

    Pelisch, Nicolas; Dan, Takashi; Ichimura, Atsuhiko; Sekiguchi, Hiroki; Vaughan, Douglas E; van Ypersele de Strihou, Charles; Miyata, Toshio

    2015-01-01

    Multiple sclerosis (MS) is characterized by inflammatory demyelination and deposition of fibrinogen in the central nervous system (CNS). Elevated levels of a critical inhibitor of the mammalian fibrinolitic system, plasminogen activator inhibitor 1 (PAI-1) have been demonstrated in human and animal models of MS. In experimental studies that resemble neuroinflammatory disease, PAI-1 deficient mice display preserved neurological structure and function compared to wild type mice, suggesting a link between the fibrinolytic pathway and MS. We previously identified a series of PAI-1 inhibitors on the basis of the 3-dimensional structure of PAI-1 and on virtual screening. These compounds have been reported to provide a number of in vitro and in vivo benefits but none was tested in CNS disease models because of their limited capacity to penetrate the blood-brain barrier (BBB). The existing candidates were therefore optimized to obtain CNS-penetrant compounds. We performed an in vitro screening using a model of BBB and were able to identify a novel, low molecular PAI-1 inhibitor, TM5484, with the highest penetration ratio among all other candidates. Next, we tested the effects on inflammation and demyelination in an experimental allergic encephalomyelitis mice model. Results were compared to either fingolimod or 6α-methylprednisolone. Oral administration of TM5484 from the onset of signs, ameliorates paralysis, attenuated demyelination, and axonal degeneration in the spinal cord of mice. Furthermore, it modulated the expression of brain-derived neurotrophic factor, which plays a protective role in neurons against various pathological insults, and choline acetyltransferase, a marker of neuronal density. Taken together, these results demonstrate the potential benefits of a novel PAI-1 inhibitor, TM5484, in the treatment of MS. PMID:25915660

  1. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis

    Zhang Tengyue

    2013-01-01

    Full Text Available Abstract Background Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1 is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of associations. Results Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52. In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77. When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00. We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57. Conclusions The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of

  2. Association of the 4 g/5 g polymorphism of plasminogen activator inhibitor-1 gene with sudden sensorineural hearing loss. A case control study

    Cho Seong; Chen Haimei; Kim Il; Yokose Chio; Kang Joseph; Cho David; Cai Chun; Palma Silvia; Busi Micol; Martini Alessandro; Yoo Tae J

    2012-01-01

    Abstract Background The 5 G/5 G genotype of PAI-1 polymorphism is linked to decreased plasminogen activator inhibitor-1 (PAI-1) levels and it has been suggested that lower PAI-1 levels may provide protective effects on inflammation, local microcirculatory disturbance, and fibrotic changes, which are likely associated with development of sudden sensorineural hearing loss (SSNHL). Methods The association of the 4 G/5 G PAI-1 polymorphism with the development and clinical outcome of SSNHL is eva...

  3. Relationship between plasminogen activator inhibitor-1 gene polymorphism and early local hemostatic activation in patients with percutaneous coronary intervention procedure

    Objective: To investigate the relationship between plasminogen activatorinhibitor-1 (PAI-1) 4 G/5 G gene polymorphism and local homeostatic activation of PAI-1, D-dimers (DD), activated factor VII (F VII Ia) and P-Selectin (CD62P), on patients under percutaneous coronary intervention (PCI)procedures, and to evaluate its prognostic value on acute stent thrombosis by gene polymorphism analysis. Methods: 20 stable angina patients with a 70% diameter stenosis by visual estimation during angiography and a clinical indication for revascularization were selected. Lesions were treated with the use of standard interventional techniques, both stents implantation underwent with adjunctive balloon angioplasty. Simultaneous blood samples were drawn in sequence from the ostium of the coronary artery before balloon angioplasty through guiding catheter, from the distal coronary artery just beyond the dilated segment after balloon angioplasty and after stent implantation, through aspiration catheter. Markers of PAI-1 and CD62P were measured by ELISA. Markers of F VII and DD were measured by technique chronometrique and ELISA VIDAS respectively. Prevalence of the 4 G/5 G polymorphism was investigated using DNA analysis. Results: The distribution of PAI-1 genotypes in French people was as follows: 4 G/4 G in 30.0%, 4 G/5 G in 60.0% and 5 G/5 G in 10.0%. Among the patients, the frequency of the 4 G and 5 G allele were 0.60 and 0.40 respectively. In patients with the 4 G/5 G polymorphism of PAI-1 gene, the activities of the PAI-1, DD and F VIIa in the coronary circulation were significantly increased after balloon angioplasty in comparing with those before balloon angioplasty (P=0.01, respectively). However, there were no significant differences between the levels of hemostatic activation at ostium before balloon angioplasty and distal to lesion after stent implantation in patients with the 4 G/5 G genotype. Conclusions: Balloon angioplasty more easily induces vessel shrinkage and

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

    Sebastian Zukowski

    2008-06-01

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

  5. Dissecting the effect of RNA aptamer binding on the dynamics of plasminogen activator inhibitor 1 using hydrogen/deuterium exchange mass spectrometry

    Trelle, Morten B; Dupont, Daniel Miotto; Madsen, Jeppe Buur;

    2014-01-01

    , about their effects on protein conformation and dynamics. We have employed hydrogen/deuterium exchange (HDX) mass spectrometry to study the effect of RNA aptamers on the structural flexibility of the serpin plasminogen activator inhibitor-1 (PAI-1). The aptamers have characteristic effects...... on the biochemical properties of PAI-1. In particular, they are potent inhibitors of the structural transition of PAI-1 from the active state to the inactive, so-called latent state. This transition is one of the largest conformational changes of a folded protein domain without covalent modification. Binding...

  6. Conformational Lability in Serine Protease Active Sites: Structures of Hepatocyte Growth Factor Activator (HGFA) Alone and with the Inhibitory Domain from HGFA Inhibitor-1B

    Hepatocyte growth factor activator (HGFA) is a serine protease that converts hepatocyte growth factor (HGF) into its active form. When activated HGF binds its cognate receptor Met, cellular signals lead to cell growth, differentiation, and migration, activities which promote tissue regeneration in liver, kidney and skin. Intervention in the conversion of HGF to its active form has the potential to provide therapeutic benefit where HGF/Met activity is associated with tumorigenesis. To help identify ways to moderate HGF/Met effects, we have determined the molecular structure of the protease domain of HGFA. The structure we determined, at 2.7 (angstrom) resolution, with no pseudo-substrate or inhibitor bound is characterized by an unconventional conformation of key residues in the enzyme active site. In order to find whether this apparently non-enzymatically competent arrangement would persist in the presence of a strongly-interacting inhibitor, we also have determined, at 2.6 (angstrom) resolution, the X-ray structure of HGFA complexed with the first Kunitz domain (KD1) from the physiological inhibitor hepatocyte growth factor activator inhibitor 1B (HAI-1B). In this complex we observe a rearranged substrate binding cleft that closely mirrors the cleft of other serine proteases, suggesting an extreme conformational dynamism. We also characterize the inhibition of 16 serine proteases by KD1, finding that the previously reported enzyme specificity of the intact extracellular region of HAI-1B resides in KD1 alone. We find that HGFA, matriptase, hepsin, plasma kallikrein and trypsin are potently inhibited, and use the complex structure to rationalize the structural basis of these results.

  7. Angiotensin II induces secretion of plasminogen activator inhibitor 1 and a tissue metalloprotease inhibitor-related protein from rat brain astrocytes

    The present study investigates angiotensin (Ang) II effects on secretory protein synthesis in brain astrocytes cultured from neonatal and 21-day-old rats. Ang II-induced changes in the de novo synthesis of [35S]methionine-labeled secretory proteins were visualized using two-dimensional NaDodSO4/PAGE. Astrocytes from 21-day-old rat brain possess specific high-affinity receptors for Ang II. These cells express two Ang II-induced secretory proteins with Mr 55,000 (AISP-55K) and Mr 30,000 (AISP-30K), which were time- and dose-dependent (EC50, 1 nM). [Sar1, Ile8]Ang II (where Sar is sarcosine) inhibited Ang II-induced secretion of AISP-55K but not AISP-30K. N-terminal amino acid sequencing indicates that AISP-55K is identical to rat plasminogen activator inhibitor 1, whereas AISP-30K exhibits 72-81% identity to three closely related proteins: human tissue inhibitor of metalloproteases, a rat phorbol ester-induced protein, and the murine growth-responsive protein 16C8. Immunofluorescent staining with rat plasminogen activator inhibitor 1 antibody was induced in the majority of cells in culture after Ang II treatment of astrocytes from 21-day-old rat brains. Absence of this response to Ang II in astrocytes from neonatal rat brain provides evidence that this action of Ang II on astrocytes is developmentally regulated

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

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

    2005-01-01

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

  9. Plasminogen Activator Inhibitor-1 Mitigates Brain Injury in a Rat Model of Infection-Sensitized Neonatal Hypoxia–Ischemia

    Yang, Dianer; Sun, Yu-Yo; Nemkul, Niza; Baumann, Jessica M.; Shereen, Ahmed; Dunn, R. Scott; Wills-Karp, Marsha; Lawrence, Daniel A.; Lindquist, Diana M.; Kuan, Chia-Yi

    2012-01-01

    Intrauterine infection exacerbates neonatal hypoxic–ischemic (HI) brain injury and impairs the development of cerebral cortex. Here we used low-dose lipopolysaccharide (LPS) pre-exposure followed by unilateral cerebral HI insult in 7-day-old rats to study the pathogenic mechanisms. We found that LPS pre-exposure blocked the HI-induced proteolytic activity of tissue-type plasminogen activator (tPA), but significantly enhanced NF-κB signaling, microglia activation, and the production of pro-inf...

  10. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer

  11. Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

    Xia LIU; Lei L(U); Bei-bei TAO; Ai-ling ZHOU; Yi-chun ZHU

    2011-01-01

    Aim:To examine the effects of all-trans retinoic acid (atRA) on renal morphology and function as well as on renal plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity in rats with 5/6 nephrectomy.Methods:Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA (5 or 10 mg/kg by gastric gavage once daily) for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments,kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements.Results:The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-SMA. However, piasmin activity remained unchanged following atRA treatment.Conclusion:Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAI-1 and α-SMA, but not with a change in plasmin activity.

  12. Lack of association between level of Plasminogen Activator Inhibitor-1 and estimates of tumor angiogenesis in early breast cancer

    Offersen, Birgitte Vrou; Riisbro, Rikke; Knoop, Ann;

    2007-01-01

    Plasminogen Activator Inhibitor type-1 (PAI-1) is involved in tumor invasion and progression. High levels of PAI-1 are associated with poor prognosis in breast cancer, and PAI-1 has been shown to play a role in angiogenic processes. Since estimates of tumor angiogenesis may predict poor prognosis...... we studied the relationship between PAI-1 and estimates of angiogenesis in breast cancer. Tumor tissue specimens from 438 breast cancer patients were included. Median follow-up was 10.3 years. Protein levels of PAI-1 were measured using an ELISA. Angiogenesis scores were performed using a Chalkley.......009) were independent markers of death from breast cancer. This study confirms high PAI-1 or high Chalkley counts as markers of poor prognosis in breast cancer patients, and suggests that the prognostic impact of PAI-1 is independent of its supposed involvement in tumor angiogenesis. Udgivelsesdato: 2007...

  13. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1α (HIF-1α), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), but had no effect on HIF-1α, whereas hypoxia stabilized HIF-1α and decreased expression of C/EBPα, but not PPARγ. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases

  14. Induction of oxidative stress and inhibition of plasminogen activator inhibitor-1 production in endothelial cells following exposure to organic extracts of diesel exhaust particles and urban fine particles

    Furuyama, Akiko; Koike, Eiko [National Institute for Environmental Studies, Inhalation toxicology Team, Tsukuba (Japan); Hirano, Seishiro [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan); Kobayashi, Takahiro [National Institute for Environmental Studies, Inhalation toxicology Team, Tsukuba (Japan); National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba (Japan)

    2006-03-15

    Endothelial cells play important roles in anticoagulant and fibrinolytic systems. Recent studies suggest that increases in ambient particulate matter (PM) levels have been associated with an increase in mortality rate from cardiovascular diseases. We examined the production of heme oxygenase-1 (HO-1) and factors related to the fibrinolytic function by rat heart microvessel endothelial cells exposed to organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) to investigate the direct effects of these soluble organic fractions in these PM on the fibrinolytic function of endothelial cells. The cell monolayer exposed to 10 {mu}g/ml OE-DEP produced a larger amount of HO-1 than cells exposed to 10 {mu}g/ml OE-UFP. OE-DEP and OE-UFP exposure reduced plasminogen activator inhibitor-1 (PAI-1) production by the cells but did not affect the production of thrombomodulin, tissue-type plasminogen activator, or urokinase-type plasminogen activator. Increased PAI-1 synthesis in response to treatment with 1.0 ng/ml tumor necrosis factor-{alpha} or 0.5 ng/ml transforming growth factor-{beta}1 was reduced by OE-DEP exposure. Suppression of PAI-1 production by OE-DEP exposure was mediated through oxidative stress and was independent of HO-1 activity. These results suggest that exposure to the soluble organic fraction of PM and DEP induced oxidative stress and reduced the PAI-1 production of endothelial cells. (orig.)

  15. Cross-talk between human mast cells and bronchial epithelial cells in plasminogen activator inhibitor-1 production via transforming growth factor-β1.

    Cho, Seong H; Lee, Sun H; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon C; Schleimer, Robert P

    2015-01-01

    Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC-epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1-mediated activation pathway. PMID:24987792

  16. Sunflower trypsin inhibitor-1.

    Korsinczky, Michael L J; Schirra, Horst Joachim; Craik, David J

    2004-10-01

    SFTI-1 is a bicyclic 14 amino acid peptide that was originally isolated from the seeds of the sunflower Helianthus annuus. It is a potent inhibitor of trypsin, with a sub-nanomolar K(i) value and is homologous to the active site region of the well-known family of serine protease inhibitors known as the Bowman-Birk trypsin inhibitors. It has a cyclic backbone that is cross-braced by a single disulfide bridge and a network of hydrogen bonds that result in a well-defined structure. SFTI-1 is amenable to chemical synthesis, allowing for the creation of synthetic variants. Alterations to the structure such as linearising the backbone or removing the disulfide bridge do not reduce the potency of SFTI-1 significantly, and minimising the peptide to as few as nine residues results in only a small decrease in reactivity. The creation of linear variants of SFTI-1 also provides a tool for investigating putative linear precursor peptides. The mechanism of biosynthesis of SFTI-1 is not yet known but it seems likely that it is a gene-coded product that has arisen from a precursor protein that may be evolutionarily related to classic Bowman-Birk inhibitors. PMID:15544530

  17. Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells

    张春; 孟宪芳; 朱忠华; 杨晓; 邓安国

    2004-01-01

    Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.

  18. Fructose Rich Diet-Induced High Plasminogen Activator Inhibitor-1 (PAI-1 Production in the Adult Female Rat: Protective Effect of Progesterone

    Eduardo Spinedi

    2012-08-01

    Full Text Available The effect of progesterone (P4 on fructose rich diet (FRD intake-induced metabolic, endocrine and parametrial adipose tissue (PMAT dysfunctions was studied in the adult female rat. Sixty day-old rats were i.m. treated with oil alone (control, CT or containing P4 (12 mg/kg. Rats ate Purina chow-diet ad libitum throughout the entire experiment and, between 100 and 120 days of age drank ad libitum tap water alone (normal diet; CT-ND and P4-ND or containing fructose (10% w/v; CT-FRD and P4-FRD. At age 120 days, animals were subjected to a glucose tolerance test or decapitated. Plasma concentrations of various biomarkers and PMAT gene abundance were monitored. P4-ND (vs. CT-ND rats showed elevated circulating levels of lipids. CT-FRD rats displayed high (vs. CT-ND plasma concentrations of lipids, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1. Lipidemia and adiponectinemia were high (vs. P4-ND in P4-FRD rats. Although P4 failed to prevent FRD-induced hyperleptinemia, it was fully protective on FRD-enhanced plasma PAI-1 levels. PMAT leptin and adiponectin mRNAs were high in CT-FRD and P4-FRD rats. While FRD enhanced PMAT PAI-1 mRNA abundance in CT rats, this effect was absent in P4 rats. Our study supports that a preceding P4-enriched milieu prevented the enhanced prothrombotic risk induced by FRD-elicited high PAI-1 production.

  19. Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.

    Giménez-Bastida, Juan Antonio; González-Sarrías, Antonio; Vallejo, Fernando; Espín, Juan Carlos; Tomás-Barberán, Francisco A

    2016-01-01

    Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 μM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange. PMID:26456097

  20. Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1. A systematic review and meta-analysis of randomised controlled trials.

    Sahebkar, Amirhossein; Catena, Cristiana; Ray, Kausik K; Vallejo-Vaz, Antonio J; Reiner, Željko; Sechi, Leonardo A; Colussi, GianLuca

    2016-07-01

    Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I² test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and "trim and fill" tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: -15.72 ng/ml, 95 % confidence interval [CI]: -25.01, -6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: -21.32 ng/ml, 95 % CI: -32.73, -9.91, I²=99 %) and particularly atorvastatin (WMD: -20.88 ng/mL, 95 % CI: -28.79, -12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations. PMID:27009446

  1. Association of the 4 g/5 g polymorphism of plasminogen activator inhibitor-1 gene with sudden sensorineural hearing loss. A case control study

    Cho Seong

    2012-06-01

    Full Text Available Abstract Background The 5 G/5 G genotype of PAI-1 polymorphism is linked to decreased plasminogen activator inhibitor-1 (PAI-1 levels and it has been suggested that lower PAI-1 levels may provide protective effects on inflammation, local microcirculatory disturbance, and fibrotic changes, which are likely associated with development of sudden sensorineural hearing loss (SSNHL. Methods The association of the 4 G/5 G PAI-1 polymorphism with the development and clinical outcome of SSNHL is evaluated via a case control study. 103 patients with SSNHL and 113 age and sex-matched controls were enrolled at University of Ferrara, Italy and hearing loss outcome was measured at least 3 months after the onset of hearing loss. DNA was isolated from peripheral blood using the QIAamp kit and the 4 G/5 G polymorphism in the −675 promoter region was genotyped with an allele-specific PCR. Genotype distribution was tested in patients and compared to controls by chi-square and odd-ratio analysis. The codominant and recessive models were used for the multiple logistic regression analyses of the PAI-1 gene allele. Results In this population, 5 G/5 G genotype had a two-time lower frequency in SSNHL patients compared to healthy controls (15.5% vs 30.1% and was associated with decreased odds compared to 4 G/5 G genotype (OR 0.37, 95% CI 0.19-0.75, p = 0.005. In addition, the patients with 5 G/5 G genotype showed a trend of more than 2 times higher ratio of hearing recovery (> 20 dB after systemic corticosteroid treatment compared to 4 G/5 G genotype (OR 2.3, 95% CI 0.32 - 16.83, p = 0.39, suggesting a better clinical outcome. Conclusions The 5 G/5 G genotype of PAI-1 may be associated with a reduced risk of SSNHL in the Italian population.

  2. Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation

    Kawazoe, Yoshinori; Naka, Tetsuji; Fujimoto, Minoru; Kohzaki, Hidetsugu; Morita, Yoshiaki; Narazaki, Masashi; Okumura, Kohichi; Saitoh, Hiroshi; Nakagawa, Reiko; Uchiyama, Yasuo; Akira, Shizuo; Kishimoto, Tadamitsu

    2001-01-01

    Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1–deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin ...

  3. A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands. Ligand-induced serpin polymerization

    Egelund, R; Einholm, A P; Pedersen, K E; Nielsen, R W; Christensen, A; Deinum, J; Andreasen, Peter A

    2001-01-01

    all tested nonfluorescent neutralizers, indicating that all neutralizers bind to a common hydrophobic area preferentially accessible in active PAI-1. Activity neutralization proceeded through two consecutive steps as follows: first step is conversion to forms displaying substrate behavior toward u...... having overlapping, but not identical, binding sites in the region around alpha-helices D and E and beta-strand 1A, known to act as a flexible joint when beta-sheet A opens and the reactive center loop inserts as beta-strand 4A during reaction with target proteinases. The defined binding area may be a...

  4. Concentrations of plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in induced sputum of asthma patients after allergen challenge

    Krzysztof Kowal,

    2010-04-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 are involved in tiisue remodeling and repairprocesses associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challengeon concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. ThirtyHDM-AAs and ten healthy persons (HCswere recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoidespteronyssinus (Dp and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputumwas induced 24 hours before (T0 and 24 hours (T24 after the challenge. Concentration of uPA and PAI-1 in induced sputumwere determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151±96 pg/ml and PAI-1(4341±1262 pg/ml concentrations were higher than in HC (18.8±6.7 pg/ml; p=0.0002 and 596±180 pg/ml; p<0.0001; foruPA and PAI-1 respectively. After allergen challenge further increase in sputum uPA (187±144 pg/ml; p=0.03 and PAI-1(6252±2323 pg/ml; p<0.0001 concentrations were observed. Moreover, in Dp challenged, but not in saline challengedHDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters werefound in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways.Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodelingand play an important role in the development of bronchial hyperreactivity.

  5. Concentrations of plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in induced sputum of asthma patients after allergen challenge.

    Marcin Moniuszko

    2011-04-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 are involved in tiisue remodeling and repair processes associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challenge on concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. Thirty HDM-AAs and ten healthy persons (HCswere recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoides pteronyssinus (Dp and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputum was induced 24 hours before (T0 and 24 hours (T24 after the challenge. Concentration of uPA and PAI-1 in induced sputum were determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151 Âą 96 pg/ml and PAI-1 (4341 Âą 1262 pg/ml concentrations were higher than in HC (18.8 Âą 6.7 pg/ml; p=0.0002 and 596 Âą 180 pg/ml; p<0.0001; for uPA and PAI-1 respectively. After allergen challenge further increase in sputum uPA (187 Âą 144 pg/ml; p=0.03 and PAI-1 (6252 Âą 2323 pg/ml; p<0.0001 concentrations were observed. Moreover, in Dp challenged, but not in saline challenged HDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters were found in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways. Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodeling and play an important role in the development of bronchial hyperreactivity.

  6. Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts

    Morita, Yoshiaki; Naka, Tetsuji; Kawazoe, Yoshinori; Fujimoto, Minoru; Narazaki, Masashi; Nakagawa, Reiko; Fukuyama, Hidehiro; Nagata, Shigekazu; Kishimoto, Tadamitsu

    2000-01-01

    Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator of Janus kinase-STAT signaling. We previously generated mice lacking the SSI-1 gene (SSI-1 −/−) and showed that thymocytes and splenocytes in SSI-1 −/− mice underwent accelerated apoptosis. In this paper, we show that murine embryonic fibroblasts lacking the SSI-1 gene are more sensitive than their...

  7. Cerebral oscillatory activity during simulated driving using MEG

    Kotoe Sakihara

    2014-12-01

    Full Text Available We aimed to examine cerebral oscillatory differences associated with psychological processes during simulated car driving. We recorded neuromagnetic signals in 14 healthy volunteers using magnetoencephalography (MEG during simulated driving. MEG data were analyzed using synthetic aperture magnetometry to detect the spatial distribution of cerebral oscillations. Group effects between subjects were analyzed statistically using a nonparametric permutation test. Oscillatory differences were calculated by comparison between “passive viewing” and “active driving.” “Passive viewing” was the baseline, and oscillatory differences during “active driving” showed an increase or decrease in comparison with a baseline. Power increase in the theta band was detected in the superior frontal gyrus (SFG during active driving. Power decreases in the alpha, beta, and low gamma bands were detected in the right inferior parietal lobe (IPL, left postcentral gyrus (PoCG, middle temporal gyrus (MTG, and posterior cingulate gyrus (PCiG during active driving. Power increase in the theta band in the SFG may play a role in attention. Power decrease in the right IPL may reflect selectively divided attention and visuospatial processing, whereas that in the left PoCG reflects sensorimotor activation related to driving manipulation. Power decreases in the MTG and PCiG may be associated with object recognition.

  8. New active machine tool drive mounting on the frame

    Švéda J.

    2007-10-01

    Full Text Available The paper deals with the new active mounting of the machine tool drives. The commonly used machine tools are at this time mainly equipped with fix-mounting of the feed drives. This structure causes full transmission of the force shocks to the machine bed and thereby restricts the dynamic properties of the motion axis and the whole machine. The spring-mounting of the feed drives is one of the possibilities how to partially suppress the vibrations. The force that reacts to the machine tool bed is transformed thereby the vibrations are lightly reduced. Unfortunately the transformation is not fully controlled. The new active mounting of the machine tool drives allows to fully control the force behaviour that react to the machine body. Thereby the number of excited frequencies on the machine tool bed is significantly reduced. The active variant of the feed drive mounting is characterized by the synergistic cooperation between two series-connected actuators (“motor on motor”. The paper briefly describes design, control techniques and optimization of the feed drives with the new active mounting conception.

  9. New active machine tool drive mounting on the frame

    Švéda J.; Válášek M.; Šika Z.

    2007-01-01

    The paper deals with the new active mounting of the machine tool drives. The commonly used machine tools are at this time mainly equipped with fix-mounting of the feed drives. This structure causes full transmission of the force shocks to the machine bed and thereby restricts the dynamic properties of the motion axis and the whole machine. The spring-mounting of the feed drives is one of the possibilities how to partially suppress the vibrations. The force that reacts to the machine tool bed ...

  10. Drive for activity in patients with anorexia nervosa

    Sternheim, Lot; Danner, Unna; Adan, Roger; van Elburg, Annemarie

    2014-01-01

    OBJECTIVE: Hyperactivity and elevated physical activity are both considered symptom characteristics of anorexia nervosa (AN). It has been suggested that a drive for activity (DFA) may underlie these expressions, yet research into DFA in AN remains scant. This study investigated DFA levels in patient

  11. Neurobiology driving hyperactivity in activity-based anorexia

    Adan, R A H; Hillebrand, J J G; Danner, U N; Cardona Cano, S; Kas, M J H; Verhagen, L A W

    2011-01-01

    Hyperactivity in anorexia nervosa is difficult to control and negatively impacts outcome. Hyperactivity is a key driving force to starvation in an animal model named activity-based anorexia (ABA). Recent research has started unraveling what mechanisms underlie this hyperactivity. Besides a general i

  12. The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

    Wei Nie; Bing Li; Qing-Yu Xiu

    2012-01-01

    BACKGROUND: A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. METHODS: Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructu...

  13. A suppressive effect of prostaglandin E2 on the expression of SERPINE1/plasminogen activator inhibitor-1 in human articular chondrocytes: An in vitro pilot study

    Kayo Masuko

    2009-04-01

    Full Text Available Kayo Masuko1, Minako Murata2, Naoya Suematsu1, Kazuki Okamoto1, Kazuo Yudoh2, Hiroyuki Shimizu3, Moroe Beppu3, Hiroshi Nakamura4, Tomohiro Kato11Department of Biochemistry; 2Department of Frontier Medicine, Institute of Medical Science; 3Department of Orthopedic Surgery, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan; 4Department of Joint Disease and Rheumatism, Nippon Medical School, Bunkyo-ku, Tokyo, JapanAbstract: Prostaglandin E2 (PGE2 is expressed in articular joints with inflammatory arthropathy and may exert catabolic effects leading to cartilage degradation. As we observed in a preliminary experiment that PGE2 suppressed the expression of SERPINE1/plasminogen activator inhibitor (PAI-1 mRNA in chondrocytes, we focused on the effect of PGE2 on PAI-1 in a panel of cultured chondrocytes obtained from osteoarthritic patients. Specifically, articular cartilage specimens were obtained from patients with osteoarthritis who underwent joint surgery. Isolated chondrocytes were cultured in vitro as a monolayer and stimulated with PGE2. Stimulated cells and culture supernatants were analyzed using Western blotting and enzyme-linked immunosorbent assay. The results confirmed that the in vitro PGE2 stimulation suppressed the expression of PAI-1 in the tested chondrocyte samples. The inhibitory effect was partly abrogated by an antagonist of EP4 receptor of PGE2, but not by an EP2 antagonist. Although PGE2 induced activations of mitogen-activated protein kinases (MAPK, blocking of the MAPK did not abrogate the suppressive effect of PGE2, implying a distinct signaling pathway. In summary, prostaglandin is suggested to modulate the plasminogen system in chondrocytes. Further elucidation of the interaction might open a new avenue to understand the degradative process of cartilage.Keywords: chondrocyte, prostaglandin, PGE2, PAI-1

  14. Brain activity during driving with distraction: an immersive fMRI study

    Tom A Schweizer; Karen Kan; Yuwen Hung; Fred Tam; Gary Naglie; Simon Graham

    2013-01-01

    Introduction: Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections. Materials and Methods: To capture brain activity during driving, we placed a driving simulator with a fully functio...

  15. Identification of a peroxisome proliferator responsive element (PPRE)-like cis-element in mouse plasminogen activator inhibitor-1 gene promoter

    PAI-1 is expressed and secreted by adipose tissue which may mediate the pathogenesis of obesity-associated cardiovascular complications. Evidence is presented in this report that PAI-1 is not expressed by preadipocyte, but significantly induced during 3T3-L1 adipocyte differentiation and the PAI-1 expression correlates with the induction of peroxisome proliferator-activated receptor γ (PPARγ). A peroxisome proliferator responsive element (PPRE)-like cis-element (-206TCCCCCATGCCCT-194) is identified in the mouse PAI-1 gene promoter by electrophoretic mobility shift assay (EMSA) combined with transient transfection experiments; the PPRE-like cis-element forms a specific DNA-protein complex only with adipocyte nuclear extracts, not with preadipocyte nuclear extracts; the DNA-protein complex can be totally competed away by non-labeled consensus PPRE, and can be supershifted with PPARγ antibody. Mutation of this PPRE-like cis-element can abolish the transactivation of mouse PAI-1 promoter mediated by PPARγ. Specific PPARγ ligand Pioglitazone can significantly induce the PAI-1 expression, and stimulate the secretion of PAI-1 into medium

  16. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

    Wei Nie

    Full Text Available BACKGROUND: A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. METHODS: Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI and Weipu Database were searched to find relevant studies. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. RESULTS: Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008, 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02, 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007, 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02, and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008. CONCLUSIONS: This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

  17. Small Interfering RNA-mediated Caveolin-1 Knockout on Plasminogen Activator Inhibitor-1 Expression in Insulin-stimulated Human Vascular Endothelial Cells

    Huiling YANG; Gebo WEN; Weixin HU; Shuya HE; Zhihua QUAN; Weixia PENG; Bin YAN; Jianghua LIU; Fang WEN; Renxian CAO; Yangyan XU

    2007-01-01

    Using human vascular endothelial cells (ECV304) as the target,we studied the effect of caveolin(CAV)-1 in the course of insulin-stimulated expression of plasminogen activator inhibitor(PAI)-1.The appropriate single-stranded oligonucleotides representing the RNAi CAV-1 gene were analyzed by Ambion software.After annealing to generate double-stranded oligonucleotides (ds oligo),it was cloned into the pENTR/U6 entry vector containing RNA polymerase Ⅲ expression element by T4 DNA ligase.The short hairpin (shRNA) sequences transferred from the pENTR/U6 entry were cloned into the pLenti6/BLOCK-iTDEST vector with an LR recombination reaction.After identification by sequencing,we successfully constructed the CAV-1 RNAi lentiviral expression system using Gateway technology.Silencing efficiency was assayed by real-time reverse transcription-polymerase chain reaction,immunofluorescence staining and Western blotting.ECV304 cells were cultured in the medium containing different concentrations of insulin(1×10-9 to 1×10-7M)with the CAV-1 gene silenced or not.The expression level and subcellular localization of PAI-1 and CAV-1 were compared using reverse transcription-polymerase chain reaction,immunofluorescence staining and Western blot assay.The results showed that the potent inhibition of CAV-1 expression could reach 85%,and it was specific to the CAV-1-derived shRNA,not the S100A13-derived shRNA.There was no dramatic difference in PAI-1 expression between the RNAi+ and RNAi-ECV304 cells incubated with physiological insulin,but PAI-1 protein did accumulate under the cell membrane.As the concentration of insulin increased,the expression of PAI-1 was up-regulated,whereas the expression of CAV-1 attenuated.Furthermore,PAl-1 clearly augmented after CAV-1 knockdown.These results indicated that hyperinsulinism could promote PAI-1 expression by inhibiting CAV-1,and stabilizing or up-regulating CAV-1 expression in endothelial cells might reduce complications of the great vessels

  18. The Glycosylation of Plasminogen Activator Inhibitor-1

    Skottrup, Peter; Pedersen, Katrine Egelund; Christensen, Anni; Thøgersen, Ida; Andreasen, Peter; Enghild, Jan Johannes

    sequences. Analyses of these mutants for the content of N-acetyl glucosamine showed that Asn209 and Asn265, but not Asn329, are glycosylated, in agreement with previous suggestions made on the basis of X-ray crystal structure analysis of PAI-1 expressed in CHO cells (Xue et al. (1998) Structure 6, 627......-636). In contrast, PAI-1, containing a total of 26 Ser and 26 Thr residues, which are potential targets for O-linked glycosylation, was found to be devoid of N-acetyl-galactosamine, demonstrating the absence of O-linked glycosylation. Analysis of PAI-1 variants with mutational inactivation of each of the...

  19. The Glycosylation of Plasminogen Activator Inhibitor-1

    Skottrup, Peter; Pedersen, Katrine Egelund; Christensen, Anni; Thøgersen, Ida; Andreasen, Peter; Enghild, Jan J.

    2002-01-01

    sequences. Analyses of these mutants for the content of N-acetyl glucosamine showed that Asn209 and Asn265, but not Asn329, are glycosylated, in agreement with previous suggestions made on the basis of X-ray crystal structure analysis of PAI-1 expressed in CHO cells (Xue et al. (1998) Structure 6, 627......-636). In contrast, PAI-1, containing a total of 26 Ser and 26 Thr residues, which are potential targets for O-linked glycosylation, was found to be devoid of N-acetyl-galactosamine, demonstrating the absence of O-linked glycosylation. Analysis of PAI-1 variants with mutational inactivation of each of the...

  20. The Glycosylation of Plasminogen Activator Inhibitor-1

    Skottrup, Peter Durand; Pedersen, Katrine Egelund; Christensen, Anni; Thøgersen, Ida; Andreasen, Peter; Enghild, Jan Johannes

    sequences. Analyses of these mutants for the content of N-acetyl glucosamine showed that Asn209 and Asn265, but not Asn329, are glycosylated, in agreement with previous suggestions made on the basis of X-ray crystal structure analysis of PAI-1 expressed in CHO cells (Xue et al. (1998) Structure 6, 627...

  1. The Glycosylation of Plasminogen Activator Inhibitor-1

    Skottrup, Peter; Pedersen, Katrine Egelund; Christensen, Anni; Thøgersen, Ida; Andreasen, Peter; Enghild, Jan Johannes

    sequences. Analyses of these mutants for the content of N-acetyl glucosamine showed that Asn209 and Asn265, but not Asn329, are glycosylated, in agreement with previous suggestions made on the basis of X-ray crystal structure analysis of PAI-1 expressed in CHO cells (Xue et al. (1998) Structure 6, 627...... sequences utilized for N-linked glycosylation by Fluorophore Assisted Carbohydrate Electrophoresis (FACE), showed a different N-linked glycosylation profile of the glycans at each of the 2 sites. The exact structure of the carbohydrate chains at each of these 2 sequences are being determined using MALDI...

  2. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.

    Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, Christian

    2015-07-15

    Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT. PMID:26182421

  3. Brain activity during driving with distraction: an immersive fMRI study

    Tom A Schweizer

    2013-02-01

    Full Text Available Introduction: Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections. Methods: To capture brain activity during driving, we placed a driving simulator with a fully functional steering wheel and pedals in a 3.0 Tesla functional magnetic resonance imaging (fMRI system. To identify the brain areas involved while performing different real-world driving maneuvers, participants completed tasks ranging from simple (right turns to more complex (left turns at busy intersections. To assess the effects of driving while distracted, participants were asked to perform an auditory task while driving analogous to speaking on a hands-free device and driving. Results: A widely distributed brain network was identified, especially when making left turns at busy intersections compared to more simple driving tasks. During distracted driving, brain activation shifted dramatically from the posterior, visual and spatial areas to the prefrontal cortex. Conclusions: Our findings suggest that the distracted brain sacrificed areas in the posterior brain important for visual attention and alertness to recruit enough brain resources to perform a secondary, cognitive task. The present findings offer important new insights into the scientific understanding of the neuro-cognitive mechanisms of driving behavior and lay down an important foundation for future clinical research.

  4. Active training and driving-specific feedback improve older drivers' visual search prior to lane changes

    Lavallière Martin

    2012-03-01

    Full Text Available Abstract Background Driving retraining classes may offer an opportunity to attenuate some effects of aging that may alter driving skills. Unfortunately, there is evidence that classroom programs (driving refresher courses do not improve the driving performance of older drivers. The aim of the current study was to evaluate if simulator training sessions with video-based feedback can modify visual search behaviors of older drivers while changing lanes in urban driving. Methods In order to evaluate the effectiveness of the video-based feedback training, 10 older drivers who received a driving refresher course and feedback about their driving performance were tested with an on-road standardized evaluation before and after participating to a simulator training program (Feedback group. Their results were compared to a Control group (12 older drivers who received the same refresher course and in-simulator active practice as the Feedback group without receiving driving-specific feedback. Results After attending the training program, the Control group showed no increase in the frequency of the visual inspection of three regions of interests (rear view and left side mirrors, and blind spot. In contrast, for the Feedback group, combining active training and driving-specific feedbacks increased the frequency of blind spot inspection by 100% (32.3 to 64.9% of verification before changing lanes. Conclusions These results suggest that simulator training combined with driving-specific feedbacks helped older drivers to improve their visual inspection strategies, and that in-simulator training transferred positively to on-road driving. In order to be effective, it is claimed that driving programs should include active practice sessions with driving-specific feedbacks. Simulators offer a unique environment for developing such programs adapted to older drivers' needs.

  5. An Active Damping Technique for Small DC-Link Capacitor Based Drive System

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Lu, Kaiyuan

    2013-01-01

    A small dc-link capacitor based drive system shows instability when it is operated with large input line inductance at operating points with high power. This paper presents a simple, new active damping technique that can stabilize effectively the drive system at unstable operating points, offering...

  6. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

    Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, C.

    2015-01-01

    Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in t

  7. Thermally active TRPV1 tonically drives central spontaneous glutamate release

    Shoudai, Kiyomitsu; Peters, James H.; McDougall, Stuart J.; Fawley, Jessica A.; Andresen, Michael C.

    2010-01-01

    Central synapses spontaneously release neurotransmitter at low rates. In brainstem, cranial visceral afferent terminals in caudal solitary tract nucleus (NTS) display pronounced activity-dependent asynchronous release of glutamate and this extra release depends on TRPV1 receptors (TRPV1+). Asynchronous release is absent for afferents lacking TRPV1 (TRPV1-) and resting EPSC frequency was greater in TRPV1+. Here, we studied this basal activity difference by assessing thermal sensitivity of spon...

  8. Low levels of Bax inhibitor-1 gene expression increase tunicamycin-induced apoptosis in human neuroblastoma SY5Y cells

    Dan Wu; Peirong Wang; Shiyao Wang

    2012-01-01

    A human SH-SY5Y neuroblastoma cell line with a low level of Bax inhibitor-1 expression was established by lentivirus-mediated RNA interference and fluorescence-activated cell sorting. In control SH-SY5Y cells, tunicamycin treatment induced endoplasmic reticulum stress-mediated apoptosis; however, after Bax inhibitor-1 gene knockdown, cell survival rates were significantly decreased and the degree of apoptosis was significantly increased following tunicamycin treatment. In addition, chromatin condensation and apparent apoptotic phenomena, such as marginalization and cytoplasmic vesicles, were observed. Our findings indicate that Bax inhibitor-1 can delay apoptosis induced by endoplasmic reticulum stress.

  9. Eruptions that Drive Coronal Jets in a Solar Active Region

    Sterling, Alphonse C.; Moore, Ronald L.; Falconer, David A.; Panesar, Navdeep K.; Akiyama, Sachiko; Yashiro, Seiji; Gopalswamy, Nat

    2016-01-01

    Solar coronal jets are common in both coronal holes and in active regions (e.g., Shibata et al. 1992, Shimojo et al. 1996, Cirtain et al. 2007. Savcheva et al. 2007). Recently, Sterling et al. (2015), using data from Hinode/XRT and SDO/AIA, found that coronal jets originating in polar coronal holes result from the eruption of small-scale filaments (minifilaments). The jet bright point (JBP) seen in X-rays and hotter EUV channels off to one side of the base of the jet's spire develops at the location where the minifilament erupts, consistent with the JBPs being miniature versions of typical solar flares that occur in the wake of large-scale filament eruptions. Here we consider whether active region coronal jets also result from the same minifilament-eruption mechanism, or whether they instead result from a different mechanism (e.g. Yokoyama & Shibata 1995). We present observations of an on-disk active region (NOAA AR 11513) that produced numerous jets on 2012 June 30, using data from SDO/AIA and HMI, and from GOES/SXI. We find that several of these active region jets also originate with eruptions of miniature filaments (size scale 20'') emanating from small-scale magnetic neutral lines of the region. This demonstrates that active region coronal jets are indeed frequently driven by minifilament eruptions. Other jets from the active region were also consistent with their drivers being minifilament eruptions, but we could not confirm this because the onsets of those jets were hidden from our view. This work was supported by funding from NASA/LWS, NASA/HGI, and Hinode. A full report of this study appears in Sterling et al. (2016).

  10. Drive for activity in patients with anorexia nervosa

    Sternheim, Lot; Danner, Unna; Adan, Roger; Van Elburg, Annemarie

    2015-01-01

    Method Two hundred and forty female patients with AN completed measures for DFA, eating disorder (ED) pathology, anxiety, and clinical parameters. Objective Hyperactivity and elevated physical activity are both considered symptom characteristics of anorexia nervosa (AN). It has been suggested that a

  11. Active damping technique for small DC-link capacitor based drive system

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Henriksen, Bjarne;

    2010-01-01

    A detailed model of Adjustable Speed Drive (ASD) is discussed, which yield a general rule for active damping in a small DC link based drive. A desired value of input LC resonance damping coefficient can be achieved by changing gain parameters. The modified state space matrix due to active damping...... terms is also presented. The performance of the active damping is evaluated based on experimental results. A simple model is presented which can be used to measure the damping factor provided by the system parameters only....

  12. Bacterial activities driving arsenic speciation and solubility in marine sediments

    Battaglia-Brunet, F.; Seby, F.; Crouzet, C.; Joulian, C.; Mamindy-Pajany, Y.; Guezennec, A. G.; Hurel, C.; Marmier, N.; Bataillard, P.

    2012-04-01

    Harbour and marina sediments represent particular environments, with high concentrations in organic carbon and pollutants. Over 50 million m3 of marine sediments are dredged every year in French maritime and commercial ports, to maintain the water depth suitable for navigation, and the most part of them is discharged in deeper sea zones. The present study aimed to elucidate, using a range of complementary approaches, the influence of bacterial activity on arsenic speciation and mobility in marina sediments. Two sites were considered: L'Estaque, impacted by metallurgical activities and by the commercial port of Marseille, and St-Mandrier, less polluted, affected by classical chemical pollutants associated to professional and recreational boating. Arsenic concentration was noticeably higher in l'Estaque sediment (200-350 mg/kg) than in St-Mandrier sediment (15-50 mg/kg). In the solid phases, As(III) was the dominant species in L'Estaque sediment, whereas As(V) was the main form in St Mandrier sediment. At both sites, arsenic was the major trace element detected in interstitial water. Free sulfide and thio-arsenic complexes were detected in the interstitial water of l'Estaque sediment, suggesting a role of sulfate-reduction bacterial activity on arsenic solubility. Anaerobic microcosm experiments confirmed this hypothesis, as stimulation of sulfate-reduction induced a dramatic increase of arsenic concentration in the liquid phase, linked to the formation of soluble thio-arsenic complexes. Nevertheless, microcosms performed in aerobic conditions showed that bacterial activity globally decreased the transfer of arsenic from the sediment toward the overlying water. A red-brown fine layer developed at the sediment-water interface. Altogether, these results suggest that the sediment-water interface zone and the close transition area between aerobic and anaerobic conditions host intense biogeochemical reactions involving As, Fe and S species. These reactions most probably

  13. Molecular motors robustly drive active gels to a critically connected state

    Alvarado, Jose; Sharma, Abhinav; MacKintosh, Fred C; Koenderink, Gijsje H

    2013-01-01

    Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially ...

  14. A charge pump for driving CMOS active pixel reset

    XU Jiang-tao; LI Bin-qiao; YAO Su-ying; SUN Zhong-yan

    2009-01-01

    To overcome the limitation of low image signal swing range and long reset time in four transistor CMOS active pixel image sensor, a charge pump circuit is presented to improve the pixel reset performance. The charge pump circuit consists of two stage switch capacitor serial voltage doubler. Cross-coupled MOSFET switch structure with well close and open perfor-mance is used in the second stage of the charge pump. The pixel reset transistor with gate voltage driven by output of the pump works in linear region, which can accelerate reset process and complete reset is achieved. The simulation results show that output of the charge pump is enhanced from 1.2 to 4.2 V with voltage tipple lower than 6 inV. The pixel reset time is reduced to 1.14 ns in dark. Image smear due to non-completely reset is eliminated and the image signal swing range is enlarged. The charge pump is successfully embedded in a CMOS image sensor chip with 0.3 ~ 106 pixeis.

