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Sample records for activated factor vii

  1. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... alloenzyme with reduced pro-fibrinolytic activity. Presently, we address whether OC use and OC formulation affect FSAP measures in human blood. Healthy women (n=588) were allocated to six cycles of OCs with estrogen contents of 20µg (n=158), 30µg (n=284), 35µg (n=79) or 50µg (n=67) combined with various...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P=0.001). OC use increased FSAP antigen by 25% and FSAP activity...

  2. Factor VII deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor VII is one such coagulation factor. Factor VII deficiency runs in families (inherited) and is very rare. Both parents must ...

  3. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Skouby, Sven O.; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... alloenzyme with reduced pro-fibrinolytic activity. Presently, we address whether OC use and OC formulation affect FSAP measures in human blood. Healthy women (n=588) were allocated to six cycles of OCs with estrogen contents of 20μg (n=158), 30μg (n=284), 35μg (n=79) or 50μg (n=67) combined with various...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity...

  4. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, th...

  5. Factor VII activating protease. Single nucleotide polymorphisms light the way.

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    Kanse, S M; Etscheid, M

    2011-08-01

    Factor VII activating protease (FSAP) is a circulating serine protease with high homology to fibrinolytic enzymes. A role in the regulation of coagulation and fibrinolysis is suspected based on in vitro studies demonstrating activation of FVII or pro-urokinase plasminogen activator (uPA). However, considering the paucity of any studies in animal models or any correlative studies in humans the role of FSAP in haemostasis remains unclear. In relation to vascular remodeling processes or inflammation it has been convincingly shown that FSAP interacts with growth factors as well as protease activated receptors (PAR). Against this sparse background there are a plethora of studies which have investigated the linkage of single nucleotide polymorphisms (SNP) in the FSAP gene (HABP2) to various diseases. The G534E SNP of FSAP is associated with a low proteolytic activity due to an amino acid exchange in the protease domain. This and other SNPs have been linked to carotid stenosis, stroke as well as thrombosis in the elderly and plaque calcification. These SNP analyses indicate an important role for FSAP in the regulation of the haemostasis system as well as fibroproliferative inflammatory processes.

  6. Recombinant activated factor VII in post partum haemorrhage

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    Navneet Magon

    2013-01-01

    Full Text Available Post-partum haemorrhage (PPH is a life-threatening obstetric complication and the leading cause of maternal death. Any bleeding that results in or could result in haemodynamic instability, if untreated, must be considered as PPH. There is no controversy about the need for prevention and treatment of PPH. The keystone of management of PPH entails first, non-invasive and nonsurgical methods and then invasive and surgical methods. However, mortality remains high. Therefore, new advancements in the treatment are most crucial. One such advancement has been the use of recombinant activated factor VII (rFVIIa in PPH. First used 12 years back in PPH, this universal haemostatic agent has been effectively used in controlling PPH. The best available indicator of rFVIIa efficacy is the arrest of haemorrhage, which is judged by visual evidence and haemodynamic stabilization. It also reduces costs of therapy and the use of blood components in massive PPH. In cases of intractable PPH with no other obvious indications for hysterectomy, administration of rFVIIa should be considered before surgery. We share our experience in a series of cases of PPH, successfully managed using rFVIIa.

  7. Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation

    NARCIS (Netherlands)

    Hendriks, HGD; Meijer, K; de Wolf, JTM; Porte, RJ; Klompmaker, IJ; Lip, H; Slooff, MJH; van der Meer, J

    Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present

  8. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

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    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  9. Factor VII-activating protease in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Vitzthum, Frank; Funding, Eva;

    2008-01-01

    Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu...

  10. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.;

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  11. Factors V and VII anticoagulant activities in the salivary glands of feeding Dermacentor andersoni ticks.

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    Gordon, J R; Allen, J R

    1991-02-01

    The salivary glands of Dermacentor andersoni ticks possess anticoagulant activities that can alter the clotting time of rabbit whole blood. Salivary gland extracts from female ticks inhibit both the intrinsic and extrinsic coagulation systems, and maximal activities against both pathways occur when the ticks attain about 250 mg feeding weight. These anticoagulants are directed against both coagulation factors V and VII, but they do not affect factors II or X. Despite this salivary anticoagulant activity, heavily tick-infested rabbits suffer no visible alteration of their peripheral blood coagulability and have no detectable circulating fibrin degradation products, suggesting that the ticks do not secrete a factor with fibrinolytic activity.

  12. Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Miller, G.J.; Bysted, Anette

    2003-01-01

    Background: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation...

  13. (111)Indium Labelling of Recombinant Activated Coagulation Factor VII

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Buch, Inge; Sigvardt, Maibritt

    2012-01-01

    . administration of 1.6-1.8 MBq (111)In-DTPA-rFVIIa up to 120-130 min. Five min after administration of (111)In-DTPA-rFVIIa, percentage of (111)In activity was 6.0% in the cardiac region and 24.5% in the liver region. After 2 hours activity was decreased to 3.3% in heart while it had increased to 42...

  14. Factor VII activating protease (FSAP) promotes the proteolysis and inhibition of tissue factor pathway inhibitor (TFPI)

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    Kanse, Sandip M.; Declerck, Paul J.; Ruf, Wolfram; Broze, George; Etscheid, Michael

    2013-01-01

    Objectives Factor VII activating protease (FSAP) activates FVII as well as pro-urokinase and inhibits platelet-derived growth factor-BB, thus regulating haemostasis- and remodeling-associated processes in the vasculature. A genetic variant of FSAP (Marburg I polymorphism) results in low enzymatic activity and is associated with an enhanced risk for carotid stenosis and stroke. We postulate that there are additional substrates for FSAP that will help to explain its role in vascular biology and have searched for such a substrate. Results and Methods Using screening procedures to determine the influence of FSAP on various haemostasis-related processes on endothelial cells we discovered that FSAP inhibited tissue factor pathway inhibitor (TFPI), a major anti-coagulant secreted by these cells. Proteolytic degradation of TFPI by FSAP could also be demonstrated by Western blotting and the exact cleavage sites were determined by N-terminal sequencing. The Marburg I variant of FSAP had a diminished ability to inhibit TFPI. A monoclonal antibody to FSAP, that specifically inhibited FSAP binding to TFPI, reversed the inhibitory effect of FSAP on TFPI. Conclusions The identification of TFPI as a sensitive substrate for FSAP increases our understanding of its role in regulating haemostasis and proliferative remodeling events in the vasculature. PMID:22116096

  15. A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, J; Gram, J

    1994-01-01

    When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro....... In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation...... of FVII is inversely related to both FVIItotal and the relative amount of FVIIa in the sample. In future studies, this new measurement system will make it possible to study the process of FVII activation in different samples, and to examine how varying concentrations of exogenous added components affect...

  16. Failure of Recombinant Activated Factor VII in Treatment of Diffuse Alveolar Hemorrhage due to Cryoglobulinemic Vasculitis

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    Dania Khoulani

    2014-01-01

    Full Text Available Diffuse alveolar hemorrhage (DAH is a serious complication of the small vessel vasculitis syndromes and carries a high mortality. Recombinant activated factor VII (rFVIIa is used to treat bleeding in patients with hemophilia and antibodies to factor VIII or IX. It is increasingly being used in life-threatening hemorrhage in a variety of other settings in which conventional therapy is unsuccessful. Randomized controlled trials of rFVIIa in DAH are lacking. However, several case reports have described a complete or sustained control of DAH using rFVIIa after patients failed to respond to medical treatment. There are no case reports in the literature describing the use or the failure of rFVIIa in DAH associated with cryoglobulinemic vasculitis. We here report the failure of rFVIIa to control DAH in a patient with CD5+ B-cell non-Hodgkin’s lymphoma and cryoglobulinemic vasculitis.

  17. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding.

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    Smith, M P; Ludlam, C A; Collins, P W; Hay, C R; Wilde, J T; Grigeri, A; Melsen, T; Savidge, G F

    2001-10-01

    We examined recombinant activated factor VII (rVIIa) administered by continuous infusion to eight patients with inhibitors to factor VIII, undergoing elective surgery. rVIIa was infused at a fixed rate of 16.5 microg/kg/h for a median of 13.5 days (range 1-26). There was effective haemostasis at this infusion rate in only one of two minor procedures and two of six major operations. Three patients experienced excessive bleeding despite plasma factor VII activity around 10 IU/ml. Serious bleeding occurred in two other patients caused by procedural errors unrelated to rVIIa and required re-operation. The median rVIIa clearance on day 1 was 57 ml/h/kg (range 18-100) and on day 3 was 100 ml/h/kg (range 61-200). Clearance on the final infusion day was not significantly different from day 3. The infusion did not induce pathological activation of the coagulation mechanism. The only thrombotic adverse events were two episodes of superficial thrombophlebitis of the infused vein in one subject. In conclusion, the 16.5 microg/kg/h infusion rate reliably achieves plasma factor VII activity levels of 10 IU/ml, but this level does not provide reliable haemostasis.

  18. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood sample...

  19. Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

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    Pär I Johansson

    2010-06-01

    Full Text Available Pär I Johansson, Sisse R OstrowskiCapital Region Blood Bank, Section for Transfusion Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkBackground: Recombinant activated factor VII (rFVIIa, NovoSeven® was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.Objective: To review the evidence supporting the use of rFVIIa for the treatment of patients with congenital bleeding disorders.Patients and methods: English-language databases were searched in September 2009 for reports of randomized controlled trials (RCTs evaluating the ability of rFVIIa to restore hemostasis in patients with congenital bleeding disorders.Results: Eight RCTs involving 256 hemophilic patients with antibodies against coagulation factors, also known as inhibitors, were identified. The evidence supporting the use of rFVIIa in these patients was weak with regard to dose, clinical setting, mode of administration, efficacy, and adverse events, given the limited sample size of each RCT and the heterogeneity of the studies.Conclusion: The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors should be based on the individual’s ability to generate thrombin and form a clot, and not on the patient’s weight alone. Therefore, assays for thrombin generation, such as whole-blood thromboelastography, have the potential to significantly improve the treatment of these patients.Keywords: hemophilia, inhibitors, coagulation factor VIII, coagulation factor IX, rFVIIa, NovoSeven, FEIBA, hemostasis, RCT

  20. Non-fasting factor VII coagulant activity (FVII:C) increased by high-fat diet

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Marckmann, P; Sandström, B

    1994-01-01

    Preliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20......% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVII:Am). The ratio FVII......:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII:Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet...

  1. Uso de fator VII recombinante ativado para tratamento e profilaxia de grandes sangramentos Use of recombinant activated factor VII for treatment and prophylaxis of major bleeding

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    Flávio Augusto Henriques Vince

    2009-09-01

    pacientes. Dessa forma, o recente aumento do uso de rFVIIa em situações ainda não aprovadas levou ao crescente questionamento sobre eficácia e segurança desta específica medicação em tais situações.INTRODUCTION: Recombinant activated factor VII (rFVIIa is a protein produced by genetic engineering, the structure is very similar to the structure of intrinsic activated factor VII (FVII. Its action is based on knowledge of the coagulation mechanism in vivo by acting in direct activation of factor X independent resulting in formation of thrombin at the injury site and thereby contributing to the formation of stable fibrin clots without the action of factor VIII and factor IX. METHODS: Was conducted extensive review of the literature in order to determine the new findings related to the use of recombinant activated factor VII in patients with severe bleeding. RESULTS: It was found that the use of rFVIIa started in the 80's for prophylaxis and treatment of bleeding in patients with a history of hemophilia A or B with inhibitors to factor VIII and IX, factor VII deficiency and Glanzmann's thrombasthenia refractory to replacement platelet. In 1999 its use was expanded to other clinical situations and thus began to be published several studies showing the efficacy of rFVIIa as a pro-hemostatic agent in patients with bleeding disorders or other previously healthy patients with a history of acute bleeding of major consequence. Trauma is the leading cause of mortality worldwide and uncontrolled bleeding the main challenge in caring for these patients. It is common for the association of trauma with coagulopathy, requiring in some cases specific therapy to treat it. At this point in adjuvant therapy with rFVIIa should be considered. Other common causes of bleeding are the heart, gynecologic/obstetric surgeries and diseases involving the liver. The coagulopathy in these cases is deficiency of factors dependent on vitamin K, and the FVII factor with smaller half life. CONCLUSION

  2. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...