  15. The Use of Active Elements to Reduce the Size and Weight of Passive Components in Adjustable Speed Drives

    Maheshwari, Ram Krishan

    shaft voltage, the common mode voltage, the conducted emissions, and the efficiency of the two systems are compared since they are major factors which affect the size of the passive components in the drives. Although the three-level inverter requires higher number of active components as compared to the......Adjustable speed drives are considered as workhorse of industry due to various applications in different kind of industries. According to a market survey, low voltage drives are most profitable in the drive industries. The drive consists of a machine and a converter, which processes grid power and...... converts into usable power for the machine. The converter consists of active and passive components. The size, weight, and volume of the drive are decided by the passive components since they typically contribute to 75% of the weight and volume of the drive. Most popular topology for the low voltage drive...

  16. IMD-4690, a Novel Specific Inhibitor for Plasminogen Activator Inhibitor-1, Reduces Allergic Airway Remodeling in a Mouse Model of Chronic Asthma via Regulating Angiogenesis and Remodeling-Related Mediators

    Tezuka, Toshifumi; Ogawa, Hirohisa; AZUMA, MASAHIKO; GOTO, HISATSUGU; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen...

  17. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling. PMID:25785861

  18. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Toshifumi Tezuka

    Full Text Available Plasminogen activator inhibitor (PAI-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp. IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  19. Operation of Active Front-End Rectifier in Electric Drive under Unbalanced Voltage Supply

    Chomát, Miroslav

    Rijeka: INTECHWEB.ORG, 2011 - (Chomát, M.), s. 195-216 ISBN 978-953-307-548-8 R&D Projects: GA ČR GA102/09/1273 Institutional research plan: CEZ:AV0Z20570509 Keywords : unbalanced voltage supply * DC-link voltage pulsations * pulse-width modulation Subject RIV: JA - Electronic s ; Optoelectronics, Electrical Engineering http://www.intechopen.com/books/electric-machines- and -drives/operation-of-active-front-end-rectifier-in-electric-drive-under-unbalanced-voltage-supply

  20. Impacts of Human Activity on Biodiversity——An Approach to Driving Force indicators

    RichardDawson; CaoZhiping

    2005-01-01

    The impact of human activity on biodiversity is very complicated, making it difficult to design practical indicators for assessment. Currently, state and response indicators are listed within Chapter 15 of Agenda 21, but no mention is made of driving force indicators and how they relate to biodiversity protection. This paper represents an effort to identify and then operationalize the idea of driving force indicators at national level. Five human induced factors affecting blodiversity were discussed: (a) habitat toss and fragmentation; (b) overexploitation of resources; (c) species introduction; (d) pollution; and (e) climate change. From these five factors, a subset was selected to serve as possible driving force indicators: (1) habitat loss, (2) the ratio of exotic species to indigenous ones, and (3) the change in pollution status. Although the three indicators are relatively simple, they cover the most important human impacts on biodiversity and offer the potential for further redefinition and ultimate use within the spirit of biodiversity protection.

  1. Active and Passive Fatigue in Simulated Driving: Discriminating Styles of Workload Regulation and Their Safety Impacts

    Saxby, Dyani J.; Matthews, Gerald; Warm, Joel S.; Hitchcock, Edward M.; Neubauer, Catherine

    2013-01-01

    Despite the known dangers of driver fatigue, it is a difficult construct to study empirically. Different forms of task-induced fatigue may differ in their effects on driver performance and safety. Desmond and Hancock (2001) defined active and passive fatigue states that reflect different styles of workload regulation. In 2 driving simulator studies we investigated the multidimensional subjective states and safety outcomes associated with active and passive fatigue. Wind gusts were used to ind...

  2. Distracted Driving

    ... 18%) in which someone was injured involved distracted driving. 1 What are the risk factors? Activities Some activities—such as texting—take the driver’s attention away from driving more frequently and for longer periods than other ...

  3. Impact of distracting activities and drivers' cognitive failures on driving performance

    Farah, H.; Zatmeh, S.; Toledo, T.

    2015-01-01

    The rapid increase in the availability of smart phones and other infotainment devices, and their widespread use while driving, contributes significantly to car crash rates. This is since the human brain has limited capacity and cannot perform two tasks at the same time, but rather switches from one to another rapidly. Understanding of the impact of distracting activities on drivers’ behavior is essential in order to support the development of effective technology and policy solutions to mitig...

  4. Shunt active filter algorithms for a three phase system fed to adjustable speed drive

    Sujatha.CH; Sravanthi.Kusam; Dr. K.Chandra shek

    2011-01-01

    This paper presents the simulation of Shunt Active Power filter by using two different control schemes, Indirect current control technique and Synchronous detection technique by using ANN. These two control techniques are working under both balanced and unbalanced three phase voltage source conditions and it is feeding to aadjustable speed drive the torque speed characteristics of a motor is presented. Indirect current control technique is implemented under dynamic load condition and load bal...

  5. Evaluation of the impact of vocal communication activities on the driving task

    Bruyas, Mp; Chapon, A.; Letisserand, D.; Lelekov-Boissard, T.; Deleurence, P.; Duraz, M.; Aillerie, I.; Perchet, C

    2004-01-01

    The main objective of this research was to develop evaluation methods of the distractive effects of various vocal communication activities. A multi-parametric approach has been used in two experimental contexts: on a driving simulator and on a test track. Three levels of disturbance were evaluated: the degradation of the road information processing (modifications of event related potentials amplitude, on the simulator), the variations of performances (response times and rate of non-detections...

  6. Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

    Gils, Ann; Pedersen, Katrine Egelund; Skottrup, Peter;

    2003-01-01

    glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended...

  7. Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer.

    Köster, Darius Vasco; Husain, Kabir; Iljazi, Elda; Bhat, Abrar; Bieling, Peter; Mullins, R Dyche; Rao, Madan; Mayor, Satyajit

    2016-03-22

    The surface of a living cell provides a platform for receptor signaling, protein sorting, transport, and endocytosis, whose regulation requires the local control of membrane organization. Previous work has revealed a role for dynamic actomyosin in membrane protein and lipid organization, suggesting that the cell surface behaves as an active composite composed of a fluid bilayer and a thin film of active actomyosin. We reconstitute an analogous system in vitro that consists of a fluid lipid bilayer coupled via membrane-associated actin-binding proteins to dynamic actin filaments and myosin motors. Upon complete consumption of ATP, this system settles into distinct phases of actin organization, namely bundled filaments, linked apolar asters, and a lattice of polar asters. These depend on actin concentration, filament length, and actin/myosin ratio. During formation of the polar aster phase, advection of the self-organizing actomyosin network drives transient clustering of actin-associated membrane components. Regeneration of ATP supports a constitutively remodeling actomyosin state, which in turn drives active fluctuations of coupled membrane components, resembling those observed at the cell surface. In a multicomponent membrane bilayer, this remodeling actomyosin layer contributes to changes in the extent and dynamics of phase-segregating domains. These results show how local membrane composition can be driven by active processes arising from actomyosin, highlighting the fundamental basis of the active composite model of the cell surface, and indicate its relevance to the study of membrane organization. PMID:26929326

  8. Commutation effect of Adjustable Speed Drives due to installation of active harmonic filters

    Asiminoaei, Lucian; Kalaschnikow, Sergej; Hansen, Steffan;

    2011-01-01

    The success of designing an industrial installation with Active Filters depends on how precise the load profile of the application is known, because this determines the amount of harmonic currents to be compensated. However, once the Active Filter is added to the installation, the harmonic currents...... may increase due to changes in the commutation behavior of diode rectifier converters. The change of natural commutation determines higher harmonics currents of the diode rectifiers and therefore higher harmonic loading of the Active Filter in the installation. This paper presents a method to estimate...... the commutation behavior of Adjustable Speed Drives when their harmonic currents are compensated by a Shunt Active Filter. The method is formulated as an analytical computation algorithm verified by simulations. Further on the method is implemented in a Harmonic Calculation Toolbox which facilitates...

  9. Driver hand activity analysis in naturalistic driving studies: challenges, algorithms, and experimental studies

    Ohn-Bar, Eshed; Martin, Sujitha; Trivedi, Mohan Manubhai

    2013-10-01

    We focus on vision-based hand activity analysis in the vehicular domain. The study is motivated by the overarching goal of understanding driver behavior, in particular as it relates to attentiveness and risk. First, the unique advantages and challenges for a nonintrusive, vision-based solution are reviewed. Next, two approaches for hand activity analysis, one relying on static (appearance only) cues and another on dynamic (motion) cues, are compared. The motion-cue-based hand detection uses temporally accumulated edges in order to maintain the most reliable and relevant motion information. The accumulated image is fitted with ellipses in order to produce the location of the hands. The method is used to identify three hand activity classes: (1) two hands on the wheel, (2) hand on the instrument panel, (3) hand on the gear shift. The static-cue-based method extracts features in each frame in order to learn a hand presence model for each of the three regions. A second-stage classifier (linear support vector machine) produces the final activity classification. Experimental evaluation with different users and environmental variations under real-world driving shows the promise of applying the proposed systems for both postanalysis of captured driving data as well as for real-time driver assistance.

  10. Lower Cortisol Activity is Associated with First-Time Driving while Impaired.

    Couture, Sophie; Ouimet, Marie Claude; Gianoulakis, Christina; Tremblay, Jacques; Ng Ying Kin, Nmk; Brochu, Serge; Pruessner, Jens; Dedovic, Katarina; Brown, Thomas G

    2015-01-01

    Driving while impaired (DWI) is a grave and persistent high-risk behavior. Previous work demonstrated that DWI recidivists had attenuated cortisol reactivity compared to non-DWI drivers. This suggests that cortisol is a neurobiological marker of high-risk driving. The present study tested the hypothesis that this initial finding would extend to first-time DWI (fDWI) offenders compared to non-DWI drivers. Male fDWI offenders (n = 139) and non-DWI drivers (n = 31) were exposed to a stress task, and their salivary cortisol activity (total output and reactivity) was measured. Participants also completed questionnaires on sensation seeking, impulsivity, substance use, and engagement in risky and criminal behaviors. As hypothesized, fDWI offenders, compared to non-DWI drivers, had lower cortisol reactivity; fDWI offenders also showed lower total output. In addition, cortisol activity was the most important predictor of group membership, after accounting for alcohol misuse patterns and consequences and other personality and problem behavior characteristics. The findings indicate that attenuated cortisol activity is an independent factor associated with DWI offending risk at an earlier stage in the DWI trajectory than previously detected. PMID:25922575

  11. Analysis of voltage modulation based active damping techniques for small DC-link drive system

    Wang, Dong; Lu, Kaiyuan; Rasmussen, Peter Omand; Máthé, Lászlo; Yang, Feng

    Small DC-link drive system, built with film capacitor in the DC link, may have the advantages of longer lifetime and the possibility to achieve a more compact design of capacitor bank at medium and high power rates. However, it exhibits instability problem, especially when it is fed by a soft grid...... without the requirements of the information of system parameters and operating conditions. Finally, active damping techniques with minimized current magnitude and total duty cycle are discussed, in order to fit various operating conditions. Simulation and experimental results are presented to verify the....... Therefore, active damping techniques are usually needed in order to stabilize the system. This paper firstly describes the essential idea of active damping methods from energy flow point of view. Then a new method named as “virtual positive impedance” method is introduced to ensure the dc-link stability...

  12. An epidemiological investigation on serum levels of leptin, adiponectin, interleukin-6and plasminogen activator inhibitor-1 in middle aged and elderly people%中老年血清瘦素、脂联素、白介素-6及纤溶酶原激活物抑制物-1的流行病学调查

    鲍蓓; 李志海; 陈卫文; 王立; 靳玉凤; 王晓燕

    2012-01-01

    目的 对广州市中老年人血清瘦素( leptin)、脂联素(adiponectin)、白介素-6(interleukin-6,IL-6)及纤溶酶原激活物抑制物-1(plasminogen activator inhibitor-1,PAI-1)进行流行病学调查.方法 在广州市生物库第三期注册登记的10 027名中老年人中随机抽取1996名中老年人进行问卷调查和健康体检.以酶联免疫吸附双抗夹心( ELISA)法测定leptin、adiponectin、IL-6、PAI-1.结果 广州市中老年人leptin、adiponectin、IL-6、PAI-1分别为( 10.46±9.75) μg/L、(9115.5±9812.91) μg/L、(13.13±6.50) pg/mL和(163.71±110.04)μg/L.校正年龄因素后,男、女性别间leptin、adiponectin、IL-6和PAI-1差异均有显著性(P<0.05).结论 本次大样本的中老年leptin、adiponectin、IL-6、PAI -1的流行病学调查数据可靠,为后期的生活方式与慢性心、脑血管和代谢性疾病关系的研究和公共卫生干预提供了依据.%Objective To conduct an epidemiological investigation on leptin,adiponectin,interleukin-6 ( IL-6 ),and plasminogen activator inhibitor-1 ( PAI-1 ) in the middle aged and elderly people in Guangzhou.Methods 1996 of 10 027 middle aged and elderly people registered at Guangzhou Database were randomly selected to be surveyed by questionnaires and to have physical examination.Levels of leptin,adiponectin,IL-6,and PAI-1 were determined by enzyme-linked immunosorbent assay ( ELISA ).Results Leptin was ( 10.46 ± 9.75 ) μg/L, adiponectin was ( 9115.5 ± 9812.91 ) μg/L,IL-6 was ( 13.13 ± 6.50 ) pg/mL,and PAI-1 was ( 163.71 ± 110.04 ) μg/L in Guangzhou middle aged and elderly people.There were significant differences in levels of leptin,adiponectin,IL-6,and PAI-1 between male and female after age adjustment.Conclusions Reliable data of leptin,adiponectin,IL-6,and PAI-1 in this large-scale epidemiological investigation provides support for the future research on the relationship between lifestyle and chronic cardiovascular,cardiocerebrovascular diseases

  13. Cutting Edge: Engineering Active IKKβ in T Cells Drives Tumor Rejection.

    Evaristo, César; Spranger, Stefani; Barnes, Sarah E; Miller, Michelle L; Molinero, Luciana L; Locke, Frederick L; Gajewski, Thomas F; Alegre, Maria-Luisa

    2016-04-01

    Acquired dysfunction of tumor-reactive T cells is one mechanism by which tumors can evade the immune system. Identifying and correcting pathways that contribute to such dysfunction should enable novel anticancer therapy design. During cancer growth, T cells show reduced NF-κB activity, which is required for tumor rejection. Impaired T cell-intrinsic NF-κB may create a vicious cycle conducive to tumor progression and further T cell dysfunction. We hypothesized that forcing T cell-intrinsic NF-κB activation might break this cycle and induce tumor elimination. NF-κB was activated in T cells by inducing the expression of a constitutively active form of the upstream activator IκB kinase β (IKKβ). T cell-restricted constitutively active IKKβ augmented the frequency of functional tumor-specific CD8(+) T cells and improved tumor control. Transfer of constitutively active IKKβ-transduced T cells also boosted endogenous T cell responses that controlled pre-established tumors. Our results demonstrate that driving T cell-intrinsic NF-κB can result in tumor control, thus identifying a pathway with potential clinical applicability. PMID:26903482

  14. Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells.

    Tesone, Amelia J; Rutkowski, Melanie R; Brencicova, Eva; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Stephen, Tom L; Allegrezza, Michael J; Payne, Kyle K; Nguyen, Jenny M; Wickramasinghe, Jayamanna; Tchou, Julia; Borowsky, Mark E; Rabinovich, Gabriel A; Kossenkov, Andrew V; Conejo-Garcia, Jose R

    2016-02-23

    Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression. PMID:26876172

  15. Physiological investigation of automobile driver's activation index using simulated monotonous driving.

    Yamakoshi, T; Yamakoshi, K; Tanaka, S; Nogawa, M; Kusakabe, M; Kusumi, M; Tanida, K

    2004-01-01

    Monotonous automobile operation in our daily life may cause the lowering of what might be termed an activation state of the human body, resulting in an increased risk of an accident. We therefore propose to create a more suitable environment in-car so as to allow active operation of the vehicle, hopefully thus avoiding potentially dangerous situations during driving. In order to develop such an activation method as a final goal, we have firstly focused on the acquisition of physiological variables, including cardiovascular parameters, during presentation to the driver of a monotonous screen image, simulating autonomous travel of constant-speed on a motorway. Subsequently, we investigated the derivation of a driver's activation index. During the screen image presentation, a momentary electrical stimulation of about 1 second duration was involuntarily applied to a subject's shoulder to obtain a physiological response. We have successfully monitored various physiological variables during the image presentation, and results suggest that a peculiar pattern in the beat-by-beat change of blood pressure in response to the involuntary stimulus may be an appropriate, and feasible, index relevant to activation state. PMID:17270774

  16. SATB1 OVEREXPRESSION DRIVES TUMOR-PROMOTING ACTIVITIES IN CANCER-ASSOCIATED DENDRITIC CELLS

    Tesone, Amelia J.; Rutkowski, Melanie R.; Brencicova, Eva; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Stephen, Tom L.; Allegrezza, Michael J.; Payne, Kyle K.; Nguyen, Jenny M.; Wickramasinghe, Jayamanna; Tchou, Julia; Borowsky, Mark E.; Rabinovich, Gabriel A.; Kossenkov, Andrew V.; Conejo-Garcia, Jose R.

    2016-01-01

    SUMMARY Special AT-rich sequence-binding protein-1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating MHC-II expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC-II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46+ inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression. PMID:26876172

  17. EEG-based decoding of error-related brain activity in a real-world driving task

    Zhang, Huaijian; Chavarriaga Lozano, Ricardo; Khaliliardali, Zahra; Gheorghe, Lucian Andrei; Iturrate, Inaki; Millán, José del R.

    2015-01-01

    Objectives. Recent studies have started to explore the implementation of brain–computer interfaces (BCI) as part of driving assistant systems. The current study presents an EEG-based BCI that decodes error-related brain activity. Such information can be used, e.g., to predict driver's intended turning direction before reaching road intersections. Approach. We executed experiments in a car simulator (N = 22) and a real car (N = 8). While subject was driving, a directional cue was shown before ...

  18. EEG-based decoding of error-related brain activity in a real-world driving task

    Zhang, H.; Chavarriaga, R.; Khaliliardali, Z.; Gheorghe, L.; Iturrate, I.; Millán, J. d. R.

    2015-12-01

    Objectives. Recent studies have started to explore the implementation of brain-computer interfaces (BCI) as part of driving assistant systems. The current study presents an EEG-based BCI that decodes error-related brain activity. Such information can be used, e.g., to predict driver’s intended turning direction before reaching road intersections. Approach. We executed experiments in a car simulator (N = 22) and a real car (N = 8). While subject was driving, a directional cue was shown before reaching an intersection, and we classified the presence or not of an error-related potentials from EEG to infer whether the cued direction coincided with the subject’s intention. In this protocol, the directional cue can correspond to an estimation of the driving direction provided by a driving assistance system. We analyzed ERPs elicited during normal driving and evaluated the classification performance in both offline and online tests. Results. An average classification accuracy of 0.698 ± 0.065 was obtained in offline experiments in the car simulator, while tests in the real car yielded a performance of 0.682 ± 0.059. The results were significantly higher than chance level for all cases. Online experiments led to equivalent performances in both simulated and real car driving experiments. These results support the feasibility of decoding these signals to help estimating whether the driver’s intention coincides with the advice provided by the driving assistant in a real car. Significance. The study demonstrates a BCI system in real-world driving, extending the work from previous simulated studies. As far as we know, this is the first online study in real car decoding driver’s error-related brain activity. Given the encouraging results, the paradigm could be further improved by using more sophisticated machine learning approaches and possibly be combined with applications in intelligent vehicles.

  19. Performance analysis of active damped small DC-link capacitor based drive for unbalanced input voltage supply

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig

    A small DC-link capacitor based drive is presented in this paper. The drive shows negative impedance instability at operating points with high power load. A phase portrait is presented for input filter states which exhibit a limit cycle. When the drive is operated with unbalanced input supply...... voltages, the rectified voltage contains all even harmonics frequencies. However, it is shown that the dominant harmonic component of the DC-link voltage is decided by the limit cycle instead of the input filter resonance frequency. An active damping technique is used to stabilize the operating point. The...... responses of the DC-link voltage with and without active damping are presented. The low order harmonics components are reduced with the increase in the gain of the active damping term. The experimental results for the DC-link voltage, input phase currents, and machine phase current are presented....

  20. Effects of urokinase type plasminogen activator and plasminogen activator inhibitor-1 expressions on the formation of aneurysm of perimembranous ventricular septal defect%尿激酶型纤溶酶原激活物及其抑制物表达在膜周型室间隔缺损自发闭合中的作用

    钱娟; 李本尚; 殷敏智; 沈萍; 孙锟

    2015-01-01

    0.05).结论 uPA及抑制物系统在VSA形成过程中起重要作用,参与瘤体的形成和纤维增殖过程.%Objective The exact mechanisms of defect closure in patients with perimembranous ventricular septal defect (PMVSD) remain unknown.We hypothesized that the expression of urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) may mediate extracellular matrix (ECM) remodeling in aneurysms.Method Seven normal heart tricuspid septal leaflet and 33 aneurysms were collected in Shanghai Renji Hospital and Shanghai Children's Medical Center from January 2008 to June 2010.Immunohistochemical expression of uPA and PAI-1 in 4 normal heart valvular tissues and 15 aneurysms was detected with immunohistochemical methods.The expression of uPA and PAI-1 mRNA in 3 normal heart valvular tissues and 7 aneurysms was studied by real time fluorescent PCR;the protein expression of uPA and PAI-1 in 4 normal heart valvular tissues and 11 aneurysms was tested with Western blotting.Result The surface of the aneurysms were completely covered by endothelial cells.Two types of granulation tissue,myxoid and fibrous,were associated with the aneurismal formation.uPA were recognized predominantly in valvar interstitial cells (VICs) which located mainly in regions adjacent to the endothelium and smooth muscle cells of blood vessels.PAI-1 was found in both VICs which located mainly in granulation tissue and endothelial cells.Nine aneurysms expressed a higher uPA activity than 4 normal valvular tissues ((74.6 ± 11.8) % vs.(49.5 ± 7.4) %;t =3.87,P =0.003) and six aneurysms expressed a low uPA activity ((10.3±3.1)% vs.(49.5±7.4)%;t=11.78,P=0.000) andahighPAI-1 activity ((55.2±1.7) % vs.(50.8 ± 3.8) %;t =2.55,P =0.034) using immunohistochemical methods.uPA / PAI-1 ratio of protein expression tested by Western blot was 0.88 ± 0.22 in four normal heart vavular tissues;five aneurysms expressed high uPA activity and low PAI-1 activity and u

  1. Active noise reduction at the rear axle drive; Aktive Geraeuschminderung am Hinterachsgetriebe

    Eulert, Sebastian; Luehrs, Georg [Volkswagen AG, Kassel (Germany); Braeunig, Jan; Bucht, Andre; Kunze, Holger [Fraunhofer-Institut fuer Werkzeugmaschinen und Umformtechnik, Dresden (Germany)

    2011-07-01

    In this article we present the results of a research project of Volkswagen AG and Fraunhofer IWU. It shows new approaches in the development of active mass dampers for transmission applications. The proposed active controlled system enables to reduce the interior sound pressure level of the rear axle gear mesh order by more than 5 dB. By detailed pre-examination of the drivetrain vibrations and transfer paths we gained new insights into the phenomenon of rear axle gear whine. In order to develop solutions to realise the damping of the vibrations we designed and constructed a test bench which consists of the main components of the rear axle unit and its bearings. The vibration phenomenon was replicated by synthetic excitation. Thus we could acquire an adequate control concept combined with a corresponding actuator and experimentally established control parameters. Validations on an experimental vehicle under synthetic excitation and finally under real driving conditions adduced the evidence for the functionality of the proposed system. (orig.)

  2. Wind from the black-hole accretion disk driving a molecular outflow in an active galaxy.

    Tombesi, F; Meléndez, M; Veilleux, S; Reeves, J N; González-Alfonso, E; Reynolds, C S

    2015-03-26

    Powerful winds driven by active galactic nuclei are often thought to affect the evolution of both supermassive black holes and their host galaxies, quenching star formation and explaining the close relationship between black holes and galaxies. Recent observations of large-scale molecular outflows in ultraluminous infrared galaxies support this quasar-feedback idea, because they directly trace the gas from which stars form. Theoretical models suggest that these outflows originate as energy-conserving flows driven by fast accretion-disk winds. Proposed connections between large-scale molecular outflows and accretion-disk activity in ultraluminous galaxies were incomplete because no accretion-disk wind had been detected. Conversely, studies of powerful accretion-disk winds have until now focused only on X-ray observations of local Seyfert galaxies and a few higher-redshift quasars. Here we report observations of a powerful accretion-disk wind with a mildly relativistic velocity (a quarter that of light) in the X-ray spectrum of IRAS F11119+3257, a nearby (redshift 0.189) optically classified type 1 ultraluminous infrared galaxy hosting a powerful molecular outflow. The active galactic nucleus is responsible for about 80 per cent of the emission, with a quasar-like luminosity of 1.5 × 10(46) ergs per second. The energetics of these two types of wide-angle outflows is consistent with the energy-conserving mechanism that is the basis of the quasar feedback in active galactic nuclei that lack powerful radio jets (such jets are an alternative way to drive molecular outflows). PMID:25810204

  3. Active Prompting to Decrease Cell Phone Use and Increase Seat Belt Use while Driving

    Clayton, Michael; Helms, Bridgett; Simpson, Cathy

    2006-01-01

    Automobile crashes are the leading cause of death for those aged 3 to 33, with 43,005 (118 per day) Americans killed in 2002 alone. Seat belt use reduces the risk of serious injury in an accident, and refraining from using a cell phone while driving reduces the risk of an accident. Cell phone use while driving increases accident rates, and leads…

  4. Reading Text While Driving

    Liang, Yulan; Horrey, William J.; Hoffman, Joshua D.

    2015-01-01

    Objective In this study, we investigated how drivers adapt secondary-task initiation and time-sharing behavior when faced with fluctuating driving demands. Background Reading text while driving is particularly detrimental; however, in real-world driving, drivers actively decide when to perform the task. Method In a test track experiment, participants were free to decide when to read messages while driving along a straight road consisting of an area with increased driving demands (demand zone)...

  5. Simulations of Xenon Activation in Indirect Drive Exploding Pushers on NIF

    Sepke, Scott M.; Hopkins, Laura Berzak; Cerjan, Charles; Marinak, Marty

    2014-10-01

    The indirect drive exploding pusher (IDEP) has proven to be a robust and well understood platform for experiments at the National Ignition Facility. We investigate the effect of adding xenon dopant in different concentrations to the DT gaseous fuel in IDEP capsules at various fill densities of experimental relevance -- 1.5-3 mg/cc -- through integrated capsule-hohlraum simulations using HYDRA. The primary metrics used to evaluate the performance are changes in neutron shock flash time and bang time, neutron yield, and the neutron time of flight temperature. In addition, the new post-processing code KUDU is used to explore the nuclear activation of the xenon dopant for natural xenon as well as pure Xe-124 and Xe-134 using the new post-processing code KUDU: a multiprocess (MPI), multithreaded (POSIX threads), and accelerator capable (CUDA and OpenACC) rate equation solver developed at Lawrence Livermore National Laboratory for radiochemistry modeling. This work (LLNL-ABS-656222) performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  6. Driving p53 Response to Bax Activation Greatly Enhances Sensitivity to Taxol by Inducing Massive Apoptosis

    Paola De Feudis

    2000-05-01

    Full Text Available The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3 were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

  7. Evaluation of the Ride-Through Capability of an Active-Front-End Adjustable Speed Drive under Real Grid Conditions

    Liserre, Marco; Klumpner, Christian; Blaabjerg, Frede;

    2004-01-01

    Better quality of the input currents, unity power factor and regenerative capability are not the only benefits of equipping an Adjustable Speed Drive (ASD) with an active front-end-stage. Controlling the power inflow may enable also the reduction of the dc-link energy storage, which will then lead...

  8. Active-Flux-Based, V/f-with-Stabilizing-Loops Versus Sensorless Vector Control of IPMSM Drives

    Moldovan, Ana; Blaabjerg, Frede; Boldea, Ion

    2011-01-01

    This paper proposes two control methods for Interior Permanent Magnet Synchronous Motor (IPMSM) Drives. The first one is a V/f control with two stabilizing loops: one loop based on active flux balance for voltage magnitude correction and a second, based on speed error, with voltage phase correction...

  9. Practical Wide-speed-range Sensorless Control System for Permanent Magnet Reluctance Synchronous Motor Drives via Active Flux Model

    Ancuti, Mihaela Codruta; Tutelea, Lucian; Andreescu, Gheorghe-Daniel;

    2014-01-01

    This article introduces a control strategy to obtain near-maximum available torque in a wide speed range with sensorless operation via the active flux concept for permanent magnet-reluctance synchronous motor drives. A new torque dq current reference calculator is proposed, with reference torque...

  10. Crowd-Sourcing Management Activity Data to Drive GHG Emission Inventories in the Land Use Sector

    Paustian, K.; Herrick, J.

    2015-12-01

    Greenhouse gas (GHG) emissions from the land use sector constitute the largest source category for many countries in Africa. Enhancing C sequestration and reducing GHG emissions on managed lands in Africa has to potential to attract C financing to support adoption of more sustainable land management practices that, in addition to GHG mitigation, can provide co-benefits of more productive and climate-resilient agroecosystems. However, robust systems to measure and monitor C sequestration/GHG reductions are currently a significant barrier to attracting more C financing to land use-related mitigation efforts.Anthropogenic GHG emissions are driven by a variety of environmental factors, including climate and soil attributes, as well as human-activities in the form of land use and management practices. GHG emission inventories typically use empirical or process-based models of emission rates that are driven by environmental and management variables. While a lack of field-based flux and C stock measurements are a limiting factor for GHG estimation, we argue that an even greater limitation may be availabiity of data on the management activities that influence flux rates, particularly in developing countries in Africa. In most developed countries there is a well-developed infrastructure of agricultural statistics and practice surveys that can be used to drive model-based GHG emission estimations. However, this infrastructure is largely lacking in developing countries in Africa. While some activity data (e.g. land cover change) can be derived from remote sensing, many key data (e.g., N fertilizer practices, residue management, manuring) require input from the farmers themselves. The explosive growth in cellular technology, even in many of the poorest parts of Africa, suggests the potential for a new crowd-sourcing approach and direct engagement with farmers to 'leap-frog' the land resource information model of developed countries. Among the many benefits of this approach

  11. Dynamic Drive, the new active rolling stabilisation system fo the new BMW 7 series; Dynamic Drive - das neue aktive Wank-Stabilisierungssystem im neuen 7er der BMW Group

    Konik, D.; Bartz, R.; Bruns, H.; Held, G.; Webers, K.; Zieglmeier, F. [Bayerische Motoren Werke AG (BMW), Muenchen (Germany)

    2001-07-01

    The new active rolling stabilisation system developed by BMW for the 7 series is described in detail. [German] Dynamic Drive ist ein energieoptimiertes aktives Wankstabilisierungssystem, das im neuen 7er der BMW Group seine Ersteinfuehrung haben wird. Dynamik Drive bewirkt neben der Reduzierung des Wankwinkels ein optimales Eigenlenkverhalten durch eine fahrzustandsabhaengige Verteilung der Stabilisierungsmomente zwischen Vorder- und Hinterachse. Das Handling und die Agilitaet werden hierdurch deutlich verbessert und fuehren so zu einer neuartigen, aber gleichzeitig BMW typischen 'Freude am Fahren'. Zudem erfaehrt man einen subjektiven Gewinn an Fahrsicherheit. Da die Aktiven Stabilisatoren des Dynamic Drive bei nahezu Geradeausfahrt fast keine Kraefte in die Karosserie einleiten, verbessert sich der Aufbauschwingkomfort - insbesondere bei asymmetrischen Fahrbahnanregungen. In diesem Beitrag werden das System sowie dessen Hauptkomponenten kurz vorgestellt. Ausfuehrlich wird die Funktionsbewertung des Dynamic Drive anhand von Messergebnissen des neuen 7er diskutiert. Neben quasistationaeren und dynamischen Fahrmanoevern wird eine statistische Untersuchung zur Wechselwirkung zwischen Fahrverhalten und Dynamic Drive eroertert. (orig.)

  12. Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving.

    Noriyuki Oka

    Full Text Available In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves, but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS.The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task. Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections.Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05, but cerebral oxygen exchange increased significantly more during left curves (p < 0.05 in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05 only in the right frontal eye field.Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

  13. Lower Cortisol Activity is Associated with First-Time Driving while Impaired

    Sophie Couture; Marie Claude Ouimet; Christina Gianoulakis; Jacques Tremblay; Ng Ying Kin, N. M. K.; Serge Brochu; Jens Pruessner; Katarina Dedovic; Brown, Thomas G.

    2015-01-01

    Driving while impaired (DWI) is a grave and persistent high-risk behavior. Previous work demonstrated that DWI recidivists had attenuated cortisol reactivity compared to non-DWI drivers. This suggests that cortisol is a neurobiological marker of high-risk driving. The present study tested the hypothesis that this initial finding would extend to first-time DWI (fDWI) offenders compared to non-DWI drivers. Male fDWI offenders (n = 139) and non-DWI drivers (n = 31) were exposed to a stress task,...

  14. The potential role of physical activity on driving performance and safety among older adults

    Marmeleira, J.; Vogelaere, P.; Godinho, M.

    2009-01-01

    The elderly represent the fastest growing driving population. Older drivers have a high crash rate per distance traveled, a high risk of injury or death in traffic accidents, and are commonly found to be ‘at fault’ in crashes. This reality has focused more interest on issues associated with the fitness to drive and the safety of older drivers. Many older adults depend greatly on their personal vehicle for transportation and suffer a marked loss of quality of life when, as a consequence of no ...

  15. Impact of distracting activities and drivers' cognitive failures on driving performance

    Farah, H.; Zatmeh, S.; Toledo, T.

    2015-01-01

    The rapid increase in the availability of smart phones and other infotainment devices, and their widespread use while driving, contributes significantly to car crash rates. This is since the human brain has limited capacity and cannot perform two tasks at the same time, but rather switches from one

  16. Analysis of Dielectric Electro Active Polymer Actuator and its High Voltage Driving Circuits

    Thummala, Prasanth; Huang, Lina; Zhang, Zhe;

    2012-01-01

    actuator is analyzed in detail and the actuator structures, for the wind turbine flap and the heating valve applications are shown. Different high voltage switch mode power supply topologies for driving the DEAP actuator are discussed. The simulation and experimental results are discussed....

  17. Comparative Analysis of Passenger Traffic Fleets in Asian Cities: Technology, Driving Activities, and Emission

    KIM Oanh, N. T.; Huynh, H. V.; Saikawa, E.

    2015-12-01

    The road transport sector is the major emission source of toxic air pollutants and greenhouse gases (GHGs) in large Asian cities. This paper comparatively analyzed on-road passenger traffic fleets (cars, buses, taxis, motorcycles), using local data collected in cities of Bangkok (BKK), Kathmandu, Hanoi, Ho Chi Minh City (HCMC), and Yangon. Surveys were done in 2010-2014 to obtain information on vehicle technology, driving activities (speed, distance, number, and types of starts), traffic density, and fuel characteristics. Large shares of pre-Euro vehicles were still observed, especially for public buses. The most advanced technology was Euro4, which was observed in small shares (traffic jams. Natural gas and LPG had considerable shares in BKK and Yangon while for other cities diesel and gasoline were still the two major fuels used in transportation. Running emission factors (EF) of buses and taxis in Kathmandu were considerably higher than other cities due to its hilly topography, low speeds, high mileage, and less advanced vehicle technologies. The number of passenger vehicles per 1000 people were 400-500 in HCMC and Hanoi (mainly by MC) and in BKK (also by cars), moderate in Kathmandu (200) and the lowest in Yangon (40) because of the MC ban. Annual emissions of the passenger fleets were calculated for each city using the International Vehicle Emission (IVE) for 14 species. BC and OC emissions were estimated using their fractions of PM10 emission. Annual emission per capita of toxic air pollutants and GHGs was analyzed. For example, the emission in kg/year/person for CO, VOC, NOx and PM10 in these cities was 24-150 for CO, 0.9-23 for VOC, 2.1-8.2 for NOx and 0.2-1.1 for PM10. The highest per capita emissions of CO and VOC were found for HCMC and the lowest for Yangon, which showed the influence of MC fleet. The per capita emission of Kathmandu was ranked second among the cities. Our results were also analyzed in comparison with the per capita emission estimated

  18. A Transformerless Hybrid Active Filter Capable of Complying with Harmonic Guidelines for Medium-Voltage Motor Drives

    Kondo, Ryota; Akagi, Hirofumi

    This paper presents a transformerless hybrid active filter that is integrated into medium-voltage adjustable-speed motor drives for fans, pumps, and compressors without regenerative braking. The authors have designed and constructed a three-phase experimental system rated at 400V and 15kW, which is a downscaled model from a feasible 6.6-kV 1-MW motor drive system. This system consists of the hybrid filter connecting a passive filter tuned to the 7th harmonic filter in series with an active filter that is based on a three-level diode-clamped PWM converter, as well as an adjustable-speed motor drive in which a diode rectifier is used as the front end. The hybrid filter is installed on the ac side of the diode rectifier with no line-frequency transformer. The downscaled system has been exclusively tested so as to confirm the overall compensating performance of the hybrid filter and the filtering performance of a switching-ripple filter for mitigating switching-ripple voltages produced by the active filter. Experimental results verify that the hybrid filter achieves harmonic compensation of the source current in all the operating regions from no-load to the rated-load conditions, and that the switching-ripple filter reduces the switching-ripple voltages as expected.

  19. Driving things

    Nevile, Maurice Richard

    2015-01-01

    I explore how participants organise involvement with objects brought into the car, relative to the demands of driving and social activity. Objects in cars commonly include phones or other technologies, food, body care products, texts, clothing, bags and carry items, toys, and even animals....... pp.155 ((http://www.infrastructure.gov.au/roads/safety/publications/2010/pdf/rsgr_2010001.pdf)) Nevile, M., Haddington, P., Heinemann, T., Rauniomaa, M. (Eds.) Interacting with objects: Language, materiality, and social activity. Amsterdam/Philadelphia: John Benjamins. Redshaw, S. (2008). In the...

  20. The effect of Beijing’s driving restrictions on pollution and economic activity

    Viard, Brian; Fu, Shihe

    2011-01-01

    We evaluate the environmental and economic effects of Beijing’s driving restrictions. Based on daily data from multiple monitoring stations, air pollution falls 19% during every-other-day and 8% during one-day-per-week restrictions. Based on hourly viewership data, the number of television viewers during the restrictions increases 1.7 to 2.3% for workers with discretionary work time but is unaffected for workers without, consistent with the restrictions’ higher per-day commute costs reducing ...

  1. Correlation of prefrontal cortical activation with changing vehicle speeds in actual driving: a vector-based functional near-infrared spectroscopy study

    Kouji Yamamoto; Hideki Takahashi; Toshinori Kato

    2013-01-01

    Traffic accidents occur more frequently during deceleration than during acceleration. However, little is known about the relationship between brain activation and vehicle acceleration because it has been difficult to measure the brain activation of drivers while they drive. In this study, we measured brain activation during actual driving using vector-based functional near-infrared spectroscopy. Subjects decelerated from 100 to 50 km/h (speed reduction task) and accelerated from 50 to 100 km/...

  2. Resonant Activation in a Stochastic Hodgkin-Huxley Model: Interplay between noise and suprathreshold driving effect

    Pankratova, Evgeniya; Polovinkin, A.V.; Mosekilde, Erik

    2005-01-01

    The paper considers an excitable Hodgkin-Huxley system subjected to a strong periodic forcing in the presence of random noise. The influence of the forcing frequency on the response of the system is examined in the realm of suprathreshold amplitudes. Our results confirm that the presence of noise...... minimum as functions of the forcing frequency. The destructive influence of noise on the interspike interval can also be reduced. With driving signals in a certain frequency range, the system can show stable periodic spiking even for relatively large noise intensities. Outside this frequency range, noise...

  3. Arabidopsis Bax Inhibitor-1 inhibits cell death induced by pokeweed antiviral protein in Saccharomyces cerevisae

    Birsen Çakır

    2015-02-01

    Full Text Available Apoptosis is an active form of programmed cell death (PCD that plays critical roles in the development, differentiation and resistance to pathogens in multicellular organisms. Ribosome inactivating proteins (RIPs are able to induce apoptotic cell death in mammalian cells. In this study, using yeast as a model system, we showed that yeast cells expressing pokeweed antiviral protein (PAP, a single-chain ribosome-inactivating protein, exhibit apoptotic-like features, such as nuclear fragmentation and ROS production. We studied the interaction between PAP and AtBI-1 (Arabidopsis thaliana Bax Inhibitor-1, a plant anti-apoptotic protein, which inhibits Bax induced cell death. Cells expressing PAP and AtBI-1 were able to survive on galactose media compared to PAP alone, indicating a reduction in the cytotoxicity of PAP in yeast. However, PAP was able to depurinate the ribosomes and to inhibit total translation in the presence of AtBI-1. A C-terminally deleted AtBI-1 was able to reduce the cytotoxicity of PAP. Since anti-apoptotic proteins form heterodimers to inhibit the biological activity of their partners, we used a co-immunoprecipitation assay to examine the binding of AtBI-1 to PAP. Both full length and C-terminal deleted AtBI-1 were capable of binding to PAP. These findings indicate that PAP induces cell death in yeast and AtBI-1 inhibits cell death induced by PAP without affecting ribosome depurination and translation inhibition.

  4. Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving

    Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

    2015-01-01

    Objectives In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The particip...

  5. The drive-wise project: driving simulator training increases real driving performance in healthy older drivers

    Casutt, Gianclaudio; Theill, Nathan; Martin, Mike; Keller, Martin; Jäncke, Lutz

    2014-01-01

    Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training. Methods: Ninety-one healthy active drivers (62–87 years) were randomly assigned to one of three groups: (1) a driving simulator training group, (2) an attention training group (vigilance and selective...

  6. Competition as an Effective Tool in Developing Social Marketing Programs: Driving Behavior Change through Online Activities

    Corina ŞERBAN

    2011-12-01

    Full Text Available Nowadays, social marketing practices represent an important part of people’s lives. Consumers’ understanding of the need for change has become the top priority for social organizations worldwide. As a result, the number of social marketing programs has increased, making people reflect more on their behaviors and on the need to take action. Competition in social marketing can bring many benefits. The more programs initiated, the more people will start to involve in society’s problems, hereby contributing to beneficial causes. However, social organizations are in the search for competitive advantages to differentiate them on the market. This paper aims to present the role of online communication in driving competitive advantage for social organizations. Using the structural equation model, the paper describes the relations between four characteristics of the online communication: credibility, attractiveness, persuasion and promotion and then presents the correlations between these variables and website competitiveness. The resulting model shows that owning a competitive advantage in social marketing can bring many advantages to both the non-profit organization and the consumer. Therefore, the online environment can be considered a good solution for better serving consumers’ social needs. Its contribution is significant especially in programs for children and adolescents, since teenagers spend more time on the Internet than adults and are more open to using the online channels of communication. In conclusion, this article opens new opportunities for social marketers to address society’s problems and supports the integration of the online communication tools in the competition strategy.

  7. Effects of Non-Driving Cognitive Activity on Driver's Eye Movement and Their Individual Difference

    Itoh, Makoto; Inagaki, Toshiyuki

    This paper investigates effects on driver's eye movement when the driver is distracted by a secondary cognitive task that demands a high mental workload. By observing drivers behavior in a fixed-base driving simulator, we analyze how the time lengths of eye fixations change when a driver is imposed to perform a cognitive secondary task. The results show that two types (Type 1: the number of short fixations increases, Type 2: the number of short fixations decreases) are found. Interestingly, our data show that both types can be seen even in one driver depending on traffic conditions. It is also shown that likelihood of occurring Type 1 or Type 2 effects depends on driver. The data suggest that it is possible to predict which effect is likely to occur for a driver if we analyze his or her eye movement under normal conditions. With these findings, this study developed and improved a driver-adaptable algorithm for detecting the state of being under high mental workload. The results suggest that the time length of an eye fixation can be useful index at least several drivers.

  8. Aurora A drives early signalling and vesicle dynamics during T-cell activation

    Blas-Rus, Noelia; Bustos-Morán, Eugenio; Pérez de Castro, Ignacio; de Cárcer, Guillermo; Borroto, Aldo; Camafeita, Emilio; Jorge, Inmaculada; Vázquez, Jesús; Alarcón, Balbino; Malumbres, Marcos; Martín-Cófreces, Noa B.; Sánchez-Madrid, Francisco

    2016-01-01

    Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3ζ-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal. PMID:27091106

  9. Electric drives

    Boldea, Ion

    2005-01-01

    ENERGY CONVERSION IN ELECTRIC DRIVESElectric Drives: A DefinitionApplication Range of Electric DrivesEnergy Savings Pay Off RapidlyGlobal Energy Savings Through PEC DrivesMotor/Mechanical Load MatchMotion/Time Profile MatchLoad Dynamics and StabilityMultiquadrant OperationPerformance IndexesProblemsELECTRIC MOTORS FOR DRIVESElectric Drives: A Typical ConfigurationElectric Motors for DrivesDC Brush MotorsConventional AC MotorsPower Electronic Converter Dependent MotorsEnergy Conversion in Electric Motors/GeneratorsPOWER ELECTRONIC CONVERTERS (PECs) FOR DRIVESPower Electronic Switches (PESs)The

  10. Experiments on functional fatigue of thermally activated shape memory alloy springs and correlations with driving force intensity

    Rao, Ashwin; Srinivasa, A. R.