  3. The use of recombinant-activated factor VII in von Willebrand disease: a case series.

    Science.gov (United States)

    von Depka, Mario; Hassan, Murtada; Blatnŷ, Jan; Smejkal, Petr; Vdovin, Vladimir

    2006-06-01

    Spontaneous and surgery-associated bleeding in patients with von Willebrand disease (vWD) cannot always be controlled with desmopressin or replacement therapy. This paper presents results on the use of recombinant-activated factor VII (rFVIIa) in patients with vWD included in the internet registry Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified from the database and included in this analysis. The bleeding episodes were classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were unspecified in three cases. The median dose of rFVIIa administered was 94 microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27 evaluable patients (85%) and markedly decreased in three patients; the total response rate was 96% (26/27 patients). Response did not correlate with the type of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other replacement therapies were infrequently used, and their use was similar in the 24 h before and after rFVIIa administration. Eighteen patients also received antifibrinolytic treatment, but its impact on response was not recorded. Only one adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as a safe and effective therapy for vWD.

  4. First military use of activated Factor VII in an APC-III pelvic fracture.

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    Williams, D J; Thomas, G O R; Pambakian, S; Parker, P J

    2005-03-01

    A male soldier in shock with an APC-III pelvic fracture was flown to an Air Assault Surgical Group (AASG) of 16 Close Support Medical Regiment at Al Amarah in Iraq. A pelvic external fixator was applied and his condition stabilized. Ultrasound scanning (FAST) showed an absent bladder, and a spreading retroperitoneal haematoma combined with intra-abdominal, free blood. Unfortunately he continued to bleed and required transfusion with the unit's entire stock of type-specific blood. At emergency laparotomy, uncontrollable pelvic bleeding was encountered and the abdominal aorta required clamping above the iliac bifurcation. Branches of the right internal iliac artery were the source and this was ligated. Some bleeding continued post-operatively: administration of activated Factor VII was associated with a marked reduction in the oozing from his fixator pin-sites and an improvement in his pH from 7.1 to 7.3. In total, 25 units of blood were transfused, 8 of which were fresh whole blood donated by individual members of the AASG. The patient survived, returned to the UK, had his injuries reconstructed, and is currently undergoing rehabilitation. This case illustrates the benefits of forward resuscitation surgery in wartime and the need for a multidisciplinary approach to trauma care.

  5. Genetics Home Reference: factor VII deficiency

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    ... VII deficiency , is caused by mutations in the F7 gene, which provides instructions for making a protein ... about the gene associated with factor VII deficiency F7 Related Information What is a gene? What is ...

  6. Recombinant-activated factor VII in patients with uncontrolled bleeding: A retrospective observational analysis

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    Said D Abuhasna

    2012-01-01

    Full Text Available Background: Factor VIIa (recombinant has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Objective: The primary objective of this study was to assess the safety and effectiveness of factor VIIa (recombinant on blood transfusion requirements and coagulation parameters when used in patients whose bleeding was uncorrected by other means. The pharmacoeconomic impact for any discrepancy from our protocol was evaluated. Secondary outcomes included 4-hour and 28-day mortality, as well as safety of this agent in terms of thromboembolic complications. Materials and Methods: We retrospectively evaluated patients who received recombinant-activated factor VII (rFVIIa for uncontrolled bleeding from June 2008 to April 2011. The medical records of 33 patients were evaluated. Coagulation parameters and blood products were determined 24 hours before and 24 hours after administration of rFVIIa, and the results compared. Patients were also screened for any thromboembolic complications. Results: Administration of rFVIIa reduced blood transfusion requirements and improved coagulation parameters significantly (P<0.05. No thromboembolic complications were reported. Most of the dosing was consistent with those recommended in our institutional protocol, with discrepancies resulting in an average cost of $56 058. Moreover, pH was reported in only 67% of patients. All patients treated with rFVIIa survived up to 4 hours after receiving this agent, while the 28-day mortality was 24% (8/33. Conclusion: The use of rFVIIa appears to be safe and effective in promoting hemostasis, as evident from reducing transfusion requirements and improving the coagulation variables.

  7. Congenital deficiency of factor VII.

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    Sikka, M; Gomber, S; Madan, N; Rusia, U; Sharma, S

    1996-01-01

    A case of congenital factor VII deficiency in a five-year-old child is reported. The patient, born of a non-consanguineous marriage, presented with repeated bouts of epistaxis since childhood. The prothrombin time (PT) was markedly prolonged with a normal bleeding time (BT), partial thromboplastin time with Kaolin (PTTK) and platelet count. The patient has been on follow up for the last four years and is doing apparently well.

  8. PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K

    2016-01-01

    with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF...

  9. Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

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    Herrera Maria

    2006-04-01

    Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

  10. Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

    2016-01-01

    after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by ELISA......Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...

  11. Evaluation of Aryoseven Safety (Recombinant Activated Factor VII) in Patients with Bleeding Disorders (An Observational Post-Marketing Surveillance Study)

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    Toogeh, Gholamreza; Abolghasemi, Hassan; Eshghi, Peyman; Managhchi, Mohammadreza; Shaverdi-niasari, Mohammadreza; Karimi, Katayoon; Roostaei, Samin; Emran, Neda; Abdollahi, Alireza

    2016-01-01

    Background: Recombinant activated factor VII induces hemostasis in patients with coagulopathy disorders. AryoSeven™ as a safe Iranian Recombinant activated factor VII has been available on our market. This study was performed to establish the safety of AryoSeven on patients with coagulopathy disorder. Methods: This single-center, descriptive, cross sectional study was carried out in Thrombus and Homeostasis Research Center ValiAsr Hospital during 2013-2014. Fifty one patients with bleeding disorders who received at least one dose of Aryoseven were enrolled. Patients’ demographic data and adverse effect of drug and reaction related to Aryoseven or previous usage of Recombinant activated FVII were recorded in questionnaires. Finally data were analyzed to compare side effects of Aryoseven and other Recombinant activated FVII brands. Results: Aryoseven was prescribed for 51 Patients. Of all participants with mean age 57.18+21.38 yr, 31 cases were male and 26 subjects had past history of recombinant activated FVII usage. Glanzman was the most frequent disorder followed by congenital FVII deficiency, hemophilia with inhibitors, factor 5 deficiency, acquired hemophilia, hemophilia A with inhibitor, and hemophilia A or B with inhibitor. The majority of bleeding episodes had occurred in joints. Three patients (5.9%) complained about adverse effects of Aryoseven vs. 11.5 % about adverse effects of other brands. However this difference was not significant, statistically. Conclusion: Based on monitor patients closely for any adverse events, we concluded that Aryoseven administration under careful weighing of benefit versus potential harm may comparable with other counterpart drugs. PMID:27799968

  12. [ELISA method for the determination of factor VII antigen].

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    Jorquera, J I; Aznar, J A; Monteagudo, J; Montoro, J M; Casaña, P; Pascual, I; Bañuls, E; Curats, R; Llopis, F

    1989-12-01

    The low plasma concentration of clotting factor VII makes it difficult to assay its antigenic fraction by the conventional methods of precipitation with specific antigens. Simple and peroxidase-conjugated antisera are currently available from commercial sources, thus allowing one to determine F VII:Ag by enzyme immunoassay. An ELISA method has been developed in this laboratory which provides sensitivity limits about 0.1% of the plasma concentration of F VII and correlates significantly with its functional activity (r = 0.603, n = 44, p less than 0.001). This technique can be highly helpful in characterising molecular variants of F VII, as well as in detecting acquired deficiencies of this factor.

  13. A high-fat meal does not activate blood coagulation factor VII in minipigs

    DEFF Research Database (Denmark)

    Olsen, A K; Larsen, L F; Bladbjerg, E-M;

    2001-01-01

    , 3.5, 4, 5, and 6 h after the first fat load. Triglycerides, activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII amidolytic activity (FVIIam) and prothrombin fragment I + 2 (F1 + 2) were analysed in plasma samples. Median plasma triglycerides were significantly raised from 0.67 mmol....../l (baseline) to 2.56 mmol/l 5 h postprandially (P high-fat meal does not seem...

  14. Decreased plasma levels of activated factor VII in patients with deep vein thrombosis

    NARCIS (Netherlands)

    Schut, A. M.; Meijers, J. C. M.; Lisman-van Leeuwen, Y.; van Montfoort, M. L.; Roest, M.; de Groot, P. G.; Urbanus, R. T.; Coppens, M.; Lisman, T.

    2015-01-01

    BackgroundThe initiating trigger in the development of deep vein thrombosis (DVT) remains unidentified. It has been suggested that tissue factor (TF)-bearing microparticles play a key role, which indicates a role for the TF pathway in the initiation of DVT. ObjectiveTo assess the role of the TF path

  15. Successful Control of Massive Bleeding in a Child with Burkitt’s Lymphoma via a Biosimilar Recombinant Activated Factor VII (AryoSeven™

    Directory of Open Access Journals (Sweden)

    Kourosh Goudarzi Pour

    2016-01-01

    Full Text Available We describe a case of a 4-year-old girl with Burkitt’s lymphoma, who suffered from a massive gastrointestinal hemorrhage 3 days after chemotherapy. In spite of applying the common practice in correction of coagulopathy, thrombocytopenia persisted and bleeding became life-threatening. In the present case report, we report a successful control of bleeding with a single-dose administration of a biosimilar recombinant activated human factor VII (AryoSeven.

  16. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII

    DEFF Research Database (Denmark)

    Larsen, L F; Bladbjerg, E-M; Jespersen, J

    1997-01-01

    , monounsaturated, or polyunsaturated fats differed regarding postprandial activation of FVII. Eighteen healthy young men participated in the study. On 6 separate days each participant consumed two meals (times, 0 and 1 3/4 hours) enriched with 70 g (15 and 55 g) of either rapeseed oil, olive oil, sunflower oil......, palm oil, or butter (42% of energy from fat) or isoenergetic low-fat meals (6% of energy from fat). Fasting and series of nonfasting blood samples (the last at time 8 1/2 hours) were collected. Plasma triglycerides, FVIIc, FVIIa, and free fatty acids were analyzed. There were marked effects of the fat...

  17. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII

    DEFF Research Database (Denmark)

    Larsen, L F; Bladbjerg, E-M; Jespersen, J

    1997-01-01

    , palm oil, or butter (42% of energy from fat) or isoenergetic low-fat meals (6% of energy from fat). Fasting and series of nonfasting blood samples (the last at time 8 1/2 hours) were collected. Plasma triglycerides, FVIIc, FVIIa, and free fatty acids were analyzed. There were marked effects of the fat...... quantity on postprandial responses of plasma triglycerides, FVII, and free fatty acids. The high-fat meals caused, in contrast to the low-fat meals, considerable increases in plasma triglycerides. Plasma levels of FVIIc and FVIIa peaks were 7% and 60% higher after consumption of high-fat meals than after...... consumption of low-fat meals. The five different fat qualities caused similar postprandial increases in plasma triglycerides, FVIIc, and FVIIa. These findings indicate that high-fat meals may be prothrombotic, irrespective of their fatty acid composition. The postprandial FVII activation was not associated...