    2013-04-01

    The issue of material performance over its designed life is of prime concern with designers lately due to increasing use of shape memory alloy (SMA) components in different engineering applications. In this work, a concept of "Driving force amplitude v/s no of cycles" is proposed to analyze functional degradation of SMA components under torsion. The model is formulated using experimentally measurable quantities such as torque and angle of twist with the inclusion of both mechanical and thermal loading in the same framework. Such an approach can potentially substitute the traditional fatigue theories like S-N, epsilon-N theories which primarily use mechanical loading effects with temperature being an external control parameter. Such traditional S-N, epsilon-N fatigue theories work well for capturing superelastic effects at a given temperature but not for shape memory effects or temperature dependent superelastic effects which involves mechanical and thermal coupling. Experiments on SMA extension springs are performed using a custom designed thermomechanical test rig capable of mimicking shape memory effect on thermally activated SMA springs held under constant deformation. For every thermomechanical cycle, load and temperature sensor readings are continually recorded as a function of time using LabVIEW software. The sensor data over the specimen lifetime is used to construct a "Driving force amplitude v/s no of cycles" relationship that can be used as a guideline for analyzing functional degradation of SMA components.

  11. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

    Lin, Jiandie; Wu, Hai; Tarr, Paul T; Zhang, Chen-Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F; Puigserver, Pere; Isotani, Eiji; Olson, Eric N; Lowell, Bradford B; Bassel-Duby, Rhonda; Spiegelman, Bruce M

    2002-08-15

    The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination. PMID:12181572

  12. The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons

    Miller-Fleming, Tyne W; Petersen, Sarah C; Manning, Laura; Matthewman, Cristina; Gornet, Megan; Beers, Allison; Hori, Sayaka; Mitani, Shohei; Bianchi, Laura; Richmond, Janet; Miller, David M

    2016-01-01

    Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons. DOI: http://dx.doi.org/10.7554/eLife.14599.001 PMID:27403890

  13. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice.

    Sidor, M M; Spencer, S M; Dzirasa, K; Parekh, P K; Tye, K M; Warden, M R; Arey, R N; Enwright, J F; Jacobsen, J P R; Kumar, S; Remillard, E M; Caron, M G; Deisseroth, K; McClung, C A

    2015-11-01

    Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood-cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviors in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behavior. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder. PMID:25560763

  14. 77 FR 59904 - Takes of Marine Mammals Incidental to Specified Activities; Pile Driving for Honolulu Seawater...

    2012-10-01

    ...) notes contextual differences between these two studies; the captive animals were not reinforced with... implementing regulations, NMFS issued a notice in the Federal Register on July 24, 2012 (77 FR 43259... description of the specified activity may be found in NMFS' proposed IHA notice in the Federal Register (77...

  15. Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik;

    2015-01-01

    internal organs and blood. Yet, little is known about the mechanism of the CTCL dissemination. Here, we show that CTCL cells express LTα in situ and that LTα expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTα functions as an autocrine factor by stimulating...

  16. Error analysis and distribution of the driving mechanism for large spherical radio telescope active reflector

    Huang Peng; Tang Xiaoqiang; Wang Liping; Yao Rui

    2008-01-01

    In order to reduce the cost, 3-PRS mechanism is introduced into the application of supporting the active reflector unit of large radio telescope. The kinematic model of 3-PRS mechanism with rotational joint errors is derived to solve the error problem in actual engineering application. Then based on the error model, inverse and forward kinematics are analyzed. Because the solutions can not be analytically expressed, a numerical method is applied. Afterwards, the parasitic motion errors are analyzed using search method and empirical formulas of the maximum parasitic motion error are put forward. Finally, the tolerance is distributed using empirical formulas to avoid interference between adjacent reflector units. The analyses provide a theoretical basis for the design and installation of large radio telescope active reflector.

  17. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice

    Sidor, Michelle M.; Spencer, Sade M.; Dzirasa, Kafui; Parekh, Puja K.; Tye, Kay M; Warden, Melissa R.; Arey, Rachel N.; Enwright, John F; Jacobsen, Jacob PR; Kumar, Sunil; Remillard, Erin M; Marc G Caron; Deisseroth, Karl; McClung, Colleen A.

    2014-01-01

    Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of e...

  18. Why did we make that cheese? An empirically based framework for understanding what drives innovation activity

    Harmsen, Hanne; Grunert, Klaus G.; Declerck, Francis

    2000-01-01

    In the more recent product development literature the interplay between R&D skills and competencies and market skills and competencies is seen as a major determinant of successful innovation. The study reported in this article was done in order to cast more light on these two constructs in an...... innovation and explaining innovation success in the case material. A new set of constructs focusing on what causes specific innovation activities to occur is proposed and a revised framework is developed. Udgivelsesdato: APR...

  19. Efficiency Factors and Motivations Driving Innovative Activity of Russian Industrial Enterprises

    Tatyana Kuznetzova; Vitaly Roud

    2011-01-01

    Innovation activity is about the intersection of economic, social and cognitive dimensions, each of which has an impact on the choice of behavioral patterns by a company as well as the extent of its involvement in the innovation process. Regarding innovation in Russia there is a "terminological paradox". The basic conceptual framework has been introduced by OECD and Eurostat as an international standard more than 20 years ago. Relevant methodological and methodical approaches are thoroughly s...

  20. ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis.

    Zipeto, Maria Anna; Court, Angela C; Sadarangani, Anil; Delos Santos, Nathaniel P; Balaian, Larisa; Chun, Hye-Jung; Pineda, Gabriel; Morris, Sheldon R; Mason, Cayla N; Geron, Ifat; Barrett, Christian; Goff, Daniel J; Wall, Russell; Pellecchia, Maurizio; Minden, Mark; Frazer, Kelly A; Marra, Marco A; Crews, Leslie A; Jiang, Qingfei; Jamieson, Catriona H M

    2016-08-01

    Post-transcriptional adenosine-to-inosine RNA editing mediated by adenosine deaminase acting on RNA1 (ADAR1) promotes cancer progression and therapeutic resistance. However, ADAR1 editase-dependent mechanisms governing leukemia stem cell (LSC) generation have not been elucidated. In blast crisis chronic myeloid leukemia (BC CML), we show that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1. In a humanized BC CML mouse model, combined JAK2 and BCR-ABL1 inhibition prevents LSC self-renewal commensurate with ADAR1 downregulation. Lentiviral ADAR1 wild-type, but not an editing-defective ADAR1(E912A) mutant, induces self-renewal gene expression and impairs biogenesis of stem cell regulatory let-7 microRNAs. Combined RNA sequencing, qRT-PCR, CLIP-ADAR1, and pri-let-7 mutagenesis data suggest that ADAR1 promotes LSC generation via let-7 pri-microRNA editing and LIN28B upregulation. A small-molecule tool compound antagonizes ADAR1's effect on LSC self-renewal in stromal co-cultures and restores let-7 biogenesis. Thus, ADAR1 activation represents a unique therapeutic vulnerability in LSCs with active JAK2 signaling. PMID:27292188

  1. Perceived social pressures and the internalization of the mesomorphic ideal: The role of drive for muscularity and autonomy in physically active men.

    Edwards, Christian; Tod, David; Molnar, Gyozo; Markland, David

    2016-03-01

    We examined if there were both direct and indirect relationships (via the drive for muscularity) between the perceived pressure to be muscular and internalization of the mesomorphic ideal, and if autonomy moderates these relationships in physically active men. A sample of 330 men, who were undergraduate students studying sport, completed the Behavioral Regulation in Exercise Questionnaire-2, the Mesomorphic Ideal Internalization subscale of the revised male version Sociocultural Attitudes Toward Appearance Questionnaire, the Perceived Sociocultural Pressure Scale-Modified, and the Drive for Muscularity Scale Attitudes subscale. Perceived pressure predicted internalization directly, and indirectly through the drive for muscularity. The direct relationship between pressure and internalization was weaker under higher levels of autonomy. The indirect path, via drive for muscularity, was stronger under higher levels of autonomy. These results provide insights into why men vary in the degree to which they internalize pressure to develop a mesomorphic ideal, supporting further examination of autonomy. PMID:26688273

  2. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL

    Tzoneva, Gannie; Garcia, Arianne Perez; Carpenter, Zachary; Khiabanian, Hossein; Tosello, Valeria; Allegretta, Maddalena; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Paganin, Maddalena; Basso, Giuseppe; Hof, Jana; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Despite intensive chemotherapy, 20% of pediatric and over 50% of adult ALL patients fail to achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most significant challenge in the treatment of this disease1,2. Using whole exome sequencing, here we identify mutations in the cytosolic 5'-nucleotidase II gene (NT5C2), which encodes a 5'-nucleotidase enzyme responsible for inactivation of nucleoside analog chemotherapy drugs, in 20/103 (19%) relapse T-ALLs and in 1/35 (3%) relapse B-precursor ALLs analyzed. NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts. These results support a prominent role for activating mutations in NT5C2 and increased nucleoside analog metabolism in disease progression and chemotherapy resistance in ALL. PMID:23377281

  3. Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation.

    Xavier, Guilherme M; Patist, Amanda L; Healy, Chris; Pagrut, Ankita; Carreno, Gabriela; Sharpe, Paul T; Martinez-Barbera, Juan Pedro; Thavaraj, Selvam; Cobourne, Martyn T; Andoniadou, Cynthia L

    2015-01-01

    In common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues, and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma. PMID:26411543

  4. Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria

    Das, Soumita; Owen, Katherine A.; Ly, Kim T.; Park, Daeho; Black, Steven G.; Wilson, Jeffrey M.; Sifri, Costi D.; Ravichandran, Kodi S.; Ernst, Peter B.; Casanova, James E.

    2011-01-01

    Bacterial recognition by host cells is essential for initiation of infection and the host response. Bacteria interact with host cells via multiple pattern recognition receptors that recognize microbial products or pathogen-associated molecular patterns. In response to this interaction, host cell signaling cascades are activated that lead to inflammatory responses and/or phagocytic clearance of attached bacteria. Brain angiogenesis inhibitor 1 (BAI1) is a receptor that recognizes apoptotic cel...

  5. Multibody dynamics driving GNC and system design in tethered nets for active debris removal

    Benvenuto, Riccardo; Lavagna, Michèle; Salvi, Samuele

    2016-07-01

    Debris removal in Earth orbits is an urgent issue to be faced for space exploitation durability. Among different techniques, tethered-nets present appealing benefits and some open points to fix. Former and latter are discussed in the paper, supported by the exploitation of a multibody dynamics tool. With respect to other proposed capture mechanisms, tethered-net solutions are characterised by a safer capturing distance, a passive angular momentum damping effect and the highest flexibility to unknown shape, material and attitude of the target to interface with. They also allow not considering the centre of gravity alignment with thrust axis as a constraint, as it is for any rigid link solution. Furthermore, the introduction of a closing thread around the net perimeter ensures safer and more reliable grasping and holding. In the paper, a six degrees of freedom multibody dynamics simulator is presented: it was developed at Politecnico di Milano - Department of Aerospace Science and Technologies - and it is able to describe the orbital and attitude dynamics of tethered-nets systems and end-bodies during different phases, with great flexibility in dealing with different topologies and configurations. Critical phases as impact and wrapping are analysed by simulation to address the tethered-stack controllability. It is shown how the role of contact modelling is fundamental to describe the coupled dynamics: it is demonstrated, as a major novel contribution, how friction between the net and a tumbling target allows reducing its angular motion, stabilizing the system and allowing safer towing operations. Moreover, the so-called tethered space tug is analysed: after capture, the two objects, one passive and one active, are connected by the tethered-net flexible link, the motion of the system being excited by the active spacecraft thrusters. The critical modes prevention during this phase, by means of a closed-loop control synthesis is shown. Finally, the connection between

  6. Impaired Driving

    ... help prevent injuries and deaths from alcohol-impaired driving. The Problem Risk Factors BAC Effects Prevention Additional Resources How big is the problem? In 2014, 9,967 people were killed in alcohol-impaired driving crashes, accounting for nearly one-third (31%) of ...

  7. Posterior Parietal Cortex Drives Inferotemporal Activations During Three-Dimensional Object Vision.

    Van Dromme, Ilse C; Premereur, Elsie; Verhoef, Bram-Ernst; Vanduffel, Wim; Janssen, Peter

    2016-04-01

    The primate visual system consists of a ventral stream, specialized for object recognition, and a dorsal visual stream, which is crucial for spatial vision and actions. However, little is known about the interactions and information flow between these two streams. We investigated these interactions within the network processing three-dimensional (3D) object information, comprising both the dorsal and ventral stream. Reversible inactivation of the macaque caudal intraparietal area (CIP) during functional magnetic resonance imaging (fMRI) reduced fMRI activations in posterior parietal cortex in the dorsal stream and, surprisingly, also in the inferotemporal cortex (ITC) in the ventral visual stream. Moreover, CIP inactivation caused a perceptual deficit in a depth-structure categorization task. CIP-microstimulation during fMRI further suggests that CIP projects via posterior parietal areas to the ITC in the ventral stream. To our knowledge, these results provide the first causal evidence for the flow of visual 3D information from the dorsal stream to the ventral stream, and identify CIP as a key area for depth-structure processing. Thus, combining reversible inactivation and electrical microstimulation during fMRI provides a detailed view of the functional interactions between the two visual processing streams. PMID:27082854

  8. A chlorite mineral surface actively drives the deposition of DNA molecules in stretched conformations

    Muscovite mica is commonly used to immobilize DNA molecules onto a flat surface. This method, however, requires either the use of divalent cations in the buffer solution or the chemical modification of the surface. Here we show that DNA molecules have different binding affinities and assume different conformations when adsorbed to different layered minerals. In particular, the effect of biotite, muscovite, talc, brucite and chlorite upon DNA binding is investigated. Using atomic force microscopy it is possible to quantify the amount of DNA deposited onto a flat surface and it is experimentally confirmed that biotite, talc and brucite have a much higher affinity than muscovite (7-, 20- and 25-fold more volume of DNA deposited, respectively). The deposition of DNA onto chlorite presents areas (brucite-like) with high DNA coverage and areas (mica-like) where DNA molecules are absent. We regularly observed isolated DNA molecules that became stretched across these regions of low affinity. The stretching is not induced by the deposition procedure but is driven by the surface potential gradient between brucite-like and mica-like regions in chlorite. The active stretching of DNA on chlorite is a clear indication of the technological potential carried by these materials when used as substrates for biomolecules

  9. What drives the dust activity of comet 67P/Churyumov-Gerasimenko?

    Gundlach, B; Keller, H U; Skorov, Y V

    2015-01-01

    We use the gravitational instability formation scenario of cometesimals to derive the aggregate size that can be released by the gas pressure from the nucleus of comet 67P/Churyumov-Gerasimenko for different heliocentric distances and different volatile ices. To derive the ejected aggregate sizes, we developed a model based on the assumption that the entire heat absorbed by the surface is consumed by the sublimation process of one volatile species. The calculations were performed for the three most prominent volatile materials in comets, namely, H_20 ice, CO_2 ice, and CO ice. We find that the size range of the dust aggregates able to escape from the nucleus into space widens when the comet approaches the Sun and narrows with increasing heliocentric distance, because the tensile strength of the aggregates decreases with increasing aggregate size. The activity of CO ice in comparison to H_20 ice is capable to detach aggregates smaller by approximately one order of magnitude from the surface. As a result of the...

  10. Posterior Parietal Cortex Drives Inferotemporal Activations During Three-Dimensional Object Vision.

    Ilse C Van Dromme

    2016-04-01

    Full Text Available The primate visual system consists of a ventral stream, specialized for object recognition, and a dorsal visual stream, which is crucial for spatial vision and actions. However, little is known about the interactions and information flow between these two streams. We investigated these interactions within the network processing three-dimensional (3D object information, comprising both the dorsal and ventral stream. Reversible inactivation of the macaque caudal intraparietal area (CIP during functional magnetic resonance imaging (fMRI reduced fMRI activations in posterior parietal cortex in the dorsal stream and, surprisingly, also in the inferotemporal cortex (ITC in the ventral visual stream. Moreover, CIP inactivation caused a perceptual deficit in a depth-structure categorization task. CIP-microstimulation during fMRI further suggests that CIP projects via posterior parietal areas to the ITC in the ventral stream. To our knowledge, these results provide the first causal evidence for the flow of visual 3D information from the dorsal stream to the ventral stream, and identify CIP as a key area for depth-structure processing. Thus, combining reversible inactivation and electrical microstimulation during fMRI provides a detailed view of the functional interactions between the two visual processing streams.

  11. An Estrogen-Responsive Module in the Ventromedial Hypothalamus Selectively Drives Sex-Specific Activity in Females

    Stephanie M. Correa

    2015-01-01

    Full Text Available Estrogen-receptor alpha (ERα neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

  12. A high voltage DC-DC converter driving a Dielectric Electro Active Polymer actuator for wind turbine flaps

    Thummala, Prasanth; Zhang, Zhe; Andersen, Michael A. E.; Thomsen, Ole Cornelius

    2012-01-01

    The Dielectric Electro Active Polymer (DEAP) material is a very thin (~80 μm) silicone elastomer film with a compliant metallic electrode layer on both sides. The DEAP is fundamentally a capacitor that is capable of very high strain. The property that the polymer changes its shape, as a result of...... topology to obtain high voltage at low current, for driving the DEAP actuator. Simulation and experimental results for uni-directional flyback converter topology are shown....... flaps. With the DEAP based high power actuator, it is expected to make a reliable and light solution with superior controllability. The current DEAP technology requires high DC voltage in the range of kV to fully utilize the DEAP material as an actuator. In this paper we propose a flyback converter......The Dielectric Electro Active Polymer (DEAP) material is a very thin (~80 μm) silicone elastomer film with a compliant metallic electrode layer on both sides. The DEAP is fundamentally a capacitor that is capable of very high strain. The property that the polymer changes its shape, as a result of...

  13. Platelet activating factor-induced ceramide micro-domains drive endothelial NOS activation and contribute to barrier dysfunction.

    Sanda Predescu

    Full Text Available The spatial and functional relationship between platelet activating factor-receptor (PAF-R and nitric oxide synthase (eNOS in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles.

  14. Driving offences

    Corbett, C

    2010-01-01

    Copyright @ 2010, Taylor & Francis Group. This material is posted on this site with the permission of the publishers. This chapter on driving offences will largely follow the template of earlier chapters except that owing to their vast number, a limited selection only will be examined based on their high volume, seriousness and public concern. The first section will define what driving offences are, how they developed alongside the emerging car culture, and it will consider the contempora...

  15. Impacts of Human Activity on Biodiversity-An Approach to Driving Force Indicators%人类活动对生物多样性的影响

    Richard Dawson; 曹志平

    2005-01-01

    The impact of human activity on biodiversity is very complicated, making it difficult to design practical indicators for assessment. Currently, state and response indicators are listed within Chapter 15 of Agenda 21, but no mention is made of driving force indicators and how they relate to biodiversity protection. This paper repre-sents an effort to identify and then operationalize the idea of driving force indicators at national level Five humaninduced factors affecting biodiversity were discussed: (a) habitat loss and fragmentation; (b) overexploitation of resources; (c) species introduction; (d) pollution; and (e) climate change. From these five factors, a subset was selected to serve as possible driving force indicators: (1) habitat loss, (2) the ratio of exotic species to indigenous ones, and (3) the change in pollution status. Although the three indicators are relatively simple, they cover the most important human impacts on biodiversity and offer the potential for further redefinition and ultimate use within the spirit of biodiversity protection.

  16. Driving Method for Compensating Reliability Problem of Hydrogenated Amorphous Silicon Thin Film Transistors and Image Sticking Phenomenon in Active Matrix Organic Light-Emitting Diode Displays

    Shin, Min-Seok; Jo, Yun-Rae; Kwon, Oh-Kyong

    2011-03-01

    In this paper, we propose a driving method for compensating the electrical instability of hydrogenated amorphous silicon (a-Si:H) thin film transistors (TFTs) and the luminance degradation of organic light-emitting diode (OLED) devices for large active matrix OLED (AMOLED) displays. The proposed driving method senses the electrical characteristics of a-Si:H TFTs and OLEDs using current integrators and compensates them by an external compensation method. Threshold voltage shift is controlled a using negative bias voltage. After applying the proposed driving method, the measured error of the maximum emission current ranges from -1.23 to +1.59 least significant bit (LSB) of a 10-bit gray scale under the threshold voltage shift ranging from -0.16 to 0.17 V.

  17. A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway

    Tundup, Smanla; Srivastava, Leena; Norberg, Thomas; Watford, Wendy; Harn, Donald

    2015-01-01

    The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewis(x) trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1. LNFPIII-NGC drives alternative activation of macrophages and dendritic cells via NF kappa B activation in a TLR4 dependent mechanism. However, ...

  18. AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells

    The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. - highlights: • CSE1L is a key player in nucleocytoplasmic traffic by forming complex with Ran. • AKT phosphorylates RanBP3 that regulates the nucleocytoplasmic gradient of Ran. • The activated oncogenic AKT drives the nuclear accumulation of CSE1L. • CSE1L in the nucleus up-regulates genes conveying pro-oncogenic signals. • CSE1L might contribute to tumor progression driven by the activated oncogenic AKT

  19. AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells

    Lorenzato, Annalisa; Biolatti, Marta [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy); Delogu, Giuseppe [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); Capobianco, Giampiero [Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari (Italy); Farace, Cristiano [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); Dessole, Salvatore; Cossu, Antonio; Tanda, Francesco [Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari (Italy); Madeddu, Roberto [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); National Institute of Biostructures and Biosystems, Rome (Italy); Olivero, Martina [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy); Di Renzo, Maria Flavia, E-mail: mariaflavia.direnzo@unito.it [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy)

    2013-10-15

    The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. - highlights: • CSE1L is a key player in nucleocytoplasmic traffic by forming complex with Ran. • AKT phosphorylates RanBP3 that regulates the nucleocytoplasmic gradient of Ran. • The activated oncogenic AKT drives the nuclear accumulation of CSE1L. • CSE1L in the nucleus up-regulates genes conveying pro-oncogenic signals. • CSE1L might contribute to tumor progression driven by the activated oncogenic AKT.

  20. Effects of angiotensin Ⅱ receptor antagonist on expression of plasminogen activator inhibitor-1 in the renal biopsy of patients with chronic kidney disease%血管紧张素Ⅱ受体拮抗剂对慢性肾脏病患者肾组织中纤溶酶原激活物抑制物-1表达的影响

    王文革; 李侠

    2010-01-01

    Objective To evaluate the effects of angiotensin Ⅱreceptor antagonist (ARB) on expression of plasminogen activator inhibitor(PAI)-1 in the human renal biopsy of patients with chronic kidney disease(CKD)and analyse its clinical significance.Methods PAI-1 expression of 63 specimens with CKD was detected by immunohistochemistry and quantitative analysis was achieved by image analysis system. meanwhile, the patients'clinical data were collected,and PAI-1 expression of 63 specimens with CKD was compared with that of normal renal tissue(19 cases).Results Compared with the normal renal tissue,the expression of PAI-1 in CKD 1,2 and 3 stage wag respectively drastically increased(P<0.05).The expression of PAI-1 in CKD 3 stage was higher than that in CKD 1 and 2 stage(P<0.05).The expression of PAI-1 in the patients treated by valsartan[renal corpuscle(4.73±1.18)%,renal tubule(37.16±6.81)%]was lower than that with no treatment[renal corpuscle(5.81±1.95)%,renal tubule(43.22 ±10.25)%](P<0.05).Conclusions It suggests that the abnormal expression of PAI-1 in CKD play an important role in the progression of glomerular and tubulointerstitiai sclerosis in patients with CKD.ARB may prevent the development of renal inflammation and sclerosis by inhibiting the production of PAI-1.ARB may contribute to the prevention and therapy of CKD.%目的 探讨血管紧张索Ⅱ受体拮抗剂(ARB)对慢性肾脏病(CKD)患者肾组织中纤溶酶原激活物抑制物(PAI)-1表达的影响及临床意义.方法 采用免疫组化法检测63例CKD患者肾穿刺标本中PAI-1的表达水平,用图像分析法对PAI-1进行定量测定,同时收集患者的相关临床资料,并与因肾肿瘤切除肾脏的远离肿瘤部分的正常肾组织19例比较.结果 CKD 1、2、3期患者PAI-1在肾组织中的表达均较正常肾组织显著增多(P<0.05);而CKD 3期患者PAI-1在肾组织中的表达明显高于CKDI期和2期患者(P<0.05).应用缬沙坦治疗的CKD 16例患者肾组织中PAI-1

  1. Proteomic Profiling of Differentially Expressed Proteins from Bax inhibitor-1 Knockout and Wild Type Mice

    Li, Bo; John C Reed; Kim, Hyung-Ryong; Chae, Han-Jung

    2012-01-01

    Bax inhibitor-1 (BI-1) is an anti-apoptotic protein located in the endoplasmic reticulum (ER). The role of BI-1 has been studied in different physiopathological models including ischemia, diabetes, liver regeneration and cancer. However, fundamental knowledge about the effects of BI-1 deletion on the proteome is lacking. To further explore this protein, we compared the levels of different proteins in bi-1−/− and bi-1+/+ mouse tissues by two-dimensional electrophoresis (2-DE) and mass spectrom...

  2. Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice

    Sui, Zhi-Yan; Chae, Han-Jung; Huang, Guang-Biao; Zhao, Tong; Shrestha Muna, Sushma; Chung, Young-Chul

    2012-01-01

    Objective The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1-/- mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1-/- mice. Methods We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were le...

  3. Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1

    Einholm, Anja P; Pedersen, Katrine E; Wind, Troels;

    2003-01-01

    -inactivated PAI-1 is inert to reaction with its target proteases and has a decreased susceptibility to non-target proteases, in spite of a generally increased proteolytic susceptibility of specific peptide bonds elsewhere in PAI-1. The properties of XR5118-inactivated PAI-1 were different from those of the so...

  4. Plasma plasminogen activator inhibitor-1 predicts myocardial infarction in HIV-1-infected individuals

    Knudsen, Andreas; Katzenstein, Terese L; Benfield, Thomas;

    2014-01-01

    (PAI-1) were measured using a Luminex assay in plasma samples from routine visits both 12 and 2 months prior to the case patient's MI. RESULTS: The two groups had similar HIV characteristics and traditional cardiovascular risk factors. In univariate analysis, PAI-1 levels were associated with MI......OBJECTIVES: Biomarkers of endothelial dysfunction, inflammation and coagulation are associated with atherosclerosis and cardiovascular disease, but their association and possible predictive value remain controversial among HIV-1-infected individuals. We sought to investigate the association of...... seven biomarkers with first-time myocardial infarction (MI) in an HIV-1-infected population. DESIGN: A matched case-control study of 54 cases and 54 controls. METHODS: We compared 54 HIV-1-infected patients with verified first-time MI and 54 HIV-1-infected controls matched for age, duration of...

  5. Plasminogen activator inhibitor-1 deficient mice are protected from angiotensin II-induced fibrosis

    Beier, Juliane I.; Kaiser, J. Phillip; Guo, Luping; Martínez-Maldonado, Manuel; Arteel, Gavin E.

    2011-01-01

    PAI-1 has been shown to be both profibrotic and antifibrotic in animal models of hepatic fibrosis. Although these models have similarities to human fibrotic liver disease, no rodent model completely recapitulates the clinical situation; indeed, transaminase values in most models of hepatic fibrosis are much higher than in chronic liver diseases in humans. Here, wild-type and PAI-1−/− mice were administered AngII (500 ng/kg/min) for 4 weeks. ECM accumulation was evaluated by Sirius red stainin...

  6. Correlation of prefrontal cortical activation with changing vehicle speeds in actual driving: a vector-based functional near-infrared spectroscopy study

    Kouji Yamamoto

    2013-12-01

    Full Text Available Traffic accidents occur more frequently during deceleration than during acceleration. However, little is known about the relationship between brain activation and vehicle acceleration because it has been difficult to measure the brain activation of drivers while they drive. In this study, we measured brain activation during actual driving using vector-based functional near-infrared spectroscopy. Subjects decelerated from 100 to 50 km/h (speed reduction task and accelerated from 50 to 100 km/h (speed increase task while driving on an expressway, in the daytime and at night. We examined correlations between average vehicle acceleration in each task and five hemodynamic indices: changes in oxygenated hemoglobin (ΔoxyHb, deoxygenated hemoglobin (ΔdeoxyHb, cerebral blood volume (ΔCBV, and cerebral oxygen exchange (ΔCOE; and the phase angle k (degrees derived from the other hemoglobin (Hb indices. ΔoxyHb and ΔCBV reflect changes in cerebral blood flow, whereas ΔdeoxyHb, ΔCOE, and k are related to variations in cerebral oxygen metabolism. Most of the resulting correlations with specific brain sites, for all the indices, appeared during deceleration rather than during acceleration. Faster deceleration resulted in greater increases in ΔdeoxyHb, ΔCOE, and k in the prefrontal cortex (r 0.4, p < 0.01, suggesting oxygen metabolism associated with transient ischemic changes. Our results suggest that vehicle deceleration requires more brain activation, focused in the prefrontal cortex, than does acceleration. From the standpoint of the indices used, we found that simultaneous analysis of multiple hemodynamic indices was able to detect not only the blood flow components of hemodynamic responses, but also more localized frontal lobe activation involving oxygen metabolism.

  7. The Drive-Wise Project: Driving Simulator Training increases real driving performance in healthy older drivers

    Gianclaudio Casutt

    2014-05-01

    Full Text Available Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training.Methods: Ninety-one healthy active drivers (62 – 87 years were randomly assigned to either (1 a driving simulator training group, (2 an attention training group (vigilance and selective attention, or (3 a control group. The main outcome variables were on-road driving and cognitive performance. Seventy-seven participants (85% completed the training and were included in the analyses. Training gains were analyzed using a multiple regression analysis with planned comparisons.Results: The driving simulator training group showed an improvement in on-road driving performance compared to the attention training group. In addition, both training groups increased cognitive performance compared to the control group. Conclusion: Driving simulator training offers the potential to enhance driving skills in older drivers. Compared to the attention training, the simulator training seems to be a more powerful program for increasing older drivers’ safety on the road.

  8. Motor Integrated Variable Speed Drives

    Singh, Yash Veer

    A new trend in the variable speed drives (VSDs) is to develop fully integrated systems, which lead to low-cost products with shorter design cycles. Motor Integrated design of VSDs will reduce cable length to connect drive with machine windings and installation time for end user. The electric drives...... converter losses and its size so it can fit inside the motor housing. Weight and volume of a filter inductor has to come down drastically to make it a suitable power converter for motor integrated variable speed drives. Introduction of active power electronic switches can ensure very high performance and...

  9. Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making, Outcome, and Peer Influence in Male Adolescents.

    Victor Vorobyev

    Full Text Available Increased propensity for risky behavior in adolescents, particularly in peer groups, is thought to reflect maturational imbalance between reward processing and cognitive control systems that affect decision-making. We used functional magnetic resonance imaging (fMRI to investigate brain functional correlates of risk-taking behavior and effects of peer influence in 18-19-year-old male adolescents. The subjects were divided into low and high risk-taking groups using either personality tests or risk-taking rates in a simulated driving task. The fMRI data were analyzed for decision-making (whether to take a risk at intersections and outcome (pass or crash phases, and for the influence of peer competition. Personality test-based groups showed no difference in the amount of risk-taking (similarly increased during peer competition and brain activation. When groups were defined by actual task performance, risk-taking activated two areas in the left medial prefrontal cortex (PFC significantly more in low than in high risk-takers. In the entire sample, risky decision-specific activation was found in the anterior and dorsal cingulate, superior parietal cortex, basal ganglia (including the nucleus accumbens, midbrain, thalamus, and hypothalamus. Peer competition increased outcome-related activation in the right caudate head and cerebellar vermis in the entire sample. Our results suggest that the activation of the medial (rather than lateral PFC and striatum is most specific to risk-taking behavior of male adolescents in a simulated driving situation, and reflect a stronger conflict and thus increased cognitive effort to take risks in low risk-takers, and reward anticipation for risky decisions, respectively. The activation of the caudate nucleus, particularly for the positive outcome (pass during peer competition, further suggests enhanced reward processing of risk-taking under peer influence.

  10. INCREASED STABLE BETA IN DIII-D BY SUPPRESSION OF A NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE AND ACTIVE FEEDBACK

    OAK A271 INCREASED STABLE BETA IN DIII-D BY SUPPRESSION OF A NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE AND ACTIVE FEEDBACK. In DIII-D, the first real-time active control of the electron cyclotron current drive stabilization of a neoclassical tearing mode (here m/n=3/2) is demonstrated. The plasma control system is put into a search and suppress mode to align the ECCD with the island by making either small rigid radial position shifts (of order 1 cm) of the entire plasma (and thus the island) or small changes in toroidal field (of order 0.5%) which radially moves the second harmonic resonance location (and thus the rf current drive). The optimum position minimizes the real-time mode amplitude signal and stabilization occurs despite changes in island location from discharge-to-discharge or from time-to-time. When the neutral beam heating power is programmed to rise after mode suppression by the ECCD, the plasma pressure increases above the peak at the onset of the neoclassical tearing mode until the magnetic island reappears due to the ECCD no longer being on the optimal position. Real-time tracking of the change in location of q=3/2 due to the Shafranov shift with increasing beta is necessary to position the ECCD in the absence of a mode so that higher stable beta can be sustained. The control techniques developed for the m/n=3/2 NTM are also being applied to the more deleterious m/n-2/1 NTM. For the first time in any tokamak, an m/n=2/1 mode has been completely suppressed using radially localized off-axis ECCD

  11. Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen.

    Schmidt, S M; König, T; Bringmann, A; Held, S; von Schwarzenberg, K; Heine, A; Holderried, T A W; Stevanovic, S; Grünebach, F; Brossart, P

    2009-10-01

    Using dendritic cells (DCs) electroporated with whole RNA isolated from blasts of a patient with acute myeloid leukemia (AML), we were able to generate leukemia-specific cytotoxic T lymphocytes (CTLs) capable of recognizing the leucemic cells. To identify T-cell epitopes mediating lysis of malignant cells, peptides were eluted from the patient's blasts and analyzed by mass spectrometry (LC/MS)-based peptide sequencing. Using this approach, an HLA-A24-binding peptide derived from Bax inhibitor-1 (BI-1), a regulator of apoptosis pathways, was identified as an epitope recognized by the generated CTLs. To further characterize this novel antigenic peptide, CTLs were induced using DCs electroporated with RNA coding for BI-1 or pulsed with the cognate peptide. These CTLs generated from healthy donors in vitro efficiently lysed the patient's blasts as well as other HLA-matched leukemic cells. In conclusion, we identified a BI-1 peptide as a novel immunogenic tumor-associated antigen (TAA) in AML. In vitro induction of BI-1-specific CTLs by RNA transfection or pulsing of DCs with the synthetically generated peptide was a feasible and highly effective method to generate leukemia-specific CTLs. As BI-1 is (over-) expressed in a broad variety of malignancies, it may represent an interesting novel TAA in the context of cancer vaccines. PMID:19609282

  12. Expression of Arabidopsis Bax Inhibitor-1 in transgenic sugarcane confers drought tolerance.

    Ramiro, Daniel Alves; Melotto-Passarin, Danila Montewka; Barbosa, Mariana de Almeida; Santos, Flavio Dos; Gomez, Sergio Gregorio Perez; Massola Júnior, Nelson Sidnei; Lam, Eric; Carrer, Helaine

    2016-09-01

    The sustainability of global crop production is critically dependent on improving tolerance of crop plants to various types of environmental stress. Thus, identification of genes that confer stress tolerance in crops has become a top priority especially in view of expected changes in global climatic patterns. Drought stress is one of the abiotic stresses that can result in dramatic loss of crop productivity. In this work, we show that transgenic expression of a highly conserved cell death suppressor, Bax Inhibitor-1 from Arabidopsis thaliana (AtBI-1), can confer increased tolerance of sugarcane plants to long-term (>20 days) water stress conditions. This robust trait is correlated with an increased tolerance of the transgenic sugarcane plants, especially in the roots, to induction of endoplasmic reticulum (ER) stress by the protein glycosylation inhibitor tunicamycin. Our findings suggest that suppression of ER stress in C4 grasses, which include important crops such as sorghum and maize, can be an effective means of conferring improved tolerance to long-term water deficit. This result could potentially lead to improved resilience and yield of major crops in the world. PMID:26872943

  13. Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases

    Burra Patrizia

    2010-04-01

    Full Text Available Abstract Background Bax inhibitor-1 (BI-1 is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1 to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2 to determine whether HCV and HBV infections modulate said expression. Methods We examined 62 patients: 39 with chronic hepatitis (CH (31 HCV-related and 8 HBV-related; 7 with cirrhosis (6 HCV-related and 1 HBV-related; 13 with hepatocellular carcinoma (HCC [7 in viral cirrhosis (6 HCV- and 1 HBV-related, 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot. Results CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P Conclusions BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.

  14. The prediction of changes of characteristics of materials and units of the drive mechanism of solar arrays of a spacecraft with the term of active existence of 10 to 15 years

    Shatikhin, V. Ye.; Pereverziev, Ye. S.; Daniiev, Yu. F.

    We consider changes of characteristics of materials and units of the drive mechanism of solar arrays of spacecraft under the influence of open space factors for the term of active existence of 10 to 15 years. The main open space factors effecting on the characteristics of materials and units of the drive mechanism are listed. The analysis of possible flaws and failures of the drive mechanism is made. We derived the probability of the penetration of meteoric bodies for a drive unit of a solar array during a 10-year and a 15-year flights. We developed some recommendations concerning the elaboration of solar array drive mechanisms for spacecraft with the long term of existence.

  15. Driving on the Descartes

    1972-01-01

    Astronaut John W. Young, Apollo 16 mission commander, drives the 'Rover', Lunar Roving Vehicle (LRV) to its final parking place near the end of the third extravehicular activity (EVA-3) at the Descartes landing site. Astronaut Charles M. Duke Jr., Lunar Module pilot, took this photograph looking southward. The flank of Stone Mountain can be seen on the horizon at left. The shadow of the Lunar Module 'Orion' is visible in the foreground.

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

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

    1995-01-01

    The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...

  17. [Driving and health at work].

    Giorgio, Marie-Thérèse

    2015-09-01

    The role of the occupational physician is to prevent occupational accidents and diseases. Therefore, he is the one to decide if a worker is fit to drive in the context of his professional activity, including in cases where no specific driving license is required (e.g. forklift truck, mobile crane). This decision is an important one, as two thirds of fatal occupational accidents occur on the road. The decision is made on the basis of both a medical examination and the regulation, which indicates all contraindications to driving. The physician's responsibility is involved, as is the employer's, as he must ensure that his employee is fit to drive and possesses a valid driving license at all times. PMID:25960440

  18. Smartphone Based Approach For Monitoring Inefficient And Unsafe Driving Behavior And Recognizing Drink And Drive Conditions.

    G. V. Mane

    2015-08-01

    Full Text Available Many automobile drivers having knowledge of the driving behaviours and habits that can lead to inefficient and unsafe driving. However it is often the case that these same drivers unknowingly manifest these inefficient and unsafe driving behaviours in their everyday driving activity. The proposed system proposes a practical and economical way to capture measure and alert drives of inefficient and unsafe driving as well as highly efficient system aimed at early detection and alert of dangerous vehicle maneuvers typically related to drunk driving. The upcoming solution consists of a mobile application running on a modern smartphone device paired with a compatible OBDII On-board diagnostics II reader.

  19. PREVALENCIA DEL DESEO SEXUAL INHIBIDO EN MUJERES EN EDAD FÉRTIL Y FACTORES RELACIONADOS PREVALENCE OF INHIBITED SEXUAL DRIVE IN WOMEN ACTIVELY REPRODUCTIVE AND RELATED FACTORS

    MÓNICA CHARNAY REBOLLEDO

    2003-06-01

    Full Text Available Estudio descriptivo correlacional cuyo objetivo fue conocer la magnitud del deseo sexual inhibido y factores que lo influyen, en mujeres en edad fértil usuarias del Sistema Municipalizado de Salud de la comuna de Concepción. La muestra estudiada correspondió a 367 mujeres. Se aplicó un cuestionario elaborado por la autora que mide las variables biosociodemográficas y factores que influyen en la presencia de deseo sexual inhibido y un instrumento de Master, Johnson y Kolodny, "Autovaloración del Deseo Sexual Inhibido", modificado y adaptado por la autora. Los resultados nos indican que un 34,9% de las mujeres presenta deseo sexual inhibido, que existe relación estadísticamente significativa entre la variable, nivel educacional de la mujer y de la pareja, situación laboral de la pareja, satisfacción de las necesidades básicas, satisfacción sexual, satisfacción con la relación de pareja y la variable dependiente deseo sexual inhibido. Para la asociación estadística, se utilizó chi cuadrado de PearsonThe objective of this descriptive correlational study was to know the magnitude of the inhibited sexual desire and the factors that affect it, in women reproductively active, registered at the Municipal Health System in Concepción city. The population studied comprised 367 women. A questionnaire made by the author measuring biosocialdemographic variables and factors affecting the inhibited sexual drive and a modified Master, Johnson and Kolodny's instrument on "Self evaluation of Inhibited Sexual Drive" were applied. The results indicate that 34.9% of women present Inhibited Sexual Drive and that there is a statistically significant relation between the variables, women's schooling, couple's schooling, couple's laboral situation, basic needs satisfaction, sexual satisfaction, satisfaction about the couple relationship and the inhibited sexual drive dependent variable. For the statistical association Pearson Chi square was used

  20. Driving electrocatalytic activity by interface electronic structure control in a metalloprotein hybrid catalyst for efficient hydrogen evolution.

    Behera, Sushant Kumar; Deb, Pritam; Ghosh, Arghya

    2016-08-17

    The rational design of metalloprotein hybrid structures and precise calculations for understanding the role of the interfacial electronic structure in regulating the HER activity of water splitting sites and their microscopic effect for obtaining robust hydrogen evolution possess great promise for developing highly efficient nano-bio hybrid HER catalysts. Here, we employ high-accuracy linear-scaling density functional theory calculations using a near-complete basis set and a minimal parameter implicit solvent model within the self-consistent calculations, on silver (Ag) ions assimilated on bacteriorhodopsin (bR) at specific binding sites. Geometry optimization indicates the formation of active sites at the interface of the metalloprotein complex and the density of states reflects the metallic nature of the active sites. The reduced value of the canonical orbital gap indicates the state of dynamic nature after Ag ion assimilation on active sites and smooth electron transfer. These incorporated active protein sites are more efficient in electrolytic splitting of water than pristine sites due to their low value of Gibbs free energy for the HER in terms of hydrogen coverages. Volcano plot analysis and the free energy diagram are compared for understanding the hydrogen evolution efficiency. Moreover, the essential role of the interfacial electronic properties in regulating the HER catalytic activity of water splitting sites and enhancing the efficiency is elucidated. PMID:27499158

  1. A spectrum of CodY activities drives metabolic reorganization and virulence gene expression in Staphylococcus aureus.

    Waters, Nicholas R; Samuels, David J; Behera, Ranjan K; Livny, Jonathan; Rhee, Kyu Y; Sadykov, Marat R; Brinsmade, Shaun R

    2016-08-01

    The global regulator CodY controls the expression of dozens of metabolism and virulence genes in the opportunistic pathogen Staphylococcus aureus in response to the availability of isoleucine, leucine and valine (ILV), and GTP. Using RNA-Seq transcriptional profiling and partial activity variants, we reveal that S. aureus CodY activity grades metabolic and virulence gene expression as a function of ILV availability, mediating metabolic reorganization and controlling virulence factor production in vitro. Strains lacking CodY regulatory activity produce a PIA-dependent biofilm, but development is restricted under conditions that confer partial CodY activity. CodY regulates the expression of thermonuclease (nuc) via the Sae two-component system, revealing cascading virulence regulation and factor production as CodY activity is reduced. Proteins that mediate the host-pathogen interaction and subvert the immune response are shut off at intermediate levels of CodY activity, while genes coding for enzymes and proteins that extract nutrients from tissue, that kill host cells, and that synthesize amino acids are among the last genes to be derepressed. We conclude that S. aureus uses CodY to limit host damage to only the most severe starvation conditions, providing insight into one potential mechanism by which S. aureus transitions from a commensal bacterium to an invasive pathogen. PMID:27116338

  2. Bax Inhibitor-1, a Conserved Cell Death Suppressor, Is a Key Molecular Switch Downstream from a Variety of Biotic and Abiotic Stress Signals in Plants

    Naohide Watanabe

    2009-07-01

    Full Text Available In Nature plants are constantly challenged by a variety of environmental stresses that could lead to disruptions in cellular homeostasis. Programmed cell death (PCD is a fundamental cellular process that is often associated with defense responses to pathogens, during development and in response to abiotic stresses in fungi, animals and plants. Although there are many characteristics shared between different types of PCD events, it remains unknown whether a common mechanism drives various types of PCD in eukaryotes. One candidate regulator for such a mechanism is Bax Inhibitor-1 (BI-1, an evolutionary conserved, endoplasmic reticulum (ER-resident protein that represents an ancient cell death regulator that potentially regulates PCD in all eukaryotes. Recent findings strongly suggested that BI-1 plays an important role in the conserved ER stress response pathway to modulate cell death induction in response to multiple types of cell death signals. As ER stress signaling pathways has been suggested to play important roles not only in the control of ER homeostasis but also in other biological processes such as the response to pathogens and abiotic stress in plants, BI-1 might function to control the convergence point that modulates the level of the “pro-survival and pro-death” signals under multiple stress conditions.

  3. Improvement in Brightness Uniformity by Compensating for the Threshold Voltages of Both the Driving Thin-Film Transistor and the Organic Light-Emitting Diode for Active-Matrix Organic Light-Emitting Diode Displays

    Ching-Lin Fan; Hao-Wei Chen; Hui-Lung Lai; Bo-Liang Guo; Bohr-Ran Huang

    2014-01-01

    This paper proposes a novel pixel circuit design and driving method for active-matrix organic light-emitting diode (AM-OLED) displays that use low-temperature polycrystalline-silicon thin-film transistors (LTPS-TFTs) as driving element. The automatic integrated circuit modeling simulation program with integrated circuit emphasis (AIM-SPICE) simulator was used to verify that the proposed pixel circuit, which comprises five transistors and one capacitor, can supply uniform output current. The v...

  4. Distractions in Everyday Driving

    ... while driving, which is one of the reasons distracted driving is such a big problem. Driver inattention is ... you’re doing any of these things while driving, you become distracted in ways that increase your risk of crashing. ...

  5. Chibby drives β catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells.

    Mancini, Manuela; Leo, Elisa; Takemaru, Ken-Ichi; Campi, Virginia; Borsi, Enrica; Castagnetti, Fausto; Gugliotta, Gabriele; Santucci, Maria Alessandra; Martinelli, Giovanni

    2013-09-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL fusion protein. However, the phenotype of leukemic stem cells (LSC) is sustained by β catenin rather than by the BCR-ABL TK. β catenin activity in CML is contingent upon its stabilization proceeding from the BCR-ABL-induced phosphorylation at critical residues for interaction with the Adenomatous polyposis coli (APC)/Axin/glycogen synthase kinase 3 (GSK3) destruction complex or GSK3 inactivating mutations. Here we studied the impact of β catenin antagonist Chibby (CBY) on β catenin signaling in BCR-ABL1+ cells. CBY is a small conserved protein which interacts with β catenin and impairs β catenin-mediated transcriptional activation through two distinct molecular mechanisms: 1) competition with T cell factor (TCF) or lymphoid enhancer factor (LEF) for β catenin binding; and 2) nuclear export of β catenin via interaction with 14-3-3. We found that its enforced expression in K562 cell line promoted β catenin cytoplasmic translocation resulting in inhibition of target gene transcription. Moreover, cytoplasmic accumulation of β catenin activated the endoplasmic reticulum (ER) stress-associated pathway known as unfolded protein response (UPR). CBY-driven cytoplasmic accumulation of β catenin is also a component of BCR-ABL1+ cell response to the TK inhibitor Imatinib (IM). It evoked the UPR activation leading to the induction of BCL2-interacting mediator of cell death (BIM) by UPR sensors. BIM, in turn, contributed to the execution phase of apoptosis in the activation of ER resident caspase 12 and mobilization of Ca(2+) stores. PMID:23707389

  6. BWR feedwater nozzle and control rod drive return line nozzle cracking: resolution of generic technical activity A-10. Technical report

    This report summarizes work performed by the NRC staff in the resolution of Generic Technical Activity A-10, 'BWR Nozzle Cracking'. Generic Technical Activity A-10 is one of the generic technical subjects designated as 'unresolved safety issues' pursuant to Section 210 of the Energy Reorganization Act of 1974. The report describes the technical issues, the technical studies and analyses performed by the General Electric Company and the NRC staff, the staff's technical positions based on these studies, and the staff's plans for continued implementation of its technical positions. It also provides information for further work to resolve the non-destructive examination issue

  7. N-Formyl peptides drive mitochondrial damage associated molecular pattern induced neutrophil activation through ERK1/2 and P38 MAP kinase signalling pathways.

    Hazeldine, Jon; Hampson, Peter; Opoku, Francis Adusei; Foster, Mark; Lord, Janet M

    2015-01-01

    Traumatic injury results in a systemic inflammatory response syndrome (SIRS), a phenomenon characterised by the release of pro-inflammatory cytokines into the circulation and immune cell activation. Released from necrotic cells as a result of tissue damage, damage associated molecular patterns (DAMPs) are thought to initiate the SIRS response by activating circulating immune cells through surface expressed pathogen recognition receptors. Neutrophils, the most abundant leucocyte in human circulation, are heavily implicated in the initial immune response to traumatic injury and have been shown to elicit a robust functional response to DAMP stimulation. Here, we confirm that mitochondrial DAMPs (mtDAMPs) are potent activators of human neutrophils and show for the first time that signalling through the mitogen-activated-protein-kinases p38 and extracellular-signal-related-kinase 1/2 (ERK1/2) is essential for this response. At 40 and/or 100 μg/ml, mtDAMPs activated human neutrophils, indicated by a significant reduction in the surface expression of L-selectin, and triggered a number of functional responses from both resting and tumour necrosis factor-α primed neutrophils, which included reactive oxygen species (ROS) generation, degranulation, secretion of interleukin-8 and activation of p38 and ERK1/2 MAPKs. Pre-treatment of neutrophils with Cyclosporin H, a selective inhibitor of formyl peptide receptor-1 (FPR-1), significantly inhibited mtDAMP-induced L-selectin shedding as well as p38 and ERK1/2 activation, suggesting that N-formyl peptides are the main constituents driving mtDAMP-induced neutrophil activation. Indeed, no evidence of L-selectin shedding or p38 and ERK1/2 activation was observed in neutrophils challenged with mitochondrial DNA alone. Interestingly, pharmacological inhibition of p38 or ERK1/2 either alone or in combination significantly inhibited L-selectin shedding and IL-8 secretion by mtDAMP-challenged neutrophils, revealing for the first time

  8. 77 FR 32943 - Takes of Marine Mammals Incidental to Specified Activities; Pile Driving in the Columbia River, WA

    2012-06-04

    ... captive animals were not reinforced with food for remaining in the noise fields, whereas free-ranging... notice in the Federal Register on August 19, 2011 (76 FR 51947), requesting comments from the public on... activity may be found in NMFS' proposed IHA document in the Federal Register (76 FR 51947, August 19,...

  9. Driving change

    Cities have an extraordinary responsibility and motivation to act on climate change. They consume three quarters of the world's energy and are responsible for four fifths of its carbon dioxide emissions. They are also highly vulnerable to the resulting impacts of climate change: to take one example, about 20 of the world's 30 largest cities, London included, stand on low lying coasts. They also have great opportunities. Concentrating people and activities at high densities, they can use energy, materials and land efficiently. They are the places where high level, knowledge-based activities congregate, with the expertise to tackle climate change. Many are the drivers of their national economies. Five US cities - New York, Los Angeles, Chicago, Boston and Philadelphia - together constitute the world's fourth largest economy. Bangkok and Sao Paulo with just 10 per cent of their countries' populations, generate 40 per cent of national wealth. Innovation and progress in taking action on climate change action is most likely to be achieved in cities. Mayors and their municipalities have the powers and levers to reduce carbon emissions, and can show leadership in taking decisive and radical action. They control the development of land, have housing powers, and regulate - and often manage - transport. They have varying degrees of responsibility for collecting and processing waste and such other environmental infrastructure as energy and water. They own and manage buildings and vehicle fleets. And they have huge purchasing power. Although leadership from national governments is crucial in negotiating international agreements, setting frameworks and standards and providing fiscal and financial incentives, cities must lead when it comes to practical action on the ground. All over the world, city governments are taking their own initiatives, recognising the need to cooperate across national and international boundaries. Almost one thousand municipalities have made substantial

  10. NLRP3 inflammasome activation drives bystander cone photoreceptor cell death in a P23H rhodopsin model of retinal degeneration.

    Viringipurampeer, Ishaq A; Metcalfe, Andrew L; Bashar, Abu E; Sivak, Olena; Yanai, Anat; Mohammadi, Zeinabsadat; Moritz, Orson L; Gregory-Evans, Cheryl Y; Gregory-Evans, Kevin

    2016-04-15

    The molecular signaling leading to cell death in hereditary neurological diseases such as retinal degeneration is incompletely understood. Previous neuroprotective studies have focused on apoptotic pathways; however, incomplete suppression of cell death with apoptosis inhibitors suggests that other mechanisms are at play. Here, we report that different signaling pathways are activated in rod and cone photoreceptors in the P23H rhodopsin mutant rat, a model representing one of the commonest forms of retinal degeneration. Up-regulation of the RIP1/RIP3/DRP1 axis and markedly improved survival with necrostatin-1 treatment highlighted necroptosis as a major cell-death pathway in degenerating rod photoreceptors. Conversely, up-regulation of NLRP3 and caspase-1, expression of mature IL-1β and IL-18 and improved cell survival with N-acetylcysteine treatment suggested that inflammasome activation and pyroptosis was the major cause of cone cell death. This was confirmed by generation of the P23H mutation on an Nlrp3-deficient background, which preserved cone viability. Furthermore, Brilliant Blue G treatment inhibited inflammasome activation, indicating that the 'bystander cell death' phenomenon was mediated through the P2RX7 cell-surface receptor. Here, we identify a new pathway in cones for bystander cell death, a phenomenon important in development and disease in many biological systems. In other retinal degeneration models different cell-death pathways are activated, which suggests that the particular pathways that are triggered are to some extent genotype-specific. This also implies that neuroprotective strategies to limit retinal degeneration need to be customized; thus, different combinations of inhibitors will be needed to target the specific pathways in any given disease. PMID:27008885

  11. Semianalytic Models of Two-Phase Disk Winds in Active Galactic Nuclei with Combined Hydromagnetic and Radiative Driving

    Everett, John E.

    2002-01-01

    (abridged) We present a semianalytic model of steady-state magnetically and radiatively driven disk outflows in Active Galactic Nuclei (AGNs) consisting of a continuous wind with embedded clouds. The continuous outflow is launched from the disk surface as a centrifugally driven wind, whereas the clouds are uplifted from the disk by the ram pressure of the continuous outflow. In addition, the continuous wind and clouds are subject to both line and continuum radiative acceleration. We describe ...

  12. Did concentration on core competencies drive merger and acquisition activities in the 1990s? Empirical evidence for Germany.

    Hussinger, Katrin

    2005-01-01

    In the context of increasing globalization of markets, merger and acquisition activities in the 1990s are said to be driven by reorganization processes with respect to concentration on firms? core competencies in order to increase or maintain market power in international markets. This paper empirically investigates a sample of German domestic mergers in the 1990s to detect the impact of technology and market relatedness on the choice of the merging partner. Results from a conditional logit m...

  13. The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes.

    Witte, Katrin; Koch, Egon; Volk, Hans-Dieter; Wolk, Kerstin; Sabat, Robert

    2015-01-01

    Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. PMID:26406906

  14. Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

    Amato, Teresa; Abate, Francesco; Piccaluga, Pierpaolo; Iacono, Michele; Fallerini, Chiara; Renieri, Alessandra; De Falco, Giulia; Ambrosio, Maria Raffaella; Mourmouras, Vaselious; Ogwang, Martin; Calbi, Valeria; Rabadan, Roul; Hummel, Michael; Pileri, Stefano; Bellan, Cristiana

    2016-01-01

    Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. PMID:26712879

  15. Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.

    Wang, Junjian; Duan, Zhijian; Nugent, Zoann; Zou, June X; Borowsky, Alexander D; Zhang, Yanhong; Tepper, Clifford G; Li, Jian Jian; Fiehn, Oliver; Xu, Jianzhen; Kung, Hsing-Jien; Murphy, Leigh C; Chen, Hong-Wu

    2016-08-10

    Metabolic reprogramming such as the aerobic glycolysis or Warburg effect is well recognized as a common feature of tumorigenesis. However, molecular mechanisms underlying metabolic alterations for tumor therapeutic resistance are poorly understood. Through gene expression profiling analysis we found that histone H3K36 methyltransferase NSD2/MMSET/WHSC1 expression was highly elevated in tamoxifen-resistant breast cancer cell lines and clinical tumors. IHC analysis indicated that NSD2 protein overexpression was associated with the disease recurrence and poor survival. Ectopic expression of NSD2 wild type, but not the methylase-defective mutant, drove endocrine resistance in multiple cell models and xenograft tumors. Mechanistically, NSD2 was recruited to and methylated H3K36me2 at the promoters of key glucose metabolic enzyme genes. Its overexpression coordinately up-regulated hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD), two key enzymes of glycolysis and the pentose phosphate pathway (PPP), as well as TP53-induced glycolysis regulatory phosphatase TIGAR. Consequently, NSD2-driven tamoxifen-resistant cells and tumors displayed heightened PPP activity, elevated NADPH production, and reduced ROS level, without significantly altered glycolysis. These results illustrate a coordinated, epigenetic activation of key glucose metabolic enzymes in therapeutic resistance and nominate methyltransferase NSD2 as a potential therapeutic target for endocrine resistant breast cancer. PMID:27164560

  16. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses

    Mittelbrunn, María; Molina, Ana; Escribese, María M.; Yáñez-Mó, María; Escudero, Ester; Ursa, Ángeles; Tejedor, Reyes; Mampaso, Francisco; Sánchez-Madrid, Francisco

    2004-07-01

    The integrin 41 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of 41 during the formation of the immune synapse is currently unknown. Here, we show that 41 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-4 antibodies, VLA-4 colocalizes with the CD3- chain at the center of the synapse. In addition, antibody engagement of 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4+ T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.

  17. Driving Care Quality: Aligning Trainee Assessment and Supervision Through Practical Application of Entrustable Professional Activities, Competencies, and Milestones.

    Carraccio, Carol; Englander, Robert; Holmboe, Eric S; Kogan, Jennifer R

    2016-02-01

    To address the long-standing challenge of meaningful trainee assessment, the authors reviewed and expanded on the Accountable Assessment for Quality Care and Supervision (AAQCS) equation. The equation proposes that care quality is the product of the interaction between trainee performance (measured by workplace assessment) and supervision (required level of intervention to ensure care quality) in the context of the environment where the care occurs: Trainee performance × Appropriate supervision = Safe, effective patient-centered care. Assessing trainee performance and matching that performance to "appropriate" supervision, however, is fraught with challenges. The authors suggest a unifying framework that integrates entrustable professional activities (EPAs), competencies, and milestones to inform trainee assessment and supervision, thereby enabling the practical application of the AAQCS equation in the workplace. Because the unit of measure for an EPA is the outcome of whether the trainee can safely and effectively perform the professional activity without supervision, the proposed unifying framework directly aligns with the dependent variable in the AAQCS equation: care quality.The value of applying a unifying framework that integrates EPAs, competencies, and milestones to the AAQCS equation in the clinical learning environment lies in its ability to provide supervisors with a shared mental model of performance expectations for trainees, reducing unwanted variability and improving assessment accuracy; guidance for aligning performance milestones of trainees with the needed level of supervisor intervention to ensure care quality; and substrate for specific feedback to improve the trainee's professional development as a way to ensure future care quality. PMID:26509601

  18. Inefficient Driving of Bulk Turbulence by Active Galactic Nuclei in a Hydrodynamic Model of the Intracluster Medium

    Reynolds, Christopher S; Schekochihin, Alexander A

    2015-01-01

    Central jetted active galactic nuclei (AGN) appear to heat the core regions of the intracluster medium (ICM) in cooling-core galaxy clusters and groups, thereby preventing a cooling catastrophe. However, the physical mechanism(s) by which the directed flow of kinetic energy is thermalized throughout the ICM core remains unclear. We examine one widely discussed mechanism whereby the AGN induces subsonic turbulence in the ambient medium, the dissipation of which provides the ICM heat source. Through controlled inviscid 3-d hydrodynamic simulations, we verify that explosive AGN-like events can launch gravity waves (g-modes) into the ambient ICM which in turn decay to volume-filling turbulence. In our model, however, this process is found to be inefficient, with less than 1% of the energy injected by the AGN activity actually ending up in the turbulence of the ambient ICM. This efficiency is an order of magnitude or more too small to explain the observations of AGN-feedback in galaxy clusters and groups with shor...

  19. Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth

    Zhou, Linli; Xu, Mingang; Yang, Yongguang; Yang, Kun; Wickett, Randall R.; Andl, Thomas; Millar, Sarah E.

    2016-01-01

    The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth. PMID:27472062

  20. Perturbation of Ribosome Biogenesis Drives Cells into Senescence through 5S RNP-Mediated p53 Activation

    Kazuho Nishimura

    2015-03-01

    Full Text Available The 5S ribonucleoprotein particle (RNP complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses.

  1. Tractor Mechanics. Maintaining and Servicing the Power Train, Learning Activity Packages 49-53; Maintaining and Servicing the Clutch, Learning Activity Packages 54-59; Maintaining and Servicing the Transmission and Differential, Learning Activity Packages 60-68; Maintaining and Servicing the Final Drive, Learning Activity Packages 69-77.

    Clemson Univ., SC. Vocational Education Media Center.

    This series of learning activity packages focuses on four areas of tractor mechanics: (1) maintaining and servicing the power train, (2) maintaining and servicing the clutch, (3) maintaining and servicing the transmission and differential, and (4) maintaining and servicing the final drive. Each of the twenty-nine illustrated learning activity…

  2. Driving Style: Determining Factors, Characteristics, Optimization Directions

    Lobanova I. I.

    2015-01-01

    Full Text Available A system of description, identification and classification of factors determining driving style is proposed in the article; stable (sustained and variable (unstable factors determining driving style are studied. Driving style is analyzed within the framework of structural approach. The variable factor are: specifications and technical condition of the vehicle, class of the car, its prestige (from a social point of view, training of the driver, social regulators, features of the road environment, psychophysiological (and emotional condition of the driver. The stable factors are: individual-typological properties, the level of suitability for driver`s activities, personal (primarily characterological features of a driver and sources of activity. Five main characteristics of driving style are selected and presented: safety-risk, confidence with parking, relation to the means of security; planning-impulsivity; driving culture. There are results of empirical research directed on discovery of relationship between styles of driving activities (planning-universal-impulsive as one characteristic of driving style, emotions typical for driver while driving and accidents. Increase of safety as a result of planning style of activities is shown (especially for women drivers. The paper offers direction of work for optimizing driving style: the formation of compensating planning style of activities, psychotherapeutic work, modeling training, psychological selection, training and education work in driving schools.

  3. Increased stable beta in DIII-D by suppression of a neoclassical tearing mode using electron cyclotron current drive and active feedback

    In DIII-D, the first real-time active control of the electron cyclotron current drive stabilization of a neoclassical tearing mode (here m/n=3/2) is demonstrated. The plasma control system is put into a 'search and suppress' mode to align the ECCD with the island by making either small rigid radial position shifts (of order 1 cm) of the entire plasma (and thus the island) or small changes in toroidal field (of order 0.5%) which radially moves the second harmonic resonance location (and thus the rf current drive). The optimum position minimizes the real-time mode amplitude signal and stabilization occurs despite changes in island location from discharge to- discharge or from time-to-time. When the neutral beam heating power is programmed to rise after mode suppression by the ECCD, the plasma pressure increases above the peak at the onset of the neoclassical tearing mode until the magnetic island reappears due to the ECCD no longer being on the optimal position. Real-time tracking of the change in location of q=3/2 due to the Shafranov shift with increasing beta is necessary to position the ECCD in the absence of a mode so that higher stable beta can be sustained. The control techniques developed for the m/n=3/2 NTM are also being applied to the more deleterious m/n=2/1 NTM. For the first time in any tokamak, an m/n=2/1 mode has been completely suppressed using radially localized off-axis ECCD. (author)

  4. Vegetation dynamics and its driving forces from climate change and human activities in the Three-River Source Region, China from 1982 to 2012.

    Zhang, Ying; Zhang, Chaobin; Wang, Zhaoqi; Chen, Yizhao; Gang, Chengcheng; An, Ru; Li, Jianlong

    2016-09-01

    The Three-River Source Region (TRSR), a region with key importance to the ecological security of China, has undergone climate changes and a shift in human activities driven by a series of ecological restoration projects in recent decades. To reveal the spatiotemporal dynamics of vegetation dynamics and calculate the contributions of driving factors in the TRSR across different periods from 1982 to 2012, net primary productivity (NPP) estimated using the Carnegie-Ames-Stanford approach model was used to assess the status of vegetation. The actual effects of different climatic variation trends on interannual variation in NPP were analyzed. Furthermore, the relationships of NPP with different climate factors and human activities were analyzed quantitatively. Results showed the following: from 1982 to 2012, the average NPP in the study area was 187.37gcm(-2)yr(-1). The average NPP exhibited a fluctuation but presented a generally increasing trend over the 31-year study period, with an increase rate of 1.31gcm(-2)yr(-2). During the entire study period, the average contributions of temperature, precipitation, and solar radiation to NPP interannual variation over the entire region were 0.58, 0.73, and 0.09gcm(-2)yr(-2), respectively. Radiation was the climate factor with the greatest influence on NPP interannual variation. The factor that restricted NPP increase changed from temperature and radiation to precipitation. The average contributions of climate change and human activities to NPP interannual variation were 1.40gcm(-2)yr(-2) and -0.08gcm(-2)yr(-2), respectively. From 1982 to 2000, the general climate conditions were favorable to vegetation recovery, whereas human activities had a weaker negative impact on vegetation growth. From 2001 to 2012, climate conditions began to have a negative impact on vegetation growth, whereas human activities made a favorable impact on vegetation recovery. PMID:27135584

  5. Dopaminergic Circuitry Underlying Mating Drive.

    Zhang, Stephen X; Rogulja, Dragana; Crickmore, Michael A

    2016-07-01

    We develop a new system for studying how innate drives are tuned to reflect current physiological needs and capacities, and how they affect sensory-motor processing. We demonstrate the existence of male mating drive in Drosophila, which is transiently and cumulatively reduced as reproductive capacity is depleted by copulations. Dopaminergic activity in the anterior of the superior medial protocerebrum (SMPa) is also transiently and cumulatively reduced in response to matings and serves as a functional neuronal correlate of mating drive. The dopamine signal is transmitted through the D1-like DopR2 receptor to P1 neurons, which also integrate sensory information relevant to the perception of females, and which project to courtship motor centers that initiate and maintain courtship behavior. Mating drive therefore converges with sensory information from the female at the point of transition to motor output, controlling the propensity of a sensory percept to trigger goal-directed behavior. PMID:27292538

  6. RADIO ACTIVE GALAXY NUCLEI IN GALAXY CLUSTERS: HEATING HOT ATMOSPHERES AND DRIVING SUPERMASSIVE BLACK HOLE GROWTH OVER COSMIC TIME

    We estimate the average radio active galactic nucleus (AGN, mechanical) power deposited into the hot atmospheres of galaxy clusters over more than three quarters of the age of the Universe. Our sample was drawn from eight major X-ray cluster surveys and includes 685 clusters in the redshift range 0.1 44 erg s–1 exceeds the X-ray luminosity of 44% of the clusters, indicating that the accumulation of radio-AGN energy is significant in these clusters. Integrating the AGN mechanical power to redshift z = 2.0, using simple models for its evolution and disregarding the hierarchical growth of clusters, we find that the AGN energy accumulated per particle in low luminosity X-ray clusters exceeds 1 keV per particle. This result represents a conservative lower limit to the accumulated thermal energy. The estimate is comparable to the level of energy needed to 'preheat' clusters, indicating that continual outbursts from radio-AGN are a significant source of gas energy in hot atmospheres. Assuming an average mass conversion efficiency of η = 0.1, our result implies that the supermassive black holes that released this energy did so by accreting an average of ∼109 M ☉ over time, which is comparable to the level of growth expected during the quasar era.

  7. Driving While Non-White: Exploring Traffic Stops and Post-Stop Activities in North Carolina, 2005-2009

    Cameron D. Lippard

    2011-11-01

    Full Text Available Research has established that Blacks face disproportionate amounts of traffic stops, searches, and arrests by police compared to Whites. However, few studies have ventured past the Black-White dichotomy and considered how Hispanics or other minorities may face the same disparities, especially in places where the Hispanic population has dramatically increased in recent years. Using traffic stop and post-stop data compiled by the North Carolina Department of Justice from 2005 to 2009, this study explored whether Hispanics, Blacks, as well as other racial minorities experienced a higher likelihood of traffic stops, citations, searches, and arrests compared to Whites within sample of city, county, and state law enforcement agencies. We found that generally all racial and ethnic minority groups face higher rates of traffic stops than Whites by almost every law enforcement agency sampled. We also found that rates of post-stop activities including searches, citations, and arrests are higher for all racial and ethnic minority groups examined compared to Whites, especially for Hispanics. Hispanic and non-White disparities in traffic stops also cannot be explained away when controlling for population size, type of law enforcement agency, or the reason stated for the traffic stop (e.g., DWI, speeding, or investigation. More important, however, is that the rate of searches for racial and ethnic minorities did not necessarily match the rates of citations and arrests minorities receive, suggesting that some stops could be racially or ethnically motivated.

  8. Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5´-methylthioadenosine/S-adenosylhomocysteine nucleosidase

    Ronning, Donald R; Iacopelli, Natalie M; Mishra, Vidhi [Toledo

    2012-03-15

    The bacterial enzyme 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) plays a central role in three essential metabolic pathways in bacteria: methionine salvage, purine salvage, and polyamine biosynthesis. Recently, its role in the pathway that leads to the production of autoinducer II, an important component in quorum-sensing, has garnered much interest. Because of this variety of roles, MTAN is an attractive target for developing new classes of inhibitors that influence bacterial virulence and biofilm formation. To gain insight toward the development of new classes of MTAN inhibitors, the interactions between the Helicobacter pylori-encoded MTAN and its substrates and substrate analogs were probed using X-ray crystallography. The structures of MTAN, an MTAN-Formycin A complex, and an adenine bound form were solved by molecular replacement and refined to 1.7, 1.8, and 1.6 Å, respectively. The ribose-binding site in the MTAN and MTAN-adenine cocrystal structures contain a tris[hydroxymethyl]aminomethane molecule that stabilizes the closed form of the enzyme and displaces a nucleophilic water molecule necessary for catalysis. This research gives insight to the interactions between MTAN and bound ligands that promote closing of the enzyme active site and highlights the potential for designing new classes of MTAN inhibitors using a link/grow or ligand assembly development strategy based on the described H. pylori MTAN crystal structures.

  9. Extended Driving Impairs Nocturnal Driving Performances

    Patricia Sagaspe; Jacques Taillard; Torbjorn Akerstedt; Virginie Bayon; Stéphane Espié; Guillaume Chaumet; Bernard Bioulac; Pierre Philip

    2008-01-01

    Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am) on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years)...

  10. Extended Driving Impairs Nocturnal Driving Performances

    SAGASPE, Patricia; Taillard, Jacques; Åkerstedt, Torbjorn; BAYON, Virginie; Espié, Stéphane; Chaumet, Guillaume; Bioulac, Bernard; Philip, Pierre

    2008-01-01

    Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3–5am, 1–5am and 9pm–5am) on open highway. Fourteen young healthy men (mean age [±SD] = 23.4 [±1.7] years) partici...

  11. HARMONIC DRIVE SELECTION

    Piotr FOLĘGA

    2014-03-01

    Full Text Available The variety of types and sizes currently in production harmonic drive is a problem in their rational choice. Properly selected harmonic drive must meet certain requirements during operation, and achieve the anticipated service life. The paper discusses the problems associated with the selection of the harmonic drive. It also presents the algorithm correct choice of harmonic drive. The main objective of this study was to develop a computer program that allows the correct choice of harmonic drive by developed algorithm.

  12. A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway.

    Smanla Tundup

    Full Text Available The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewisx trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1. LNFPIII-NGC drives alternative activation of macrophages and dendritic cells via NFκB activation in a TLR4 dependent mechanism. However, the connection between LNFPIII-NGC activation of APCs, TLR4 signaling and subsequent MAP kinase signaling leading to anti-inflammatory activation of APCs remains unknown. In this study we determined that the innate receptor CD14 was essential for LNFPIII-NGC induction of both ERK and NFkB activation in APCs. Induction of ERK activation by LNFPIII-NGC was completely dependent on CD14/TLR4-Ras-Raf1/TPL2-MEK axis in bone marrow derived dendritic cells (BMDCs. In addition, LNFPIII-NGC preferentially induced the production of Th2 "favoring" chemokines CCL22 and matrix metalloprotease protein-9 in a CD14 dependent manner in BMDCs. In contrast, LNFPIII-NGC induces significantly lower levels of Th1 "favoring" chemokines, MIP1α, MIP1β and MIP-2 compared to levels in LPS stimulated cells. Interestingly, NGC of the identical human milk sugar LNnT, minus the alpha 1-3 linked fucose, failed to activate APCs via TLR4/MD2/CD14 receptor complex, suggesting that the alpha 1-3 linked fucose in LNFPIII and not on LNnT, is required for this process. Using specific chemical inhibitors of the MAPK pathway, we found that LNFPIII-NGC induction of CCL22, MMP9 and IL-10 production was dependent on ERK activation. Over all, this study suggests that LNFPIII-NGC utilizes CD14/TLR4-MAPK (ERK axis in modulating APC activation to produce anti-inflammatory chemokines and cytokines in a manner distinct from that seen for the pro-inflammatory PAMP LPS. These pathways may explain the in vivo

  13. Human activities and climate variability drive fast-paced change across the world's estuarine-coastal ecosystems

    Cloern, James E.; Abreu, Paulo C.; Carstensen, Jacob; Chauvaud, Laurent; Elmgren, Ragnar; Grall, Jacques; Greening, Holly; Johansson, John O.R.; Kahru, Mati; Sherwood, Edward T.; Xu, Jie; Yin, Kedong

    2016-01-01

    Time series of environmental measurements are essential for detecting, measuring and understanding changes in the Earth system and its biological communities. Observational series have accumulated over the past 2–5 decades from measurements across the world's estuaries, bays, lagoons, inland seas and shelf waters influenced by runoff. We synthesize information contained in these time series to develop a global view of changes occurring in marine systems influenced by connectivity to land. Our review is organized around four themes: (i) human activities as drivers of change; (ii) variability of the climate system as a driver of change; (iii) successes, disappointments and challenges of managing change at the sea-land interface; and (iv) discoveries made from observations over time. Multidecadal time series reveal that many of the world's estuarine–coastal ecosystems are in a continuing state of change, and the pace of change is faster than we could have imagined a decade ago. Some have been transformed into novel ecosystems with habitats, biogeochemistry and biological communities outside the natural range of variability. Change takes many forms including linear and nonlinear trends, abrupt state changes and oscillations. The challenge of managing change is daunting in the coastal zone where diverse human pressures are concentrated and intersect with different responses to climate variability over land and over ocean basins. The pace of change in estuarine–coastal ecosystems will likely accelerate as the human population and economies continue to grow and as global climate change accelerates. Wise stewardship of the resources upon which we depend is critically dependent upon a continuing flow of information from observations to measure, understand and anticipate future changes along the world's coastlines.

  14. DRIVING OUTFLOWS WITH RELATIVISTIC JETS AND THE DEPENDENCE OF ACTIVE GALACTIC NUCLEUS FEEDBACK EFFICIENCY ON INTERSTELLAR MEDIUM INHOMOGENEITY

    We examine the detailed physics of the feedback mechanism by relativistic active galactic nucleus (AGN) jets interacting with a two-phase fractal interstellar medium (ISM) in the kpc-scale core of galaxies using 29 three-dimensional grid-based hydrodynamical simulations. The feedback efficiency, as measured by the amount of cloud dispersal generated by the jet-ISM interactions, is sensitive to the maximum size of clouds in the fractal cloud distribution but not to their volume filling factor. Feedback ceases to be efficient for Eddington ratios Pjet/Ledd ∼–4, although systems with large cloud complexes ∼> 50 pc require jets of Eddington ratio in excess of 10–2 to disperse the clouds appreciably. Based on measurements of the bubble expansion rates in our simulations, we argue that sub-grid AGN prescriptions resulting in negative feedback in cosmological simulations without a multi-phase treatment of the ISM are good approximations if the volume filling factor of warm-phase material is less than 0.1 and the cloud complexes are smaller than ∼25 pc. We find that the acceleration of the dense embedded clouds is provided by the ram pressure of the high-velocity flow through the porous channels of the warm phase, flow that has fully entrained the shocked hot-phase gas it has swept up, and is additionally mass loaded by ablated cloud material. This mechanism transfers 10% to 40% of the jet energy to the cold and warm gas, accelerating it within a few 10 to 100 Myr to velocities that match those observed in a range of high- and low-redshift radio galaxies hosting powerful radio jets.

  15. Drunk Driving Among Novice Drivers, Possible Prevention with Additional Psychological Module in Driving School Curriculum

    Eensoo, Diva; Paaver, Marika; Harro, Jaanus

    2011-01-01

    Road traffic collisions caused by drunk driving pose a significant public health problem all over the world. Therefore additional preventive activities against drunk driving should be worked out. The aim of the study was to assess drunk driving in novice drivers after a psychological intervention taking into account also impulsivity, law obedience, and alcohol-related measures. An intervention study was started with 1889 car driver’s license attempters during their driving school studies. Sub...

  16. Generation of Domestic Hot Water, Space Heating and Driving Pattern Profiles for Integration Analysis of Active Loads in Low Voltage Grids

    Diaz de Cerio Mendaza, Iker; Pigazo, Alberto; Bak-Jensen, Birgitte;

    2013-01-01

    household level. Despite of the well-known flexible service that this kind of loads can provide, their flexibility is highly dependent of the domestic hot water and space heating demand and the driving habits of each user. This paper presents two methodologies employed to randomly generate thermal power...... demand and electric vehicle driving profiles, to be used for power grid calculations. The generated thermal profiles relied on a statistical analysis made from real domestic hot water and space heating data from 25 households of a typical Danish residential area. The driving profiles instead were formed...... based on conclusions derived from previous analysis on Danish driving patterns and the driving cycles extracted from the European project ARTEMIS. The obtained random profiles will allow electrical networks in Denmark to be analyzed while maintaining the probability of the original data set....

  17. Are We Driving Our Kids to Unhealthy Habits? Results of the Active Healthy Kids Canada 2013 Report Card on Physical Activity for Children and Youth

    Casey E. Gray

    2014-06-01

    Full Text Available This article examines the time trends in patterns of school travel mode among Canadian children and youth to inform the Active Transportation (AT indicator of the 2013 Active Healthy Kids Canada Report Card on Physical Activity for Children and Youth. The AT grade was assigned based on a comprehensive synthesis of the 2000 and 2010 Physical Activity Monitor studies from the Canadian Fitness and Lifestyle Research Institute and the 1992, 1998, 2005, and 2010 General Social Survey from Statistics Canada. The results showed that in 2013, AT was graded a D, because less than half of Canadian children and youth used only active modes of transportation to get to and from school. The proportion of Canadian children and youth who used only inactive modes of transportation for school travel increased significantly from 51% to 62% over the last decade. Children and youth from larger communities and those with lower household income levels were significantly more likely to use AT than those living in smaller communities and those in higher income households, respectively. In conclusion, motorized transport for school travel has increased steadily over the last decade across Canada. Regional and socio-demographic disparities should be considered in efforts to increase the number of children using AT.

  18. Older Drivers' Reasons for Reducing the Overall Amount of Their Driving and for Avoiding Selected Driving Situations

    Meng, Annette; Siren, Anu Kristiina

    2015-01-01

    Structured telephone interviews were conducted with 840 older drivers to explore their reasons for self-regulating their driving. The main reason for reduced driving was having fewer activities to drive to, and for avoidance of driving situations, reasons also included not liking or feeling insec...... when designing interventions aimed at enhancing safe mobility....

  19. Dementia and driving

    ... this page: //medlineplus.gov/ency/patientinstructions/000028.htm Dementia and driving To use the sharing features on ... please enable JavaScript. If your loved one has dementia, deciding when they can no longer drive may ...

  20. AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells.

    Lorenzato, Annalisa; Biolatti, Marta; Delogu, Giuseppe; Capobianco, Giampiero; Farace, Cristiano; Dessole, Salvatore; Cossu, Antonio; Tanda, Francesco; Madeddu, Roberto; Olivero, Martina; Di Renzo, Maria Flavia

    2013-10-15

    The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. PMID:23948303

  1. The protective role of Bax Inhibitor-1 against chronic mild stress through the inhibition of monoamine oxidase A

    Hwa-Young Lee; Geum-Hwa Lee; Anu Marahatta; Shun-Mei Lin; Mi-Rin Lee; Kyu Yun Jang; Kyung Min Kim; Hee Jae Lee; Jae-Won Lee; Tarique Rajasaheb Bagalkot; Young-Chul Chung; Yong-Chul Lee; Hyung-Ryong Kim; Han-Jung Chae

    2013-01-01

    The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress. It has been hypothesized that BI-1 protects against neuron degenerative diseases. In this study, BI-1−/− mice showed increased vulnerability to chronic mild stress accompanied by alterations in the size and morphology of the hippocampi, enhanced ROS accumulation and an ER stress response compared with BI-1+/+ mice. BI-1−/− mice exposed to chronic mild stress showed signif...

  2. Gear bearing drive

    Weinberg, Brian (Inventor); Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor)

    2011-01-01

    A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

  3. Universal drive unit

    Sehnálek, Lubomír

    2011-01-01

    This document deal with design of universal driving unit. For the final solution is required driving unit which will be controled with help of sensory unit placed on the chassis of driving unit. In theoretical part of this labour are examined possibilities of a power, electric motor operation by PWM, kind of chassis and odometry which could be taken into account. From this section is finally chosen concrete configuration which is then described in chapter concerned oneself with driving unit d...

  4. Heart rate variability (HRV) and muscular system activity (EMG) in cases of crash threat during simulated driving of a passenger car

    Krystyna Zużewicz; Danuta Roman-Liu; Maria Konarska; Paweł Bartuzi; Krzysztof Matusiak; Dariusz Korczak; Zbigniew Lozia; Marek Guzek

    2013-01-01

    Objectives: The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. Materials and Methods: The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interv...

  5. High performance AC drives

    Ahmad, Mukhtar

    2010-01-01

    This book presents a comprehensive view of high performance ac drives. It may be considered as both a text book for graduate students and as an up-to-date monograph. It may also be used by R & D professionals involved in the improvement of performance of drives in the industries. The book will also be beneficial to the researchers pursuing work on multiphase drives as well as sensorless and direct torque control of electric drives since up-to date references in these topics are provided. It will also provide few examples of modeling, analysis and control of electric drives using MATLAB/SIMULIN

  6. Simple Driving Techniques

    Rosendahl, Mads

    2002-01-01

    -like language. Our aim is to extract a simple notion of driving and show that even in this tamed form it has much of the power of more general notions of driving. Our driving technique may be used to simplify functional programs which use function composition and will often be able to remove intermediate data......Driving was introduced as a program transformation technique by Valentin Turchin in some papers around 1980. It was intended for the programming language REFAL and used in metasystem transitions based on super compilation. In this paper we present one version of driving for a more conventional lisp...

  7. Auxin influx inhibitors 1-NOA, 2-NOA, and CHPAA interfere with membrane dynamics in tobacco cells

    Laňková, M. (Martina); Smith, R. S.; Pešek, B. (Bedřich); Kubeš, M. (Martin); Zažímalová, E. (Eva); Petrášek, J. (Jan); Hoyerová, K.

    2010-01-01

    The phytohormone auxin is transported through the plant body either via vascular pathways or from cell to cell by specialized polar transport machinery. This machinery consists of a balanced system of passive diffusion combined with the activities of auxin influx and efflux carriers. Synthetic auxins that differ in the mechanisms of their transport across the plasma membrane together with polar auxin transport inhibitors have been used in many studies on particular auxin carriers and their ro...

  8. Interactions of plasminogen activator inhibitor-1 with vitronectin involve an extensive binding surface and induce mutual conformational rearrangements

    Blouse, Grant E; Dupont, Daniel Miotto; Schar, Christine R; Jensen, Jan K; Minor, Kenneth H; Anagli, John Y; Gårdsvoll, Henrik; Ploug, Michael; Peterson, Cynthia B; Andreasen, Peter A

    2009-01-01

    full-length vitronectin is present. Nonetheless, in all cases, the initial fast interaction is followed by slower fluorescence changes attributed to a conformational change in PAI-1. Complementary experiments using an engineered, fluorescently silent PAI-1 with non-natural amino acids showed that...

  9. Effect of daptomycin on local interleukin-6, matrix metalloproteinase-9, and metallopeptidase inhibitor 1 in patients with MRSA-infected diabetic foot.

    Ambrosch, Andreas; Halevy, Daniel; Fwity, Boushra; Brin, Thomas; Lobmann, Ralf

    2014-03-01

    Infection is a major cause of the diabetic foot syndrome that is promoted by the increased burden of multiresistant germs like methicillin-resistant Staphylococcus aureus (MRSA). Maximizing positive outcome for serious MRSA infections requires an aggressive treatment approach and careful monitoring of the healing process. Therefore, we examined 8 patients with MRSA-infected diabetic foot syndrome of Wagner classification grade 2 or 3 (corresponding to the Texas classification stage 2 or 3) during antibiotic treatment with daptomycin. We documented the wound size and obtained samples of wound secretion for analyses of proinflammatory interleukin-6 (IL-6), protease (matrix metalloproteinase-9 [MMP-9]), and antiprotease (metallopeptidase inhibitor 1 [TIMP-1]) activity. During the course of anti-MRSA therapy, we observed a decrease in the concentration of local IL-6 within the first 3 days followed by a decrease of MMP-9 and an increase of TIMP-1. Finally, a reduction of wound size was documented. The present data show that efficient antimicrobial treatment with daptomycin has a number of beneficial effects on wound healing at the molecular level in MRSA-infected diabetic foot ulcers. PMID:24659622

  10. Superluminal warp drive

    In this Letter we consider a warp drive spacetime resulting from that suggested by Alcubierre when the spaceship can only travel faster than light. Restricting to the two dimensions that retains most of the physics, we derive the thermodynamic properties of the warp drive and show that the temperature of the spaceship rises up as its apparent velocity increases. We also find that the warp drive spacetime can be exhibited in a manifestly cosmological form

  11. Universal Drive Train Facility

    Federal Laboratory Consortium — This vehicle drive train research facility is capable of evaluating helicopter and ground vehicle power transmission technologies in a system level environment. The...

  12. Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria.

    Das, Soumita; Owen, Katherine A; Ly, Kim T; Park, Daeho; Black, Steven G; Wilson, Jeffrey M; Sifri, Costi D; Ravichandran, Kodi S; Ernst, Peter B; Casanova, James E

    2011-02-01

    Bacterial recognition by host cells is essential for initiation of infection and the host response. Bacteria interact with host cells via multiple pattern recognition receptors that recognize microbial products or pathogen-associated molecular patterns. In response to this interaction, host cell signaling cascades are activated that lead to inflammatory responses and/or phagocytic clearance of attached bacteria. Brain angiogenesis inhibitor 1 (BAI1) is a receptor that recognizes apoptotic cells through its conserved type I thrombospondin repeats and triggers their engulfment through an ELMO1/Dock/Rac1 signaling module. Because thrombospondin repeats in other proteins have been shown to bind bacterial surface components, we hypothesized that BAI1 may also mediate the recognition and clearance of pathogenic bacteria. We found that preincubation of bacteria with recombinant soluble BAI1 ectodomain or knockdown of endogenous BAI1 in primary macrophages significantly reduced binding and internalization of the Gram-negative pathogen Salmonella typhimurium. Conversely, overexpression of BAI1 enhanced attachment and engulfment of Salmonella in macrophages and in heterologous nonphagocytic cells. Bacterial uptake is triggered by the BAI1-mediated activation of Rac through an ELMO/Dock-dependent mechanism, and inhibition of the BAI1/ELMO1 interaction prevents both Rac activation and bacterial uptake. Moreover, inhibition of ELMO1 or Rac function significantly impairs the proinflammatory response to infection. Finally, we show that BAI1 interacts with a variety of Gram-negative, but not Gram-positive, bacteria through recognition of their surface lipopolysaccharide. Together these findings identify BAI1 as a pattern recognition receptor that mediates nonopsonic phagocytosis of Gram-negative bacteria by macrophages and directly affects the host response to infection. PMID:21245295

  13. Piezoelectric drive circuit

    Treu, Jr., Charles A.

    1999-08-31

    A piezoelectric motor drive circuit is provided which utilizes the piezoelectric elements as oscillators and a Meacham half-bridge approach to develop feedback from the motor ground circuit to produce a signal to drive amplifiers to power the motor. The circuit automatically compensates for shifts in harmonic frequency of the piezoelectric elements due to pressure and temperature changes.

  14. Fundamentals of electrical drives

    Veltman, André; De Doncker, Rik W

    2007-01-01

    Provides a comprehensive introduction to various aspects of electrical drive systems. This volume provides a presentation of dynamic generic models that cover all major electrical machine types and modulation/control components of a drive as well as dynamic and steady state analysis of transformers and electrical machines.

  15. Electric Vehicle - Economical driving

    Jensen, VCE, Steen V.; Schøn, Henriette

    1999-01-01

    How do you reduce the energy-wast when driving and loading EV's - or rather: How do I get more km/l out of an EV......How do you reduce the energy-wast when driving and loading EV's - or rather: How do I get more km/l out of an EV...

  16. Heart rate variability (HRV and muscular system activity (EMG in cases of crash threat during simulated driving of a passenger car

    Krystyna Zużewicz

    2013-10-01

    Full Text Available Objectives: The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. Materials and Methods: The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interval in the ECG signal was assessed. A HRV analysis was performed in the time and frequency domains for 1-minute record segments at rest (seated position, during undisturbed driving as well as during and several minutes after the crash. For the left and right side muscles: m. trapezius (TR and m. flexor digitorum superficialis (FDS, the EMG signal amplitude was determined. The percentage of maximal voluntary contraction (MVC was compared during driving and during the crash. Results: As for the ECG signal, it was found that in most of the drivers changes occurred in the parameter values reflecting HRV in the time domain. Significant changes were noted in the mean length of RR intervals (mRR. As for the EMG signal, the changes in the amplitude concerned the signal recorded from the FDS muscle. The changes in ECG and EMG were simultaneous in half of the cases. Conclusion: Such parameters as mRR (ECG signal and FDS-L amplitude (EMG signal were the responses to accident risk. Under simulated conditions, responses from the circulatory and musculoskeletal systems are not always simultaneous. The results indicate that a more complete driver's response to a crash in road traffic is obtained based on parallel recording of two physiological signals (ECG and EMG.