  18. [Risk assessment of thrombotic events after the use of activated factor VII].

    Science.gov (United States)

    Martínez López, M C; Alcaraz Romero, A J; Martínez López, A B; Fernández-Llamazares, C M; Ramos Navarro, C

    2013-09-01

    The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor viia (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=.540), or in the mortality rate (16% vs 9.5%, P=.208). In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  19. The unsialylated subpopulation of recombinant activated factor VII binds to the asialo-glycoprotein receptor (ASGPR) on primary rat hepatocytes.

    Science.gov (United States)

    Seested, Torben; Nielsen, Hanne M; Christensen, Erik I; Appa, Rupa S

    2010-12-01

    Recombinant activated factor VII (rFVIIa; NovoSeven®) is a heterogeneously glycosylated serine protease used for treatment of haemophiliacs with inhibitors. The drug substance contains a subpopulation consisting of ~20% of rFVIIa molecules which are unsialylated and consists of carbohydrate moieties with terminally exposed galactose and N-acetyl-D-galactosamine (GalNAc). Recently, data from an in situ perfused liver model showed that a subpopulation of rFVIIa, appearing to be unsialylated rFVIIa, was cleared by the liver, thus suggesting a carbohydrate-moiety mediated mechanism. The parenchymal cells of the liver, hepatocytes, are known to abundantly express functional carbohydrate-specific receptors and in this study we therefore used primary rat hepatocytes to study binding and intracellular fate of rFVIIa at a cellular level. Immunofluorescence microscopy showed that rFVIIa was distributed into distinct intracellular vesicles and electron microscopic autoradiography revealed that radioiodinated rFVIIa distributed only into cytoplasmic free vesicles resembling endosomes and lysosomes. These findings suggest that endocytosis of rFVIIa in hepatocytes could be partly mediated via initial membrane binding to a receptor. Quantitative binding studies showed that the presence of excess unlabelled asialo-orosomucoid, asialo-rFVIIa and GalNAc significantly decreased binding of 125I-rFVIIa. An antibody which specifically binds to the carbohydrate recognition domain of the asialoglycoprotein receptor (ASGPR) significantly decreased binding of asialo-rFVIIa by ~36% and rFVIIa by ~19%. Together our data showed that a receptor-mediated mechanism involving the ASGPR is able to bind a subpopulation of unsialylated rFVIIa, while a hepatic mechanism for binding and clearing sialylated rFVIIa is still unknown.

  20. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: Differences between older men and women

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII

  1. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: Differences between older men and women

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII

  2. Use of activated recombinant factor VII for severe coagulopathy post ventricular assist device or orthotopic heart transplant

    Directory of Open Access Journals (Sweden)

    Despotis George J

    2007-07-01

    Full Text Available Abstract Background Ventricular assist devices(VAD implantation/removal is a complex surgical procedure with perioperative bleeding complications occurring in nearly half of the cases. Recombinant activated factor VII (rFVIIa has been used off-label to control severe hemorrhage in surgery and trauma. We report here our experience with rFVIIa as a rescue therapy to achieve hemostasis in patients undergoing orthotopic heart transplant (OHT and/or VAD implantation. Methods A retrospective review was conducted from Jan 03 to Aug 05 for patients who received rFVIIa for the management of intractable bleeding unresponsive to standard hemostatic blood component therapy. Blood loss and the quantity of blood products, prior to, and for at least 12 hours after, administration of rFVIIa were recorded. Results Mean patient age was 53, (38–64 yrs, mean dose of rFVIIa administered was 78.3 μg/kg (24–189 μg/kg in 1–3 doses. All patients received the drug either intraoperatively or within 6 hours of arrival in ICU. Mean transfusion requirements and blood loss were significantly reduced after rFVIIa administration (PRBC's; 16.9 ± 13.3 to 7.1 ± 6.9 units, FFP; 13.1 ± 8.2 to 4.1 ± 4.9 units, platelets; 4.0 ± 2.8 to 2.1 ± 2.2 units, p Conclusion In this review, there was a significant decrease in transfusion requirement and blood loss after rFVIIa administration. Although, 5/17 developed thromboembolic complications, these patients may have been at higher risk based on the multiple modality therapy used to manage intractable bleeding. Nevertheless, the exact role of rFVIIa with respect to development of thromboembolic complications cannot be clearly determined. Further investigation is needed to determine rFVIIa's safety and its effectiveness in improving postoperative morbidity and mortality.

  3. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II plus VII plus X activity in subjects infused with the drug. Influence of time and temperature

    DEFF Research Database (Denmark)

    Thorsen, S.; Teisner, A.; Jensen, S.A.;

    2009-01-01

    Objectives: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...

  4. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature

    DEFF Research Database (Denmark)

    Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup;

    2009-01-01

    OBJECTIVES: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...

  5. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery

    DEFF Research Database (Denmark)

    Gill, Ravi; Herbertson, Mike; Vuylsteke, Alain

    2009-01-01

    BACKGROUND: Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed...... after cardiac surgery. METHODS AND RESULTS: In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients...... for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa....

  6. Genotype–phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease

    Indian Academy of Sciences (India)

    Jayashree Shanker; Ganapathy Perumal; Arindam Maitra; Veena S. Rao; B. K. Natesha; Shibu John; Sridhar Hebbagodi; Vijay V. Kakkar

    2009-12-01

    Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed significantly across R353Q genotype ($P \\lt 0.0001$). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively ($P \\lt 0.0001$). F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score $-1.82$; $P = 0.002$). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506–2.850) and 2.472 (95% c.i. = 1.679–3.641), respectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.

  7. Genotype-phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease.

    Science.gov (United States)

    Shanker, Jayashree; Perumal, Ganapathy; Maitra, Arindam; Rao, Veena S; Natesha, B K; John, Shibu; Hebbagodi, Sridhar; Kakkar, Vijay V

    2009-12-01

    Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed ignificantly across R353Q genotype (P F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score -1.82; P = 0.002). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506-2.850) and 2.472 (95% c.i. = 1.679-3.641), espectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.

  8. A massive transfusion protocol incorporating a higher FFP/RBC ratio is associated with decreased use of recombinant activated factor VII in trauma patients.

    Science.gov (United States)

    Tan, Josenia N M; Burke, Peter A; Agarwal, Suresh K; Mantilla-Rey, Nelson; Quillen, Karen

    2012-04-01

    We implemented a protocol incorporating a higher fresh frozen plasma (FFP)/RBC ratio for the management of trauma patients requiring massive transfusion in 2007. This study aims to identify issues that affected the effective deployment of the massive transfusion protocol (MTP) and compare outcome variables with a historic cohort. Data from 49 trauma patients who received at least 10 units of packed RBCs within 24 hours were analyzed and compared with a historic massively transfused cohort who had received recombinant activated factor VII (rFVIIa). Of the patients, 28 received an FFP/RBC ratio of 1:1 to 1:2; 12 received a lower ratio of 1:2 to 1:4; 3 received more than 1:1 and 6 had less than 1:4. Compared with the historic cohort, the 1:1-1:2 group received significantly fewer blood components and did not require rescue rFVIIa. An MTP incorporating a higher FFP/RBC ratio of 1:1 to 1:2 is associated with decreased use of blood components and may obviate the need for rFVII.

  9. Haplotype and genotype effects of the F7 gene on circulating factor VII, coagulation activation markers and incident coronary heart disease in UK men.

    Science.gov (United States)

    Ken-Dror, G; Drenos, F; Humphries, S E; Talmud, P J; Hingorani, A D; Kivimäki, M; Kumari, M; Bauer, K A; Morrissey, J H; Ireland, H A

    2010-11-01

    Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS-II). A second cohort, Whitehall II study (WH-II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. In NPHS-II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12-1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01-1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH-II, as was the association of H5 with higher CHD risk [pooled-estimate odds ratio (OR) 1.16 (1.00-1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD.  tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not. © 2010 International Society on Thrombosis and Haemostasis.

  10. Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER).

    Science.gov (United States)

    Napolitano, Mariasanta; Giansily-Blaizot, Muriel; Dolce, Alberto; Schved, Jean F; Auerswald, Guenter; Ingerslev, Jørgen; Bjerre, Jens; Altisent, Carmen; Charoenkwan, Pimlak; Michaels, Lisa; Chuansumrit, Ampaiwan; Di Minno, Giovanni; Caliskan, Umran; Mariani, Guglielmo

    2013-04-01

    Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 μg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.

  11. Critical appraisal of the role of recombinant activated factor VII in the treatment of hemophilia patients with inhibitors

    Directory of Open Access Journals (Sweden)

    Ampaiwan Chuansumrit

    2010-03-01

    Full Text Available Ampaiwan Chuansumrit1, Pantep Angchaisuksiri2, Nongnuch Sirachainan11Departments of Pediatrics and 2Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University,  Bangkok, ThailandAbstract: Hemophilia patients with inhibitors faced the constraint of inadequate treatment for several years before the era of recombinant factor VIIa (rFVII. Initially, rFVIIa was used in the compassionate-use programs. After a worldwide license was issued, more than 1.5 million doses were administered. Bleeding of joints and muscles was controlled effectively by means of an early home treatment program, with either a standard dose of 90 μg/kg every 2 to 3 hours for a few doses or a single dose of 270 μg/kg. For more serious bleeding episodes or minor surgery, an initial dose of 90 μg/kg was given every 2 hours for 24 to 48 hours followed by increased intervals of 3 to 6 hours according to the severity of bleeding and efficacy of bleeding control. In cases of major surgery such as orthopedic procedures, the same regimen can be applied except for a higher initial dose of 120 to 180 μg/kg. However, increasing the dose should be considered if there are unexpected bleeding complications since the half-life and clearance of rFVIIa differ between individuals. In addition, prophylaxis is administered to a small number of patients. Finally, the reported thromboembolic events found in hemophilia patients with inhibitors receiving rFVIIa are extremely low, much less than 1%.Keywords: bleeding disorder, hemophilia, inhibitor, NovoSeven, recombinant factor VIIa

  12. 111Indium Labelling of Recombinant Activated Coagulation Factor VII: In Vitro and Preliminary In Vivo Studies in Healthy Rats

    Directory of Open Access Journals (Sweden)

    Amarnadh Nalla

    2012-01-01

    Full Text Available The aim of this study is to investigate whether 111Indium-labelled recombinant FVIIa (rFVIIa could be a potential radiopharmaceutical for localization of bleeding sources. DTPA-conjugated rFVIIa was radiolabelled with 111In chloride. In vitro binding efficiency of 111In-DTPA-rFVIIa to F1A2-Mab-sepharose was 99% in buffer, while it was 88–82% in serum. The binding efficiency of 111In-DTPA-rFVIIa to TF (1–209-sepharose was 48% in buffer whereas 39%–36% in serum, respectively. In vivo experiment was conducted in healthy rats, and gamma camera images were taken immediately after iv. administration of 1.6–1.8 MBq 111In-DTPA-rFVIIa up to 120–130 min. Five min after administration of 111In-DTPA-rFVIIa, percentage of 111In activity was 6.0% in the cardiac region and 24.5% in the liver region. After 2 hours activity was decreased to 3.3% in heart while it had increased to 42.0% in the liver. The 111In-DTPA-rFVIIa might be a potential radiopharmaceutical for visualisation of tissues with significant TF expression such as acute bleeding lesions in the gastrointestinal tract.