  17. DriveID: safety innovation through individuation.

    Sawyer, Ben; Teo, Grace; Mouloua, Mustapha

    2012-01-01

    The driving task is highly complex and places considerable perceptual, physical and cognitive demands on the driver. As driving is fundamentally an information processing activity, distracted or impaired drivers have diminished safety margins compared with non- distracted drivers (Hancock and Parasuraman, 1992; TRB 1998 a & b). This competition for sensory and decision making capacities can lead to failures that cost lives. Some groups, teens and elderly drivers for example, have patterns of systematically poor perceptual, physical and cognitive performance while driving. Although there are technologies developed to aid these different drivers, these systems are often misused and underutilized. The DriveID project aims to design and develop a passive, automated face identification system capable of robustly identifying the driver of the vehicle, retrieve a stored profile, and intelligently prescribing specific accident prevention systems and driving environment customizations. PMID:22317376

  18. Fast wave current drive

    Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

    1985-07-01

    Fast wave current drive is demonstrated in the Princeton ACT-I toroidal device. The fast Alfven wave, in the range of high ion-cyclotron harmonics, produced 40 A of current from 1 kW of rf power coupled into the plasma by fast wave loop antenna. This wave excites a steady current by damping on the energetic tail of the electron distribution function in the same way as lower-hybrid current drive, except that fast wave current drive is appropriate for higher plasma densities.

  19. Driving When You Have Cataracts

    ... when they want. I Driving is a complex skill. Our ability to drive safely can be challenged by changes in our ... drive with you to see how well you drive with your cataract. I The ... to improve your driving skills. Improving your skills could help keep you and ...

  20. The influence of music on mood and performance while driving

    van der Zwaag, Marjolein D.; Dijksterhuis, Chris; de Waard, Dick; Mulder, Ben L. J. M.; Westerink, Joyce H. D. M.; Brookhuis, Karel A.

    2012-01-01

    Mood can influence our everyday behaviour and people often seek to reinforce, or to alter their mood, for example by turning on music. Music listening while driving is a popular activity. However, little is known about the impact of music listening while driving on physiological state and driving pe

  1. Antihistamines and driving ability: Evidence from 30 years Dutch on-road driving research

    Verster, J.C.; Van De Loo, A.J.A.E.; Garssen, J.

    2015-01-01

    Background: Since all antihistamines are capable of crossing the blood-brain barrier, they may also cause sedation which may impair daily activities such as driving a car. The purpose of this review was to examine the effects of antihistamines on driving ability. Method: A literature search revealed

  2. Dual drive; Doppelt angetrieben

    Wilms, Jan

    2011-09-15

    The Opel Ampera was designed as an everyday car with an alternative drive system. A hybrid concept comprising both an electric motor and a gasoline engine ensures long mileage, but there is still the problem of high purchase cost.

  3. Safe driving for teens

    ... for crashes. Drivers and passengers should use automobile safety features at all times. These include: seat belts, shoulder straps, and headrests. Only drive cars that have air bags, padded dashes, safety glass, ...

  4. Decreased driving ability in people with Parkinson's disease

    Heikkila, V; Turkka, J; Korpelainen, J; Kallanranta, T; Summala, H

    1998-01-01

    BACKGROUND—Driving is a complex form of activity involving especially cognitive and psychomotor functions. These functions may be impaired by Parkinson's disease. The relation between Parkinson's disease and driving ability is still obscure and clinicians have to make decisions concerning the driving ability of their patients based on insufficent information. Until now no studies have compared different methods for evaluating the driving ability of patients with Parkinson...

  5. The influence of music on mood and performance while driving

    van der Zwaag, Marjolein D.; Dijksterhuis, Chris; de Waard, Dick; Mulder, Ben L. J. M.; Westerink, Joyce H.D.M.; Brookhuis, Karel A

    2012-01-01

    Mood can influence our everyday behaviour and people often seek to reinforce, or to alter their mood, for example by turning on music. Music listening while driving is a popular activity. However, little is known about the impact of music listening while driving on physiological state and driving performance. In the present experiment, it was investigated whether individually selected music can induce mood and maintain moods during a simulated drive. In addition, effects of positive, negative...

  6. Drunk Driving Campaign

    Christoffersen, Mette Buhl; Vogel, Klara Elisa Pingel

    2014-01-01

    This project evaluates a communication product, consisting of three flush-ad posters against drunk driving. The target group of this campaign is young men in the ages 18-22 in the outskirts of Denmark. The project's scientific theoretical approach is phenomenology which will give insight in the target groups life situation, furthermore the social constructivist perspective is used to understand the target group's opinions in relation to product and subject drunk driving because of the interac...

  7. Drinking and driving

    2003-01-01

    Alcohol misuse generates many health and social problems at a cost that society is increasingly unwilling to sustain. One of the most tragic consequences of alcohol misuse is the result of drinking and driving. Each week, impaired drivers kill 40 Canadian men, women and children and injure 1250 others. The Canadian Medical Association (CMA), in its campaign against drinking and driving, has recommended that a condition of obtaining or renewing a driver's licence include the individual's writt...

  8. Engineering Autonomous Driving Software

    Berger, Christian; Rumpe, Bernhard

    2014-01-01

    A larger number of people with heterogeneous knowledge and skills running a project together needs an adaptable, target, and skill-specific engineering process. This especially holds for a project to develop a highly innovative, autonomously driving vehicle to participate in the 2007 DARPA Urban Challenge. In this contribution, we present essential elements of a software and systems engineering process to develop a so-called artificial intelligence capable of driving autonomously in complex u...

  9. Direct drive wind turbine

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

    2006-07-11

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  10. Instant Google Drive starter

    Procopio, Mike

    2013-01-01

    This book is a Starter which teaches you how to use Google Drive practically. This book is perfect for people of all skill levels who want to enjoy the benefits of using Google Drive to safely store their files online and in the cloud. It's also great for anyone looking to learn more about cloud computing in general. Readers are expected to have an Internet connection and basic knowledge of using the internet.

  11. Inside Solid State Drives (SSDs)

    Micheloni, Rino; Eshghi, Kam

    2013-01-01

    Solid State Drives (SSDs) are gaining momentum in enterprise and client applications, replacing Hard Disk Drives (HDDs) by offering higher performance and lower power. In the enterprise, developers of data center server and storage systems have seen CPU performance growing exponentially for the past two decades, while HDD performance has improved linearly for the same period. Additionally, multi-core CPU designs and virtualization have increased randomness of storage I/Os. These trends have shifted performance bottlenecks to enterprise storage systems. Business critical applications such as online transaction processing, financial data processing and database mining are increasingly limited by storage performance. In client applications, small mobile platforms are leaving little room for batteries while demanding long life out of them. Therefore, reducing both idle and active power consumption has become critical. Additionally, client storage systems are in need of significant performance improvement as well ...

  12. Self-driving carsickness.

    Diels, Cyriel; Bos, Jelte E

    2016-03-01

    This paper discusses the predicted increase in the occurrence and severity of motion sickness in self-driving cars. Self-driving cars have the potential to lead to significant benefits. From the driver's perspective, the direct benefits of this technology are considered increased comfort and productivity. However, we here show that the envisaged scenarios all lead to an increased risk of motion sickness. As such, the benefits this technology is assumed to bring may not be capitalised on, in particular by those already susceptible to motion sickness. This can negatively affect user acceptance and uptake and, in turn, limit the potential socioeconomic benefits that this emerging technology may provide. Following a discussion on the causes of motion sickness in the context of self-driving cars, we present guidelines to steer the design and development of automated vehicle technologies. The aim is to limit or avoid the impact of motion sickness and ultimately promote the uptake of self-driving cars. Attention is also given to less well known consequences of motion sickness, in particular negative aftereffects such as postural instability, and detrimental effects on task performance and how this may impact the use and design of self-driving cars. We conclude that basic perceptual mechanisms need to be considered in the design process whereby self-driving cars cannot simply be thought of as living rooms, offices, or entertainment venues on wheels. PMID:26446454

  13. Epilepsy and driving

    Moetamedi M

    2000-09-01

    Full Text Available Epilepsy is a disease with high prevalence, which interferes driving and may lead to car accident; This case-control study has been done on 100 epileptic patients and 100 persons as control group, who had history of driving. We gathered our patients with face to face interview and registering their information in special forms which were prepared for this study. There were three times more accidents among epileptic cases comparing with control group and this difference was more considerable in men and in patients under 35 years old. The cause of accident were not seizure attack in more than 60% of the patients and these ordinary accidents were also more in case group. Epileptic patients with history of car accidents during driving had poor drug compliance comparing with the epileptics without history of an accident so drug compliance may be valuable in predicting accident in these patients. We have also found poor drug compliance in whom seizure attacks caused accident for them. 58% of the epileptics had not consulted their physician about driving. 43.3% of seizures during driving were of generalized type and none of the patients had inform police about their disease during getting driving license.

  14. Dangers of Texting While Driving

    ... and share information, we created a dedicated website . Distracted Driving Information Clearinghouse In addition, to collect and share ... technology that could potentially reduce the problem of distracted driving, the Commission’s staff created the FCC Distracted Driving ...

  15. α-Amylase inhibitor-1 gene from Phaseolus vulgaris expressed in Coffea arabica plants inhibits α-amylases from the coffee berry borer pest

    Oliveira-Neto Osmundo B

    2010-06-01

    Full Text Available Abstract Background Coffee is an important crop and is crucial to the economy of many developing countries, generating around US$70 billion per year. There are 115 species in the Coffea genus, but only two, C. arabica and C. canephora, are commercially cultivated. Coffee plants are attacked by many pathogens and insect-pests, which affect not only the production of coffee but also its grain quality, reducing the commercial value of the product. The main insect-pest, the coffee berry borer (Hypotheneumus hampei, is responsible for worldwide annual losses of around US$500 million. The coffee berry borer exclusively damages the coffee berries, and it is mainly controlled by organochlorine insecticides that are both toxic and carcinogenic. Unfortunately, natural resistance in the genus Coffea to H. hampei has not been documented. To overcome these problems, biotechnological strategies can be used to introduce an α-amylase inhibitor gene (α-AI1, which confers resistance against the coffee berry borer insect-pest, into C. arabica plants. Results We transformed C. arabica with the α-amylase inhibitor-1 gene (α-AI1 from the common bean, Phaseolus vulgaris, under control of the seed-specific phytohemagglutinin promoter (PHA-L. The presence of the α-AI1 gene in six regenerated transgenic T1 coffee plants was identified by PCR and Southern blotting. Immunoblotting and ELISA experiments using antibodies against α-AI1 inhibitor showed a maximum α-AI1 concentration of 0.29% in crude seed extracts. Inhibitory in vitro assays of the α-AI1 protein against H. hampei α-amylases in transgenic seed extracts showed up to 88% inhibition of enzyme activity. Conclusions This is the first report showing the production of transgenic coffee plants with the biotechnological potential to control the coffee berry borer, the most important insect-pest of crop coffee.

  16. Effect of Guanxinshutong capsule on the expression of matrix metalloproteinases-9 and tissue matrix metalloproteinase inhibitor-1 of atherosclerotic plaque in apoE-/- mice

    霍煜

    2014-01-01

    Objective To approach the possible mechanism of Guanxinshutong capsule on the progression and stability of atherosclerotic plaque through observing the effects of Guanxinshutong capsule on pathologic morphology and expression of tissue matrix metalloproteinase inhibitor-1(TIMP-1),matrix metalloproteinases-9(MMP-9)of atherosclerotic plaque in Apo E-/-mice model with experimental atherosclerosis.Methods The animals were fed

  17. Improvement in Brightness Uniformity by Compensating for the Threshold Voltages of Both the Driving Thin-Film Transistor and the Organic Light-Emitting Diode for Active-Matrix Organic Light-Emitting Diode Displays

    Ching-Lin Fan

    2014-01-01

    Full Text Available This paper proposes a novel pixel circuit design and driving method for active-matrix organic light-emitting diode (AM-OLED displays that use low-temperature polycrystalline-silicon thin-film transistors (LTPS-TFTs as driving element. The automatic integrated circuit modeling simulation program with integrated circuit emphasis (AIM-SPICE simulator was used to verify that the proposed pixel circuit, which comprises five transistors and one capacitor, can supply uniform output current. The voltage programming method of the proposed pixel circuit comprises three periods: reset, compensation with data input, and emission periods. The simulated results reflected excellent performance. For instance, when ΔVTH=±0.33 V, the average error rate of the OLED current variation was low (<0.8%, and when ΔVTH_OLED=+0.33 V, the error rate of the OLED current variation was 4.7%. Moreover, when the I×R (current × resistance drop voltage of a power line was 0.3 V, the error rate of the OLED current variation was 5.8%. The simulated results indicated that the proposed pixel circuit exhibits high immunity to the threshold voltage deviation of both the driving poly-Si TFTs and OLEDs, and simultaneously compensates for the I×R drop voltage of a power line.

  18. 基于驾驶行为及意图的汽车主动安全技术研究%Study on automotive active safety technology based on driving behavior and intention

    储颖; 肖献强; 朱家诚

    2011-01-01

    针对国内汽车主动安全技术研究的现状,提出了基于驾驶员行为及意图判断的汽车主动安全研究方法,在此汽车主动安全系统中利用采集到的驾驶员各种操作信号及环境信息,进行驾驶员的驾驶行为及意图分析.根据驾驶员的各种操作信息对常见驾驶行为及意图判断的权重的不同,建立了用于判别典型驾驶行为及意图的权重矩阵.通过MATLAB软件编程仿真,建立了八种典型驾驶状态下权重判断矩阵,仿真表明,该权重矩阵设计合理,可以准确地判断和识别出典型的驾驶行为及意图,为未来汽车主动安全技术的研究提供了一种有效的方法.%To the status of domestic automotive safety technology research,the vehicle active safety research method that was based on the identifying of driver behavior and intention was proposed.it safety system,the analysis of driving behavior and intention was made by collecting a variety of driver's operating signal and environmental information.The weight matrix for identifying the typical driving behavior and intention was built according to the different proportion of variety operating information on identifying cornmon intention of driving behavior and intention. Through programming emulation with MATLAB, the weight matrix under the eight typical given state of driving was established. The emulation indicates that the weight matrix was designed reasonably. The matrix can identify the driving behavior and intention exactly. It offers an effective method for researching automotive active safety technology.

  19. [Drug use and driving].

    Lemaire-Hurtel, Anne-Sophie; Goullé, Jean-Pierre; Alvarez, Jean-Claude; Mura, Patrick; Verstraete, Alain G

    2015-10-01

    Some drugs are known to impair driving because they can change the vision or hearing, and/or disrupt the intellectual or motor abilities: impaired vigilance, sedation, disinhibition effect, the coordination of movement disorders and the balance. The doctor during prescribing and the pharmacist during deliverance of drug treatment should inform their patients of the potential risks of drugs on driving or operating machinery. The driver has direct responsibility, who hired him and him alone, to follow the medical advice received. The pictograms on the outer packaging of medicinal products intended to classify substances according to their risk driving: The driver can whether to observe simple precautions (level one "be prudent"), or follow the advice of a health professional (level two "be very careful"), or if it is totally not drive (level three "danger caution: do not drive"). This classification only evaluates the intrinsic danger of drugs but not the individual variability. Medicines should be taken into account also the conditions for which the medication is prescribed. It is important to inform the patient on several points. PMID:25956300

  20. Control rod drives

    Purpose: To fix a magnetic rotor to a drive shaft and at the time of non-driving, to restrain the rotor by permanent magnets thereby to hold the position of the control rod safely and accurately. Constitution: A control rod position holding device is provided in a motor or a drive shaft of a control rod drive. This device consists of a rotor and a stator, the rotor being provided on its circumference with salient-poles arranged equidistantly, and the position of the rotor being determined depending upon the transfer distance of the control rod and the conversion ratio of the converter. On the other hand, the stator has salient-poles (any of them is a permanent magnet) having the number of poles and the positional relationship equivalent to those of the rotor, and provided in the inner periphery of a cylinder using the drive shaft as a central shaft and wound with a winding. When the control rod is not driven, the poles of the rotor are attracted by the magnetic force of the confronting poles of the stator, thereby to prevent the inverse rotation of the motor shaft due to the dead weight of the control rod. When a current is caused to flow through the winding, the magnetic force of the permanent magnet, and the stator release the rotor. (Yoshino, Y.)

  1. Plasma autoantibodies against heat shock protein 70, enolase 1 and ribonuclease/angiogenin inhibitor 1 as potential biomarkers for cholangiocarcinoma.

    Rucksak Rucksaken

    Full Text Available The diagnosis of cholangiocarcinoma (CCA is often challenging, leading to poor prognosis. CCA arises via chronic inflammation which may be associated with autoantibodies production. This study aims to identify IgG antibodies directed at self-proteins and tumor-associated antigens. Proteins derived from immortalized cholangiocyte cell line (MMNK1 and CCA cell lines (M055, M214 and M139 were separated using 2-dimensional electrophoresis and incubated with pooled plasma of patients with CCA and non-neoplastic controls by immunoblotting. Twenty five immunoreactive spots against all cell lines-derived proteins were observed on stained gels and studied by LC-MS/MS. Among these, heat shock protein 70 (HSP70, enolase 1 (ENO1 and ribonuclease/angiogenin inhibitor 1 (RNH1 obtained the highest matching scores and were thus selected for further validation. Western blot revealed immunoreactivity against HSP70 and RNH1 in the majority of CCA cases and weakly in healthy individuals. Further, ELISA showed that plasma HSP70 autoantibody level in CCA was significantly capable to discriminate CCA from healthy individuals with an area under the receiver operating characteristic curve of 0.9158 (cut-off 0.2630, 93.55% sensitivity and 73.91% specificity. Plasma levels of IgG autoantibodies against HSP70 were correlated with progression from healthy individuals to cholangitis to CCA (r = 0.679, P<0.001. In addition, circulating ENO1 and RNH1 autoantibodies levels were also significantly higher in cholangitis and CCA compared to healthy controls (P<0.05. Moreover, the combinations of HSP70, ENO1 or RNH1 autoantibodies positivity rates improved specificity to over 78%. In conclusion, plasma IgG autoantibodies against HSP70, ENO1 and RNH1 may represent new diagnostic markers for CCA.

  2. Ceramic vane drive joint

    Smale, Charles H. (Inventor)

    1981-01-01

    A variable geometry gas turbine has an array of ceramic composition vanes positioned by an actuating ring coupled through a plurality of circumferentially spaced turbine vane levers to the outer end of a metallic vane drive shaft at each of the ceramic vanes. Each of the ceramic vanes has an end slot of bow tie configuration including flared end segments and a center slot therebetween. Each of the vane drive shafts has a cross head with ends thereof spaced with respect to the sides of the end slot to define clearance for free expansion of the cross head with respect to the vane and the cross head being configured to uniformly distribute drive loads across bearing surfaces of the vane slot.

  3. Gears and gear drives

    Jelaska, Damir T

    2012-01-01

    Understanding how gears are formed and how they interact or 'mesh' with each other is essential when designing equipment that uses gears or gear trains. The way in which gear teeth are formed and how they mesh is determined by their geometry and kinematics, which is the topic of this book.  Gears and Gear Drives provides the reader with comprehensive coverage of gears and gear drives. Spur, helical, bevel, worm and planetary gears are all covered, with consideration given to their classification, geometry, kinematics, accuracy control, load capacity and manufacturing. Cylindric

  4. Toyota hybrid synergy drive

    Gautschi, H.

    2008-07-01

    This presentation made at the Swiss 2008 research conference on traffic by Hannes Gautschi, director of service and training at the Toyota company in Switzerland, takes a look at Toyota's hybrid drive vehicles. The construction of the vehicles and their combined combustion engines and electric generators and drives is presented and the combined operation of these components is described. Braking and energy recovery are discussed. Figures on the performance, fuel consumption and CO{sub 2} output of the hybrid vehicles are compared with those of conventional vehicles.

  5. Permanent magnet brushless drives

    Chan, CC; Xia, W.; Jiang, JZ; Chau, KT; Zhu, ML

    1998-01-01

    The purpose of this paper is to present an optimal efficiency control scheme for constant power operation of phase decoupling (PD) PM brushless DC motor drives. The key is to adaptively adjust the advanced conduction angle to minimize the system losses for a given operation point in the constant power region. The strategy for constant power operation of PD PM brushless DC motor drives is exemplified using a 5-phase 22-pole PD PM brushless DC motor. In the sections that follow, the newly-devel...

  6. Evaluation of Driver Stress Using Motor-vehicle Driving Simulator

    Deguchi, Mitsuo; Wakasugi, Junichi; Ikegami, Tatsuya; Nanba, Shinji; Yamaguchi, Masaki

    This paper proposes a method for evaluating driver stress using a motor-vehicle driving simulator and a biomarker as an index of stress. Software has been developed, which can deliberately control driving tasks, in addition to analyzing driving information, such as frequency of the use of accelerator and/or brakes and the degree of deviation from the driving course. Sympathetic nervous activity was noninvasively evaluated using a hand-held monitor of salivary amylase activity, which chemically measured a biomarker every few minutes. Using healthy 20 female adults, the appropriateness of the proposed method was evaluated in vivo. The experimental results showed that the driving stress might be caused to the drivers in only 20 minutes by adding more severe driving tasks than normally experienced by the subjects without endangering them. Furthermore, the result indicate that frequent measurements of sympathetic nervous activity were possible without putting the subjects under restraint by using salivary amylase activity as the index.

  7. Chaos in drive systems

    Kratochvíl C.

    2007-10-01

    Full Text Available The purpose of this article is to provide an elementary introduction to the subject of chaos in the electromechanical drive systems. In this article, we explore chaotic solutions of maps and continuous time systems. These solutions are also bounded like equilibrium, periodic and quasiperiodic solutions.

  8. Magnetized drive fluids

    Rosensweig, R.E.; Zahn, M.

    1986-04-01

    A process is described for recovering a first fluid from a porous subterranean formation which comprises injecting a displacement fluid in an effective amount to displace the first fluid, injecting a ferrofluid, applying a magnetic field containing a gradient of field intensity within the formation, driving the displacement fluid through the formation with the ferrofluid and recovering first fluid.

  9. Gaze-controlled Driving

    Tall, Martin; Alapetite, Alexandre; San Agustin, Javier;

    2009-01-01

    We investigate if the gaze (point of regard) can control a remote vehicle driving on a racing track. Five different input devices (on-screen buttons, mouse-pointing low-cost webcam eye tracker and two commercial eye tracking systems) provide heading and speed control on the scene view transmitted...

  10. Control rod drives

    Purpose: To prevent damages in control rod drives upon connection and disconnection with control rods by providing, to an extension rod, a closure and opening guide mechanism which is adapted to open and close depending upon connection and disconnection with the control rod. Constitution: In control rod drives having a driving section and a lower mechanism, the lower mechanism has a guide tube engaged into the upper cover of a reactor container and suspended therefrom into the reactor container. An opening and closure mechanism with guide blades capable of contacting the inner wall of the guide tube is secured to an extension rod for fastening the gripper which supports the control rod. Such a mechanism cap prevent damages in the control rod drives and the control rods due to the connection after disconnection of them by the buffering action between the extension rod and the control rod, as well as damages in both of them caused by rolling such as in earthquakes by the buffering action between the extension rod and the guide tube. (Moriyama, K.)

  11. Efficient driving; Effizientes Fahren

    Dillmann, Gerhard; Prys, Gerhard; Klinkert, Carsten; Sauer, Juergen; Otasevic, Aleksandar; Steinbock, Robert [BMW Group, Muenchen (Germany)

    2008-11-15

    With the BMW Efficient Dynamics development strategy, the new BMW 7 Series is proving that a superior, dynamic driving experience with simultaneous reduction of fuel consumption and emissions can be combined with the premium standards of the luxury automobile class. (orig.)

  12. Texting while driving: the development and validation of the distracted driving survey and risk score among young adults

    Bergmark, Regan W.; Gliklich, Emily; Guo, Rong; Gliklich, Richard E.

    2016-01-01

    Background: Texting while driving and other cell-phone reading and writing activities are high-risk activities associated with motor vehicle collisions and mortality. This paper describes the development and preliminary evaluation of the Distracted Driving Survey (DDS) and score. Methods: Survey questions were developed by a research team using semi-structured interviews, pilot-tested, and evaluated in young drivers for validity and reliability. Questions focused on texting while driving and ...

  13. Lower hybrid current drive in tokamak plasmas

    Past ten years progress on Lower Hybrid Current Drive (LHCD) experiments have demonstrated the largest non-inductive current (3.6 MA, JT-60U), the longest current sustainment (2 hours, TRIAM-1M), non-inductive current drive at the highest density (n-bare - 1020m-3, ALCATOR-C) and the highest current drive efficiency (ηCD = 3.5x1019 m-2A/W, JT-60). These results indicate that LHCD is one of the most promising methods to drive non-inductive current in the present tokamak plasmas. This paper presents recent experimental results on LHCD experiments. Basic theories of LH waves, the wave propagation and the current drive are briefly summarized. The main part of this paper describes several important results and their physical pictures on recent LHCD experiments; 1) the experimental set-up, 2) the current drive efficiency, 3) the control of current profile and MHD activities, 4) the global energy confinement, 5) the global power flow, 6) fast electron behavior, 7) interaction between LH waves and thermal/fast ions, 8) combination with other CD method. (author)

  14. Driving without a GPS

    Lauridsen, Karen M.

    the best way possible; and that the differences in their knowledge systems is acknowledged and used as an asset in these international programmes. With these factors in place, on the other hand, programmes with international faculty and diverse student audiences in which this diversity is exploited in...... an appropriate way, may have a considerable added value that positively impacts on the knowledge, skills and competences developed by their graduates. However, lecturers often feel at a loss because they are not sure how to do this and teaching becomes like driving in unknown territory without a GPS......, thereby contributing to a possible typology of challenges and solutions in international programmes from which all attendees may benefit. They will then not have to drive without a GPS, but will have a better background for navigating the international university. Singh, P. and C. Doherty (2004) “Global...

  15. Mitigating Distracted Driving

    Cox, Tim; Kolberg, Kenny

    2014-01-01

    The scourge of distracted driving is not limited to any one demographic group or nation. It is global and affects every victim and victims’ families. This dire situation, caused largely by technology such as texting, requires technological solutions, including new traffic safety countermeasures. The transverse rumble strip, a countermeasure reinvented in 2009 as the temporary portable rumble strip, is already proving a significant, innovative addition to work zone safety processes and procedu...

  16. Driving and Neurodegenerative Diseases

    Uc, Ergun Y.; Rizzo, Matthew

    2008-01-01

    The proportion of elderly in the general population is rising, resulting in greater numbers of drivers with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). These neurodegenerative disorders impair cognition, visual perception, and motor function, leading to reduced driver fitness and greater crash risk. Yet medical diagnosis or age alone is not reliable enough to predict driver safety or crashes, or revoke the driving privileges of these drivers. Dri...

  17. Control rod drives

    Purpose: To enable fine positioning by using an induction motor of a simple structure as a driving source and thereby improve the reliability of control rod drives. Constitution: A step actuator is directly coupled with an induction motor, in which the induction motor is connected by way of a pulse driving control circuit to an AC power source, while the step actuator is connected to a DC power source. When a thyristor is turned ON, the motor outputs a positive torque and rotates and starts to rotate in the forward direction. When the other thyristor is turned ON, the motor is applied with braking by a reverse excitation in a manner equivalent to the change for the exciting phase sequence. When the speed is lowered to a predetermined value, braking is actuated by the torque of the step actuator and the motor stops at a zero position or balanced position. In this way, braking is actuated from the decelerating step to the stopping with no abrasion and a highly accurate positioning is possible due to the characteristics of the step actuator. (Horiuchi, T.)

  18. Control rod drive mechanisms

    Purpose: To accurately measure the loads generated upon scram and judge the absence or presence of deceleration in control rod drive mechanisms. Constitution: Control rod drive mechanisms for use in a BWR type reactor includes an index tube vertically movably, connected at the upper end to the control rod and having a drive piston at the lower end. A piezoelectric member for detecting the load generated upon uprise of the index tube is disposed and signals from the piezoelectric member is connected to a calculation processing device. A load exerted when the index tube uprises is measured by way of the piezoelectric member upon scram thereby judging the absence or presence of the decelerating operation. Therefore, the nuclear reactor can be shutdown only when it is required with no excess safety operation than required. As a result, the reactor availability can be improved and, in addition, it is also possible to mitigate the burden of in-service inspection and reduce the operators' exposure. (Kamimura, M.)

  19. Control rod drive

    Object: To provide a simple and compact construction of an apparatus for driving a drive shaft inside with a magnetic force from the outside of the primary system water side. Structure: The weight of a plunger provided with an attraction plate is supported by a plunger lift spring means so as to provide a buffer action at the time of momentary movement while also permitting the load on lift coil to be constituted solely by the load on the drive shaft. In addition, by arranging the attraction plate and lift coil so that they face each other with a small gap there-between, it is made possible to reduce the size and permit efficient utilization of the attracting force. Because of the small size, cooling can be simply carried out. Further, since there is no mechanical penetration portion, there is no possibility of leakage of the primary system water. Furthermore, concentration of load on a latch pin is prevented by arranging so that with a structure the load of the control rod to be directly beared through the scrum latch. (Kamimura, M.)

  20. Control rod drive system

    The present invention concerns an electromotive driving-type control rod driving system of a BWR type reactor, for which sliding resistance (friction) test can be performed of a movable portion of the control rod driving mechanisms. Namely, a hydraulic pressure control unit has following constitutions in addition to a conventional constitution as a sliding resistance test performing function. (1) A restricting valve is disposed downstream of the scram valve of scram pipelines to control flow rate and pressure of pressurized water flown in the pipelines. (2) A pressure gauge detects a pressure between the scram valve and the restricting valve. (3) A flow meter detects the flow rate of pipelines controlled by the restricting valve. (4) A recording pressure detector detects the pressure at the downstream of the restricting valve. (5) The recording device is attached when the sliding resistant test is performed for tracing the pressure measured by the pressure detection device. Further, the scram valve sends electric signals to a central operation chamber when it is fully closed. The central operation chamber has a function of fully opening the restricting valve by way of the electric signals. (I.S.)

  1. Driving Strategy Alters Neuronal Responses to Self-Movement: Cortical Mechanisms of Distracted Driving

    Kishore, Sarita; Hornick, Noah; Sato, Nobuya; Page, William K.; Duffy, Charles J.

    2011-01-01

    We presented naturalistic combinations of virtual self-movement stimuli while recording neuronal activity in monkey cerebral cortex. Monkeys used a joystick to drive to a straight ahead heading direction guided by either object motion or optic flow. The selected cue dominates neuronal responses, often mimicking responses evoked when that stimulus is presented alone. In some neurons, driving strategy creates selective response additivities. In others, it creates vulnerabilities to the disrupti...

  2. Micro-drive Array for Chronic in vivo Recording: Drive Fabrication

    Kloosterman, Fabian; Davidson, Thomas J.; Gomperts, Stephen N.; Layton, Stuart P.; Hale, Gregory; Nguyen, David P.; Wilson, Matthew A

    2009-01-01

    Chronic recording of large populations of neurons is a valuable technique for studying the function of neuronal circuits in awake behaving rats. Lightweight recording devices carrying a high density array of tetrodes allow for the simultaneous monitoring of the activity of tens to hundreds of individual neurons. Here we describe a protocol for the fabrication of a micro-drive array with twenty one independently movable micro-drives. This device has been used successfully to record from hippoc...

  3. Constructing a Distracted Driving Dataset

    Foley, James; Ebe, Kazu; Owens, Justin M.; Angell, Linda; Hankey, Jonathan M.

    2014-01-01

    Distracted driving has become a topic of critical importance to driving safety research over the past several decades. Naturalistic driving data offer a unique opportunity to study how drivers engage with secondary tasks in real-world driving; however, the complexities involved with identifying and coding relevant epochs of naturalistic data have limited its accessibility to the general research community. Method This project was developed to help address this problem by creating an accessibl...

  4. Nuclear refueling platform drive system

    This patent describes a drive system. It comprises: a gantry including a bridge having longitudinal and transverse axes and supported by spaced first and second end frames joined to fist and second end frames joined to first and second drive trucks for moving the bridge along the transverse axis; first means for driving the first drive truck; second means for driving the second drive truck being independent from the first driving means; and means for controlling the first and second driving means for reducing differential transverse travel between the first and second drive trucks, due to a skewing torque acting on the bridge, to less than a predetermined maximum, the controlling means being in the form of an electrical central processing unit and including: a closed-loop first velocity control means for controlling velocity of the first drive truck by providing a first command signal to the first driver means; a close loop second velocity control means for controlling velocity of the second drive truck by providing a second command signal to the second driving means; and an auxiliary closed-loop travel control means

  5. Digital control of a high-voltage (2.5 kV) bidirectional DC-DC converter for driving a dielectric electro active polymer (DEAP) based capacitive actuator

    Thummala, Prasanth; Zhang, Zhe; Andersen, Michael A. E.;

    2014-01-01

    the valley switchingtechnique during both charge and discharge processes, withoutthe need to sense signals on the output high-voltage side.Experimental results verifying the bidirectional operation of asingle high voltage flyback converter are presented, using afilm capacitor as the load. Energy......This paper presents a digital control technique toachieve valley switching in a bidirectional flyback converterused to drive a dielectric electro active polymer basedincremental actuator. The incremental actuator consists ofthree electrically isolated, mechanically connected capacitiveactuators....... The incremental actuator requires three highvoltage (~2.5 kV) bidirectional DC-DC converters, toaccomplish the incremental motion by charging anddischarging the capacitive actuators. The bidirectional flybackconverter employs a digital controller to improve efficiencyand charge/discharge speed using...

  6. Automatic system for driving probes of electron cyclotron

    The automatic system for driving six probes used on electron model of the ring cyclotron is described. This system allows one to move probes one by one or simultaneously. The active forcing of the process of switching on of the current in phase windings is used a driving scheme of step-motors. The shift of probes from one radius to other can be carried out both from the front panel of driving device (autonomous regime), and from the computer

  7. Offset Compound Gear Drive

    Stevens, Mark A.; Handschuh, Robert F.; Lewicki, David G.

    2010-01-01

    The Offset Compound Gear Drive is an in-line, discrete, two-speed device utilizing a special offset compound gear that has both an internal tooth configuration on the input end and external tooth configuration on the output end, thus allowing it to mesh in series, simultaneously, with both a smaller external tooth input gear and a larger internal tooth output gear. This unique geometry and offset axis permits the compound gear to mesh with the smaller diameter input gear and the larger diameter output gear, both of which are on the same central, or primary, centerline. This configuration results in a compact in-line reduction gear set consisting of fewer gears and bearings than a conventional planetary gear train. Switching between the two output ratios is accomplished through a main control clutch and sprag. Power flow to the above is transmitted through concentric power paths. Low-speed operation is accomplished in two meshes. For the purpose of illustrating the low-speed output operation, the following example pitch diameters are given. A 5.0 pitch diameter (PD) input gear to 7.50 PD (internal tooth) intermediate gear (0.667 reduction mesh), and a 7.50 PD (external tooth) intermediate gear to a 10.00 PD output gear (0.750 reduction mesh). Note that it is not required that the intermediate gears on the offset axis be of the same diameter. For this example, the resultant low-speed ratio is 2:1 (output speed = 0.500; product of stage one 0.667 reduction and stage two 0.750 stage reduction). The design is not restricted to the example pitch diameters, or output ratio. From the output gear, power is transmitted through a hollow drive shaft, which, in turn, drives a sprag during which time the main clutch is disengaged.

  8. Electric drive design methodology

    Jufer, Marcel

    2013-01-01

    An electric drive that is designed or adapted to a specific application must take into account all the elements of the chain of constituent elements in its use and deployment. In addition to the motor, the transmission, power electronics, control, sensors, and electrical protection systems must be taken into account. The motor and the transmission can be optimized and designed to obtain the best energy efficiency assessment, in particular for dynamic nodes. An inventory and a characterization of these various components is proposed as part of this book's examination and explanation

  9. Electrical machines & drives

    Hammond, P

    1985-01-01

    Containing approximately 200 problems (100 worked), the text covers a wide range of topics concerning electrical machines, placing particular emphasis upon electrical-machine drive applications. The theory is concisely reviewed and focuses on features common to all machine types. The problems are arranged in order of increasing levels of complexity and discussions of the solutions are included where appropriate to illustrate the engineering implications. This second edition includes an important new chapter on mathematical and computer simulation of machine systems and revised discussions o

  10. Modular droplet actuator drive

    Pollack, Michael G. (Inventor); Paik, Philip (Inventor)

    2011-01-01

    A droplet actuator drive including a detection apparatus for sensing a property of a droplet on a droplet actuator; circuitry for controlling the detection apparatus electronically coupled to the detection apparatus; a droplet actuator cartridge connector arranged so that when a droplet actuator cartridge electronically is coupled thereto: the droplet actuator cartridge is aligned with the detection apparatus; and the detection apparatus can sense the property of the droplet on a droplet actuator; circuitry for controlling a droplet actuator coupled to the droplet actuator connector; and the droplet actuator circuitry may be coupled to a processor.

  11. PURE DRIVE GT

    2009-01-01

    在2004年奥林匹克赛事中,中国的李婷,孙甜甜取得了中国网球第一个金牌一女子双打冠军。忘记不了当时李婷挥动着她的BABOLAT(百保力)网拍Pure Drive Zylon 360°激动地拥抱着孙甜甜吵闹着,幸福地哭着的情景。

  12. Spatial variability in photosynthetic and heterotrophic activity drives localized δ13C org fluctuations and carbonate precipitation in hypersaline microbial mats.

    Houghton, J; Fike, D; Druschel, G; Orphan, V; Hoehler, T M; Des Marais, D J

    2014-11-01

    Modern laminated photosynthetic microbial mats are ideal environments to study how microbial activity creates and modifies carbon and sulfur isotopic signatures prior to lithification. Laminated microbial mats from a hypersaline lagoon (Guerrero Negro, Baja California, Mexico) maintained in a flume in a greenhouse at NASA Ames Research Center were sampled for δ(13) C of organic material and carbonate to assess the impact of carbon fixation (e.g., photosynthesis) and decomposition (e.g., bacterial respiration) on δ(13) C signatures. In the photic zone, the δ(13) C org signature records a complex relationship between the activities of cyanobacteria under variable conditions of CO2 limitation with a significant contribution from green sulfur bacteria using the reductive TCA cycle for carbon fixation. Carbonate is present in some layers of the mat, associated with high concentrations of bacteriochlorophyll e (characteristic of green sulfur bacteria) and exhibits δ(13) C signatures similar to DIC in the overlying water column (-2.0‰), with small but variable decreases consistent with localized heterotrophic activity from sulfate-reducing bacteria (SRB). Model results indicate respiration rates in the upper 12 mm of the mat alter in situ pH and HCO3- concentrations to create both phototrophic CO2 limitation and carbonate supersaturation, leading to local precipitation of carbonate minerals. The measured activity of SRB with depth suggests they variably contribute to decomposition in the mat dependent on organic substrate concentrations. Millimeter-scale variability in the δ(13) C org signature beneath the photic zone in the mat is a result of shifting dominance between cyanobacteria and green sulfur bacteria with the aggregate signature overprinted by heterotrophic reworking by SRB and methanogens. These observations highlight the impact of sedimentary microbial processes on δ(13) C org signatures; these processes need to be considered when attempting to relate

  13. Technology as a driving force

    The competitiveness of the Norwegian Continental shelf has been put firmly on the agenda in Norway since the report from a working group set up by the Ministry of Industry and Energy was released in February this year. If there is to be secured a long future for oil and gas activities, a reduction in the time and costs used in the projects of the order of 40-50%, without jeopardizing the high safety and environmental standards achieved in Norway. The paper addresses how technology can be a driving force in achieving these aims. But technology alone cannot do the job. Progress and changes in several other areas are also necessary, and the new scenario also calls for improved relations between all actors in the North Sea, authorities, oil companies, contractors and labour unions. 15 figs

  14. Mobile Money in developing markets : What should Mobile Money providers consider when trying to drive activity from the already registered user base?

    Fallah, Milad; Luo, Johanna

    2014-01-01

    For the past decade, there has been many innovations made to the mobile phone and new features such as payments have been added to the mobile phone’s capabilities. East Africa is the region with the fastest uptake and highest adoption rates of mobile money in the world. Despite the success, the amount of active users of mobile money is still low in comparison to the number of registered users. The purpose of this master thesis is to analyze what mobile money providers should consider when try...

  15. High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner

    Polansky, Julia K.; Rajia Bahri; Mylene Divivier; Duitman, Erwin H.; Christina Vock; Goyeneche-Patino, Diego A.; Zane Orinska; Silvia Bulfone-Paus

    2016-01-01

    The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8+ T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor ...

  16. Cycloconverter drive systems. Cycloconverter gijutsu

    Chiashi, M.; Osawa, H.; Endo, K. (Fuji Electric Co. Ltd., Tokyo (Japan))

    1991-10-10

    Fuji Electric has completed preparation for the production of various cycloconverter variable-speed AC drive systems used for low-speed large-capacity drives, and is ready to supply the optimum system to meet purposes. Among cycloconverter drive systems of Fuji Electric, circulating current-free cycloconverter fed synchronous motor drive is superior in respect of input power factor and equipment capacity, induction motor drive is superior in respect of maintenance, and circulating current cycloconverter fed motor drive is superior in respect of controllability. This report describes outlines, system components, comparison of performances, control systems and their characteristics, and technology for advanced performance of these various cycloconverter drive systems. Furthermore, was introduced a development of hybrid cycloconverter using a GTO thyristor which can regulate input power factor at 1. 2 refs., 14 figs., 1 tab.

  17. Fast wave current drive

    Experiments on the fast wave in the range of high ion cyclotron harmonics in the ACT-1 device show that current drive is possible with the fast wave just as it is for the lower hybrid wave, except that it is suitable for higher plasma densities. A 1400 loop antenna launched the high ion cyclotron harmonic fast wave [ω/Ω = O(10)] into a He+ plasma with n/sub e/approx. =4 x 1012 cm-3 and B = 4.5 kG. Probe and magnetic loop diagnostics and FIR laser scattering confirmed the presence of the fast wave, and the Rogowski loop indicated that the circulating plasma current increased by up to 40A with 1 kW of coupled power, which is comparable to lower hybrid current drive in the same device with the same unidirectional fast electron beam used as the target for the RF. A phased antenna array would be used for FWCD in a tokamak without the E-beam

  18. Control rod drives

    Purpose: To rapidly detect the position to which a control rod has been rapidly inserted into the reactor core upon scram in the control rod drives for use in LMFBR type reactors. Constitution: In control rod drives comprising an acceleration spring disposed to the outside of an extension pipe and an acceleration pipe for conducting the spring force to a control rod for rapidly dropping the rod into the reactor core, a magnet having a repulsive force is disposed to each acceleration pipe and guide pipe as decelerating and buffering means for the acceleration pipe. The position of the control rod is detected by the interaction between the magnet and the coils attached to the inside of the guide pipe or reactor lead switch. According to this invention, 85 % scram signal which has hitherto been difficult to be processed electrically can be obtained with a sufficient intensity and with no delay to thereby improve the entire safety of the reactor system. Then, the inserted position and the insertion time can accurately and rapidly be detected. (Horiuchi, T.)

  19. Polar drive on OMEGA

    High-convergence polar-drive experiments are being conducted on OMEGA [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] using triple-picket laser pulses. The goal of OMEGA experiments is to validate modeling of oblique laser deposition, heat conduction in the presence of nonradial thermal gradients in the corona, and implosion energetics in the presence of laser-plasma interactions such as crossed-beam energy transfer. Simulated shock velocities near the equator, where the beams are obliquely incident, are within 5% of experimentally inferred values in warm plastic shells, well within the required accuracy for ignition. High, near-one-dimensional areal density is obtained in warm-plastic-shell implosions. Simulated back-lit images of the compressing core are in good agreement with measured images. Outstanding questions that will be addressed in the future relate to the role of cross-beam transfer in polar drive irradiation and increasing the energy coupled into the target by decreasing beam obliquity. (authors)

  20. Turbulent current drive

    The Ohm's law is modified when turbulent processes are accounted for. Besides an hyper-resistivity, already well known, pinch terms appear in the electron momentum flux. Moreover it appears that turbulence is responsible for a source term in the Ohm's law, called here turbulent current drive. Two terms contribute to this source. The first term is a residual stress in the momentum flux, while the second contribution is an electro-motive force. A non zero average parallel wave number is needed to get a finite source term. Hence a symmetry breaking mechanism must be invoked, as for ion momentum transport. E × B shear flows and turbulence intensity gradients are shown to provide similar contributions. Moreover this source term has to compete with the collision friction term (resistivity). The effect is found to be significant for a large scale turbulence in spite of an unfavorable scaling with the ratio of the electron to ion mass. Turbulent current drive appears to be a weak effect in the plasma core, but could be substantial in the plasma edge where it may produce up to 10 % of the local current density

  1. High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner.

    Polansky, Julia K; Bahri, Rajia; Divivier, Mylene; Duitman, Erwin H; Vock, Christina; Goyeneche-Patino, Diego A; Orinska, Zane; Bulfone-Paus, Silvia

    2016-01-01

    The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8(+) T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8(+) T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of "free" IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired. PMID:26822794

  2. Closed-loop control of respiratory drive using pressure-support ventilation: target drive ventilation.

    Spahija, Jadranka; Beck, Jennifer; de Marchie, Michel; Comtois, Alain; Sinderby, Christer

    2005-05-01

    By using diaphragm electrical activity (multiple-array esophageal electrode) as an index of respiratory drive, and allowing such activity above or below a preset target range to indicate an increased or reduced demand for ventilatory assistance (target drive ventilation), we evaluated whether the level of pressure-support ventilation can be automatically adjusted in response to exercise-induced changes in ventilatory demand. Eleven healthy individuals breathed through a circuit (18 cm H2O/L/second inspiratory resistance at 1 L/second flow; 0.5-1.0 L/second expiratory flow limitation) connected to a modified ventilator. Subjects breathed for 6-minute periods at rest and during 20 and 40 W of bicycle exercise, with and without target drive ventilation (the target was set to 60% of the increase in diaphragm electrical activity observed between rest and 20 W of unassisted exercise). With target drive ventilation during exercise, the level of pressure-support ventilation was automatically increased, reaching 13.3 +/- 4.0 and 20.3 +/- 2.8 cm H2O during 20- and 40-W exercise, respectively, whereas diaphragm electrical activity was reduced to a level within the target range. Both diaphragmatic pressure-time product and end-tidal CO2 were significantly reduced with target drive ventilation at the end of the 20- (p < 0.01) and 40-W (p < 0.001) exercise periods. Minute ventilation was not altered. These results demonstrate that target drive ventilation can automatically adjust pressure-support ventilation, maintaining a constant neural drive and compensating for changes in respiratory demand. PMID:15665323

  3. Torque Vibration Active Disturbance Rejection Control of Double-Fed Wind Turbine Drive Train%双馈风电机组传动系统扭振抑制自抗扰控制

    捌色兴佳; 王晓东; 单光坤; 刘姝

    2012-01-01

    Torque vibration is an important reason of wind turbine drive train fatigue damage.The nonlinear and uncertainty characteristics in drive train are analyzed firstly in this paper.A torque vibration control method is designed based on active disturbances rejection control technique.The external disturbances and uncertainties of drive train,which include gear engaging dynamic stiffness,gear engaging error and flexible coupling nonlinear stiffness and damping etc.,are integrated as compositive disturbances.The compositive disturbances are estimated with extended state observer and compensated during torque vibration control.The torque vibration controller is evaluated based on a 3MW doubly fed variable speed wind turbine.The simulation result shows that the gearbox torque vibration is mitigated obviously on the premise of not affecting generator output power.%扭振是造成风电机组传动系统零部件疲劳损伤的主要原因之一。为了通过控制减小风电机组传动系统疲劳载荷,本文在分析风电机组传动系统中非线性不确定因素作用的基础上,设计了一种扭振抑制自抗扰控制器。该控制器将传动系统中的非线性不确定因素作用和外界扰动归结为系统总扰动,通过扩张状态观测器进行实时估计,并在发电机转矩控制中给予补偿,增强了控制器的适应性和鲁棒性。以3MW双馈风电机组为控制对象的试验结果表明,该控制器可以在不影响机组发电量的前提下抑制传动系统扭振,明显减小齿轮箱的转矩波动,从而减轻扭转载荷对主要零部件的疲劳损伤。

  4. Why did we make that cheese? An empirically based framework for understanding what drives innovation activities in a low-tech industry

    Harmsen, Hanne; Grunert, Klaus G.