  13. Factor VII Activating Protease Polymorphism (G534E) Is Associated with Increased Risk for Stroke and Mortality.

    Science.gov (United States)

    Trompet, Stella; Pons, Douwe; Kanse, Sandip M; de Craen, Anton J M; Ikram, M Arfan; Verschuren, Jeffrey J W; Zwinderman, Aeilko H; Doevendans, Pieter A F M; Tio, René A; de Winter, Robbert J; Slagboom, P Eline; Westendorp, Rudi G J; Jukema, J Wouter

    2011-01-01

    Introduction. The FSAP-Marburg I polymorphism (1704G > A), which reduces FSAP activity, is associated with late complications of carotid stenosis in humans. Therefore, this study examines the influence of the Marburg I polymorphism and the closely linked Marburg II polymorphism (1280G > C) on various cardiovascular outcomes in two large independent study populations. Methods. The two Marburg polymorphisms in the HABP2 gene encoding FSAP were genotyped in a large population of elderly patients at risk for vascular disease (the PROSPER-study, n = 5804) and in a study population treated with a percutaneous coronary intervention (the GENDER-study, n = 3104). Results. In the PROSPER study, the Marburg I polymorphism was associated with an increased risk of clinical stroke (HR: 1.60, 95% CI: 1.13-2.28) and all-cause mortality (HR: 1.33, 95% CI: 1.04-1.71). In the GENDER study carriers of this variant seemed at lower risk of developing restenosis (HR: 0.59, 95% CI: 0.34-1.01). The Marburg II polymorphism showed similar but weaker results. Conclusion. The increase in stroke risk in Marburg I carriers could be due to differential effects on smooth muscle cells and on matrix metalloproteinases, thereby influencing plaque stability. The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.

  14. Factor VII Activating Protease Polymorphism (G534E Is Associated with Increased Risk for Stroke and Mortality

    Directory of Open Access Journals (Sweden)

    Stella Trompet

    2011-01-01

    Full Text Available Introduction. The FSAP-Marburg I polymorphism (1704G > A, which reduces FSAP activity, is associated with late complications of carotid stenosis in humans. Therefore, this study examines the influence of the Marburg I polymorphism and the closely linked Marburg II polymorphism (1280G > C on various cardiovascular outcomes in two large independent study populations. Methods. The two Marburg polymorphisms in the HABP2 gene encoding FSAP were genotyped in a large population of elderly patients at risk for vascular disease (the PROSPER-study, n=5804 and in a study population treated with a percutaneous coronary intervention (the GENDER-study, n=3104. Results. In the PROSPER study, the Marburg I polymorphism was associated with an increased risk of clinical stroke (HR: 1.60, 95% CI: 1.13–2.28 and all-cause mortality (HR: 1.33, 95% CI: 1.04–1.71. In the GENDER study carriers of this variant seemed at lower risk of developing restenosis (HR: 0.59, 95% CI: 0.34–1.01. The Marburg II polymorphism showed similar but weaker results. Conclusion. The increase in stroke risk in Marburg I carriers could be due to differential effects on smooth muscle cells and on matrix metalloproteinases, thereby influencing plaque stability. The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.

  15. Ineffective off-label use of recombinant activated factor VII in a case of bone-marrow transplantation-related gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Wiedermann CJ

    2006-01-01

    Full Text Available Abstract Background For patients with a normal coagulation system, who experience serious bleeding, sound evidence for recombinant activated factor VII (rFVIIa as an effective haemostatic agent is only scarcely available so far from controlled clinical trials. In systematic reviews on the clinical use of rFVIIa, treatment failures were only rarely reported. Case presentation We present a 45-year old, Caucasian male with persistent intestinal bleeding due to enterocolitis associated with cytomegalovirus infection and acute graft-versus-host-disease. He had received allogeneic peripheral blood stem cell transplantation from an unrelated HLA-identical donor because of chronic myelogenous leukaemia diagnosed two years earlier. Bleeding started at day 18 after transplantation with bloody diarrhea, which was treated with multiple transfusions of fresh frozen plasma, platelet, and red blood cell concentrates, and continued relentlessly, despite all efforts, including continued transfusions, high-dose prednisolone, broad antibiotic and antiviral coverage, and tranexamic acid. Recombinant FVIIa was started at boluses of 90–120 μg/kg every 4–8 hours. Despite more than 10 doses, recurrent severe bleeding progressed to refractory shock, multiorgan failure and death. Conclusions Little can be concluded from single case reports of clinical improvement, because publication bias in favour of positive effects is likely. Our case suggests that rFVIIa is not a panacea, in particular for severe bleeding after bone-marrow transplantation. As long as rigorous, controlled studies or comprehensive registries are lacking, conventional interventions remain the standard of care in non-haemophilic patients with severe bleeding.

  16. Treatment of bleeding in acquired hemophilia A with the proper administration of recombinant activated factor VII: single-center study of 7 cases

    Science.gov (United States)

    Saito, Makoto; Kanaya, Minoru; Izumiyama, Koh; Mori, Akio; Irie, Tatsuro; Tanaka, Masanori; Morioka, Masanobu; Ieko, Masahiro

    2016-01-01

    Recombinant activated factor VII (rFVIIa) is the bypassing agent used in the first-line hemostatic therapy for acquired hemophilia A (AHA); however, the occurrence of thrombotic complications in rFVIIa-treated AHA patients was recently reported to be 2.9–6.5%. Therefore, the investigation of the proper administration of rFVIIa for AHA is needed. In the present study, we retrospectively investigated the clinical features of AHA with regards to the use of rFVIIa (presence or absence of use and total amount) in 7 AHA patients encountered in our department for 7 years between January 2008 and December 2014. Ages were 63–89 years old (median: 79 years old), and there were 5 male and 2 female patients. The coexistence of cardiovascular risk factors and arteriosclerotic diseases, such as hypertension, diabetes mellitus, and cerebral infarction were present in 6 patients. Anemia progressed to less than 7 g/dL of hemoglobin and required red blood cell transfusion in 5 patients, showing “severe” hemorrhage. Factor VIII inhibitors were removed by immunological treatments in 6 patients. As a hemostatic therapy, rFVIIa was used in 4 patients. rFVIIa was not administered or was administered at a very low dose (20 mg) to 3 and 1 patient, respectively, and bleeding stopped as inhibitor titers decreased and disappeared in these patients. Inhibitors did not disappear in 1 patient and the control of hemostasis became poor and was accompanied by intestinal hemorrhage. Although a large amount of rFVIIa (265 mg in total) was administered, the patient bled to death. Therefore, bleeding may be stopped without the administration of rFVIIa in some AHA cases, while the dose of rFVIIa is not necessarily related to hemostatic effects in other cases. Since the main aim of AHA treatments is the removal of inhibitors, caution is needed to ensure that more than the necessary amount of rFVIIa is not administered. PMID:27843336

  17. Factor VII deficiency impairs cutaneous wound healing in mice.

    Science.gov (United States)

    Xu, Zhi; Xu, Haifeng; Ploplis, Victoria A; Castellino, Francis J

    2010-01-01

    Skin keratinocytes express tissue factor (TF) and are highly associated with skin wound healing. Although it has been demonstrated that perivascular TF expression in granulation tissue formed after dermal injury is downregulated during healing, studies of the mechanism of factor (F) VII, a TF ligand, in skin wound healing are lacking. We reported the use of a dermal punch model to demonstrate that low-expressing FVII mice (approximately 1% of wild type [WT]) exhibited impaired skin wound healing compared with WT controls. These low-FVII mice showed defective reepithelialization and reduced inflammatory cell infiltration at wound sites. This attenuated reepithelialization was associated with diminished expression of the transcription factor early growth response 1 (Egr-1). In vitro, Egr-1 was shown to be essential for the FVIIa-induced regulation of keratinocyte migration and inflammation. Both Egr-1 upregulation and downstream inflammatory cytokine appearance in keratinocytes depended on FVIIa/TF/protease-activated receptor 2 (PAR-2)-induced signaling and did not require subsequent generation of FXa and thrombin. The participation of Egr-1 in FVIIa-mediated regulation of keratinocyte function was confirmed by use of Egr-1-deficient mice, wherein a significant delay in skin wound healing after injury was observed, relative to WT mice. The results from these studies demonstrate an in vivo mechanistic relationship between FVIIa, Egr-1 and the inflammatory response in keratinocyte function during the wound healing process.

  18. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael;

    2011-01-01

    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  19. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Münster, A M; Marckmann, P

    2000-01-01

    tissue factor, the cofactor of FVII, to circulating blood; therefore, thrombin formation in response to FVII activation is more likely to occur in such patients. This hypothesis was tested in a randomized crossover study of 30 patients (aged 43 to 70 years) with stable angina pectoris...

  20. Association of factor VII protein concentration with lifestyle factors

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Møller, L; Jespersen, J

    1998-01-01

    -sectional study examined the association between several behavioural variables (body mass index, physical activity, tobacco or alcohol consumption) or physiological variables (total cholesterol, HDL-cholesterol, triglycerides, glucose, insulin, fibrinogen, resting pulse, systolic blood pressure, bleeding time......) and FVII:Ag in 439 51-y-old Danish men. In the multivariate analyses, body mass index (BMI), low physical activity, total cholesterol, short bleeding time, and insulin showed an independent positive association with FVII:Ag. The strongest independent association with FVII:Ag was found for total cholesterol...

  1. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F;

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... after progestin intake. The integrated response, AUC, for TFPI was significantly lower in the HRT groups compared with the reference group. CONCLUSION: The observed changes may increase the early thrombotic risk associated with HRT use. Udgivelsesdato: 2002-Dec...

  2. Genotype and phenotype correlation in intracranial hemorrhage in neonatal factor VII deficiency among Thai children

    Directory of Open Access Journals (Sweden)

    Traivaree C

    2017-06-01

    Full Text Available Chanchai Traivaree,1 Chalinee Monsereenusorn,1 Arunotai Meekaewkunchorn,2 Premsak Laoyookhong,3 Saranya Suwansingh,4 Boonchai Boonyawat5 1Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, 2Division of Hematology/Oncology, Department of Pediatrics, 3Division of Neonatology, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, 4Division of Hematology/Oncology, Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, 5Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Abstract: Congenital factor VII (FVII deficiency is a rare inherited coagulopathy. The clinical manifestations and clinical findings vary widely, ranging from asymptomatic to life-threatening bleeding, including intracranial hemorrhage (ICH, with prolonged prothrombin time, normal partial thromboplastin time and normal platelet counts, which are confirmed by the low level of FVII assay. Treatment consists of fresh frozen plasma (FFP, prothrombin complex concentrates (PCCs, and recombinant activated FVII to treat bleeding and prophylactic therapy. Here, we report four patients with FVII levels <5% (severe type who presented ICH during the neonatal period. The IVS6+1G>T was the most common (50% mutation identified in our study, followed by the K376X nonsense mutation (37.5%. In our study, we found that genetic information affected the severity of congenital FVII deficiency with ICH. Keywords: mutation analysis, factor VII deficiency, Thai children

  3. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    plasma, in cold activated plasma and in FVII deficient plasma. There was a positive correlation (r=0.96) between FVII:Ag and FVII:Am with slightly but significantly higher values for FVII:Ag (FVII:Ag= 106 U/ml and FVII:Am=100 U/ml; p ...Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII......:Ag) or estimated with an amidolytic method (FVII:Am). We have investigated whether FVII:Am is a valuable alternative to FVII:Ag. FVII:Ag and FVII:Am were measured in 147 plasma samples from blood donors, patients on oral anticoagulant therapy, postmenopausal women on hormone replacement therapy, in postprandial...

  4. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Münster, A M; Marckmann, P

    2000-01-01

    for triglycerides, activated FVII (FVIIa), FVII protein concentration (FVII:Ag), prothrombin fragment 1+2 (F1+2), and soluble fibrin. Triglyceride levels increased from fasting levels on both diets, but they increased most markedly on the high-fat diet. FVIIa and FVIIa/FVII:Ag increased with the high-fat diet...... and decreased with the low-fat diet. For both diets, FVII:Ag and F1+2 decreased slightly. No postprandial changes were observed for soluble fibrin. Postprandial mean values of triglycerides, FVIIa, FVII:Ag, and FVIIa/FVII:Ag were significantly higher for the high-fat diet than for the low-fat diet. Our findings...... confirm that high-fat meals cause immediate activation of FVII. The clinical implication is debatable because FVII activation was not accompanied by an increase in plasma F1+2 concentrations in patients with severe atherosclerosis. However, a local thrombin generation on the plaque surface cannot...

  5. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE).

    Science.gov (United States)

    Gruppo, R A; Kessler, C M; Neufeld, E J; Cooper, D L

    2013-07-01

    Recent data from the Dosing Observational Study in Hemophilia diary study has described home treatment with recombinant activated factor VII (rFVIIa) in congenital haemophilia with inhibitors (CHwI). The current analysis compares prescribed and patient/caregiver-reported rFVIIa administration in paediatric and adult CHwI patients in this study. Patients with ≥ 4 bleeding episodes within a 3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were eligible. Patients/caregivers completed a diary for ≥ 90 days or until the patient experienced four bleeds. Initial, total and mean rFVIIa doses reported for each bleeding episode were calculated and compared with the physician-prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%) completed the study. Children and adults had similar mean durations of bleeding episodes. Both patient groups were administered higher initial rFVIIa doses for joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs. 200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs. 123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but children received significantly more doses per joint bleed than adults (median 6.5 vs. 3.0). The median total dose per joint bleed was higher in children than adults (1248.7 vs. 441.6). For children and adults, both initial and additional doses administered for bleeds were higher than prescribed. Children received higher total doses per bleed due to an increased number of infusions per bleed.

  6. Polymorphisms in the genes for coagulation factor II,V,VII in patients undergoing coronary angiography

    Institute of Scientific and Technical Information of China (English)

    徐耕; 金国栋; 傅国胜; 马骥; 单江; 王建安

    2003-01-01

    Objective: To determine whether polymorphisms in the genes for coagulation factor II,V, VII could predispose an individual to increase risk for coronary artery disease (CAD) and/or myocardial infarction (MI) in Chinese. Methods: We screened coagulation factor II(G20210A),V(G1691A),VII (R353Q and HVR4) genotype in 374 patients undergoing coronary angiography by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay. Results: The R353Q and HVR4 genotype of the factor VII distribution was in accordance with Hardy-Weinberg equilibrium. The frequencies of FVII genotype or allele did not show statistically significant differences between CAD group and controls or between male and female. The frequencies of the Q allele and (RQ+QQ) genotype were significantly higher among the CAD patients without myocardial infarction (MI) history than among those with MI history (P<0.05). However, HVR4 polymorphism was not significantly different within groups. We only find one normal control of factorII(G20210A) mutation. No coagulation factor V(G1691A) mutation was found in the CAD patients and controls. Conclusion: The factor II(G20210A),V(G1691A) mutation is absent and may not be a major genetic factor for CAD and/or MI; the Q allele of the R353Q polymorphism of the factor VII gene may be a protective genetic factor against myocardial infarction in Chinese.

  7. Dietary effects on coagulation factor VII vary across genotypes of the R/Q353 polymorphism in elderly people

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Witteman, J.C.M.; Hofman, A.; Grobbee, D.E.

    1998-01-01

    The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation

  8. Double heterozygous mutations Gln100Leu and His348Gln of the F7 gene in a patient with factor VII deficiency.

    Science.gov (United States)

    Li, Min; Zheng, Fangxiu; Jin, Yanhui; Wang, Mingshan; Zhu, Liqing; Yang, Lihong

    2013-03-01

    A 25-year-old Chinese woman who had a history of easy bruising was admitted to hospital due to uncontrolled epistaxis. She showed factor VII activity level of 2% and factor VII antigen level of 4% of the normal value. We detected a novel missense mutation g.8355 A>T (p.Gln100Leu) in the second epidermal growth factor-like (EGF) domain and a g.11482 T>G (p.His348Gln) in the catalytic domain. Although the Gln100 residue is close to the junction of EGF-2 domain with the serine protease domain, we infer that the substitution of polar negatively charged Gln residue at the position 100 with introduction of nonpolar Leu residue may be likely to perturb proper folding, resulting in decreasing factor VII activity.

  9. Coexistence of Factor VII Deficiency and Hereditary Spastic Paraplegia in Two Siblings

    Directory of Open Access Journals (Sweden)

    Hortensia De la Corte-Rodriguez

    2016-01-01

    Full Text Available We present the case of two patients aged 12 years and 7 years who were referred to our hospital for factor VII deficiency inherited in an autosomal recessive pattern, who had suffered from previous multiple joint haemarthroses. They presented with fine motor symptoms and difficulty in walking. During physical examination we observed neurological symptoms (general hypotonia, muscular hypotrophy, exaggerated tendon reflexes, pes cavus, and spastic gait. Given that the symptoms were not justified by the deficiency of coagulation factor VII and on suspicion of hereditary spastic paraplegia (HSP, tests were carried out. Findings from the tests confirmed the diagnosis of HSP (axonal degeneration of the central motor pathway and pyramidal tracts, further complicated by mixed neuropathy. This disease was also inherited in an autosomal recessive pattern with no direct genetic association with factor VII deficiency. Neurological symptoms had gone unnoticed due to a history of multiple joint haemarthrosis; musculoskeletal examination led to a satisfactory differential diagnosis. Haematological prophylaxis was commenced with rFVIIa at 30 mcg/kg, three days per week. A rehabilitation programme was prescribed so that the patient could remain independent for as long as possible, based on orthosis, physiotherapy, and occupational therapy. Response to treatment is currently satisfactory and no new bleeding has presented. As far as we are aware, the coexistence of these two diseases (factor VII deficiency and HSP has not been previously reported in the literature.

  10. Prevalence of factor VII deficiency and molecular characterization of the F7 gene in Brazilian patients.

    Science.gov (United States)

    Rodrigues, Dalva N; Siqueira, Lucia H; Galizoni, Andréa M; Arruda, Valder R; Annichino-Bizzacchi, Joyce M

    2003-04-01

    The prevalence of factor VII (FVII) deficiency in 267 Brazilian patients was estimated to be 4.1%, including one patient with significant bleeding, five with minor bleeding and five patients asymptomatic. Only one novel mutation 8926G F7 polymorphisms and FVII activity were found in these patients, as those with higher levels of FVII activity presented the genotype described in the literature as related to reduced FVII activity. As the R304Q mutation was the most frequent in these patients, and may be associated with an asymptomatic form of the disease, particularly in Blacks, we examined this mutation and FVII activity in 49 Blacks and 49 Caucasian blood donors with no clinical bleeding. None of the individuals showed the R304Q mutation, and FVII activity was normal in all of them, thus indicating that FVII deficiency is not common in normal individuals of these two ethnic groups in Brazil. This is the first study in South America to examine the prevalence and molecular basis of FVII deficiency, including the description of a novel mutation.

  11. Vena porta thrombosis in patient with inherited factor VII deficiency

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S;

    2010-01-01

    with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal...... vein with well expressed portosystemic collaterals, heterozygosity for three common polymorphisms in FVII gene, associated with reduction in plasma FVII levels, and no other factors predisposing to thrombosis....

  12. Combined congenital dysfibrinogenemia and factor VII deficiency from mutations in the FGB and F7 genes.

    Science.gov (United States)

    Woo, Hye In; Park, In-Ae; Lee, Ki-O; Kim, Sun-Hee; Kim, Hee-Jin

    2012-07-01

    Dysfibrinogenemia and factor VII (FVII) deficiency are rare congenital coagulopathies. In this report, the authors describe a man with both defects confirmed by molecular genetic tests. The patient was a 51-year-old man referred for prolonged prothrombin time (PT) that had been accidentally detected on preoperative screening. He had no history of bleeding tendency even on occasions of surgery. Routine coagulation studies revealed prolonged PT (1.53 INR) and thrombin time (42.2 s), and decreased fibrinogen level (57 mg/dl) and FVII activity (44%). Direct sequencing analyses were performed on FGA, FGB, and FGG genes to confirm dysfibrinogenemia and on the F7 gene to confirm FVII deficiency. As a result, the patient was shown to be heterozygous for a point mutation in exon 8 of the FGB gene (c.1475A > G, p.*492Trpext*12; Fibrinogen Magdeburg II) and for a missense mutation in exon 6 of the F7 gene (c.466G  > A, p.Gly156Ser). To our knowledge, this is the first report on a case of combined dysfibrinogenemia and FVII deficiency confirmed by molecular genetic tests.

  13. Mutagenesis in sequence encoding of human factor VII for gene therapy of hemophilia

    Directory of Open Access Journals (Sweden)

    B Kazemi

    2009-12-01

    Full Text Available "nBackground: Current treatment of hemophilia which is one of the most common bleeding disorders, involves replacement therapy using concentrates of FVIII and FIX .However, these concentrates have been associated with viral infections and thromboembolic complications and development of antibodies. "nThe use of recombinant human factor VII (rhFVII is effective  for the treatment of patients with  hemophilia A or B, who develop antibodies ( referred as inhibitors against  replacement therapy , because it induces coagulation independent of FVIII and FIX. However, its short half-life and high cost have limited its use. One potential solution to this problem may be the use of FVIIa gene transfer, which would attain continuing therapeutic levels of expression from a single injection. The aim of this study was to engineer a novel hFVII (human FVII gene containing a cleavage site for the intracellular protease and furin, by PCR mutagenesis "nMethods: The sequence encoding light and heavy chains of hFVII, were amplified by using hFVII/pTZ57R and specific primers, separately. The PCR products were cloned in pTZ57R vector. "nResults and discussion: Cloning was confirmed by restriction analysis or PCR amplification using specific primers and plasmid universal primers. Mutagenesis of sequence encoding light and heavy chain was confirmed by restriction enzyme. "nConclusion: In the present study, it was provided recombinant plasmids based on mutant form of DNA encoding light and heavy chains.  Joining mutant form of DNA encoding light chain with mutant heavy chain led to a new variant of hFVII. This variant can be activated by furin and an increase in the proportion of activated form of FVII. This mutant form of hFVII may be used for gene therapy of hemophilia.