    The interplay between R&D skills and competencies and market skills and competencies is in the more recent product development literature seen as a major determinant of success for innovation. The study reported in this paper was done in order to more light on these two contructs in a traditionally...... low-tech industry, where product development is nevertheless considered to be strategically important, ie, the food processing industry. The results of a series of case studies indicate that oth constructs than R&D and market orientation may be more appropriate for understanding innovation and...... explaining innovation success in the case material. A new set of constructs focusing on what causes specific innovation activities to occur is prop and a revised framework is developed....

  5. The interaction of R&D and market orientation in improving business performance: An empirically based framework for understanding what drives innovation activity

    Grunert, Klaus G.; Harmsen, Hanne

    1997-01-01

    The interplay between R&D skills and competencies and market skills and competencies is in the more recent product development literature seen as a major determinant of successful innovation. The study reported in this paper was done in order to c more light on these two constructs in a...... traditionally low-tech industry, where product development is nevertheless considered to be strategically important, i.e., the food processing industry. The results of a series of case studies indicate that constructs than R&D and market orientation may be more appropriate for understanding innovation and...... explaining innovation success in the case material. A new set of constructs focusing on what causes specific innovation activities to occur is prop and a revised framework is developed....

  6. Limitations of Short Range Mexican Hat Connection for Driving Target Selection in a 2D Neural Field: Activity Suppression and Deviation from Input Stimuli.

    Geoffrey eMégardon

    2015-10-01

    Full Text Available Dynamic Neural Field models (DNF often use a kernel of connection with short range excitation and long range inhibition. This organization has been suggested as a model for brain structures or for artificial systems involved in winner-take-all processes such as saliency localisation, perceptual decision or target/action selection. A good example of such a DNF is the superior colliculus (SC, a key structure for eye movements. Recent results suggest that the superficial layers of the SC (SCs exhibit relatively short range inhibition with a longer time constant than excitation. The aim of the present study was to further examine the properties of a DNF with such an inhibition pattern in the context of target selection. First we tested the effects of stimulus size and shape on when and where self-maintained clusters of firing neurons appeared, using three variants of the model. In each model variant, small stimuli led to rapid formation of a spiking cluster, a range of medium sizes led to the suppression of any activity on the network and hence to no target selection, while larger sizes led to delayed selection of multiple loci. Second, we tested the model with two stimuli separated by a varying distance. Again single, none, or multiple spiking clusters could occur, depending on distance and relative stimulus strength. For short distances, activity attracted towards the strongest stimulus, reminiscent of well-known behavioural data for saccadic eye movements, while for larger distances repulsion away from the second stimulus occurred. All these properties predicted by the model suggest that the SCs, or any other neural structure thought to implement a short range MH, is an imperfect winner-take-all system. Although those properties call for systematic testing, the discussion gathers neurophysiological and behavioural data suggesting that such properties are indeed present in target selection for saccadic eye movements.

  7. Type III Transforming Growth Factor-β Receptor Drives Cardiac Hypertrophy Through β-Arrestin2-Dependent Activation of Calmodulin-Dependent Protein Kinase II.

    Lou, Jie; Zhao, Dan; Zhang, Ling-Ling; Song, Shu-Ying; Li, Yan-Chao; Sun, Fei; Ding, Xiao-Qing; Yu, Chang-Jiang; Li, Yuan-Yuan; Liu, Mei-Tong; Dong, Chang-Jiang; Ji, Yong; Li, Hongliang; Chu, Wenfeng; Zhang, Zhi-Ren

    2016-09-01

    The role of type III transforming growth factor-β receptor (TβRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TβRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TβRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TβRIII expression was substantially increased in transverse aortic constriction (TAC)- and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TβRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TβRIII in vitro. Cardiac-specific transgenic expression of TβRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TβRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TβRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TβRIII in vivo. Our data suggest that TβRIII mediates stress-induced cardiac hypertrophy through activation of Ca(2+)/calmodulin-dependent protein kinase II, which requires a physical interaction of β-arrestin2 with both TβRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TβRIII expression results in cardiac hypertrophy through β-arrestin2-dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-β and β-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac

  8. Activation of TAK1 by MYD88 L265P drives malignant B-cell Growth in non-Hodgkin lymphoma

    Massively parallel sequencing analyses have revealed a common mutation within the MYD88 gene (MYD88L265P) occurring at high frequencies in many non-Hodgkin lymphomas (NHLs) including the rare lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia (WM). Using whole-exome sequencing, Sanger sequencing and allele-specific PCR, we validate the initial studies and detect the MYD88L265P mutation in the tumor genome of 97% of WM patients analyzed (n=39). Due to the high frequency of MYD88 mutation in WM and other NHL, and its known effects on malignant B-cell survival, therapeutic targeting of MYD88 signaling pathways may be clinically useful. However, we are lacking a thorough characterization of the role of intermediary signaling proteins on the biology of MYD88L265P-expressing B cells. We report here that MYD88L265P signaling is constitutively active in both WM and diffuse large B-cell lymphoma cells leading to heightened MYD88L265P, IRAK and TRAF6 oligomerization and NF-κB activation. Furthermore, we have identified the signaling protein, TAK1, to be an essential mediator of MYD88L265P-driven signaling, cellular proliferation and cytokine secretion in malignant B cells. Our studies highlight the biological significance of MYD88L265P in NHL and reveal TAK1 inhibition to be a potential therapeutic strategy for the treatment of WM and other diseases characterized by MYD88L265P

  9. Driving during alcohol hangover among dutch professional truck drivers

    Verster, Joris C; Van Der Maarel, Martin A; McKinney, Adele; Olivier, Berend; De Haan, Lydia

    2014-01-01

    OBJECTIVES: Alcohol hangover may impair potentially dangerous daily activities such as driving a car or operating heavy machinery. The purpose of the present study was to determine (1) whether driving during alcohol hangover is a problem of concern among professional Dutch truck drivers and (2) to w

  10. Music mood induction and maintenance while driving : A simulator study

    Dijksterhuis, Chris; van der Zwaag, Marjolein; de Waard, Dick; Westerink, Joyce; Brookhuis, Karel; Mulder, Ben L. J. M.

    2010-01-01

    It is common knowledge that mood can influence our everyday behaviour and people often seek to reinforce, or to alter their mood, for example by turning on music. Music listening while driving is a common activity. However, the actual impact of music listening while driving on physical state and dri

  11. What is strenuous? Driving itself or the driving situation?

    Schießl, Caroline; Vollrath, Mark; Altmüller, Tobias; Dambier, Michael; Kornblum, Christian

    2006-01-01

    To avoid driver overload, assistance systems can be adapted regarding the driver’s current strain. Physiological and performance workload measures require special sensors and are problematic concerning sensitivity and specificity. Within the presented study the driver’s stress level was estimated in real-driving based on an analysis of different driving manoeuvres and environmental factors. The analyses show that different driving manoeuvres result in significantly different subjective strain...

  12. The man behind the curtain: X-rays drive the UV through NIR variability in the 2013 active galactic nucleus outburst in NGC 2617

    After the All-Sky Automated Survey for SuperNovae discovered a significant brightening of the inner region of NGC 2617, we began a ∼70 day photometric and spectroscopic monitoring campaign from the X-ray through near-infrared (NIR) wavelengths. We report that NGC 2617 went through a dramatic outburst, during which its X-ray flux increased by over an order of magnitude followed by an increase of its optical/ultraviolet (UV) continuum flux by almost an order of magnitude. NGC 2617, classified as a Seyfert 1.8 galaxy in 2003, is now a Seyfert 1 due to the appearance of broad optical emission lines and a continuum blue bump. Such 'changing look active galactic nuclei (AGNs)' are rare and provide us with important insights about AGN physics. Based on the Hβ line width and the radius-luminosity relation, we estimate the mass of central black hole (BH) to be (4 ± 1) × 107 M ☉. When we cross-correlate the light curves, we find that the disk emission lags the X-rays, with the lag becoming longer as we move from the UV (2-3 days) to the NIR (6-9 days). Also, the NIR is more heavily temporally smoothed than the UV. This can largely be explained by a simple model of a thermally emitting thin disk around a BH of the estimated mass that is illuminated by the observed, variable X-ray fluxes.

  13. Driving Forces for Covalent Assembly of Porphyrins by Selective C-H Bond Activation and Intermolecular Coupling on a Copper Surface.

    Floris, Andrea; Haq, Sam; In't Veld, Mendel; Amabilino, David B; Raval, Rasmita; Kantorovich, Lev

    2016-05-11

    Recent synthesis of covalent organic assemblies at surfaces has opened the promise of producing robust nanostructures for functional interfaces. To uncover how this new chemistry works at surfaces and understand the underlying mechanisms that control bond-breaking and bond-making processes at specific positions of the participating molecules, we study here the coupling reaction of tetra(mesityl)porphyrin molecules, which creates covalently connected networks on the Cu(110) surface by utilizing the 4-methyl groups as unique connection points. Using scanning tunneling microscopy (STM), state-of-the-art density functional theory (DFT), and Nudged Elastic Band (NEB) calculations, we show that the unique directionality of the covalent bonding is found to stem from a chain of highly selective C-H activation and dehydrogenation processes, followed by specific intermolecular C-C coupling reactions that are facilitated by the surface, by steric constraints, and by anisotropic molecular diffusion. These insights provide the first steps toward developing synthetic rules for complex two-dimensional covalent organic chemistry that can be enacted directly at a surface to deliver specific macromolecular structures designed for specific functions. PMID:27097295

  14. Persistent Activation of NF-κB in BRCA1-Deficient Mammary Progenitors Drives Aberrant Proliferation and Accumulation of DNA Damage.

    Sau, Andrea; Lau, Rosanna; Cabrita, Miguel A; Nolan, Emma; Crooks, Peter A; Visvader, Jane E; Pratt, M A Christine

    2016-07-01

    Human BRCA1 mutation carriers and BRCA1-deficient mouse mammary glands contain an abnormal population of mammary luminal progenitors that can form 3D colonies in a hormone-independent manner. The intrinsic cellular regulatory defect in these presumptive breast cancer precursors is not known. We have discovered that nuclear factor kappaB (NF-κB) (p52/RelB) is persistently activated in a subset of BRCA1-deficient mammary luminal progenitors. Hormone-independent luminal progenitor colony formation required NF-κB, ataxia telangiectasia-mutated (ATM), and the inhibitor of kappaB kinase, IKKα. Progesterone (P4)-stimulated proliferation resulted in a marked enhancement of DNA damage foci in Brca1(-/-) mouse mammary. In vivo, NF-κB inhibition prevented recovery of Brca1(-/-) hormone-independent colony-forming cells. The majority of human BRCA1(mut/+) mammary glands showed marked lobular expression of nuclear NF-κB. We conclude that the aberrant proliferative capacity of Brca1(-/-) luminal progenitor cells is linked to the replication-associated DNA damage response, where proliferation of mammary progenitors is perpetuated by damage-induced, autologous NF-κB signaling. PMID:27292187

  15. ER-Coordinated Activities of Rab22a and Rab5a Drive Phagosomal Compaction and Intracellular Processing of Borrelia burgdorferi by Macrophages

    Xenia Naj

    2015-09-01

    Full Text Available Borrelia burgdorferi is the causative agent of Lyme disease, a multisystemic disorder affecting the skin, joints, and nervous system. Macrophages and dendritic cells counteract Borrelia dissemination through internalization and degradation of spirochetes. We now show that Borrelia internalization by primary human macrophages involves uptake and compaction into Rab22a-positive phagosomes that are in close contact with Rab5a-positive vesicles. Compaction of borreliae involves membrane extrusion from phagosomes, is driven by Rab22a and Rab5a activity, and is coordinated by ER tubules forming contact sites of Rab22a phagosomes with Rab5a vesicles. Importantly, Rab22a and Rab5a depletion leads to reduced localization to lysosomes and to increased intracellular survival of spirochetes. These data show that Rab22a- and Rab5a-driven phagosomal uptake is a crucial step in the vesicular cascade that leads to elimination of spirochetes by macrophages. Rab22a and Rab5a thus present as potential molecular targets for the modulation of intracellular processing of borreliae in human immune cells.

  16. Control rod drives

    Purpose: To improve the reliability of a device for driving an LMFBR type reactor control rod by providing a buffer unit having a stationary electromagnetic coil and a movable electromagnetic coil in the device to thereby avord impact stress at scram time and to simplify the structure of the buffer unit. Constitution: A non-contact type buffer unit is constructed with a stationary electromagnetic coil, a cable for the stationary coil, a movable electromagnetic coil, a spring cable for the movable coil, and a backup coil spring or the like. Force produced at scram time is delivered without impact by the attracting or repelling force between the stationary coil and the movable coil of the buffer unit. Accordingly, since the buffer unit is of a non-contact type, there is no mechanical impact and thus no large impact stress, and as it has simple configuration, the reliability is improved and the maintenance can be conducted more easily. (Yoshihara, H.)

  17. Magnetostrictive direct drive motors

    Naik, Dipak; Dehoff, P. H.

    1992-01-01

    A new rare earth alloy, Terfenol-D, combines low frequency operation and extremely high energy density with high magnetostriction. Its material properties make it suitable as a drive element for actuators requiring high output torque. The high strains, the high forces and the high controllability of Terfenol alloys provide a powerful and challenging basis for new ways to generate motion in actuators. Two prototypes of motors using Terfenol-D rods were developed at NASA Goddard. The basic principles of operation are provided of the motor along with other relevant details. A conceptual design of a torque limiting safety clutch/brake under development is illustrated. Also, preliminary design drawings of a linear actuator using Terfenol-D is shown.

  18. Do emotions drive psychosis?

    João Guilherme Ribeiro

    2013-11-01

    Full Text Available Introduction: How important is the emotional life of persons who manifest psychotic symptoms? Aims: The aim of this paper is to review evidence on a causal role for emotions in psychotic processes. Methods: Selective review of literature on affective symptoms in psychoses, on emotions in the production of psychotic symptoms and on dopaminergic models of psychosis. Results: Affective symptoms are relevant across psychoses. Persons with schizophrenia have high levels of emotional reactivity and the intensification of negative affects not only is associated with but also precedes the intensification of psychotic symptoms, which is evidence that negative emotions drive the course of psychotic symptoms. Negative self‑representations are central in psychotic processes and can be the link between negative emotions and psychosis. Evidence favours the notion that persecutory delusions are consistent with negative affects and self‑representations, while grandiose delusions are consistent with a defensive amplification of positive affects and self‑representations. Shame has been proposed as the core emotional experience of psychosis, one in which the self becomes vulnerable to the external world, which is consistent with persecutory experiences. Assaults on the self, under the form of hostility in the family environment and society, are strong predictors of relapse and development of schizophrenia. Assaults on the self which induce social defeat are also strong stimulants of mesolimbic dopaminergic pathways, whose hyperactivity is associated with acute psychotic episodes and the experience of “aberrant salience”, put forward as a dopaminergic model of psychosis. Conclusions: The “defeat of the self” emerges as a central link that binds the experience of negative emotions to the expression of psychotic symptoms and its psychological and neurobiological correlates. The hypothesis gains support that the emotions related to that defeat control

  19. Do emotions drive psychosis?

    João G. Ribeiro

    2012-12-01

    Full Text Available Introduction: How important is the emotional life of persons who manifest psychotic symptoms? Aims: The aim of this paper is to review evidence on a causal role for emotions in psychotic processes. Methods: Selective review of literature on affective symptoms in psychoses, on emotions in the production of psychotic symptoms and on dopaminergic models of psychosis. Results: Affective symptoms are relevant across psychoses. Persons with schizophrenia have high levels of emotional reactivity and the intensification of negative affects not only is associated with but also precedes the intensification of psychotic symptoms, which is evidence that negative emotions drive the course of psychotic symptoms. Negative self‑representations are central in psychotic processes and can be the link between negative emotions and psychosis. Evidence favours the notion that persecutory delusions are consistent with negative affects and self‑representations, while grandiose delusions are consistent with a defensive amplification of positive affects and self‑representations. Shame has been proposed as the core emotional experience of psychosis, one in which the self becomes vulnerable to the external world, which is consistent with persecutory experiences. Assaults on the self, under the form of hostility in the family environment and society, are strong predictors of relapse and development of schizophrenia. Assaults on the self which induce social defeat are also strong stimulants of mesolimbic dopaminergic pathways, whose hyperactivity is associated with acute psychotic episodes and the experience of “aberrant salience”, put forward as a dopaminergic model of psychosis. Conclusions: The “defeat of the self” emerges as a central link that binds the experience of negative emotions to the expression of psychotic symptoms and its psychological and neurobiological correlates. The hypothesis gains support that the emotions related to that defeat control

  20. The man behind the curtain: X-rays drive the UV through NIR variability in the 2013 active galactic nucleus outburst in NGC 2617

    Shappee, B. J.; Kochanek, C. S.; Stanek, K. Z.; De Rosa, G.; Mathur, S.; Zu, Y.; Peterson, B. M.; Pogge, R. W.; Jencson, J.; Holoien, T.W-S.; Basu, U.; Beacom, J. F.; Adams, S. [Department of Astronomy, The Ohio State University, Columbus, OH 43210 (United States); Prieto, J. L. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Grupe, D. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Komossa, S. [Max-Planck Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Im, M. [CEOU/Department of Physics and Astronomy, Seoul National University, Seoul 151-742 (Korea, Republic of); Szczygieł, D. M. [Warsaw University Astronomical Observatory, Al. Ujazdowskie 4, 00-478 Warsaw (Poland); Brimacombe, J. [Coral Towers Observatory, Cairns, Queensland A-4870 (Australia); Campillay, A., E-mail: shappee@astronomy.ohio-state.edu [Carnegie Observatories, Las Campanas Observatory, Colina El Pino, Casilla 601 (Chile); and others

    2014-06-10

    After the All-Sky Automated Survey for SuperNovae discovered a significant brightening of the inner region of NGC 2617, we began a ∼70 day photometric and spectroscopic monitoring campaign from the X-ray through near-infrared (NIR) wavelengths. We report that NGC 2617 went through a dramatic outburst, during which its X-ray flux increased by over an order of magnitude followed by an increase of its optical/ultraviolet (UV) continuum flux by almost an order of magnitude. NGC 2617, classified as a Seyfert 1.8 galaxy in 2003, is now a Seyfert 1 due to the appearance of broad optical emission lines and a continuum blue bump. Such 'changing look active galactic nuclei (AGNs)' are rare and provide us with important insights about AGN physics. Based on the Hβ line width and the radius-luminosity relation, we estimate the mass of central black hole (BH) to be (4 ± 1) × 10{sup 7} M {sub ☉}. When we cross-correlate the light curves, we find that the disk emission lags the X-rays, with the lag becoming longer as we move from the UV (2-3 days) to the NIR (6-9 days). Also, the NIR is more heavily temporally smoothed than the UV. This can largely be explained by a simple model of a thermally emitting thin disk around a BH of the estimated mass that is illuminated by the observed, variable X-ray fluxes.

  1. CLIC Drive Beam Phase Stabilisation

    Gerbershagen, Alexander; Schulte, Daniel

    The thesis presents phase stability studies for the Compact Linear Collider (CLIC) and focuses in particular on CLIC Drive Beam longitudinal phase stabilisation. This topic constitutes one of the main feasibility challenges for CLIC construction and is an essential component of the current CLIC stabilisation campaign. The studies are divided into two large interrelated sections: the simulation studies for the CLIC Drive Beam stability, and measurements, data analysis and simulations of the CLIC Test Facility (CTF3) Drive Beam phase errors. A dedicated software tool has been developed for a step-by-step analysis of the error propagation through the CLIC Drive Beam. It uses realistic RF potential and beam loading amplitude functions for the Drive and Main Beam accelerating structures, complete models of the recombination scheme and compressor chicane as well as of further CLIC Drive Beam modules. The tool has been tested extensively and its functionality has been verified. The phase error propagation at CLIC h...

  2. Aggressive Driving Behavior: Undergraduate Students Study

    Rungson Chomeya

    2010-01-01

    Problem statement: The main purposes of this research were (1) to study the aggressive driving behavior of graduate students, (2) to develop aggressive driving behavior standard test, (3) to compare the aggressive driving behavior between gender, years of study, academic achievement, driving confidence and driving experience and (4) to study the relationship among aggressive driving behavior, driving confidence, driving experience and accident experience. Approach: The subjects consisted of 4...

  3. Automobile Driving and Aggressive Behavior

    Novaco, Raymond W.

    1991-01-01

    Automobile driving and aggressive behavior have had an extensive association. Themes of dominance and territoriality have long been part of automobile driving, which has also involved flagrant assaultive actions. Recent episodes of roadway violence in metropolitan areas have raised community concern about aggressive behavior in driving, although common beliefs about why such violence occurs can be seen as pseudoexplanations. Various themes in the psychology of aggression are presented as they...

  4. Quantum effects in warp drives

    Finazzi Stefano

    2013-01-01

    Warp drives are interesting configurations that, at least theoretically, provide a way to travel at superluminal speed. Unfortunately, several issues seem to forbid their realization. First, a huge amount of exotic matter is required to build them. Second, the presence of quantum fields propagating in superluminal warp-drive geometries makes them semiclassically unstable. Indeed, a Hawking-like high-temperature flux of particles is generated inside the warp-drive bubble, which causes an expon...

  5. Searching in Lists While Driving

    Koerner, Julia

    2006-01-01

    More and more in-vehicle systems are rapidly becoming commercially available, making the driving task more and more complex. Driving performance in such multiple-task situations depends primarily on the level of task demands imposed on the driver by certain situations. The higher the perceived task difficulty, the higher the workload level of that individual. The aim of this dissertation was therefore to investigate possible trade-offs between primary task (driving) and secondary task (se...

  6. Distracted Driving, A Major Preventable Cause of Motor Vehicle Collisions: "Just Hang Up and Drive".

    Kahn, Christopher A; Cisneros, Victor; Lotfipour, Shahram; Imani, Ghasem; Chakravarthy, Bharath

    2015-12-01

    For years, public health experts have been concerned about the effect of cell phone use on motor vehicle collisions, part of a phenomenon known as "distracted driving." The Morbidity and Mortality Weekly Report (MMWR) article "Mobile Device Use While Driving - United States and Seven European Countries 2011" highlights the international nature of these concerns. Recent (2011) estimates from the National Highway Traffic Safety Administration are that 10% of fatal crashes and 17% of injury crashes were reported as distraction-affected. Of 3,331 people killed in 2011 on roadways in the U.S. as a result of driver distraction, 385 died in a crash where at least one driver was using a cell phone. For drivers 15-19 years old involved in a fatal crash, 21% of the distracted drivers were distracted by the use of cell phones. Efforts to reduce cell phone use while driving could reduce the prevalence of automobile crashes related to distracted driving. The MMWR report shows that there is much ground to cover with distracted driving. Emergency physicians frequently see the devastating effects of distracted driving on a daily basis and should take a more active role on sharing the information with patients, administrators, legislators, friends and family. PMID:26759649

  7. Noninductive current drive in tokamaks

    Various current drive mechanisms may be grouped into four classes: (1) injection of energetic particle beams; (2) launching of rf waves; (3) hybrid schemes, which are combinations of various rf schemes (rf plus beams, rf and/or beam plus ohmic heating, etc.); and (4) other schemes, some of which are specific to reactor plasma conditions requiring the presence of alpha particle or intense synchrotron radiation. Particle injection schemes include current drive by neutral beams and relativistic electron beams. The rf schemes include current drive by the lower hybrid (LH) waves, the electron waves, the waves in the ion cyclotron range of frequencies, etc. Only a few of these approaches, however, have been tested experimentally, with the broadest data base available for LH waves. Included in this report are (1) efficiency criteria for current drive, (2) current drive by neutral beam injection, (3) LH current drive, (4) electron cyclotron current drive, (5) current drive by ion cyclotron waves - minority species heating, and (6) current drive by other schemes (such as hybrids and low frequency waves)

  8. Functional brain mapping of actual car-driving using [18F]FDG-PET

    This study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving. Thirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n=10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n=10) participated as passengers on the front seat. The control subjects (n=10) remained seated in a lit room with their eyes open. Voxel-based t-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above. Significant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyms, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum. The result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design. (author)

  9. Heat resistant driving coil and control rod drive mechanism

    Ceramic materials are used for each part of driving coils and used as the driving coils for a driving shaft. That is, a cylindrical bobbin having outwardly protruding flanges on the entire circumference at the upper and the lower portions is made of stainless steels. Ceramics sheets are appended as necessary to the outer circumferential surface of the bobbin. Then, ceramic electric wires are wound around the outer circumference of the bobbin by a required number of turns to constitute coils. The electric wire is prepared by coating the conductor of nickel-plated copper with ceramic coating material, disposing an insulation material to the outer circumference thereof the further coating the outside with ceramic coating material. This can improve the heat resistance and, since the control rod drives using such heat resistant driving coils can operate at a high temperature. It requires no cooling device and can simplify the reactor and its peripheral structures. (T.M.)

  10. Electric motor drive unit, especially adjustment drive for vehicles

    Litterst, P.

    1980-05-29

    An electric motor drive unit, particularly an adjustment drive for vehicles with at least two parallel drive shafts is described, which is compact and saves space, and whose manufacturing costs are low compared with those of well-known drive units of this type. The drive unit contains a suitable number of magnet systems, preferably permanent magnet systems, whose pole axes are spaced and run parallel. The two pole magnet systems have diametrically opposite shell-shaped segments, to which the poles are fixed. In at least one magnet system the two segments are connected by diametrically opposite flat walls parallel to the pole axes to form a single magnetic circuit pole housing. The segments of at least one other magnet system are arranged on this pole housing so that one of these flat walls is a magnetically conducting, connecting component of the magnetic circuit of the other magnet system.

  11. Detonation drive pellet injector

    Detonation drive pellet injector has been developed and tested. By this method the free piston is not necessary because the pellet accelerated the high pressure shock directly. In the experiment, the Teflon pellet (5 mm dia., 5 mm length) was accelerated by hydrogen, oxygen and dilution gas mixtured detonation. When the gas pressure was only 500 kPa and the mixture rates of hydrogen, oxygen and helium were 3:6:1 or 3:6:0, the Teflon pellet speed was up to 747 m/s. Typical experimental results over 300 kPa of the initial gas pressure range are 78--92% of the one-dimensional calculational values. It showed that the pellet could be accelerated by a relative low pressure gas. When the helium dilution rate is larger than 20%, it was often found the strong detonation of which speed is more than the Chapman-Jouguet speed. Then the pellet speed above 1,100 m/s was obtained

  12. Sleeping and Driving Don't Mix: Sleep Quiz

    ... Don't Mix Sleeping and Driving Don't Mix Primary tabs View (active tab) Take if ($view_ ... Sign up for our Email Newsletter For Email Marketing you can trust Footer Contact Info Home | Contact | ...

  13. Induction-drive magnetohydrodynamic propulsion

    The use of magnetohydrodynamic propulsion for marine applications is reviewed with emphasis on induction-drive systems such as the open-quotes rippleclose quotes motor. Comparisons are made with direct-drive MHD propulsion systems. Application to pumps for hazardous fluids and liquid-metal coolants is also discussed. 13 refs., 8 figs., 2 tabs

  14. Distracted Driving Raises Crash Risk

    ... a Seriously Ill Child Featured Website: NIDA for Teens Past Issues Most Viewed February 2014 Print RSS Find us on Facebook External link, please review our exit disclaimer . Subscribe Distracted Driving Raises Crash Risk Video technology and in-vehicle sensors showed that distracted driving, ...

  15. Driving Resistance from Railroad Trains

    Lindgreen, Erik Bjørn Grønning; Sorenson, Spencer C

    2005-01-01

    This report methods and parameters for calculating the driving resistance of railroad trains. Calculations and comparisons are presented for aerodynamic, rolling and total resistance for a variety of freight trains under different loading conditions, operating speed and configuration. Simplified...... methods are presented for the estimation of the driving resistance for passenger trains. This report is a supplement to the ARTEMIS rail emissions model....

  16. Warp Drive With Zero Expansion

    Natario, Jose

    2001-01-01

    It is commonly believed that Alcubierre's warp drive works by contracting space in front of the warp bubble and expanding space behind it. We show that this expansion/contraction is but a marginal consequence of the choice made by Alcubierre, and explicitly construct a similar spacetime where no contraction/expansion occurs. Global and optical properties of warp drive spacetimes are also discussed.

  17. Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice

    Naka, Tetsuji; Matsumoto, Tomoshige; Narazaki, Masashi; Fujimoto, Minoru; Morita, Yoshiaki; Ohsawa, Yoshiyuki; SAITO, HIROSHI; Nagasawa, Takashi; Uchiyama, Yasuo; Kishimoto, Tadamitsu

    1998-01-01

    Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase–signal transducers and activators of transcription (JAK-STAT) signal pathway is an important component of cytokine signaling. We have previously shown that STAT3 induces a molecule designated as SSI-1, which inhibits STAT3 functions. To clarify the physiological roles of SSI-1 in vivo, we generated, here, mice lacking SSI-1. These SSI-1−/− mice displayed growth retardation and d...

  18. Driving the Landscape

    Haff, P. K.

    2012-12-01

    Technological modification of the earth's surface (e.g., agriculture, urbanization) is an old story in human history, but what about the future? The future of landscape in an accelerating technological world, beyond a relatively short time horizon, lies hidden behind an impenetrable veil of complexity. Sufficiently complex dynamics generates not only the trajectory of a variable of interest (e.g., vegetation cover) but also the environment in which that variable evolves (e.g., background climate). There is no way to anticipate what variables will define that environment—the dynamics creates its own variables. We are always open to surprise by a change of conditions we thought or assumed were fixed or by the appearance of new phenomena of whose possible existence we had been unaware or thought unlikely. This is especially true under the influence of technology, where novelty is the rule. Lack of direct long-term predictability of landscape change does not, however, mean we cannot say anything about its future. The presence of persistence (finite time scales) in a system means that prediction by a calibrated numerical model should be good for a limited period of time barring bad luck or faulty implementation. Short-term prediction, despite its limitations, provides an option for dealing with the longer-term future. If a computer-controlled car tries to drive itself from New York to Los Angeles, no conceivable (or possible) stand-alone software can be constructed to predict a priori the space-time trajectory of the vehicle. Yet the drive is normally completed easily by most drivers. The trip is successfully completed because each in a series of very short (linear) steps can be "corrected" on the fly by the driver, who takes her cues from the environment to keep the car on the road and headed toward its destination. This metaphor differs in a fundamental way from the usual notion of predicting geomorphic change, because it involves a goal—to reach a desired

  19. Efficiency studies of high frequency current drive

    Pulsed high power free-electron-lasers (FELs) offer new possibilities for the current drive in tokamaks. High intensity FELs apply to the excitation of nonlinear wave-wave processes, such as beat-waves (BW) and stimulated Raman scattering (SRS), in which large phase velocity (vph>>ve) electrostatic modes are generated. These can accelerate resonant electrons to high parallel velocities v||∼vph, which produces a slowly decaying current. Furthermore, the fast electrons with v||>>v are not toroidally trapped into banana orbits. The operation at high frequencies provides for the FEL beam an easy access into the plasma centre. This makes possible to suppress sawtooth activity by profile control and to expand the operational limits in parameter space. Raman and beat-wave methods apply particularly well to bootstrap current seeding, which may considerably enhance the overall current drive efficiency. Both Raman forward (SRS-F) and backward (SRS-B) scattering can be applied to current drive. At high, reactor relevant temperatures SRS-F is the dominant process, because SRS-B is suppressed due to heavy damping of the plasma wave. At temperatures of a few keV, SRS-B dominates because of its short gain length. In this report we shall estimate the current drive efficiency at temperatures relevant for MTX and for a tokamak reactor. We shall also consider the dependence of the efficiency on the peak intensity of FEL in these two cases. (author) 8 refs., 2 figs., 1 tab

  20. Driving Cars by Means of Genetic Algorithms

    Sáez, Yago; Pérez, Diego; Sanjuan, Óscar; Isasi, Pedro

    2008-01-01

    The techniques and the technologies supporting Automatic Vehicle Guidance are an important issue. Automobile manufacturers view automatic driving as a very interesting product with motivating key features which allow improvement of the safety of the car, reducing emission or fuel consumption or optimizing driver comfort during long journeys. Car racing is an active research field where new advances in aerodynamics, consumption and engine power are critical each season. Our proposal is to rese...

  1. Linear Back-Drive Differentials

    Waydo, Peter

    2003-01-01

    Linear back-drive differentials have been proposed as alternatives to conventional gear differentials for applications in which there is only limited rotational motion (e.g., oscillation). The finite nature of the rotation makes it possible to optimize a linear back-drive differential in ways that would not be possible for gear differentials or other differentials that are required to be capable of unlimited rotation. As a result, relative to gear differentials, linear back-drive differentials could be more compact and less massive, could contain fewer complex parts, and could be less sensitive to variations in the viscosities of lubricants. Linear back-drive differentials would operate according to established principles of power ball screws and linear-motion drives, but would utilize these principles in an innovative way. One major characteristic of such mechanisms that would be exploited in linear back-drive differentials is the possibility of designing them to drive or back-drive with similar efficiency and energy input: in other words, such a mechanism can be designed so that a rotating screw can drive a nut linearly or the linear motion of the nut can cause the screw to rotate. A linear back-drive differential (see figure) would include two collinear shafts connected to two parts that are intended to engage in limited opposing rotations. The linear back-drive differential would also include a nut that would be free to translate along its axis but not to rotate. The inner surface of the nut would be right-hand threaded at one end and left-hand threaded at the opposite end to engage corresponding right- and left-handed threads on the shafts. A rotation and torque introduced into the system via one shaft would drive the nut in linear motion. The nut, in turn, would back-drive the other shaft, creating a reaction torque. Balls would reduce friction, making it possible for the shaft/nut coupling on each side to operate with 90 percent efficiency.

  2. Empathic concern drives costly altruism.

    FeldmanHall, Oriel; Dalgleish, Tim; Evans, Davy; Mobbs, Dean

    2015-01-15

    Why do we self-sacrifice to help others in distress? Two competing theories have emerged, one suggesting that prosocial behavior is primarily motivated by feelings of empathic other-oriented concern, the other that we help mainly because we are egoistically focused on reducing our own discomfort. Here we explore the relationship between costly altruism and these two sub-processes of empathy, specifically drawing on the caregiving model to test the theory that trait empathic concern (e.g. general tendency to have sympathy for another) and trait personal distress (e.g. predisposition to experiencing aversive arousal states) may differentially drive altruistic behavior. We find that trait empathic concern--and not trait personal distress--motivates costly altruism, and this relationship is supported by activity in the ventral tegmental area, caudate and subgenual anterior cingulate, key regions for promoting social attachment and caregiving. Together, this data helps identify the behavioral and neural mechanisms motivating costly altruism, while demonstrating that individual differences in empathic concern-related brain responses can predict real prosocial choice. PMID:25462694

  3. Semiclassical instability of warp drives

    Warp drives, at least theoretically, provide a way to travel at superluminal speeds. However, even if one succeeded in providing the necessary exotic matter to construct them, it would still be necessary to check whether they would survive to the switching on of quantum effects. In this contribution we will report on the behaviour of the Renormalized Stress-Energy Tensor (RSET) in the spacetimes associated with superluminal warp drives. We find that the RSET will exponentially grow in time close to the front wall of the superluminal bubble, hence strongly supporting the conclusion that the warp-drive geometries are unstable against semiclassical back-reaction.

  4. Phoning while driving II: a review of driving conditions influence.

    Collet, C; Guillot, A; Petit, C

    2010-05-01

    The first paper examined how the variables related to driving performance were impacted by the management of holding a phone conversation. However, the conditions under which this dual task is carried out are dependent upon a set of factors that may particularly influence the risk of crash. These conditions are defined by several independent variables, classified into five main categories: i) legislation; ii) phone type (hands-free or hand-held); iii) drivers' features regarding age, gender, personal individual profile and driving experience; iv) conversation content (casual or professional) and its context (held with passengers or with a cell (mobile) phone); v) driving conditions (actual or simulated driving, road type, traffic density and weather). These independent variables determine the general conditions. The way in which these factors are combined and interact one with another thus determines the risk that drivers undergo when a cell phone is used while driving. Finally, this review defined the general conditions of driving for which managing a phone conversation is likely to elicit a high risk of car crash or, conversely, may provide a situation of lower risk, with sufficient acceptance to ensure safety. PMID:20432083

  5. Lunar Core Drive Tubes Summary

    National Aeronautics and Space Administration — Contains a brief summary and high resolution imagery from various lunar rock and core drive tubes collected from the Apollo and Luna missions to the moon.

  6. Quantum effects in warp drives

    Finazzi Stefano

    2013-09-01

    Full Text Available Warp drives are interesting configurations that, at least theoretically, provide a way to travel at superluminal speed. Unfortunately, several issues seem to forbid their realization. First, a huge amount of exotic matter is required to build them. Second, the presence of quantum fields propagating in superluminal warp-drive geometries makes them semiclassically unstable. Indeed, a Hawking-like high-temperature flux of particles is generated inside the warp-drive bubble, which causes an exponential growth of the energy density measured at the front wall of the bubble by freely falling observers. Moreover, superluminal warp drives remain unstable even if the Lorentz symmetry is broken by the introduction of regulating higher order terms in the Lagrangian of the quantum field. If the dispersion relation of the quantum field is subluminal, a black-hole laser phenomenon yields an exponential amplification of the emitted flux. If it is superluminal, infrared effects cause a linear growth of this flux.

  7. Optimal Drunk Driving Penalty Structure

    Darren Grant

    2007-01-01

    The expected penalty for drunk driving can and does vary by blood alcohol content. This paper outlines the "penalty structure" that does this optimally, using two different metrics, shows how the optimality conditions can be implemented with available data to analyze policy ex ante or ex post, and then uses these findings to investigate four fundamental features of current U.S. drunk driving policy. The paper provides theoretical and empirical support for large penalties at very high alcohol ...

  8. Warp drive with zero expansion

    Natario, J

    2002-01-01

    It is commonly believed that Alcubierre's warp drive works by contracting space in front of the warp bubble and expanding the space behind it. We show that this contraction/expansion is but a marginal consequence of the choice made by Alcubierre and explicitly construct a similar spacetime where no contraction/expansion occurs. Global and optical properties of warp-drive spacetimes are also discussed.

  9. Warp drive with zero expansion

    It is commonly believed that Alcubierre's warp drive works by contracting space in front of the warp bubble and expanding the space behind it. We show that this contraction/expansion is but a marginal consequence of the choice made by Alcubierre and explicitly construct a similar spacetime where no contraction/expansion occurs. Global and optical properties of warp-drive spacetimes are also discussed

  10. Mulholland Drive: An Intertextual Reading

    Ebrahim Barzegar

    2015-07-01

    Full Text Available This article examines David Lynch’s Mulholland Drive from Kristeva’s concept of intertextuality. To achieve this aim, this study provides a close reading of the selected film so as to trace and illustrate the polyphonic network of references, citations, quotations and intertexts of Mulholland Drive to the significant already-made films such as Sunset Boulevard, The Wizard of Oz, and Persona.

  11. Neural substrates of driving behaviour

    Spiers, H. J.; Maguire, E. A.

    2007-01-01

    Driving a vehicle is an indispensable daily behaviour for many people, yet we know little about how it is supported by the brain. Given that driving in the real world involves the engagement of many cognitive systems that rapidly change to meet varying environmental demands, identifying its neural basis presents substantial problems. By employing a unique combination of functional magnetic resonance imaging (fMRI), an accurate interactive virtual simulation of a bustling central London (UK) a...

  12. SP-100 Control Drive Assembly Development Plan

    Demuth, Scott F.

    1994-07-01

    The Control Drive Assemblies are the only active components in the entire SP-100 system. Consequently, the design challenges dealing with self-welding, wear, and misalignment in the high temperature and high radiation environment are significant. Because of the harsh environment, it has been necessary to test a variety of materials for such components as bearings, electromagnetic coils, clutches, brakes, and gears. The current Control Drive Assembly technology status is adequate for the 20-KWe design with a five-year life, but has not yet been completely demonstrated for the 100-KWe design with a full ten-year life. The difference in technology status for the 20-KWe and 100-KWe designs is due to the shorter lifetime requirement of the 20-KWe system.

  13. Dual drive series actuator

    Janko, Balazs

    2015-01-01

    Industrial robotic manipulators can be found in most factories today. Their tasks are accomplished through actively moving, placing and assembling parts. This movement is facilitated by actuators that apply a torque in response to a command signal. The presence of friction and possibly backlash have instigated the development of sophisticated compensation and control methods in order to achieve the desired performance may that be accurate motion tracking, fast movement or in fa...

  14. Drive Electric Vermont Case Study

    Wagner, Fred [Energetics Incorporated, Columbia, MD (United States); Roberts, Dave [Vermont Energy Investment Corporation (VEIC), Burlington, VT (United States); Francfort, Jim [Idaho National Lab. (INL), Idaho Falls, ID (United States); White, Sera [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-03-01

    Currently in the United States, the heavy majority of plug-in electric vehicle (PEV) sales have been in highly conducive, selected, metropolitan areas; opposed to more broad distribution across the country. The U.S. Department of Energy’s EV Everywhere Grand Challenge is looking carefully at the barriers and opportunities that exist to enable small and midsize communities to partake in the PEV market and benefit from the economic and environmental advantages of PEVs. In order to gain insight into these challenges and barriers, DOE selected a success story (i.e., Drive Electric Vermont) as the subject of this case study, as the state of Vermont is tied with Detroit, Michigan in having the highest percentage of 2014 (most recent complete data) PEV registrations for cold weather U.S. cities and has seen more than a sixfold increase in charging stations over the last three years. The overall objective of this case study was to use the lessons learned from Drive Electric Vermont to determine what activities are most effective at encouraging acquisitions of PEVs and deployment of charging infrastructure in small to midsize communities, prioritizing and sequencing their implementation, identifying robust means for extrapolation, and applying this understanding to other small to midsize communities across the nation. The Drive Electric Vermont Program was formed in 2012 with a goal of increasing the use of electrified transportation in Vermont through policy development, education and outreach, and infrastructure development. The Drive Electric Vermont Program can be broadly broken into four components: (1) strategic planning/leadership, (2) stakeholder/partnership development, (3) education and outreach, and (4) incentives. The early phases of the program focused heavily on strategic planning, and stakeholder and partnership development, followed by a transition to education and outreach activities, charging infrastructure development, and grant and incentive programs

  15. 基于自抗扰控制器的直驱式永磁同步风电系统双PWM控制%Direct-drive permanent magnet synchronous wind power generation system based on active disturbance rejection controller

    伍亮; 杨金明; 贾盼盼

    2013-01-01

    Based on the mathematical model of direct-drive permanent magnet synchronous wind power generation system,the active disturbance rejection controllers (ADRC) are designed for the generator-side converter and the grid-side converter respectively.Using the ADRC,the wind power generation system with dual PWM converter can track maximum power point by the generator-side converter and maintain a constant voltage of DC capacitor by the grid-side converter under rated wind speed.The simulation result shows that comparing with the traditional PI controller,wind power generation system with ADRC can track the reference turbine speed quickly without overshoot.At the same time,voltage disturbance on DC capacitor caused by the variation of wind speed and grid voltage disturbance is effectively restrained.So the wind power generation system with ADRC has outstanding control performance.%针对直驱式永磁同步风力发电机组,分别设计了电机侧和电网侧的变换器自抗扰控制器,从而实现在额定风速以下对电机侧的最大风能跟踪控制、电网侧直流电容电压恒定控制.与常规PI控制器相比,采用自抗扰控制器的直驱动式永磁同步发电系统,能够实现对指令转速快速及无超调跟踪、有效抑制风速变化及电网电压扰动对电容电压的影响,具有较为优秀的控制性能.