  14. Conserved water-mediated hydrogen bond network between TM-I, -II, -VI, and -VII in 7TM receptor activation

    DEFF Research Database (Denmark)

    Nygaard, Rie; Hansen, Louise Valentin; Mokrosinski, Jacek;

    2010-01-01

    Five highly conserved polar residues connected by a number of structural water molecules together with two rotamer micro-switches, TrpVI:13 and TyrVII:20, constitute an extended hydrogen bond network between the intracellular segments of TM-I, -II, -VI, and -VII of 7TM receptors. Molecular dynamics...... to apparently function as a catching trap for water molecules. Mutational analysis of the beta2-adrenergic receptor demonstrated that the highly conserved polar residues of the hydrogen bond network were all important for receptor signaling but served different functions, some dampening constitutive activity...... (AsnI:18, AspII:10, and AsnVII:13), whereas others (AsnVII:12 and AsnVII:16) located one helical turn apart and sharing a water molecule were shown to be essential for agonist-induced signaling. It is concluded that the conserved water hydrogen bond network of 7TM receptors constitutes an extended...

  15. Abnormal secretion and function of recombinant human factor VII as the result of modification to a calcium binding site caused by a 15-base pair insertion in the F7 gene.

    Science.gov (United States)

    Peyvandi, F; Carew, J A; Perry, D J; Hunault, M; Khanduri, U; Perkins, S J; Mannucci, P M; Bauer, K A

    2001-02-15

    A case of a novel mutation in the F7 gene that results in factor VII coagulant activity (VII:c) of less than 1% and VII antigen (VII:Ag) levels of 10% is presented. DNA analysis revealed a homozygous 15-base pair (bp) in-frame insertion-type mutation at nucleotide 10554. This insertion consisted of a duplication of residues leucine (L)213 to aspartic acid (D)217 (leucine, serine, glutamic acid, histidine, and aspartic acid), probably arising by slipped mispairing between 2 copies of a direct repeat (GCGAGCACGAC) separated by 4 bp. Molecular graphic analyses showed that the insertion is located at the surface of the catalytic domain in an exposed loop stabilized by extensive salt-bridge and hydrogen bond formation at which the calcium binding site is located. The mutation probably interferes with protein folding during VII biosynthesis and/or diminishes functional activity through the loss of calcium binding. In vitro expression studies demonstrated that the levels of VII:Ag in lysates of cells transfected with wild type VII (VIIWT) were equivalent to those with mutant type VII (VIIMT), but the level of secreted VIIMT was 5% to 10% that of VIIWT. Pulse chase studies demonstrated that VIIMT did not accumulate intracellularly, and studies with inhibitors of protein degradation showed that recombinant VIIMT was partially degraded in the pre-Golgi compartment. Accordingly, only small amounts of VIIMT with undetectable procoagulant activity were secreted into conditioned media. These results demonstrate that a combination of secretion and functional defects is the mechanism whereby this insertion causes VII deficiency.

  16. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  17. The F7 gene and clotting factor VII levels: dissection of a human quantitative trait locus.

    Science.gov (United States)

    Soria, Jose Manuel; Almasy, Laura; Souto, Juan Carlos; Sabater-Lleal, Maria; Fontcuberta, Jordi; Blangero, John

    2005-10-01

    Localization of human quantitative trait loci (QTLs) is now routine. However, identifying their functional DNA variants is still a formidable challenge. We present a complete dissection of a human QTL using novel statistical techniques to infer the most likely functional polymorphisms of a QTL that influence plasma levels of clotting factor VII (FVII), a risk factor for cardiovascular disease. Resequencing of 15 kb in and around the F7 gene identified 49 polymorphisms, which were then genotyped in 398 people. Using a Bayesian quantitative trait nucleotide (BQTN) method, we identified four to seven functional variants that completely account for this QTL. These variants include both rare coding variants and more common, potentially regulatory polymorphisms in intronic and promoter regions.

  18. The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Overgaard, K; Gram, J

    1995-01-01

    In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation...... samples. Results were compared by means of linear regression, where y = 0.984 x +0.770, r = 0.96. No systematic variation existed between FVII:Ag in plasma and serum. The mean difference in FVII:Ag between plasma and serum was -1.17 (SD 11.92) arbitrary units, compared with a mean difference of 0.18 (SD 8.......31) arbitrary units between duplicate measurements of the same plasma dilution. Our findings indicate that there is a good agreement between FVII:Ag in plasma and serum. Udgivelsesdato: 1995-May...

  19. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P;

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...... to investigate the effect of unfractionated heparin and TFPI, which is released from the endothelium by heparin, on FVII:C, FVIIa, and FVII:Ag. Heparin infusion decreased triglycerides and increased FFA and TFPI. This was accompanied by significant reductions in FVIIa, FVII:C and FVII:Ag. In vitro, anti...

  20. Quality of Activities of General Medicine Subjects VII Teachers in the Different Scenarios Calidad de las actividades de la asignatura medicina general integral VII en los diferentes escenarios docentes

    Directory of Open Access Journals (Sweden)

    Maricel Felicia Castellanos González

    2012-06-01

    Full Text Available Background: as part of the educational process developed in consultation rooms or in any other setting, previously taught contents should be taken into account in order to attain an integration of theoretical knowledge and clinical practice. Objective: to assess teaching settings according to the quality of the activities developed in the subject General Medicine VII, in the context of University Polyclinics. Methods: we conducted a quantitative and qualitative research as to compliance with quality indicators by applying an observation guide in teaching settings of the subject General Medicine VII in the University Polyclinics. Teaching settings evaluated included consultation rooms, vaccination areas, kindergardens, maternity homes, and family planning consultation rooms. Results: consultation rooms, vaccination areas, family planning consultation rooms, schools and kindergardens were assessed as medium proficiency. Only maternity homes and emergency rooms obtained a satisfactory category. Teaching activities with the greatest difficulties were: epidemiological surveillance for the investigation of risk factors, control of communicable disease outbreak, and presentation of the analysis of general health condition of the community. Conclusions: the educational setting was generally assessed as medium proficiency in the subject General Medicine VII. This was caused by the fact that consultation rooms, vaccination areas, family planning consultation rooms, schools and kindergardens were assessed as medium proficiency while only maternity homes and emergency rooms obtained a satisfactory category.Fundamento: en el proceso de enseñanza-aprendizaje que se desarrolla en los diferentes escenarios docentes, se deben tener en cuenta los contenidos ya impartidos, para logar una integración entre los conocimientos teóricos con la práctica m

  1. Coagulation factor VII R353Q polymorphism and the risk of puerperal cerebral venous thrombosis.

    Science.gov (United States)

    Kruthika-Vinod, T P; Nagaraja, Dindagur; Christopher, Rita

    2012-01-01

    Puerperal cerebral venous thrombosis (CVT) is a relatively common form of stroke in young women in India. The blood coagulation factor VII (FVII) R353Q polymorphism increases the risk for venous thrombosis. Our aim was to investigate the association of FVII R353Q polymorphism with the risk of puerperal CVT. A total of 100 women with puerperal CVT and 102 age-matched women without postpartum complications were investigated. FVII R353Q genotypes were identified using restriction fragment length polymorphism analysis. Our results showed that the homozygous FVII 353QQ genotype was present in 9% and 8% of patients and controls, respectively; and 42% of patients and 31.4% of controls had the heterozygous 353RQ genotype (odds ratio = 1.55, 95% confidence interval = 0.89-2.70; p = 0.243). Our findings suggest that the FVII R353Q polymorphism is not associated with increased risk for CVT occurring during the puerperal period in Indian women.

  2. Management of Pregnancy in a Chilean Patient with Congenital Deficiency of Factor VII and Glanzmann’s Thrombasthenia Variant

    Directory of Open Access Journals (Sweden)

    Nigel P. Murray

    2014-01-01

    Full Text Available Patients with inherited bleeding disorders are rare in obstetric practice but present with prolonged bleeding even after minor invasive procedures. They require a combined approach with obstetric and hematological management of each case, including the neonatal management of a possibly affected fetus. We present the case of a pregnancy in a patient with combined Factor VII deficiency and Glanzmann’s thrombasthenia, the successful obstetric and hematological management of the case, and a review of the literature.

  3. Katimavik Participant's Manual, Book VII, Socio-Cultural Activities = Katimavik manuel du participant, cahier VII, activites socio-culturelles.

    Science.gov (United States)

    OPCAN, Montreal (Quebec).

    The bilingual student manual, devoted to the socio-cultural learning activity portion of Katimavik (a nine-month volunteer community service and experiential learning program for 17 to 21 year old Canadians), contains sections on learning program objectives and trimester guidelines, optional activities, resume recordkeeping, general topic…

  4. HEREDITARY FACTOR VII DEFICIENCY IN THE ASIAN ELEPHANT (ELEPHAS MAXIMUS) CAUSED BY A F7 MISSENSE MUTATION.

    Science.gov (United States)

    Lynch, Michael; McGrath, Ken; Raj, Karthik; McLaren, Philippa; Payne, Karen; McCoy, Richard; Giger, Urs

    2017-04-01

    Hereditary disorders and genetic predispositions to disease are rarely reported in captive and free-ranging wildlife, and none have been definitively identified and characterized in elephants. A wild-caught, 41-yr-old male Asian elephant ( Elephas maximus ) without an apparent increased bleeding tendency was consistently found to have prolonged prothrombin times (PTs, mean=55±35 s) compared to 17 other elephants (PT=10±2 s). This elephant's partial thromboplastin times (PTT) fell within the normal range of the other elephants (12-30 s). A prolonged PT in the presence of a normal PTT suggests disruption of the extrinsic pathway via deficiency of coagulation Factor VII (FVII). This elephant's plasma FVII activity was very low (2%) compared to that of 15 other elephants (57-80%), but other coagulation factors' activities did not differ from the control elephants. Sequencing of genomic DNA from ethylenediaminetetraacetic acid blood revealed a single homozygous point mutation (c.202A>G) in the F7 gene of the FVII deficient elephant that was not present in unrelated elephants. This mutation causes an amino acid substitution (p.Arg68Gly) that is predicted to be deleterious. Two living offspring of the affected elephant were heterozygous for the mutation and had normal plasma FVII activities and coagulation profiles. Tissue from a third offspring, a deceased calf, was utilized to show that it was also a heterozygote. A DNA test has been developed to enable the screening of additional elephants for this mutation. Consistent with FVII deficiency investigations in other species, the condition did not cause a serious bleeding tendency in this individual elephant.

  5. An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

    Science.gov (United States)

    Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

    2016-06-24

    Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

  6. Recombinant activated factor VII for uncontrolled bleeding postcardiac surgery

    Directory of Open Access Journals (Sweden)

    Aly Makram Habib

    2016-10-01

    Conclusion: In this analysis, rFVIIa succefully reduced the chest tube bleeding and blood products transfused during severe post cardiac surgical bleeding. However, safety of rFVIIa remains unclear. Prospective controlled trials are still needed to confirm the role of rFVIIa.

  7. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Pérez-Jiménez Francisco

    2011-04-01

    Full Text Available Abstract Background Heterozygous Familial Hypercholesterolemia (FH is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls. We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag and whether they could be predictive factors for cardiovascular risk. 75% (410 of the patients with FH were RR, 23% (127 RQ and 1.6% (9 QQ; in the control group 75.3% (131 were RR, 21.3% (37 RQ and 3.4% (6 QQ (p = 0.32. No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease, either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96. In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97. Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  8. Altered lumbar spine structure, biochemistry and biomechanical properties in a canine model of mucopolysaccharidosis type VII

    Science.gov (United States)

    Smith, Lachlan J; Martin, John T; Szczesny, Spencer E; Ponder, Katherine P; Haskins, Mark E; Elliott, Dawn M

    2010-01-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disorder characterized by a deficiency in β-glucuronidase activity, leading to systemic accumulation of poorly degraded glycosaminoglycans (GAG). Along with other morbidities, MPS VII is associated with paediatric spinal deformity. The objective of this study was to examine potential associations between abnormal lumbar spine matrix structure and composition in MPS VII, and spine segment and tissue-level mechanical properties, using a naturally occurring canine model with a similar clinical phenotype to the human form of the disorder. Segments from juvenile MPS VII and unaffected dogs were allocated to: radiography, gross morphology, histology, biochemistry, and mechanical testing. MPS VII spines had radiolucent lesions in the vertebral body epiphyses. Histologically, this corresponded to a GAG-rich cartilaginous region in place of bone, and elevated GAG staining was seen in the annulus fibrosus. Biochemically, MPS VII samples had elevated GAG in the outer annulus fibrosus and epiphyses, low calcium in the epiphyses, and high water content in all regions except the nucleus pulposus. MPS VII spine segments had higher range of motion and lower stiffness than controls. Endplate indentation stiffness and failure loads were significantly lower in MPS VII samples, while annulus fibrosus tensile mechanical properties were normal. Vertebral body lesions in MPS VII spines suggest a failure to convert cartilage to bone during development. Low stiffness in these regions likely contributes to mechanical weakness in motion segments and is a potential factor in the progression of spinal deformity. PMID:19918911

  9. Group VII Ethylene Response Factors Coordinate Oxygen and Nitric Oxide Signal Transduction and Stress Responses in Plants1

    Science.gov (United States)

    Gibbs, Daniel J.; Conde, Jorge Vicente; Berckhan, Sophie; Prasad, Geeta; Mendiondo, Guillermina M.; Holdsworth, Michael J.

    2015-01-01

    The group VII ethylene response factors (ERFVIIs) are plant-specific transcription factors that have emerged as important regulators of abiotic and biotic stress responses, in particular, low-oxygen stress. A defining feature of ERFVIIs is their conserved N-terminal domain, which renders them oxygen- and nitric oxide (NO)-dependent substrates of the N-end rule pathway of targeted proteolysis. In the presence of these gases, ERFVIIs are destabilized, whereas an absence of either permits their accumulation; ERFVIIs therefore coordinate plant homeostatic responses to oxygen availability and control a wide range of NO-mediated processes. ERFVIIs have a variety of context-specific protein and gene interaction partners, and also modulate gibberellin and abscisic acid signaling to regulate diverse developmental processes and stress responses. This update discusses recent advances in our understanding of ERFVII regulation and function, highlighting their role as central regulators of gaseous signal transduction at the interface of ethylene, oxygen, and NO signaling. PMID:25944828

  10. Are olive oil diets antithrombotic? Diets enriched with olive, rapeseed, or sunflower oil affect postprandial factor VII differently

    DEFF Research Database (Denmark)

    Larsen, L.F.; Jespersen, J; Marckmann, P.

    1999-01-01

    BACKGROUND: The incidence of ischemic heart disease (IHD) in Crete was lower than expected on the basis of blood lipid concentrations of participants in the Seven Countries Study. A favorable effect of a high intake of olive oil on thrombogenesis may have contributed to this finding. OBJECTIVE: We...... compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis. DESIGN: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive...... FVII (FVIIa) were 11.3 +/- 5.1 U/L lower after olive oil than after sunflower oil, an 18% reduction (P Olive oil also tended to cause lower FVIIa peak concentrations than did rapeseed oil (mean difference: 8.6 U/L, a 15% reduction; P = 0.09). There were no significant differences between diets...

  11. Recombinant factor VII (NovoSeven in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Novak Vesna

    2007-01-01

    Full Text Available Background. Cerebral arteriovenous (AV malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven significantly reduce complications during surgical treatment. Case report. We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scale, in the brain. Due to a possible heavy bleeding we used a apparatus for intrasurgical blood recovery, Cell Saver, Sequestra 1 000, Medtronic, U.S.A., and recombinant human factor VIIa (rFVIIa - NovoSeven, NovoNordisk, Denmark to control bleeding and restore an adequate hemostasis. Conclusion. The use of an apparatus for intraoperative blood saving, as well as the NovoSeven preparation in the management of AV malformation of IV stage, showed to be successful.

  12. Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency.

    Science.gov (United States)

    Nichols, Timothy C; Dillow, Aaron M; Franck, Helen W G; Merricks, Elizabeth P; Raymer, Robin A; Bellinger, Dwight A; Arruda, Valder R; High, Katherine A

    2009-01-01

    Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.

  13. Using a minigene approach to characterize a novel splice site mutation in human F7 gene causing inherited factor VII deficiency in a Chinese pedigree.

    Science.gov (United States)

    Yu, T; Wang, X; Ding, Q; Fu, Q; Dai, J; Lu, Y; Xi, X; Wang, H

    2009-11-01

    Factor VII deficiency which transmitted as an autosomal recessive disorder is a rare haemorrhagic condition. The aim of this study was to identify the molecular genetic defect and determine its functional consequences in a Chinese pedigree with FVII deficiency. The proband was diagnosed as inherited coagulation FVII deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%). All nine exons and their flanking sequence of F7 gene were amplified by polymerase chain reaction (PCR) for the proband and the PCR products were directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572-1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband's F7 gene. To investigate the splicing patterns associated with F7 c.572-1G>A, ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes, spanning from intron 4 to intron 7 and carrying either an A or a G at position -1 of intron 5, were constructed and transiently transfected into human embryonic kidney (HEK) 293T cells, followed by RT-PCR analysis. The aberrant transcripts from the F7 c.572-1G>A mutant allele were not detected by ectopic transcription study. Sequencing of the RT-PCR products from the mutant transfectant demonstrated the production of an erroneously spliced mRNA with exon 6 skipping, whereas a normal splicing occurred in the wide type transfectant. The aberrant mRNA produced from the F7 c.572-1G>A mutant allele is responsible for the factor VII deficiency in this pedigree.

  14. Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency.

    Science.gov (United States)

    Varricchio, Antonio; Schettino, Michela; Ciampa, Antonio; Iannace, Carlo; Lo Conte, Domenico; Donnarumma, Bernadette; Vigorito, Raffaella; Lepore, Mariolina

    2014-06-24

    emorragiche. In questo articolo descriviamo un caso di una paziente di 46 anni con deficit congenito del fattore VII che si è sottoposta a trattamento chirurgico con successo grazie al trattamento con Novoseven prima della procedura. È stato utilizzato il modello riportato sotto per valutare i livelli di PTT e aPTT nel paziente. Per il prelievo ematico il sangue venoso della paziente è stato raccolto in provette di plastica (0.129 M di citrato di sodio, con sistema Vacutainer). Il tempo di protrombina è stato misurato con Recombiplastin (IL, Milano Italy), l’aPTT è stato misurato con l’APTT-SP (IL, Milano Italy). Come primo approccio profilattico alla paziente è stata utilizzata la vitamina K intramuscolo ma con scarsi risultati, poi si è valutato l’uso del Prothromplex, senza però ottenere un effetto significativo. L’ultimo step è stata la somministrazione di una terapia con Novoseven ® 15μg/kg somministrato 30 minuti prima dell’intervento and 4-5 h dopo la prima infusione. L’infusione del farmaco ha risolto i problemi di coagulazione permettendo il trattamento chirurgico, senza rischio nè emorragico nè trombotico per la paziente.

  15. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    , but no effects on clotting time indicating that haemodilution does not affect clot formation, but the clot formed at high haemodilution may not be so firm. In conclusion, the activity of recombinant activated factor VII was affected in vitro by pH, temperature, and haemodilution. Additional studies are necessary...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30...... activity in plasma. Significant effects of pH were observed for clotting time, clot formation time, maximum clot firmness, and factor VII coagulant activity in the direction of longer clot formation times and less firm clots with decreasing pH. Temperature had significant effects on clotting time, clot...

  16. Group VII Ethylene Response Factors Coordinate Oxygen and Nitric Oxide Signal Transduction and Stress Responses in Plants.

    Science.gov (United States)

    Gibbs, Daniel J; Conde, Jorge Vicente; Berckhan, Sophie; Prasad, Geeta; Mendiondo, Guillermina M; Holdsworth, Michael J

    2015-09-01

    The group VII ethylene response factors (ERFVIIs) are plant-specific transcription factors that have emerged as important regulators of abiotic and biotic stress responses, in particular, low-oxygen stress. A defining feature of ERFVIIs is their conserved N-terminal domain, which renders them oxygen- and nitric oxide (NO)-dependent substrates of the N-end rule pathway of targeted proteolysis. In the presence of these gases, ERFVIIs are destabilized, whereas an absence of either permits their accumulation; ERFVIIs therefore coordinate plant homeostatic responses to oxygen availability and control a wide range of NO-mediated processes. ERFVIIs have a variety of context-specific protein and gene interaction partners, and also modulate gibberellin and abscisic acid signaling to regulate diverse developmental processes and stress responses. This update discusses recent advances in our understanding of ERFVII regulation and function, highlighting their role as central regulators of gaseous signal transduction at the interface of ethylene, oxygen, and NO signaling. © 2015 American Society of Plant Biologists. All Rights Reserved.

  17. Basement membrane zone remodeling during appendageal development in human fetal skin. The absence of type VII collagen is associated with gelatinase-A (MMP2) activity.

    Science.gov (United States)

    Karelina, T V; Bannikov, G A; Eisen, A Z

    2000-02-01

    Epithelial cell adhesion, migration, and differentiation are controlled by interactions at the basement membrane zone (BMZ). Type VII collagen is the major collagenous component of anchoring fibrils that are essential for the attachment of the epidermis to the dermis. Gelatinase A (MMP-2) is believed to be necessary for the degradation of type VII collagen. In this study we have examined the in vivo distribution of type VII collagen and gelatinase A (Gel A) in the developing human epidermis and its appendages. At 13-15 wk of gestation a marked decrease in type VII collagen immunoreactivity was seen in the BMZ surrounding invading appendageal buds; however, type VII collagen mRNA was strongly expressed in the budding epidermal keratinocytes adjacent to the BMZ. At these stages, Gel A-positive mesenchymal-like cells were found scattered throughout the stroma with numerous Gel A-containing cells in direct contact with the developing appendageal buds. In situ zymography was used to show Gel A-activity in vivo. Gel A-mediated lysis was present at the interface between the appendageal buds and the underlying BMZ. By 20-25 wk of gestational age, immunostaining for type VII collagen protein was absent from the BMZ surrounding the distal portion of invading appendageal epithelial cords of both hair follicles and sweat glands. In contrast, type VII collagen mRNA was present in the basal keratinocytes adjacent to the BMZ surrounding the distal portion of these invading appendageal epithelial cords. At these stages Gel A-positive cells were present in the stroma directly adjacent to the distal portion of developing appendageal cords that lacked type VII collagen. In situ zymography showed zones of Gel A-mediated stromal lysis at the distal portion of developing appendageal cords. Interestingly, no differences were seen in the distribution of type IV collagen in the BMZ of both budding and resting fetal epidermis. These observations suggest that the absence of type VII collagen

  18. Production of coagulation factor VII in human cell lines Sk-Hep-1 and HKB-11.

    Science.gov (United States)

    Corrêa de Freitas, Marcela Cristina; Bomfim, Aline de Sousa; Mizukami, Amanda; Picanço-Castro, Virgínia; Swiech, Kamilla; Covas, Dimas Tadeu