  16. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    Santos, Camila Ramos; Meza, Andreia Navarro [Laboratorio Nacional de Biociencias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto [Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Giesel, Guilherme Menegon; Verli, Hugo [Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Squina, Fabio Marcio [Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Prade, Rolf Alexander [Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK (United States); Murakami, Mario Tyago, E-mail: mario.murakami@lnbio.org.br [Laboratorio Nacional de Biociencias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil)

    2010-12-10

    Research highlights: {yields} The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. {yields} Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. {yields} Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 {sup o}C, and exclusively xylobiose at 90 {sup o}C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  17. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    Research highlights: → The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. → Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. → Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 oC, and exclusively xylobiose at 90 oC as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  18. Movable coil type magnetic drives

    In movable coil type magnetic drives suitable to reactor control element drives, if it is intended to increase the retaining force thereof, there has been a problem that the size of the device is increased. Then in electromagnetic coils surrounding a plunger mounted to a driving shaft, auxiliary annular poles are disposed to each of inner ends of poles at both ends of the coils so as to cover almost of the surface on the side of the plunger. As a result, the magnetic bonding force between the electromagnetic coils and the plunger is enhanced, and the retaining force for the driving shaft can be increased by a small sized device without increasing current supplied to the electromagnetic coils and the number of the electromagnetic coils. The present invention is not limited to reactor control element drives, but it can be applied to various kinds of fields such as a driving device for moving materials in contactless manner, for example, in a case of removing drum cans containing radioactive materials or harmful materials. (N.H.)

  19. PHENOMENON OF CARVED DRIVING WHEELS

    LI Xianghua; ZHANG Jianwu

    2007-01-01

    A newly found phenomenon of carved driving wheels of a rea-wheel-drive tractor used in an airport is discussed. The circum of every driving wheel is damaged at three regions, which distribute regularly and uniformly. Everyday, the tractor tows a trailer which are times heavier than the tractor, and moves on the same road in the airport. The phenomenon is explained by the torsional self-excited vibration system of the powertrain. The simplified torsional vibration system is discribed by a 2-order ordinary differential equation, which has a limit circle. Experiments and numerical simulations show the followings: Because of the heavy trailer, the slip ratio of the tractor's driving wheels is very large. Therefore, there is severe torsional self-excited vibration in the tractor's drivetrain, and the self-excited vibration results in severe and regular fluctuations of the rear wheel's velocity. The severe fluctuations in velocity fastens the damage of the driving wheels. At the same time, the time interval in which an arbitrary point in the circum of the driving wheel contacts with the road twice is two times more than the period of the torsional self-excited vibration, and this times explained the existence of three damaged regions. At last, it points out that the phenomenon can be avoided when the torsional damping is large enough.

  20. Giving up driving: does social engagement buffer declines in mental health after driving cessation in older women?

    Rebok, George W; Jones, Vanya C

    2016-08-01

    Many older adults consider driving as essential to maintaining their quality of life and independence, and this may be particularly true for individuals residing in more rural areas where transportation options may be limited. Although it is normative for individuals to eventually stop driving as they age, very few plan ahead for their driving retirement (Curl et al., 2014). The process of driving cessation has been associated with a host of negative consequences for physical and mental well-being, including increased depressive symptoms, reduced network of friends, lower activity levels, and accelerated health decline (Mezuk & Rebok, 2008; Edwards et al., 2009; Curl et al., 2014). Previous studies have found that, at all ages, women are more likely to stop driving in later life than men, and often stop driving prematurely, and that various factors such as education and marital status influence the likelihood of cessation differently for women and men (Ross et al., 2009; Choi et al., 2012). Thus, factors associated with driving cessation and its consequences for older women are important to understand, particularly factors that might help buffer the negative effects of giving up driving and that might serve as early targets for preventive interventions. PMID:27374895

  1. Drowsy Driving: Asleep at the Wheel

    ... a major problem in the United States. The risk, danger, and often tragic results of drowsy driving are alarming. Drowsy driving is the dangerous combination of driving and sleepiness or fatigue. This usually happens when a driver has not ...

  2. CDC Vital Signs: Teen Drinking and Driving

    ... 2.58 MB] Read the MMWR Science Clips Teen Drinking and Driving A Dangerous Mix Recommend on ... Drinking and driving can be deadly, especially for teens Fewer teens are drinking and driving, but this ...

  3. Donor-donor energy migration for determining intramolecular distances in proteins: I. Application of a model to the latent plasminogen activator inhibitor-1 (PAI-1).

    Karolin, J.; Fa, M; Wilczynska, M; Ny, T; Johansson, L B

    1998-01-01

    A new fluorescence spectroscopic method is presented for determining intramolecular and intermolecular distances in proteins and protein complexes, respectively. The method circumvents the general problem of achieving specific labeling with two different chromophoric molecules, as needed for the conventional donor-acceptor transfer experiments. For this, mutant forms of proteins that contain one or two unique cysteine residues can be constructed for specific labeling with one or two identical...

  4. Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors of the low density lipoprotein receptor family by a peptide isolated from a phage displayed library

    Jensen, Jan K.; Malmendal, Anders; Schiøtt, Birgit;

    2006-01-01

    (DVPCFGWCQDA) was determined by NMR. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the u...

  5. Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique.

    Samuel Pichardo

    Full Text Available Efficient driving of piezoelectric materials is desirable when operating transducers for biomedical applications such as high intensity focused ultrasound (HIFU or ultrasound imaging. More efficient operation reduces the electric power required to produce the desired bioeffect or contrast. Our preliminary work [Cole et al. Journal of Physics: Condensed Matter. 2014;26(13:135901.] suggested that driving transducers by applying orthogonal electric fields can significantly reduce the coercivity that opposes ferroelectric switching. We present here the experimental validation of this biaxial driving technique using piezoelectric ceramics typically used in HIFU. A set of narrow-band transducers was fabricated with two sets of electrodes placed in an orthogonal configuration (following the propagation and the lateral mode. The geometry of the ceramic was chosen to have a resonance frequency similar for the propagation and the lateral mode. The average (± s.d. resonance frequency of the samples was 465.1 (± 1.5 kHz. Experiments were conducted in which each pair of electrodes was driven independently and measurements of effective acoustic power were obtained using the radiation force method. The efficiency (acoustic/electric power of the biaxial driving method was compared to the results obtained when driving the ceramic using electrodes placed only in the pole direction. Our results indicate that the biaxial method increases efficiency from 50% to 125% relative to the using a single electric field.

  6. Driving time modulates accommodative response and intraocular pressure.

    Vera, Jesús; Diaz-Piedra, Carolina; Jiménez, Raimundo; Morales, José M; Catena, Andrés; Cardenas, David; Di Stasi, Leandro L

    2016-10-01

    Driving is a task mainly reliant on the visual system. Most of the time, while driving, our eyes are constantly focusing and refocusing between the road and the dashboard or near and far traffic. Thus, prolonged driving time should produce visual fatigue. Here, for the first time, we investigated the effects of driving time, a common inducer of driver fatigue, on two ocular parameters: the accommodative response (AR) and the intraocular pressure (IOP). A pre/post-test design has been used to assess the impact of driving time on both indices. Twelve participants (out of 17 recruited) completed the study (5 women, 24.42±2.84years old). The participants were healthy and active drivers with no visual impairment or pathology. They drove for 2h in a virtual driving environment. We assessed AR and IOP before and after the driving session, and also collected subjective measures of arousal and fatigue. We found that IOP and AR decreased (i.e., the accommodative lag increased) after the driving session (p=0.03 and p<0.001, respectively). Moreover, the nearest distances tested (20cm, 25cm, and 33cm) induced the highest decreases in AR (corrected p-values<0.05). Consistent with these findings, the subjective levels of arousal decreased and levels of fatigue increased after the driving session (all p-values<0.001). These results represent an innovative step towards an objective, valid, and reliable assessment of fatigue-impaired driving based on visual fatigue signs. PMID:27235337

  7. Exploring Forensic Implications of the Fusion Drive

    Shruti Gupta

    2014-09-01

    Full Text Available This paper explores the forensic implications of Apple's Fusion Drive. The Fusion Drive is an example of auto-tiered storage. It uses a combination of a flash drive and a magnetic drive. Data is moved between the drives automatically to maximize system performance. This is different from traditional caches because data is moved and not simply copied. The research included understanding the drive structure, populating the drive, and then accessing data in a controlled setting to observe data migration strategies. It was observed that all the data is first written to the flash drive with 4 GB of free space always maintained. If data on the magnetic drive is frequently accessed, it is promoted to the flash drive while demoting other information. Data is moved at a block-level and not a file-level. The Fusion Drive didn't alter the timestamps of files with data migration.

  8. Driving Difficulties and Adaptive Strategies: The Perception of Individuals Having Sustained a Mild Traumatic Brain Injury

    Carolina Bottari

    2012-01-01

    Full Text Available Introduction. After a mild traumatic brain injury (mTBI, individuals quickly resume driving. However, relatively little is known about the impact of mTBI on driving ability and, notably, on the perceived influence of postconcussive symptoms on driving. Hence, the objective of this study was to document the perception of driving abilities in individuals with mTBI. Method. Twenty-seven drivers with mTBI were interviewed to document their perception regarding their driving abilities. Both driving-related difficulties and compensatory strategies used to increase driving safety were documented. A mixed quantitative and qualitative analysis of the data was completed. Results. 93% of participants reported at least one difficulty perceived as having an impact on everyday activities. Most frequently named problems affecting driving were fatigue and reduced concentration. In addition, 74% of participants had adapted their driving or developed strategies to compensate for driving difficulties. Discussion/Conclusion. Postconcussive symptoms have repercussions on driving ability. However, people with mTBI tend to be aware of their difficulties and develop, over time, adaptive strategies. Preventive measures are thus warranted to increase health care professionals' awareness of the potential consequences of mTBI on driving ability and to promote guidelines for the safe resumption of driving after injury.

  9. Factors affecting return to driving post-stroke.

    Tan, K M

    2012-02-01

    BACKGROUND: Stroke can affect a person\\'s ability to drive, an important means of transportation in the developed world. AIMS: To determine percentage of patients and factors associated with return to driving post-stroke in a service with emphasis on driver assessment. METHODS: Retrospective study of patients discharged from the Stroke Service of our 470-bed teaching hospital from 1998 to 2002. RESULTS: Of 72 drivers pre-stroke, 54% recalled a driving assessment and 68% returned to driving. Younger patients (58.6 +\\/- 12.0 vs. 66.5 +\\/- 10.5, p = 0.008) with lower Modified Rankin Score (median 1 vs. 2, p = 0.0001) and normal cognition (55 vs. 43%, p = 0.45) were more likely to resume driving. More patients who were assessed returned to driving than those who were not (74 vs. 61%, p = 0.31). CONCLUSIONS: A relatively high level of return to driving can be achieved post-stroke with a pro-active approach to driver assessment and rehabilitation. A structured assessment and referral programme should be offered where appropriate.

  10. Drive: Theory and Construct Validation.

    Siegling, Alex B; Petrides, K V

    2016-01-01

    This article explicates the theory of drive and describes the development and validation of two measures. A representative set of drive facets was derived from an extensive corpus of human attributes (Study 1). Operationalised using an International Personality Item Pool version (the Drive:IPIP), a three-factor model was extracted from the facets in two samples and confirmed on a third sample (Study 2). The multi-item IPIP measure showed congruence with a short form, based on single-item ratings of the facets, and both demonstrated cross-informant reliability. Evidence also supported the measures' convergent, discriminant, concurrent, and incremental validity (Study 3). Based on very promising findings, the authors hope to initiate a stream of research in what is argued to be a rather neglected niche of individual differences and non-cognitive assessment. PMID:27409773

  11. Inhibition of Kallikrein-Related Peptidases 7 and 5 by Grafting Serpin Reactive-Center Loop Sequences onto Sunflower Trypsin Inhibitor-1 (SFTI-1).

    Jendrny, Cathleen; Beck-Sickinger, Annette G

    2016-04-15

    Serpin proteins irreversibly inhibit serine proteases, but only a small part of the serpin reactive-center loop (RCL) is responsible for the initial protein-protein interaction (PPI). To develop peptidic protease inhibitors, kallikrein-related peptidases 7 (KLK7) and 5 (KLK5) were chosen. Firstly, we demonstrated that short peptides derived from RCL sequences can be cleaved by KLK7 in a substrate-like manner. Next, these substrates were grafted onto the protease-binding loop of sunflower trypsin inhibitor-1 (SFTI-1). Peptides based on kallistatin, α1 -antichymotrypsin, and protein C inhibitor (PCI) inhibited KLK7 with Ki =0.4, 0.5, and 0.7 μm, respectively. In contrast, the trypsin-like KLK5 was only blocked by the peptide derived from PCI (Ki =0.6 μm). Thus, serpin function can be mimicked by introducing its PPI site into the rigid structure of the SFTI-1 scaffold. This approach might be applicable not only to KLKs but also to other serine protease members, thus opening up new therapeutic fields. PMID:26574674

  12. The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame

    Highlights: ► CDKN1A mRNA is a bona fide NMD substrate. ► The uORF of CDKN1A mRNA is efficiently translated. ► Translation of downstream main ORF is negatively regulated by translation of uORF in CDKN1A mRNA. -- Abstract: The first round of translation occurs on mRNAs bound by nuclear cap-binding complex (CBC), which is composed of nuclear cap-binding protein 80 and 20 (CBP80/20). During this round of translation, aberrant mRNAs are recognized and downregulated in abundance by nonsense-mediated mRNA decay (NMD), which is one of the mRNA quality control mechanisms. Here, our microarray analysis reveals that the level of cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as Waf1/p21) mRNAs increases in cells depleted of cellular NMD factors. Intriguingly, CDKN1A mRNA contains an upstream open reading frame (uORF), which is a NMD-inducing feature. Using chimeric reporter constructs, we find that the uORF of CDKN1A mRNA negatively modulates translation of the main downstream ORF. These findings provide biological insights into the possible role of NMD in diverse biological pathways mediated by CDKN1A.

  13. Influence of roadside infrastructure on driving behavior: driving simulator study

    Horst, A.R.A. van der; Ridder, S. de

    2007-01-01

    This paper describes the results of a driving simulator study that focused on the influence of roadside infrastructure on speed choice and lateral placement of car drivers. A review of the RISER detailed accident database revealed that lateral positioning and speed of the vehicle were two of the pri

  14. The warp drive and antigravity

    Ellis, Homer G.

    2004-01-01

    The warp drive envisioned by Alcubierre that can move a spaceship faster than light can, with modification, levitate it as if it were lighter than light, even allow it to go below a black hole's horizon and return unscathed. Wormhole-like versions of the author's `drainhole' (1973) might provide the drive, in the form of a by-pass of the spaceship composed of a multitude of tiny topological tunnels. The by-pass would divert the gravitational `ether' into a sink covering part of the spaceship'...

  15. Warp drives, wavefronts and superluminality

    Baird, Eric

    1999-01-01

    Coule's primary objection to the Alcubierre "warpdrive" is that the material producing the warp field needs to be superluminal. This difficulty is solved by placing the drive material inside its own warp field (making the drive system part of the payload), but we then have to deal with Low's related objection, that there is then a restricted rate at which this "naked" warp-field can propagate through the background metric. We argue that the propagation of this sort of gravitational wave is no...

  16. The onset of driving phobias.

    Munjack, D J

    1984-12-01

    Thirty driving phobics who called the Psychiatry Outpatient Phobia Clinic (25 females and five males) were given a 20-min semi-standardized telephone interview during which they were asked about the circumstances of the onset of their driving fears. Twelve (40%) reported that their fears were precipitated by a panic attack on the freeway; six (20%) by a collision; and three (10%) by other frightening experiences in automobiles. Four (13.3%) related the onset to family stress or upheaval. Other modes of onset also occurred. The implications of these findings are discussed in terms of existing theories of fear acquisition and treatment approaches. PMID:6526942

  17. Digital control of electric drives

    Koziol, R; Szklarski, L

    1992-01-01

    The electromechanical systems employed in different branches of industry are utilized most often as drives of working machines which must be fed with electric energy in a continuous, periodic or even discrete way. Some of these machines operate at constant speed, others require wide and varying energy control. In many designs the synchronous cooperation of several electric drives is required in addition to the desired dynamic properties. For these reasons the control of the cooperation and dynamics of electromechanical systems requires the use of computers.This book adopts an unusual approach

  18. Confidence in, and self-rating of, driving ability among older drivers.

    Marottoli, R A; Richardson, E D

    1998-05-01

    Active drivers (n = 125) in a representative cohort of older individuals age 77 years and older in New Haven, Connecticut were interviewed. Confidence in different driving situations, self-rating of driving ability, and driving patterns were assessed during these in-person interviews. A history of crashes, moving violations and being stopped by police was available for approximately the past 6 years. Concurrent driving performance was assessed in a subsample (n = 35). Analyses focused on determining the relationship of confidence and self-rating of driving ability to: (1) each other; (2) driving patterns; (3) adverse driving events; and (4) driving performance. All participants rated themselves as being average or above average drivers compared to others their age, with the majority rating themselves as above average. Individuals who drove more miles and more frequently were more likely to rate themselves better drivers than same-age peers. Individuals who rated themselves as "much better" drivers than their peers tended to have higher confidence levels than those who rated themselves a "little bit better" or the "same" as other drivers. On-road driving performance and history of adverse events were not associated with self-ratings of driving ability. Confidence was associated with driving frequency and mileage, but not age or education. Although men were more likely to drive under risky conditions, for those conditions in which each drove, men and women were equally confident. No relationship was found between confidence and adverse driving events or driving performance. Understanding the relationship of confidence and self-rating of driving ability to driving patterns, adverse events and driving performance may provide additional insights into identifying older drivers at increased risk for problems and formulating intervention strategies to help lower risk. PMID:9663292

  19. Driving and Age-Related Macular Degeneration

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  20. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  1. Drive reconfiguration mechanism for tracked robotic vehicle

    Drive reconfiguration apparatus for changing the configuration of a drive unit with respect to a vehicle body may comprise a guide system associated with the vehicle body and the drive unit which allows the drive unit to rotate about a center of rotation that is located at about a point where the drive unit contacts the surface being traversed. An actuator mounted to the vehicle body and connected to the drive unit rotates the drive unit about the center of rotation between a first position and a second position

  2. Evaluation, Generation, and Transformation of Driving Cycles

    Nyberg, Peter

    2015-01-01

    Driving cycles are important components for evaluation and design of vehicles. They determine the focus of vehicle manufacturers, and indirectly they affect the environmental impact of vehicles since the vehicle control system is usually tuned to one or several driving cycles. Thus, the driving cycle affects the design of the vehicle since cost, fuel consumption, and emissions all depend on the driving cycle used for design. Since the existing standard driving cycles cannot keep up with the c...

  3. Simulation of Surrounding Vehicles in Driving Simulators

    Olstam, Johan

    2009-01-01

    Driving simulators and microscopic traffic simulation are important tools for making evaluations of driving and traffic. A driving simulator is de-signed to imitate real driving and is used to conduct experiments on driver behavior. Traffic simulation is commonly used to evaluate the quality of service of different infrastructure designs. This thesis considers a different application of traffic simulation, namely the simulation of surrounding vehicles in driving simulators. The surrounding tr...

  4. Driving Under the Influence of Our Fathers

    Hjalmarsson, Randi; Lindquist, Matthew

    2009-01-01

    This paper studies intergenerational correlations in drunk driving between fathers and their children using the Stockholm Birth Cohort. We find strong evidence of an intergenerational drunk driving relationship. Cohort members who have fathers with a drunk driving record have 2.59 times higher odds of having a drunk driving conviction themselves than cohort members with non-drunk driving fathers. We then go on to investigate the underlying mechanisms that give rise to these correlations. The ...

  5. Anomalous-viscosity current drive

    Stix, T.H.; Ono, M.

    1986-04-25

    The present invention relates to a method and apparatus for maintaining a steady-state current for magnetically confining the plasma in a toroidal magnetic confinement device using anomalous viscosity current drive. A second aspect of this invention relates to an apparatus and method for the start-up of a magnetically confined toroidal plasma.

  6. Foreign driving licences in Switzerland

    DG Unit

    2009-01-01

    1. Persons residing in Switzerland 1.1 Holders of a B, C, D, E or P-type "carte de légitimation" For holders of a B, C, D, E or P-type "carte de légitimation" issued by the Swiss Federal Department for Foreign Affairs (DFAE), current non-Swiss national driving licences are valid in Switzerland. If they so wish, holders of such driving licences may apply to the relevant road licensing authority in the canton where they live (Service des Automobiles et de la Navigation; for Geneva call + 41 22 388 30 30, website http://www.geneve.ch/san; for Vaud call + 41 21 316 82 10, website http://www.san.vd.ch/index.html) to exchange their driving licence for an equivalent Swiss licence (they must pass a test if they are not citizens of countries with which Switzerland has concluded an agreement on this matter, e.g. Member States of the European Union, the United States and Japan). However, such an exchange is not possible if the driving licence was issued in a foreign country during a...

  7. Death Drive in Tourism Studies

    Buda, Dorina

    2014-01-01

    The psychoanalytical concept of the death drive refers to a constant metapsychological force at the junction between life and death: it is not understood in a biological sense of physical demise of the body, nor in opposition to life. Geographies of tourist performances in places in the proximity of

  8. Police enforcement and driving speed.

    2008-01-01

    Speed limits are violated frequently in the Netherlands. As speed is an important factor in road crashes, the surveillance of driving speeds is one of the spearheads in the policy plans of the Dutch police. Different methods of speed enforcement have proved to be effective in reducing speed and cras

  9. FOREIGN DRIVING LICENCES IN SWITZERLAND

    Relatiopns with the Host States Service

    2001-01-01

    1. PERSONS RESIDING IN SWITZERLAND 1.1 Holders of a B, C, D or E-type carte de légitimation For holders of B, C, D or E-type cartes de légitimation issued by the Swiss Federal Department for Foreign Affairs (Département fédéral suisse des Affaires étrangères, hereinafter called DFAE), current non-Swiss national driving licences are valid in Switzerland. Should they so wish, holders of such driving licences may apply to the relevant roads authority in the canton where they live (Service des Automobiles et de la Navigation ; for Geneva call 022/343 02 00, website: http://www.geneve.ch/san/welcome.html, for Vaud call 021/316 82 10, website: http://www.dse.vd.ch/auto/index.html) in order to exchange their driving licence for an equivalent Swiss licence. However, exchanges are not permitted if the driving licence was issued in a foreign country during a stay there of less than six months' duration while the person concerned was officially...

  10. Design of a novel chimeric tissue plasminogen activator with favorable Vampire bat plasminogen activator properties.

    Kazemali, MohammadReza; Majidzadeh-A, Keivan; Sardari, Soroush; Saadatirad, Amir Hossein; Khalaj, Vahid; Zarei, Najmeh; Barkhordari, Farzaneh; Adeli, Ahmad; Mahboudi, Fereidoun

    2014-12-01

    Fibrinolytic agents are widely used in treatment of the thromboembolic disorders. The new generations like recombinant tissue plasminogen activator (t-PA, alteplase) are not showing promising results in clinical practice in spite of displaying specific binding to fibrin in vitro. Vampire bat plasminogen activator (b-PA) is a plasminogen activator with higher fibrin affinity and specificity in comparison to t-PA resulting in reduced probability of hemorrhage. b-PA is also resistant to plasminogen activator inhibitor-1 (PAI-1) showing higher half-life compared to other variants of t-PA. However, its non-human origin was a driving force to design a human t-PA with favorable properties of b-PA. In the present study, we designed a chimeric t-PA with desirable b-PA properties and this new molecule was called as CT-b. The construct was prepared through kringle 2 domain removal and replacement of t-PA finger domain with b-PA one. In addition, the KHRR sequence at the initial part of protease domain was replaced by four alanine residues. The novel construct was integrated in Pichia pastoris genome by electroporation. Catalytic activity was investigated in the presence and absence of fibrin. The purified protein was analyzed by western blot. Fibrin binding and PAI resistance assays were also conducted. The activity of the recombinant protein in the presence of fibrin was 1560 times more than its activity in the absence of fibrin, showing its higher specificity to fibrin. The fibrin binding of CT-b was 1.2 fold more than t-PA. In addition, it was inhibited by PAI enzyme 44% less than t-PA. Although the presented data demonstrate a promising in vitro activity, more in vivo studies are needed to confirm the therapeutic advantage of this novel plasminogen activator. PMID:25442953

  11. Estrogens, selective estrogen receptor modulators, and a selective estrogen receptor down-regulator inhibit endothelial production of tissue factor pathway inhibitor 1

    Ree Anne

    2006-10-01

    Full Text Available Abstract Background Hormone therapy, oral contraceptives, and tamoxifen increase the risk of thrombotic disease. These compounds also reduce plasma content of tissue factor pathway inhibitor-1 (TFPI, which is the physiological inhibitor of the tissue factor pathway of coagulation. The current aim was to study if estrogens and estrogen receptor (ER modulators may inhibit TFPI production in cultured endothelial cells and, if so, identify possible mechanisms involved. Methods Human endothelial cell cultures were treated with 17β-estradiol (E2, 17α-ethinylestradiol (EE2, tamoxifen, raloxifene, or fulvestrant. Protein levels of TFPI in cell media and cell lysates were measured by an enzyme-linked immunosorbent assay, and TFPI mRNA levels were assessed by quantitative PCR. Expression of ERα was analysed by immunostaining. Results All compounds (each in a concentration of 10 nM reduced TFPI in cell medium, by 34% (E2, 21% (EE2, 16% (tamoxifen, and 28% (raloxifene, respectively, with identical inhibitory effects on cellular TFPI levels. Expression of TFPI mRNA was principally unchanged. Treatment with fulvestrant, which was also associated with down-regulation of secreted TFPI (9% with 10 nM and 26% with 1000 nM, abolished the TFPI-inhibiting effect of raloxifene, but not of the other compounds. Notably, the combination of 1000 nM fulvestrant and 10 nM raloxifene increased TFPI secretion, and, conversely, 10 nM of either tamoxifen or raloxifene seemed to partly (tamoxifen or fully (raloxifene counteract the inhibitory effect of 1000 nM fulvestrant. The cells did not express the regular nuclear 66 kDa ERα, but instead a 45 kDa ERα, which was not regulated by estrogens or ER modulators. Conclusion E2, EE2, tamoxifen, raloxifene, and fulvestrant inhibited endothelial production of TFPI by a mechanism apparently independent of TFPI transcription.

  12. AC drives for industrial plants. Plant kudoyo AC drive sochi

    Miyazaki, M.; Shibata, M.; Yamada, S. (Toshiba Corp., Tokyo (Japan))

    1992-08-01

    Features and product series of AC drives for industrial plants were outlined. Configurations and features of various types of AC drives were briefly discussed which are put into market to meet various requirements for industrial plants and wide ranges of output voltage and capacity. The following product series were outlined; the power bipolar transistor inverter for 3.5-600 kVA in output capacity, IGBT inverter for AC 400 V in output voltage and 1,000 kVA or less, GTO inverter for AC 600 V and 700-2,000 kVA, and cycloconverter for AC 1,000-3,000 V and 1,000 kW-20 MW. The following subjects were outlined as current technical trends of AC drives for industrial plants; increasing in capacity of voltage-source PWM inverters, downsizing of converters through highly efficient cooling and highly dense mounting, spreading of sensorless vector controls, and development of high-voltage large-capacity PWM inverters. 6 figs., 2 tabs.

  13. [Driving fitness/driving capacity of patients treated with methadone].

    Hauri-Bionda, R; Bär, W; Friedrich-Koch, A

    1998-10-10

    To answer the question whether or not therapeutic methadone doses significantly reduce traffic-related performance of drivers on medically supervised methadone programmes, 34 methadone substitution patients, all of them volunteers, were subjected to a test series: the focus of the study was a psychophysical test battery consisting of 10 individual performance tests to assess essential functions with regard to driving ability, such as concentration, attention, reaction capability, memory, perception and sensorimotor coordination. In evaluating the results of the psychophysical tests, multiple drug use and subjective methadone influence at the time of the examination were taken into consideration but current methadone blood level was neglected. The results were compared to those of a control group. The methadone group (n = 34) consisted of 25 men and 9 women aged between 18 and 38. At the time of the study, the majority of the test persons (29) were on low dosage methadone maintenance (up to 60 mg/day). In the urine samples of approximately 2/3 of the test persons, evidence was found for multiple drug use together with other psychotropic substances, the most frequent (14) being cannabis metabolites. Referring to their driving practices, a mere 4 out of 29 drivers had not committed any driving offences. A comparison of the psychophysical performance of the whole methadone group (n = 34) with a control group demonstrated that the methadone substitution patients achieved rather lower results in almost all variables. These performance deficits were particularly conspicuous in sustained attention, sensorimotor coordination and reaction capability. 12 "methadone only" participants, i.e. methadone probands without any additional consumption of psychotropic substances showed-partly considerably-better performance than the methadone group as a whole and also achieved normal results in relation to the test norm. Nevertheless, once again, results tended to be of lower level in

  14. The warp drive and antigravity

    Ellis, H G

    2004-01-01

    The warp drive envisioned by Alcubierre that can move a spaceship faster than light can, with modification, levitate it as if it were lighter than light, even allow it to go below a black hole's horizon and return unscathed. Wormhole-like versions of the author's `drainhole' (1973) might provide the drive, in the form of a by-pass of the spaceship composed of a multitude of tiny topological tunnels. The by-pass would divert the gravitational `ether' into a sink covering part of the spaceship's hull, connected by the tunnels to a source covering the remainder of the hull, to produce an ether flow like that of a river that disappears underground only to spring forth at a point downstream. This diversion would effectively shield the spaceship from external gravity.

  15. Warp-Drive Quantum Computation

    Nakahara, M; Kondo, Y; Tanimura, S; Hata, K; Nakahara, Mikio; Vartiainen, Juha J.; Kondo, Yasushi; Tanimura, Shogo; Hata, Kazuya

    2004-01-01

    Recently it has been shown that time-optimal quantum computation is attained by using the Cartan decomposition of a unitary matrix. We extend this approach by noting that the unitary group is compact. This allows us to reduce the execution time of a quantum algorithm $U_{\\rm alg}$ further by adding an extra gate $W$ to it. This gate $W$ sends $U_{\\rm alg}$ to another algorithm $WU_{\\rm alg}$ which is executable in a shorter time than $U_{\\rm alg}$. We call this technique warp-drive. Here we show both theoretically and experimentally that the execution time of Grover's algorithm is reduced in two-qubit NMR quantum computer. Warp-drive is potentially a powerful tool in accelerating algorithms and reducing the errors in any realization. of a quantum computer

  16. Warp Drive: A New Approach

    Obousy, Richard

    2007-01-01

    Certain classes of higher dimensional models suggest that the Casimir Effect is a candidate for the cosmological constant. In this paper we demonstrate that a sufficiently advanced civilization could, in principal, manipulate the radius of the extra dimension to locally adjust the value of the cosmological constant. This adjustment could be tuned to generate an expansion/contraction of spacetime around a spacecraft creating an exotic form of field-propulsion. Due to the fact that spacetime expansion itself is not restricted by relativity, a faster-than-light 'warp drive' could be created. Calculations of the energy requirements of such a drive are performed and an 'ultimate' speed limit, based on the Planckian limits on the size of the extra dimensions is found.

  17. Fabrication and characterization of a tethered rotational planar variable capacitance micro drive

    In this paper, we present the design, fabrication and characterization of a planar variable capacitance micro drive. The rotational micro drive is developed for high-speed applications with contactless active electrostatic micro bearings. The associated low-temperature process allows the fabrication of devices with narrow stator–rotor gaps. The drive performance is characterized by means of tethered functional prototype devices. The multicompliant devices have silicon rotors and a soft polymer suspension, which allows the validated modeling of the drive capacitance and accurate measurement of the static drive torques. The devices achieve up to 2.6 nNm static drive torque per phase at an actuation voltage of 12 V. These results demonstrate the highest torque generation of a planar variable capacitance drive at low actuation voltages. (paper)

  18. Warp drive space-time

    González-Díaz, Pedro F.

    2000-01-01

    In this paper the problem of the quantum stability of the two-dimensional warp drive spacetime moving with an apparent faster than light velocity is considered. We regard as a maximum extension beyond the event horizon of that spacetime its embedding in a three-dimensional Minkowskian space with the topology of the corresponding Misner space. It is obtained that the interior of the spaceship bubble becomes then a multiply connected nonchronal region with closed spacelike curves and that the m...

  19. On translating "The Sunday Drive"

    Ziegler, Heide

    1991-01-01

    What difficulties confront the translator of a text by William H. Gass? Apart, that is, from the difficulties known to any translator of any literary text, differences of environment, culture, and mental habits, as well as linguistic problems regarding tense, aspect, or mode? The following text will point out a few of those difficulties by facing eight paragraphs from Gass's piece "The Sunday Drive" with a German translation, each section to be followed by a commentary on the text and an eval...

  20. Inbreeding drives maize centromere evolution

    Schneider, Kevin L.; Xie, Zidian; Wolfgruber, Thomas K.; Presting, Gernot G

    2016-01-01

    The diversity of centromere-specific DNA repeats in different species (centromere paradox) and the seemingly parallel rapid evolution of the cenH3 histone protein have previously been interpreted to be related to evolutionary pressures acting on both molecules based on their interaction (centromere drive hypothesis). Here we describe the detailed mechanism and chronology of centromere repeat replacement, and identify inbreeding as a major driver of centromeric DNA replacement that ultimately ...

  1. High-performance motor drives

    Kazmierkowski, Marian P.; García Franquelo, Leopoldo; Rodríguez, José; Pérez, Marcelo; León Galván, José Ignacio

    2011-01-01

    This article reviews the present state and trends in the development of key parts of controlled induction motor drive systems: converter topologies, modulation methods, as well as control and estimation techniques. Two- and multilevel voltage-source converters, current-source converters, and direct converters are described. The main part of all the produced electric energy is used to feed electric motors, and the conversion of electrical power into mechanical power involves motors ranges from...

  2. Opportunities and Cooperation Drive Prosperity

    2004-01-01

    The old industrial base is lying in Northeast China. Although boasting many advantages such as talents, resources, transportation, environment, the region still have many disadvantages that needs opening up and reform. Revitalizing the Northeast region is an important task for China to built well-off society in an all-round way in the new century. It is also a big strategy made after developing costal region and western region by Chinese leaders according to current situation, which is a driving force

  3. Foreign driving licences in Switzerland

    2009-01-01

    1. Persons residing in Switzerland 1.1 Holders of a B, C, D, E or P-type "carte de légitimation" For holders of a B, C, D, E or P-type "carte de légitimation" issued by the Swiss Federal Department for Foreign Affairs (DFAE), current non-Swiss national driving licences are valid in Switzerland. (see the official news about the new "Carte de légitimation P") If they so wish, holders of such driving licences may apply to the relevant road licensing authority in the canton where they live (Service des Automobiles et de la Navigation; for Geneva call + 41 22 388 30 30, website http://www.geneve.ch/san; for Vaud call + 41 21 316 82 10, website http://www.san.vd.ch/index.html) to exchange their driving licence for an equivalent Swiss licence (they must pass a test if they are not citizens of countries with which Switzerland has concluded an agreement on this matter, e.g. Member States of the European Union, the United States and Japan). However, such an exchange is not possible...

  4. Foreign driving licences in France

    HR Department

    2009-01-01

    The following information is subject to possible amendments decided by the competent French authorities. Those wishing to undertake the necessary steps with the prefectural services of the Departments of the Ain and Haute-Savoie may obtain information by calling the following numbers: + 33 4 74 32 30 65 for the Ain and + 33 4 50 33 60 00 for Haute-Savoie. 1. PERSONS RESIDING IN FRANCE 1.1 Driving licences issued by a State belonging to the EU or the EEA a) Recognition on French territory All currently valid driving licences issued by States belonging to the European Union (EU) or to the European Economic Area (EEA) are generally valid for driving on French territory. However, if the licence was originally obtained in exchange for a licence issued by a State not belonging to the EU or to the EEA and with which France has not concluded a reciprocity agreement, it will be recognised for a maximum of one year following the date of establishment of normal residence in France ...

  5. FOREIGN DRIVING LICENCES IN FRANCE

    DSU Unit

    2008-01-01

    The following information is provided subject to possible amendments decided by the competent French authorities. Those wishing to undertake the necessary steps with the prefectural services of the Departments of Ain and Haute-Savoie may obtain information by calling the following numbers: + 33 474 32 30 65 for Ain and + 33 450 33 60 00 for Haute-Savoie. 1. PEOPLE RESIDING IN FRANCE 1.1 Driving licences issued by a state belonging to the EU or the EEA a) Recognition on French territory All currently valid driving licences issued by States belonging to the European Union (EU) or to the European Economic Area (EEA) are generally valid for driving on French territory. However, if the licence was originally obtained in exchange for a licence issued by a State not belonging to the EU or to the EEA with which France has not concluded a reciprocity agreement, it is recognised only up to one year following the date of establishment of normal residence in France (date of the first special residence permit issu...

  6. FOREIGN DRIVING LICENCES IN FRANCE

    Service des relations avec les Pays Hôtes

    2000-01-01

    1. PERSONS RESIDING IN FRANCE1.1 National driving licences from countries belonging to the EEAa) ValidityCurrent national driving licences issued by a country belonging to the European Economic Area (here inafter called EEA) are, in principle, valid in France. N.B. : The countries belonging to the EEA are Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Liechtenstein, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden and the United Kingdom.b)\tRegistrationTo ensure that all the conditions of validity in France have been met, holders of driving licences issued by a country belonging to the EEA, who reside in France (i.e. hold a residence permit issued by a Préfecture, or a carte spéciale issued by the French Ministry of Foreign Affairs, which is equivalent to a residence permit), can have their licences registered with the Préfecture of the department where they live (for Ain, call 04 74 32 30 00, for Haute Savoie call 04 50 33 ...

  7. Energy Optimal Control of Induction Motor Drives

    Abrahamsen, Flemming

    system. The dynamic performances were also evaluated in a vector controlled drive for CT applications. Based on these tests, the displacement power factor control and the direct air-gap flux control appeared to be best for small HVAC applications. Energy optimal control of medium-size drives was analyzed......This thesis deals with energy optimal control of small and medium-size variable speed induction motor drives for especially Heating, Ventilation and Air-Condition (HVAC) applications. Optimized efficiency is achieved by adapting the magnetization level in the motor to the load, and the basic...... purpose is demonstrate how this can be done for low-cost PWM-VSI drives without bringing the robustness of the drive below an acceptable level. Four drives are investigated with respect to energy optimal control: 2.2 kW standard and high-efficiency motor drives, 22 kW and 90 kW standard motor drives. The...

  8. Novel prediction method of beer foam stability using protein Z, barley dimeric alpha-amylase inhibitor-1 (BDAI-1) and yeast thioredoxin.

    Iimure, Takashi; Takoi, Kiyoshi; Kaneko, Takafumi; Kihara, Makoto; Hayashi, Katsuhiro; Ito, Kazutoshi; Sato, Kazuhiro; Takeda, Kazuyoshi

    2008-09-24

    Foam stability is an important quality trait of beer. Our previous results of two-dimensional gel electrophoresis (2DE) analyses of beer proteins implied a relationship between barley dimeric alpha-amylase inhibitor-1 (BDAI-1) and beer foam stability as judged by the NIBEM-T analyzer. To develop a novel prediction method of beer foam stability under different conditions of barley cultivar and malt modification, multiple linear regression analysis was applied. The spot intensities of major beer proteins on 2DE gel were quantified and used as explanatory variables. The foam stabilities of 25 beer samples each brewed from malt with different malt modification in one of the three cultivars (cultivars A, B, and C) were explained by the spot intensities of BDAI-1 at the 5% significance level ( r = 0.421). Furthermore, two other major protein spots (b0 and b5) were observed on the 2DE gels of Japanese commercial beer samples with different foam stability. Then, multiple regression for foam stability was calculated using these three spot intensities as explanatory variables. As a result, 72.1% of the beer foam stability in 25 beer samples was explained by a novel multiple regression equation calculated using spot b0 and BDAI-1 as positive explanatory variables and spot b5 as a negative variable. To verify the validity of the multiple regression equation and the explanatory variables, the beer foam stability in practical beer samples was analyzed. As a result, 81.5% of the beer foam stability in 10 Japanese commercial beer samples was also explained by using spot b0 and BDAI-1 as positive explanatory variables and spot b5 as a negative variable. Mass spectrometry analyses followed by database searches revealed that protein spots b0 and b5 were identified as protein Z originated from barley and thioredoxin originated from yeast, respectively. These results confirm that BDAI-1 and protein Z are foam-positive factors and identify yeast thioredoxin as a possible novel foam

  9. Modeling human learning involved in car driving

    Wewerinke, P.H.

    1994-01-01

    In this paper, car driving is considered at the level of human tracking and maneuvering in the context of other traffic. A model analysis revealed the most salient features determining driving performance and safety. Learning car driving is modelled based on a system theoretical approach and based on a neural network approach. The aim of this research is to assess the relative merit of both approaches to describe human learning behavior in car driving specifically and in operating dynamic sys...

  10. Development of portable driving simulator system

    Itoh, Y; Nemoto, T.; Matsuura, H.; M. Kihira; S. Yanai

    2008-01-01

    Purpose: In accordance with aging of populations in many developed countries, number of drivers who suffer from mild cognitive impairment (MCI drivers) is increasing. Since it has been reported that driving skill of the MCI drivers are deteriorated, it is important to train themselves in driving situation to preserve their driving skills. The present study was conducted to develop the simple driving simulator system, and to examine the effect of training in this system.Design/methodology/appr...

  11. 77 FR 51610 - Distracted Driving Grant Program

    2012-08-24

    ... National Highway Traffic Safety Administration Distracted Driving Grant Program AGENCY: Department of... and enforcing distracted driving laws. The FY 2013 funds are subject to an annual obligation... FY 2013 may be less than the amount identified above. A State's distracted driving law must...

  12. Implicit attitudes towards risky and safe driving

    Martinussen, Laila Marianne; Sømhovd, Mikael Julius; Møller, Mette;

    ; further, self-reports of the intention to drive safely (or not) are socially sensitive. Therefore, we examined automatic preferences towards safe and risky driving with a Go/No-go Association Task (GNAT). The results suggest that (1) implicit attitudes towards driving behavior can be measured reliably...

  13. Driving When You Have Parkinson's Disease

    Driving When You Have Parkinson’s Disease DRIVEWELL You have been a safe driver for years. For you, driving means freedom and control. As you get ... mental health can affect how safely you drive. Parkinson’s disease is a disorder of the central nervous ...

  14. Classifying visuomotor workload in a driving simulator using subject specific spatial brain patterns

    ChrisDijksterhuis; KarelBrookhuis

    2013-01-01

    A passive Brain Computer Interface (BCI) is a system that responds to the spontaneously produced brain activity of its user and could be used to develop interactive task support. A human-machine system that could benefit from brain-based task support is the driver-car interaction system. To investigate the feasibility of such a system to detect changes in visuomotor workload, 34 drivers were exposed to several levels of driving demand in a driving simulator. Driving demand was manipulated by ...

  15. Driving Path Predication Based Routing Protocol in Vehicular Ad hoc Networks

    Yong Feng; Feng Wang; Jingjing Liao; Qian Qian

    2013-01-01

    The vehicular mobility is reflection and extension of the human social activity. Since human trajectories show a high degree of temporal and spatial regularity, thus vehicular driving paths are predictable to a large extent. In this paper, we firstly analyze the predictabilities of different types of vehicles and then propose a new driving path predication based routing protocol (DPPR). With hello messages to broadcast vehicles’ driving path predication information to neighbor vehicles, DPPR ...

  16. Warp-Drive Quantum Computation

    Nakahara, Mikio; Vartiainen, Juha J.; Kondo, Yasushi; Tanimura, Shogo; Hata, Kazuya

    2004-01-01

    Recently it has been shown that time-optimal quantum computation is attained by using the Cartan decomposition of a unitary matrix. We extend this approach by noting that the unitary group is compact. This allows us to reduce the execution time of a quantum algorithm $U_{\\rm alg}$ further by adding an extra gate $W$ to it. This gate $W$ sends $U_{\\rm alg}$ to another algorithm $WU_{\\rm alg}$ which is executable in a shorter time than $U_{\\rm alg}$. We call this technique warp-drive. Here we s...

  17. Error signals driving locomotor adaptation

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo; Bouyer, Laurent J

    2016-01-01

    perturbations. Forces were applied to the ankle joint during the early swing phase using an electrohydraulic ankle-foot orthosis. Repetitive 80 Hz electrical stimulation was applied to disrupt cutaneous feedback from the superficial peroneal nerve (foot dorsum) and medial plantar nerve (foot sole) during...... anaesthesia (n = 5) instead of repetitive nerve stimulation. Foot anaesthesia reduced ankle adaptation to external force perturbations during walking. Our results suggest that cutaneous input plays a role in force perception, and may contribute to the 'error' signal involved in driving walking adaptation when...

  18. Perceptual and Cognitive Impairments and Driving

    Korner-Bitensky, Nicol; Coopersmith, Henry; Mayo, Nancy; Leblanc, Ginette; Kaizer, Franceen

    1990-01-01

    Perceptual and cognitive disorders that frequently accompany stroke and head injury influence an individual's ability to drive a motor vehicle. Canadian physicians are legally responsible for identifying patients who are potentially unsafe to drive and, if they fail to do so, may be held liable in a civil action suit. The authors review the guidelines for physicians evaluating a patient's fitness to drive after brain injury. They also examine the actions a physician should take when a patient with perceptual and cognitive problems wants to drive. Ultimately, by taking these actions, physicians will help to prevent driving accidents. PMID:21234047

  19. Drive-by-Wireless with the eCar Demonstrator

    Staehle, Hauke; Huang, Kai; Knoll, Alois

    2016-01-01

    Drive-by-wire technology has been gradually adopted by the car companies in recent years to integrate active assistance systems in vehicles to increase comfort and safety. To push the technologies for the electronic control systems of vehicles to extreme, we investigate the so-called drive-by-wireless, i.e., using wireless network to control steering, braking, accelerating, and other functions within an automobile. We use commercial off-the-shelf ZigBee MSP-EXP430F5438 Development Board for w...

  20. Drive-by-Wireless with the eCar Demonstrator

    Hauke Stähle, Kai Huang, Alois Knoll

    2013-01-01

    Drive-by-wire technology has been gradually adopted by the car companies in recent years to integrate active assistance systems in vehicles to increase comfort and safety. To push the technologies for the electronic control systems of vehicles to extreme, we investigate the so-called drive-by-wireless, i.e., using wireless network to control steering, braking, accelerating, and other functions within an automobile. We use commercial off-the-shelf ZigBee MSP-EXP430F5438 Development Board for w...

  1. What are the impacts of giving up the driving licence?

    Siren, Anu Kristiina; Haustein, Sonja

    2014-01-01

    Driving cessation is a gradual process, where driver’s self-regulation plays an important role. Age-based licence renewal may interfere with this process and trigger premature driving cessation. The present study compares Danish drivers (aged 69 years at the baseline) who either renewed or gave up...... their activities after giving up their licence. In travel frequency, neither the differences between renewers and non-renewers nor the changes over time within the groups were pronounced. The groups differed in their use of transport modes already at the baseline: the renewers drove, while nonrenewers...

  2. Current Sensor Fault Reconstruction for PMSM Drives.

    Huang, Gang; Luo, Yi-Ping; Zhang, Chang-Fan; He, Jing; Huang, Yi-Shan

    2016-01-01

    This paper deals with a current sensor fault reconstruction algorithm for the torque closed-loop drive system of an interior PMSM. First, sensor faults are equated to actuator ones by a new introduced state variable. Then, in αβ coordinates, based on the motor model with active flux linkage, a current observer is constructed with a specific sliding mode equivalent control methodology to eliminate the effects of unknown disturbances, and the phase current sensor faults are reconstructed by means of an adaptive method. Finally, an αβ axis current fault processing module is designed based on the reconstructed value. The feasibility and effectiveness of the proposed method are verified by simulation and experimental tests on the RT-LAB platform. PMID:26840317

  3. Current Sensor Fault Reconstruction for PMSM Drives

    Gang Huang

    2016-01-01

    Full Text Available This paper deals with a current sensor fault reconstruction algorithm for the torque closed-loop drive system of an interior PMSM. First, sensor faults are equated to actuator ones by a new introduced state variable. Then, in αβ coordinates, based on the motor model with active flux linkage, a current observer is constructed with a specific sliding mode equivalent control methodology to eliminate the effects of unknown disturbances, and the phase current sensor faults are reconstructed by means of an adaptive method. Finally, an αβ axis current fault processing module is designed based on the reconstructed value. The feasibility and effectiveness of the proposed method are verified by simulation and experimental tests on the RT-LAB platform.

  4. Chopper Circuits Developed for EV Drive Application

    Tsuruta, Yukinori; Kawamura, Atsuo

    In this paper, the technical stream on a high efficiency and high frequency chopper for the automotive industry, new energy and energy conservation technology field is surveyed. QRAS (Quasi-resonant Regenerating Active Snubber) and SAZZ (Snubber Assisted Zero Voltage and Zero Current Transition) topologies aimed for the electric vehicle (EV) drive application are proposed. 25kHz-8kW QRAS, 100kHz-8kW SAZZ choppers and 50kHz-25kW bilateral SAZZ-1 chopper are constructed and tested under rating conditions. It is verified that SAZZ topology retains high efficiency even at the increased operating frequency of 100kHz. It is shown that high efficiency can be realized at high operating frequency even in high power converters by QRAS and newly proposed SAZZ soft switching topologies.

  5. Kinematics and Dynamics of Roller Chain Drives

    Fuglede, Niels

    There are two main subjects of this work: Kinematic and dynamic modeling and analysis of roller chain drives. In the kinematic analysis we contribute first with a complete treatment of the roller chain drive modeled as a four-bar mechanism. This includes a general, exact and approximate analysis...... parameters which is useful for predicting the characteristic loading of the roller chain drive. As a completely novel contribution, a kinematic model and analysis is presented which includes both spans and sprockets in a simple chain drive system. A general procedure for determination of the total wrapping...... conditions for real chain drives. Examples are presented of both decoupled and coupled motion. Together, the kinematic and dynamic model and analytical results provides a framework for numerical and experimental investigations of roller chain drive motion and deepens the understanding of roller chain drive...

  6. Absorber rod drive for nuclear reactors

    The invention concerns an absorber rod drive for Boiling Water Reactors, in which a mechanical drive is combined with a hydraulic drive working separately from it, so that both drives are situated concentric within an overall length. The driving torque of a motor is transmitted to a threaded spindle, which moves a free adjacent hollow piston vertically via a fixed nut. The same means are used for the hydraulic liquid which is used as coolant or moderator and there are nozzles, annular gaps and/or bores between the hydraulic system and the reactor pressure vessel for the purpose of pressure compensation. All the components of the absorber rod drive except the sealing housing and the setting drive are situated in one casing tube taking the differential pressure. (orig./HP)

  7. Driving Extreme Efficiency to Market

    Garbesi, Karina

    2014-03-01

    The rapid development of extremely energy efficient appliances and equipment is essential to curtail catastrophic climate disruption. This will require the on-going development of products that apply all best-practices and that take advantage of the synergies of hybridization and building integration. Beyond that, it requires the development of new disruptive technologies and concepts. To facilitate these goals, in 2011 the Lawrence Berkeley National Laboratory and the U.S. Department of Energy launched the Max Tech and Beyond Design Competition for Ultra-Low-Energy-Use Appliances and Equipment. Now in its third year, the competition supports faculty-lead student design teams at U.S. universities to develop and test new technology prototypes. This talk describes what the competition and the Max Tech Program are doing to drive such rapid technology progress and to facilitate the entry to the market of successful Max Tech prototypes. The talk also initiates a discussion of physicists' unique role in driving that technology progress faster and farther. Emerging Technologies, Building Technologies Office, U.S. Department of Energy.

  8. Computer Security: drive-bye

    Stefan Lueders, Computer Security Team

    2016-01-01

    Like a lion waiting to ambush gazelles at a waterhole, malware can catch you by surprise.    As some of you might have noticed, the Computer Security Team had to block the news site “20min.ch” a while ago, as it was found to be distributing malware. This block comes after similar incidents at other Swiss organizations. Our blocking is protective in order to safeguard your computers, laptops, tablets and smartphones. Unfortunately, this is not the first time we have seen these so-called drive-by/waterhole attacks: once you have visited an affected website, embedded third-party malicious code is downloaded to your computer and subsequently infects it (if running Windows or Android as well as, less likely, Mac operating systems). Hence the name “drive-by”. As “20min.ch” is a very frequented website among CERN staff members and users, it makes it a perfect source for attacks against CERN (or other Geneva-based organisations): inste...

  9. Development of a chinese motorcycle rider driving violation questionnaire.

    Cheng, Andy Shu-Kei; Ng, Terry Chi-Kwong

    2010-07-01

    The primary purpose of this study was to develop a self-report questionnaire to assess the driving violations of Chinese motorcycle riders and evaluate its screening accuracy between accident-involved and accident-free motorcycle riders. A Chinese Motorcycle Rider Driving Violation (CMRDV) scale, consisting of 19 items, was developed and administered to a sample of motorcycle riders (n=920). Exploratory factor analysis revealed a two-factor solution, which supported the theoretical premise that there are two types of driving violations, aggressive violations and ordinary violations, and that they also apply to motorcycle riders. Cronbach's alpha for these two sub-scales was between 0.876 and 0.914. The test-retest reliability was satisfactory with intra-class correlations of individual item scores ranging from 0.729 to 0.891. Respondents with a past history of active accidents scored significantly high than those without (priders. PMID:20441839

  10. Driving Experience, Alcohol and Monotonous Simulated Driving: Behavioural, Psychophisiological and Subjective measures

    Ferrier, Laurent; Galy, Edith; BERTHELON, Catherine

    2015-01-01

    The aim of the study is to evaluate driving performance during monotonous task depending on Blood Alcohol Concentration (BAC), and driving experience. Assuming that, during monotonous driving task, performance should be impaired with a BAC increased. This impairment should be more pronounced for Young Novice Drivers (YND) than for Young Experienced Drivers (YED). YND (18 years, less than two months of driving license) and YED (21 years, 3 years of driving license) were invited to participate ...

  11. Driving behavior and ergonomics of in-vehicle communicating systems

    PAUZIE, A

    2001-01-01

    In-vehicle systems display information in order to support the driver in his/her activity. This paper describes two main methodologies allowing to investigate driver's behaviour while using these systems : computation of glance frequency and duration toward the implemented screen displaying visual information for the visual strategies and computation of the Driving Activity Load Index for the mental workload. Both evaluation are complementary, being respectively objective and subjectiv...

  12. Statistical Properties of Car Following: Theory and Driving Simulator Experiments

    Ando, Hiromasa; Zgonnikov, Arkady; Saito, Yoshiaki

    2015-01-01

    A fair simple car driving simulator was created based on the open source engine TORCS and used in car-following experiments aimed at studying the basic features of human behavior in car driving. Four subjects with different skill in driving real cars participated in these experiments. The subjects were instructed to drive a car without overtaking and losing sight of a lead car driven by computer at a fixed speed. Based on the collected data the distributions of the headway distance, the car velocity, acceleration, and jerk are constructed and compared with the available experimental data for the real traffic flow. A new model for the car-following is proposed to capture the found properties. As the main result, we draw a conclusion that human actions in car driving should be categorized as generalized intermittent control with noise-driven activation. Besides, we hypothesize that the car jerk together with the car acceleration are additional phase variables required for describing the dynamics of car motion g...

  13. Psychosocial function of driving as redictor of risk-taking behaviour

    Møller, Mette; Gregersen, Nils Petter

    2008-01-01

    This study examined the relation between risk-taking behaviour while driving, the psychosocial function of driving, leisure time activities, car oriented peer group interaction and educational attainment. Two thousand four hundred seventeen drivers aged 18-25, randomly selected from the Danish...... Driving Licence Register, participated in the study. Data was colleted through a mail survey. The response rate was 60,4%. A positive significant effect on risk-taking behaviour based on the score on the psychosocial function of driving was found (p...

  14. Circuit for Driving Piezoelectric Transducers

    Randall, David P.; Chapsky, Jacob

    2009-01-01

    The figure schematically depicts an oscillator circuit for driving a piezoelectric transducer to excite vibrations in a mechanical structure. The circuit was designed and built to satisfy application-specific requirements to drive a selected one of 16 such transducers at a regulated amplitude and frequency chosen to optimize the amount of work performed by the transducer and to compensate for both (1) temporal variations of the resonance frequency and damping time of each transducer and (2) initially unknown differences among the resonance frequencies and damping times of different transducers. In other words, the circuit is designed to adjust itself to optimize the performance of whichever transducer is selected at any given time. The basic design concept may be adaptable to other applications that involve the use of piezoelectric transducers in ultrasonic cleaners and other apparatuses in which high-frequency mechanical drives are utilized. This circuit includes three resistor-capacitor networks that, together with the selected piezoelectric transducer, constitute a band-pass filter having a peak response at a frequency of about 2 kHz, which is approximately the resonance frequency of the piezoelectric transducers. Gain for generating oscillations is provided by a power hybrid operational amplifier (U1). A junction field-effect transistor (Q1) in combination with a resistor (R4) is used as a voltage-variable resistor to control the magnitude of the oscillation. The voltage-variable resistor is part of a feedback control loop: Part of the output of the oscillator is rectified and filtered for use as a slow negative feedback to the gate of Q1 to keep the output amplitude constant. The response of this control loop is much slower than 2 kHz and, therefore, does not introduce significant distortion of the oscillator output, which is a fairly clean sine wave. The positive AC feedback needed to sustain oscillations is derived from sampling the current through the

  15. Older drivers with cognitive impairment: Perceived changes in driving skills, driving-related discomfort and self-regulation of driving

    Meng, A.; Siren, A.; Teasdale, Thomas William

    2013-01-01

    The results of a previous study indicate that in general, older drivers who recognise cognitive problems show realistic self-assessment of changes in their driving skills and that driving-related discomfort may function as an indirect monitoring of driving ability, contributing to their safe...... driving performance. The aim of the present study was to examine whether these findings also apply to cognitively impaired older drivers. Structured face-to-face interviews were conducted with 25 cognitively impaired older drivers. The results showed that the participants were most likely to report their...... driving skills as unchanged. There was an association between level of discomfort and avoidance of driving situations, but not between cognitive status and discomfort or avoidance. The results suggest that cognitively impaired older drivers constitute a unique group; while cognitively impaired older...

  16. [Stress of driving: general overview].

    Costa, G

    2012-01-01

    Driving is a stressful task that requires high levels of attention and vigilance to cope properly with job demands, mainly related to working hours and timetables, weather and traffic conditions, passengers and goods safety, responsibility in case of error and/or accident. Scientific literature shows a higher prevalence of cardiovascular, gastrointestinal, neuropsychic and musculoskeletal disorders, and consequent sick leaves, in professional bus/lorry and train drivers. Several studies have emphasized that stress, fatigue and excessive sleepiness give a significant contribution to occupational road and rail accidents. There are noteworthy, interindividual differences concerning alertness/sleepiness and tolerance to fatigue, related to psychophysiological and behavioural characteristics and health status, in particular: age, ability to overcome drowsiness, morningness/eveningness, diet and intake of psychotropic substances (alcohol, drugs, medicaments), primary and secondary sleep disorders (insomnia, ipersomnias, parasomnias). PMID:23213814

  17. What Drives Politicians’ Online Popularity?

    Nielsen, Rasmus Kleis; Vaccari, Cristian

    2013-01-01

    The number of website visits, Facebook friends, or Twitter followers that politicians attract varies greatly, but little is known about what drives politicians' online popularity. In this article, we use data from a systematic tracking of congressional candidates' popularity on four web platforms...... in the 112 most competitive congressional districts in the 2010 U.S. midterm elections to address that question. Using multivariate regression models, we show that while district-level socioeconomic characteristics have little effect on candidates' online popularity, challengers and candidates in...... open-seat races tend to attract larger audiences online, as do candidates who are more visible on political blogs. Surprisingly, how intensely candidates are covered in news media, how popular they are in opinion polls, and how much money they spend during the campaign show no significant effect. These...

  18. Unsafe driving behaviors and hospitalization.

    Van Tuinen, M

    1994-04-01

    The medical costs associated with motor vehicle crashes are difficult to measure. Most attempts have used crash data and cost data that are only indirectly related to each other or have followed patients in a few hospitals or trauma centers. These studies produce localized estimates or rough national estimates of limited use to policy makers. The result has been a dependence on more readily available mortality data, such as the Fatal Accident Reporting System, to guide automotive safety efforts. The limitations of mortality data and the increasing sophistication of medical care data bases have resulted in a strong interest in obtaining crash-linked morbidity data. Hence, in 1993, the National Highway Traffic Safety Administration (NHTSA) awarded the Missouri Department of Health and six other applicants grants to link automotive crash records to statewide ambulance trip, outpatient care, hospitalization and mortality records. By identifying an individual across multiple data sets, states would be able to determine directly the relationship of driver behaviors and crash characteristics to hospitalization rates and other medical outcomes. Examination of hospital pay source information would expose the toll of automotive crashes on public tax dollars. Having recently completed the record linkage phase of this project, Missouri Department of Health staff are beginning to analyze the impact of automotive crashes on health care costs in Missouri. In this report, three unsafe driving behaviors, failure to use a safety device (seatbelts and motorcycle helmets), driving under the influence of alcohol, and speeding, are related to the risk of hospitalization or death, hospital costs, and expected pay source. PMID:8202067

  19. Electromagnetic drive system of robotic fish

    ZHU Hong-xiu; SUN Nai-di; YUE Yao-hui; DENG Jing; LI Fei-hang; GU Yue; JIA Rui-qing

    2012-01-01

    With the aim to apply the electric fish into practice to assist coal mine water disaster life detection and rescue work,based on the analysis on swing propulsion movements of tail fin,this paper integrates the electromagnet technology with tail fin drive system by analyzing how the fish swims with tail fin under the law of progression.The principle,structure,and drive signals of tail fin electromagnetic drive are researched,the enforced situation of fish under electromagnetic driving modes are analyzed,and the experimental plat-form of tail fin electromagnetic drive is established.The best distance between electromagnet and armature,which can realize the swing of tail fin,was researched in the experiment under water.The robotic fish structure parameters of tail fin electromagnetic drive was finalized by theoretical analysis and experimental measurement.

  20. Special Considerations in Distracted Driving with Teens

    Durbin, Dennis R.; McGehee, Daniel V.; Fisher, Donald; McCartt, Anne

    2014-01-01

    Novice teen drivers have long been known to have an increased risk of crashing, as well as increased tendencies toward unsafe and risky driving behaviors. Teens are unique as drivers for several reasons, many of which have implications specifically in the area of distracted driving. This paper reviews several of these features, including the widespread prevalence of mobile device use by teens, their lack of driving experience, the influence of peer passengers as a source of distraction, the r...

  1. Instruction or distraction in the driving school?

    Andersen, Mike Kirk; Caglio, Agnese

    In this paper we report an ongoing study of driving school practice. We recorded several hours of driving lessons in different environments, which we analyze with the Interaction Analysis method. Our initial analysis suggests that looking at how teachers make use of different communicative resour...... resources to instruct students in driving, can provide insights for the development of technologies that support drivers in managing distractions....

  2. Driving Style: Determining Factors, Characteristics, Optimization Directions

    Lobanova I. I.

    2015-01-01

    A system of description, identification and classification of factors determining driving style is proposed in the article; stable (sustained) and variable (unstable) factors determining driving style are studied. Driving style is analyzed within the framework of structural approach. The variable factor are: specifications and technical condition of the vehicle, class of the car, its prestige (from a social point of view), training of the driver, social regulators, features of the road enviro...

  3. Fundamental limitations on "warp drive" spacetimes

    Lobo, Francisco S N; Visser, Matt

    2004-01-01

    "Warp drive" spacetimes are useful as "gedanken-experiments" that force us to confront the foundations of general relativity, and among other things, to precisely formulate the notion of "superluminal" communication. We verify the non-perturbative violation of the classical energy conditions of the Alcubierre and Natario warp drive spacetimes and apply linearized gravity to the weak-field warp drive, testing the energy conditions to first and second order of the non-relativistic warp-bubble v...

  4. A causally connected superluminal Warp Drive spacetime

    Loup, F.; Held, R.; Waite, D; Halerewicz, Jr., E.; Stabno, M.; Kuntzman, M.; Sims, R.

    2002-01-01

    It will be shown that while horizons do not exist for warp drive spacetimes traveling at subluminal velocities horizons begin to develop when a warp drive spacetime reaches luminal velocities. However it will be shown that the control region of a warp drive ship lie within the portion of the warped region that is still causally connected to the ship even at superluminal velocities, therefore allowing a ship to slow to subluminal velocities. Further it is shown that the warped regions which ar...

  5. Perceptual and Cognitive Impairments and Driving

    Korner-Bitensky, Nicol; Coopersmith, Henry; Mayo, Nancy; Leblanc, Ginette; Kaizer, Franceen

    1990-01-01

    Perceptual and cognitive disorders that frequently accompany stroke and head injury influence an individual's ability to drive a motor vehicle. Canadian physicians are legally responsible for identifying patients who are potentially unsafe to drive and, if they fail to do so, may be held liable in a civil action suit. The authors review the guidelines for physicians evaluating a patient's fitness to drive after brain injury. They also examine the actions a physician should take when a patient...

  6. Switched reluctance drives for electric vehicle applications

    Andrada Gascón, Pedro; Torrent Burgués, Marcel; Blanqué Molina, Balduino; Perat Benavides, Josep Ignasi

    2003-01-01

    Electric vehicles are the only alternative for a clean, efficient and environmentally friendly urban transport system. With the increasing interest in electric drives for electric vehicle propulsion. This paper first tries to explain why the switched reluctance drive is a strong candidate for electric vehicle applications. It then gives switched reluctance drive design guidelines for battery or fuel cell operated electric vehicles. Finally, it presents the design and simulation of a switched ...

  7. Driving Miss Bradley: performance measurement to support thermal driving

    Piccione, Dino; Ferrett, Donald A.

    1998-07-01

    The Driver's Vision Enhancer (DVE) program is providing a system to enlarge the driving envelope for the community of military wheeled and tracked vehicles. The DVE, an IR device, provides the driver with images of the forward scene under night and adverse day conditions. During the DVE development program, several questions emerged requiring performance-based data to resolve. A comprehensive program to provide the Project Manager, Night Vision/Reconnaissance, Surveillance and Target Acquisition with driver performance data that will aid in the decision-making process is described in this paper. The program involves several linked efforts including: the relative merits of the DVE and night vision goggles (NVG); drivers' ability to detect the presence of drop-offs when using the DVE and NVG; the effect on performance of various levels of nonuniformity and nonresponsiveness in the display/sensor system; the analysis of drivers' vision using an eye-tracker in a vehicle; and the evaluation of candidate symbology to enhance the DVE's utility in the M2 Bradley. The data collected will aid in making decisions on how to write a system specification to reduce cost without sacrificing driver performance, gain an understanding of how drivers use the DVE in operational settings, and determine where training is needed to enhance safety and reduce risk on the battlefield.

  8. The Driven Pendulum at Any Drive Angle

    VanDalen, G J

    2002-01-01

    The driven inverted pendulum undergoes stable oscillations if the drive amplitude and frequency are large enough. This classroom demonstration is best used in junior or graduate level Classical Mechanics courses. This paper reintroduces the equation of motion of the driven pendulum, generalizing to arbitrary driving angle. The pendulum will oscillate about a stable angle, other than straight down, if the drive amplitude and frequency are large enough for a given drive angle. We will explore what is meant by ``large enough.'' Emphasis is given to parameters associated with a simply made demonstration apparatus.

  9. Effects of driving time on microsaccadic dynamics.

    Di Stasi, Leandro L; McCamy, Michael B; Pannasch, Sebastian; Renner, Rebekka; Catena, Andrés; Cañas, José J; Velichkovsky, Boris M; Martinez-Conde, Susana

    2015-02-01

    Driver fatigue is a common cause of car accidents. Thus, the objective detection of driver fatigue is a first step toward the effective management of fatigue-related traffic accidents. Here, we investigated the effects of driving time, a common inducer of driver fatigue, on the dynamics of fixational eye movements. Participants drove for 2 h in a virtual driving environment while we recorded their eye movements. Microsaccade velocities decreased with driving time, suggesting a potential effect of fatigue on microsaccades during driving. PMID:25417191

  10. Women drive better if not stereotyped.

    Moè, Angelica; Cadinu, Mara; Maass, Anne

    2015-12-01

    A commonly held stereotype is that women are poor drivers. This stereotype is recognized and endorsed by women and girls very early on, long before taking their driving licence, nevertheless they are less involved in accidents and drive safer and less fast than men. In line with the stereotype threat theory, the present study tests the hypothesis that making the driving stereotype salient will lead women to underperform in a driving simulation task. In Experiment 1women in the stereotype threat condition were told that the aim of the study was to detect gender differences in driving whereas in a control condition no study aim was provided. In Experiment 2, two conditions were compared: stereotype threat (same instructions as in Experiment 1), and stereotype boost (the alleged goal was to compare driving ability of young vs. old people). As predicted, the results of both experiments showed that women under stereotype threat, as compared to either control or stereotype boost participants, doubled the number of mistakes. Nevertheless, they overall expected/self-reported to drive/have driven poorly. Importantly, their level of expectation was a significant predictor of their actual driving performance only in the stereotype threat condition. Implications of these effects of stereotype threat on women's driving performance and self-assessment are discussed. PMID:26457739

  11. Interannual variability of the stratospheric wave driving during northern winter

    H. M. Kelder

    2007-05-01

    Full Text Available The strength of the stratospheric wave driving during northern winter is often quantified by the January–February mean poleward eddy heat flux at 100 hPa, averaged over 40°–80° N (or a similar area and period. Despite the dynamical and chemical relevance of the wave driving, the causes for its variability are still not well understood. In this study, ERA-40 reanalysis data for the period 1979–2002 are used to examine several factors that significantly affect the interannual variability of the wave driving. The total poleward heat flux at 100 hPa is poorly correlated with that in the troposphere, suggesting a decoupling between 100 hPa and the troposphere. However, the individual zonal wave-1 and wave-2 contributions to the wave driving at 100 hPa do exhibit a significant coupling with the troposphere, predominantly their stationary components. The stationary wave-1 contribution to the total wave driving significantly depends on the latitude of the stationary wave-1 source in the troposphere. The results suggest that this dependence is associated with the varying ability of stationary wave-1 activity to enter the tropospheric waveguide at mid-latitudes. The wave driving anomalies are separated into three parts: one part due to anomalies in the zonal correlation coefficient between the eddy temperature and eddy meridional wind, another part due to anomalies in the zonal eddy temperature amplitude, and a third part due to anomalies in the zonal eddy meridional wind amplitude. It is found that year-to-year variability in the zonal correlation coefficient between the eddy temperature and the eddy meridional wind is the most dominant factor in explaining the year-to-year variability of the poleward eddy heat flux.

  12. Risky driving and recorded driving offences: a 24-year follow-up study.

    Summala, Heikki; Rajalin, Sirpa; Radun, Igor

    2014-12-01

    Permanent individual differences in driver behavior and accident risk have long been under active debate. Cognitive and personality factors have correlated with risky driving indicators in cross-sectional studies, and prospective cohort studies are now increasingly revealing early antecedents of risky behavior and injury mortality in adult age, with connections to stable personality traits. However, long-term stability in driver behavior or accident involvement has not been documented in a general driver population.This study reports 24-year follow-up data from a study that compared the recorded offenses between 134 drivers stopped by the police because of sustained risky driving and 121 control drivers stopped at the same locations at the same time in 1987 (Rajalin, 1994. Accid. Anal. Prev., 26, 555-562). Data were compiled from national driver records and accident statistics for the same drivers again 24 years later, and their yearly mileage and speed behavior was requested in a mail survey. The results showed that the two groups of drivers sampled on one trip a quarter of a century ago still differ from each other. The offenders still have more entries in their driver record, also when adjusted for age and mileage (OR=1.59, CI=1.03-2.46), they still report in the survey that they drive faster and overtake other cars more often. The results show that individual differences in driver behavior persist for decades, perhaps for life. However, in this on-road sample, the effect seems to be moderated by occupation which also presumably explains the lower mortality among the offenders during this 24-year follow-up. PMID:25171522

  13. Viral infection drives tissue fibrosis in vitro

    Andrea P. Malizia

    2008-04-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT, the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  14. The Thermodynamics of Drunk Driving

    Thompson, Robert Q.

    1997-05-01

    Chemical and instrumental tests for driving under the influence of alcohol (DUI) measure the concentration of ethanol in the breath (BrAC), while state DUI laws are described in terms of blood alcohol concentration (BAC). Consequently, accurate and fair conversion from BrAC to BAC is crucial to the judicial process. Theoretical treatment of the water-air-ethanol equilibrium system and the related blood-breath-ethanol system, based on principles from general chemistry and biology, yields an equation relating the ratio of BAC to BrAC to the absolute temperature of the breath, the fraction of water in the blood, and the enthalpy and entropy of vaporization of ethanol from aqueous solution. The model equation predicts an average value for the ratio of 2350+100, not significantly different from reported experimental values. An exponential temperature dependence is predicted and has been confirmed experimentally as well. Biological, chemical, and instrumental variables are described along with their contributions to the overall uncertainty in the value of BrAC/BAC. While the forensic science community uses, and debates, a fixed ratio of 2100, the theoretical model suggests that a value of 1880 should be used to reduce the fraction of false positives to <1%.

  15. Redundant arrays of IDE drives

    The authors report tests of redundant arrays of IDE disk drives for use in offline high energy physics data analysis. Parts costs of total systems using commodity EIDE disks are now at the $4000 per Terabyte level. Disk storage prices have now decreased to the point where they equal the cost per Terabyte of Storage Technology tape silos. The disks, however, offer far better granularity; even small institutions can afford to deploy systems. The tests include reports on software RAID-5 systems running under Linux 2.4 using Promise Ultra 100trademark disk controllers. RAID-5 protects data in case of a single disk failure by providing parity bits. Tape backup is not required. Journaling file systems are used to allow rapid recovery from crashes. The data analysis strategy is to encapsulate data and CPU processing power. Analysis for a particular part of a data set takes place on the PC where the data resides. The network is only used to put results together. They explore three methods of moving data between sites; internet transfers, not pluggable IDE disks in FireWire cases, and DVD-R disks

  16. Redundant arrays of IDE drives

    D.A. Sanders et al.

    2002-01-02

    The authors report tests of redundant arrays of IDE disk drives for use in offline high energy physics data analysis. Parts costs of total systems using commodity EIDE disks are now at the $4000 per Terabyte level. Disk storage prices have now decreased to the point where they equal the cost per Terabyte of Storage Technology tape silos. The disks, however, offer far better granularity; even small institutions can afford to deploy systems. The tests include reports on software RAID-5 systems running under Linux 2.4 using Promise Ultra 100{trademark} disk controllers. RAID-5 protects data in case of a single disk failure by providing parity bits. Tape backup is not required. Journaling file systems are used to allow rapid recovery from crashes. The data analysis strategy is to encapsulate data and CPU processing power. Analysis for a particular part of a data set takes place on the PC where the data resides. The network is only used to put results together. They explore three methods of moving data between sites; internet transfers, not pluggable IDE disks in FireWire cases, and DVD-R disks.

  17. We need a better understanding of what drives right-wing extremist violence

    Briggs, Rachel; Goodwin, Matthew

    2012-01-01

    Rachel Briggs and Matthew Goodwin explore some of the factors that drive individuals to adopt a right-wing extremist identity and maintain that more research needs to be conducted into why some engage in violent activities.

  18. Variable-speed drive and control systems for rolling mills; Atsuenkiyo drive seigyo system

    Kasai, T.; Tochigi, T. [Fuji Electric Co. Ltd., Tokyo (Japan)

    2000-11-10

    The drive systems of large rolling mills is of a cycloconverter type, a GTO (gate turn-off thyristor) type or high-voltage IGBT (insulated gate bipolar transistor) type. Drive systems for bar, rod and pipe mills use three and/or two level IGBT inverters. This paper describes recent technical trends of drives and control systems in rolling mills, including each drive application and the PLC (programmable controller) and HCI (human communication interface) controlling the total rolling mill line. (author)

  19. DeepDriving: Learning Affordance for Direct Perception in Autonomous Driving

    Chen, Chenyi; Seff, Ari; Kornhauser, Alain; Xiao, Jianxiong

    2015-01-01

    Today, there are two major paradigms for vision-based autonomous driving systems: mediated perception approaches that parse an entire scene to make a driving decision, and behavior reflex approaches that directly map an input image to a driving action by a regressor. In this paper, we propose a third paradigm: a direct perception approach to estimate the affordance for driving. We propose to map an input image to a small number of key perception indicators that directly relate to the affordan...

  20. Automobile driving in seniors: Factors affecting driving restriction in men and women

    MARIE-DIT-ASSE, Laetitia; Fabrigoule, Colette; Helmer, Catherine; Laumon, Bernard; Lafont, Sylviane

    2014-01-01

    Background/Objectives: Independence for older people is linked to driving, this being their main mode of travel. Even in normal aging, sensory, functional, and cognitive deficits appear, and are more severe in brain pathology leading to dementia. These may profoundly affect driving, which is a complex task involving all of these functions. Many studies show that older drivers modify their driving habits (reduced distance, avoiding certain driving situations ...). When this regulation process ...

  1. Perception of the Risks Associated with Impaired Driving and Effects on Driving Behavior

    Georges Dionne; Claude Fluet; Denise Desjardins

    2006-01-01

    This research studies the perception of the risks associated with impaired driving-probability of being apprehended or of having an accident-and the relation between the perception of risks and driving behavior. The most important determinants of perceptual biases are age, an accumulation of violations in the year preceding the survey, being a non-drinker, knowledge of the legal alcohol limit for driving, opinion about zero tolerance for impaired driving, and family income. Perceptual biases ...

  2. Are child occupants a significant source of driving distraction?

    Koppel, Sjaan; Charlton, Judith; Kopinathan, Chelvi; Taranto, David

    2011-05-01

    Driver distraction represents a well-documented and growing contribution to the road safety problem. This study used a naturalistic, observational approach to examine if children in vehicles are a significant source of driving distraction. Families with children aged between 1 and 8 years drove an instrumented "study vehicle" on their regular trips for 3 weeks. A discrete video recording system in the vehicle provided images of the driver and front seat passenger, the rear seat child passengers and the traffic ahead. The video-recordings inside and outside the vehicle were analysed to identify potential distracting activities, where 'distraction' was broadly defined as any activity that distracted the driver or competed for their attention while driving. In addition, all potentially distracting activities that involved the driver looking away from the forward roadway for more than 2s while the vehicle was in motion were also coded. Video-recordings were analysed for 92 driving journeys undertaken by 12 families including 25 children and 19 drivers. The mean journey duration was approximately 16 min (range: 2 min-3h 34 min). Most journeys were undertaken during the day (89%), with the mother driving (65%) and without a front seat passenger (64%). Driving journeys were predominantly undertaken in urban areas (97%), on suburban roads/streets (94%), and under low complexity traffic conditions (91%). Most journeys involved some source of potential driver distraction (98%), with drivers distracted for 18% of the driving journey. The most frequent types of distracting activities that drivers engaged in included: touching their head or their face (35%), interacting with child passengers in the rear seat (12%), and engaging with the front seat passenger (9%). Almost three-quarters of these potentially distracting activities were engaged in by the driver while the study vehicle was in motion (72%) and 14% of all potentially distracting activities involved the driver's eyes

  3. Driving Green: Toward the Prediction and Influence of Efficient Driving Behavior

    Newsome, William D.

    Sub-optimal efficiency in activities involving the consumption of fossil fuels, such as driving, contribute to a miscellany of negative environmental, political, economic and social externalities. Demonstrations of the effectiveness of feedback interventions can be found in countless organizational settings, as can demonstrations of individual differences in sensitivity to feedback interventions. Mechanisms providing feedback to drivers about fuel economy are becoming standard equipment in most new vehicles, but vary considerably in their constitution. A keystone of Radical Behaviorism is the acknowledgement that verbal behavior appears to play a role in mediating apparent susceptibility to influence by contingencies of varying delay. In the current study, samples of verbal behavior (rules) were collected in the context of a feedback intervention to improve driving efficiency. In an analysis of differences in individual responsiveness to the feedback intervention, the rate of novel rules per week generated by drivers is revealed to account for a substantial proportion of the variability in relative efficiency gains across participants. The predictive utility of conceptual tools, such as the basic distinction among contingency-shaped and rule governed behavior, the elaboration of direct-acting and indirect-acting contingencies, and the psychological flexibility model, is bolstered by these findings.

  4. 77 FR 61048 - Distracted Driving Grant Program

    2012-10-05

    ... National Highway Traffic Safety Administration Distracted Driving Grant Program AGENCY: National Highway... Transportation (DOT) announced the availability of funding authorized for distracted driving grants on August 24... Progress in the 21st Century Act'' (MAP-21), Public Law 112-141, which created a new distracted...

  5. Reflector driving device of FBR type reactor

    The present invention provides a reflector driving device which eliminates driving at outside and rapidly start-up and shuts down the reactor. Namely, the device has an electromagnetic holding mechanism attracted to a reactor core barrel by electromagnetic attracting force. Electromagnetic repulsion coils for generating instantaneous electromagnetic repulsion force are disposed between the reflector and the electromagnet retaining mechanism. The reflector is driven using inertia force of the electromagnetic repulsion force and the reflector. Then, the reflector driving device is attracted and held at a start-up position of the reactor upon start-up of the reactor. The reflector elevated by fluid pressure is secured at a position of the start-up of the reactor while having the reflector driving device as a stopper. The reflector moves at an extremely slow speed while being secured to the reflector driving device along with the elevation of the reflector driving device. As a result, a driving shaft sealing material which supports a conventional driving device at the outside and the reflector is eliminated thereby simplifying the structure of the outside of the reactor. (I.S.)

  6. The ripple effect of automated driving

    Milakis, D.; Van Arem, B.; van Wee, B

    2015-01-01

    Most papers published so far focus on traffic implications of automated driving, while papers that focus more on wider impacts do not present a respective conceptualization. This paper aims to fill this gap by proposing a conceptualization of policy and society related implications of automated driving inspired by the ripple effect model.

  7. Truck platooning : Driving the future of transportation

    Janssen, G.R.; Zwijnenberg, J; Blankers, I.J.; Kruijff, J.S. de

    2015-01-01

    Truck Platooning is the future of transportation in which trucks drive cooperatively at less than 1 second apart made possible by automated driving technology. Transportation companies benefit from lower fuel consumption and improvements in (driver) productivity, while society benefits from fewer accidents, safer traffic and less congested roads, and lower carbon emissions.

  8. Use of mobile phone while driving.

    2008-01-01

    Using a mobile phone while driving has negative effects on driving behaviour. This is the case for conducting a conversation, dialling a number, and sending text messages as well as for using the extra functions that smartphones offer, like accessing internet or social networking sites. The negative

  9. Determining the focus of driving fears.

    Taylor, J E; Deane, F P; Podd, J V

    2000-01-01

    Fear of driving has been recognized as a complex diagnostic entity. Studies on flying phobia have drawn similar conclusions, although increasing clarity has been gained through research that indicates that there may be subtypes of flying phobia based on the focus of fear. However, it is unclear if similar subtypes exist for fear of driving. The aim of the present study was to conduct a preliminary investigation of driving fear subtypes and to clarify further whether there were differences between driving-fearful respondents who had been in a motor vehicle accident (MVA) and those who had not. Eighty-five driving-fearful, media-recruited respondents completed a questionnaire that assessed anxiety, avoidance, and concerns related to their driving fears. The sample had high expectations of negative events while driving. There were no significant differences between those who had experienced an MVA and those who had not on various measures of fear severity. Cluster analysis revealed two main foci of fear, one characterized by danger expectancies and the other based on anxiety expectancies and unpleasant driving situations. This emphasizes the importance of assessing both internal and external foci of fear. Although this finding is consistent with the results obtained for flying phobia, more research is required to replicate and extend these results and to develop and evaluate differential treatment programs. PMID:11095540

  10. Adjustable Speed Drives and Power Quality

    Davari, Pooya; Yang, Yongheng; Zare, Firuz;

    2016-01-01

    This paper provides an overview and proposes cost-effective and efficient opportunities in improving power quality in Adjustable Speed Drive (ASD) systems. In particular, an Electronic Inductor (EI) technique has been used in single drives to overcome the existing challenges in conventional...

  11. A coding and high voltage driving module

    A coding and high-voltage pulse driving module used in free-space quantum communication is described. This module generate random control signal to drive High-Voltage Pulse generator to control receiver’s polarization, receive detector signal and encode them by signal channel. (authors)

  12. Seismic appraisal test of control rod drive mechanism of China experiment fast reactor

    The structure of the control rod drive mechanism in pool type sodium-cooled fast reactor is the characterized by long, thin, and geometric nonlinearity, and the seismic load is multiple activation. The anti-seismic evaluation is always paid great attention by the countries developing the technology worldwide. This article introduces the seismic appraisal test of the control rod drive mechanism of China Experimental Fast Reactor (CEFR) performed on a seismic platform which is vertical shaft style and multiple activation. The result of the test shows the structural integrity and the function of the control rod drive mechanism could meet the design requirements of the earthquake intensity. (authors)

  13. Influence of unexpected events on driving behaviour at different hierarchical levels: a driving simulator experiment

    Schaap, T.W.; Horst, A.R.A. van der; Arem, B. van

    2008-01-01

    Computer based simulation models of human driving behaviour can be used effectively to model driving and behavioural adaptation to Intelligent Transport System (ITS). This can be a useful step in human centered design of ITS. To construct a comprehensive model of driving behaviour, the interaction b

  14. Musculoskeletal analysis of driving fatigue: The influence of seat adjustments

    Majid, Noor Aliah binti Abdul; Abdullah, Mohd Fareez Edzuan; Jamaludin, Mohd Syahmi;

    2013-01-01

    Main causes for discomfort experienced by vehicle drivers during driving were investigated using a rigid-body model originally developed in the AnyBody Modeling System [1]. The interactions between the human body and the car-seat in various combinations of seat-pan/backrest inclinations...... that various seat adjustments (e.g., seat-pan and backrest inclinations) and the pedal spring stiffness have complex influences on the muscle activation and spinal joint forces of the human body. From the results, an optimal adjustment for the car-seat is proposed, i.e. the backrest inclination is 10......° and the seat-pan inclination is between 0º to 5 º. This study can in general capture the overall interactions between human body and environment (i.e. the maximum muscle activity and spine forces), which is thought to be the factors of driving fatigue....

  15. Cognitive problems, self-rated changes in driving skills, driving-related discomfort and self-regulation of driving in old drivers

    Meng, Annette; Siren, Anu Kristiina

    2012-01-01

    that driving-related discomfort is an important factor affecting the self-regulation of driving. Finally, the findings indicate that driving-related discomfort functions as an indirect self-monitoring of driving ability and may contribute to the safe driving performance of Danish older drivers.......Ageing in general is associated with functional decline that may have an adverse effect on driving. Nevertheless, older drivers have been found to show good judgement and to self-regulate their driving, which may enable them to continue driving safely despite functional decline. The process of the...... self-monitoring of driving ability and the awareness of functional decline, and its association with the self-regulation of driving is, however, not fully understood. The aim of the present study was to examine the perceived changes in driving skills, the discomfort experienced in driving, and the self...

  16. Driving Ability Index: an instrument for assessing elderly people’s performance

    Pinna, Claudia

    2015-01-01

    Aging causes the decline of driving related skills, so accident rates are higher for older drivers. However, being able to use the car motivates older people to maintain an active life and participate in social activities. When deprived of their driving licence, the elderly often suffer from isolation and depression so this phenomenon also has social implications. For these reasons it is necessary to recognize drivers who are potentially risky, because they no longer have the skills required ...

  17. Drive linac for the Argonne Wakefield Accelerator

    Chojnacki, E.; Konecny, R.; Rosing, M.; Simpson, J.

    1993-08-01

    The drive linac in Phase I of the Argonne Wakefield Accelerator (AWA) will be used to accelerate short duration (10 ps), high charge (100 nC) electron bunches from 2 MV to 20 MV for use in a variety of wakefield acceleration and measurement studies. The high charge is required since this drive bunch will generate the wakefields of interest in various test sections and their amplitudes are proportional to bunch charge. The short bunch duration is required to drive high-frequency wakefields without intra-bunch cancellation effects. The drive linac design was a balance between having a small wake function to maintain a drive bunch energy spread of {le}10% and obtaining an adequate accelerating gradient of {ge}10 MV/m. This yielded a large aperture, low shunt impedance, high group velocity, L-band, standing-wave linac. Details of the design, fabrication, and testing are presented in the following.

  18. Extracting periodic driving signal from chaotic noise

    MU Jing; TAO Chao; DU Gonghuan

    2003-01-01

    After periodic signals pass through some nonlinear systems, they are usually transformed into noise-like and wide-band chaotic signals. The discrete spectrums of the original periodic signals are often covered by the chaotic spectrums. Recovering the periodic driving signals from the chaotic signals is important not only in theory but also in practical applications. Based on the modeling theory of nonlinear dynamic system, a "polynomial-simple harmonic drive" non-autonomous equation (P-S equation) to approximate the original system is proposed and the approximation error between P-S equation and the original system is obtained. By changing the drive frequency, we obtain the curve of the approximation error vs. drive frequency. Based on the relation between this curve and the spectrums of the original periodic signals, the spectrum of the original driving signal is extracted and the original signal is recovered.

  19. RF current drive components in a tokamak

    Theoretical analysis of low frequency current drive in a tokamak is presented. The global model discussed includes kinetic hot plasma effects and collisions. It is found that all kinds of wave-plasma interactions (resonant wave-electron interaction, resonant wave-ion interaction and collisions) can contribute to the current drive. The analysis presented stresses the two new current drive components, the resonant helicity current and the nonresonant collisionless current. Helicity current drive is proportional to the parallel helicity flux and to the wave damping strength, which is defined by the wave-plasma interaction process. The collisionless part of the nonresonant current is proportional to wave damping on ions. However, this is an electron current, and wave-ion interaction just creates necessary polarization of the wave to drive a current. The resistive MHD limit is considered as well, and the correct expression for the RF driven current including the Alfven resonance effect, is given. (author) 17 refs

  20. Special Considerations in Distracted Driving with Teens

    Durbin, Dennis R; McGehee, Daniel V; Fisher, Donald; McCartt, Anne

    2014-01-01

    Novice teen drivers have long been known to have an increased risk of crashing, as well as increased tendencies toward unsafe and risky driving behaviors. Teens are unique as drivers for several reasons, many of which have implications specifically in the area of distracted driving. This paper reviews several of these features, including the widespread prevalence of mobile device use by teens, their lack of driving experience, the influence of peer passengers as a source of distraction, the role of parents in influencing teens’ attitudes and behaviors relevant to distracted driving and the impact of laws designed to prevent mobile device use by teen drivers. Recommendations for future research include understanding how engagement in a variety of secondary tasks by teen drivers affects their driving performance or crash risk; understanding the respective roles of parents, peers and technology in influencing teen driver behavior; and evaluating the impact of public policy on mitigating teen crash risk related to driver distraction. PMID:24776228