    2017-09-01

    Recombinant factor VII (rFVII) is the main therapeutic choice for hemophilia patients who have developed inhibitory antibodies against conventional treatments (FVIII and FIX). Because of the post-translational modifications, rFVII needs to be produced in mammalian cell lines. In this study, for the first time, we have shown efficient rFVII production in HepG2, Sk-Hep-1, and HKB-11 cell lines. Experiments in static conditions for a period of 96 h showed that HepG2-FVII produced the highest amounts of rhFVII, with an average of 1843 ng/mL. Sk-hep-1-FVII cells reached a maximum protein production of 1432 ng/mL and HKB-11-FVII cells reached 1468 ng/mL. Sk-Hep-1-rFVII and HKB-11-rFVII were selected for the first step of scale-up. Over 10 days of spinner flask culture, HKB-11 and SK-Hep-1 cells showed a cumulative production of rFVII of 152 μg and 202.6 μg in 50 mL, respectively. Thus, these human cell lines can be used for an efficient production of recombinant FVII. With more investment in basic research, human cell lines can be optimized for the commercial production of different bio therapeutic proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Hansen, M B; Rønn, A M;

    1997-01-01

    The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

  20. Tratamiento de sangrado postoperatorio en cirugía cardiaca con Factor VII Recombinante

    OpenAIRE

    Burbano Paredes, Claudia C.; Rincón Riveros, Jose Domingo; Rincón Franco, Ismael

    2010-01-01

    El sangrado posterior a cirugía cardiaca es una complicación importante dada la alta morbimortalidad asociada. La hemotransfusión es la terapia mandatoria, pero la administración masiva de hemoderivados también es un factor de riesgo independiente de morbimortalidad. El factor VIIr se ha propuesto para disminuir las trasfusiones y controlar sangrado. El propósito de este estudio fue determinar si el factor VIIr es una herramienta útil para disminuir el consumo de hemoderivados en sangrado pos...

  1. Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome, Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher-Zweymüller syndrome, parietal foramina (cranium bifidum, Apert syndrome, craniomicromelic syndrome, XX-agonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

  2. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    plasma, in cold activated plasma and in FVII deficient plasma. There was a positive correlation (r=0.96) between FVII:Ag and FVII:Am with slightly but significantly higher values for FVII:Ag (FVII:Ag= 106 U/ml and FVII:Am=100 U/ml; p ... omitting the data from patients on oral anticoagulant therapy, with mean values of 113 U/ml for FVII:Ag and 110 U/ml for FVII:Am (p

  3. Impaired secretion of carboxyl-terminal truncated factor VII due to an F7 nonsense mutation associated with FVII deficiency.

    Science.gov (United States)

    Tanaka, Ryoko; Nakashima, Daisuke; Suzuki, Atsuo; Miyawaki, Yuhri; Fujimori, Yuta; Yamada, Takayuki; Takagi, Akira; Murate, Takashi; Yamamoto, Koji; Katsumi, Akira; Matsushita, Tadashi; Naoe, Tomoki; Kojima, Tetsuhito

    2010-03-01

    Factor VII (FVII) is a vitamin K-dependent glycoprotein secreted into the blood circulation from hepatic cells. We investigated the molecular basis of the congenital FVII deficiency found in a Japanese patient. We analyzed the F7 gene of the patient, who was diagnosed with a FVII deficiency at pregnancy. We expressed a carboxyl-terminal truncated FVII (Arg462X FVII) corresponding to the identified mutation in CHO-K1 cells. To study roles of the carboxyl-terminus in the secretion of FVII, we also expressed a series of recombinant FVIIs deleted of limited numbers of carboxyl-terminal amino acids (462Arg-466Pro). We identified a nonsense mutation (c.1384C>T: p.Arg462X) in F7, leading to a lack of five amino acids in the carboxyl-terminus. In expression experiments, Arg462X FVII was undetectable not only by Western blotting, but also by ELISA. A Western blot analysis of the truncated FVIIs revealed that all mutants were expressed in the cells the same as the wild type, but were secreted into the culture medium in lesser amounts than the wild type depending on the length of the deletion, which was confirmed by ELISA. Arg462X FVII did not colocalize with the Golgi on immunofluorescence staining, suggesting that it might be retained in the ER and degraded in the cell. The carboxyl-terminal amino acids of FVII play an important role in its secretion, and the p.Arg462X mutation was likely to have caused the FVII deficiency in this patient. (c) 2009 Elsevier Ltd. All rights reserved.

  4. Role of lysine and tryptophan residues in the biological activity of toxin VII (Ts gamma) from the scorpion Tityus serrulatus.

    Science.gov (United States)

    Hassani, O; Mansuelle, P; Cestèle, S; Bourdeaux, M; Rochat, H; Sampieri, F

    1999-02-01

    Toxin VII (TsVII), also known as Ts gamma, is the most potent neurotoxin in the venom of the Brazilian scorpion Tityus serrulatus. It has been purified to homogeneity using a new fast and efficient method. Chemical modification of TsVII with the tryptophan-specific reagent o-nitrophenylsulfenyl chloride yielded three modified derivatives (residues Trp39, Trp50 and Trp54). Acetylation of TsVII mostly generated the monoacetylated Lys12 derivative. No side reactions were detected, as indicated by endoproteinase Lys-C peptide mapping, Edman degradation and electrospray mass spectrometry. Circular dichroism and fluorimetric measurements showed that none of the chemical modifications altered the overall structure of the derivatives. The acetylation of Lys12 or the sulfenylation of Trp39 or Trp54 led to a loss of both toxicity in mice and apparent binding affinity for rat brain and cockroach synaptosomal preparations. Sulfenylation of Trp50, however, moderately affected the toxicity of TsVII in mice and had almost no effect on its binding properties. A 3-dimensional model of TsVII was constructed by homology modeling. It suggests that the most reactive residues (Lys12 and Trp39 and Trp54) are all important in the functional disruption of neuronal sodium channels by TsVII, and are close to each other in the hydrophobic conserved region.

  5. Expression of Recombinant Human Coagulation Factor VII by the Lizard Leishmania Expression System

    Directory of Open Access Journals (Sweden)

    Sina Mirzaahmadi

    2011-01-01

    Full Text Available The variety of recombinant protein expression systems have been developed as a resource of FVII gene expression. In the current study, the authors used a novel protein expression system based on the Iranian Lizard Leishmania, a trypanosomatid protozoan as a host for expression of FVII. Plasmid containing cDNA encoding full-length human FVII was introduced into Lizard Leishmania and positive transfectants were analyzed by SDS-PAGE and Western blot analysis. Furthermore, biological activity of purified protein was detected by PT assay. The recombinant strain harboring a construct was analyzed for expression of FVII at the mRNA and protein level. Purified rFVII was obtained and in order to confirm the purified compound was in fact rFVII. Western blot analysis was carried out. Clotting time in PT assay was reduced about 30 seconds with the purified rFVII. In Conclusion, this study has demonstrated, for the first time, that Leishmania cells can be used as an expression system for producing recombinant FVII.

  6. Mono- and di-halogenated histamine, histidine and carnosine derivatives are potent carbonic anhydrase I, II, VII, XII and XIV activators.

    Science.gov (United States)

    Saada, Mohamed-Chiheb; Vullo, Daniela; Montero, Jean-Louis; Scozzafava, Andrea; Supuran, Claudiu T; Winum, Jean-Yves

    2014-09-01

    Mono- and di-halogenated histamines, l-histidine methyl ester derivatives and carnosine derivatives incorporating chlorine, bromine and iodine were prepared and investigated as activators of five carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the transmembrane hCA XII and XIV. All of them were activated in a diverse manner by the investigated compounds, with a distinct activation profile.

  7. Roche tomography of cataclysmic variables - VII. The long-term magnetic activity of AE Aqr

    CERN Document Server

    Hill, C A; Steeghs, D; Dhillon, V S; Shahbaz, T

    2016-01-01

    We present a long-term study of the secondary star in the cataclysmic variable AE~Aqr, using Roche tomography to indirectly image starspots on the stellar surface spanning 8~years of observations. The 7 maps show an abundance of spot features at both high and low latitudes. We find that all maps have at least one large high-latitude spot region, and we discuss its complex evolution between maps, as well as its compatibility with current dynamo theories. Furthermore, we see the apparent growth in fractional spot coverage, $f_{\\mathrm{s}}$, around $45^{\\circ}$~latitude over the duration of observations, with a persistently high $f_{\\mathrm{s}}$ near latitudes of $20^{\\circ}$. These bands of spots may form as part of a magnetic activity cycle, with magnetic flux tubes emerging at different latitudes, similar to the `butterfly' diagram for the Sun. We discuss the nature of flux tube emergence in close binaries, as well as the activity of AE~Aqr in the context of other stars.

  8. Photometric properties for selected Algol-type binaries. VII. V404 and with magnetic activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Li-Yun; Pi, Qing-Feng; Zhu, Zhongzhong [College of Science/Department of Physics and NAOC-GZU Center for Astronomy, Guizhou University, Guiyang 550025 (China); Yang, Yuan-Gui, E-mail: liy_zhang@hotmail.com [School of Physics and Electronic Information, Huaibei Normal University, Huaibei 235000 Anhui Province (China)

    2014-03-01

    We present new CCD light curves of the short-period Algol-type eclipsing binary V404 And obtained in 2009-2011. The time-resolving multiple BVRI color light curves of the year 2011 with full phase coverage were analyzed simultaneously using the latest Wilson-Devinney program. We concluded that the configuration of two starspots on the primary is the most reliable explanation for the light curve distortions observed in 2011. Based on the new photometric solution, we further applied the spot model to explain the other light curves, including the previously published R-band light curves. We revealed that the starspots changed on a long timescale in terms of the spot parameters and the differences between Max. I and Max. II. Moreover, the O – C diagram spanning about 15 yr shows an upward parabola, which indicates a secular increase in the orbital period of V404 And. The orbital period increases at a rate of dP/dt = 5.3(0.3) × 10{sup –7} days yr{sup –1}, which might be interpreted by the angular momentum exchange via magnetic activity.

  9. Study of FK Comae Berenices: VII. Correlating photospheric and chromospheric activity

    CERN Document Server

    Vida, K; Ilyin, I V; Oláh, K; Andersen, M I; Hackman, T

    2015-01-01

    We study the connection between the chromospheric and photospheric behaviour of the active late-type star FK Comae. We use spot temperature modelling, light curve inversion based on narrow- and wide-band photometric measurements, Halpha observations from 1997-2010, and Doppler maps from 2004-2010 to compare the behaviour of chromospheric and photospheric features. Investigating low-resolution Halpha spectra we find that the changes in the chromosphere seem to happen mainly on a time scale longer than a few hours, but shorter variations were also observed. According to the Halpha measurements prominences are often found in the chromosphere that reach to more than a stellar radius and are stable for weeks, and which seem to be often, but not every time connected with dark photospheric spots. The rotational modulation of the Halpha emission seems to typically be anticorrelated with the light curve, but we did not find convincing evidence of a clear connection in the long-term trends of the Halpha emission and th...

  10. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity.

    Science.gov (United States)

    Jansen, Jan O; Scarpelini, Sandro; Pinto, Ruxandra; Tien, Homer C; Callum, Jeannie; Rizoli, Sandro B

    2011-11-01

    Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity--which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors

  11. PENGARUH MODEL ACTIVE LEARNING BERBANTUAN MEDIA FLASH TERHADAP PEMAHAMAN KONSEP DAN AKTIVITAS BELAJAR SISWA SMP KELAS VII PADA TEMA KALOR DAN PERPINDAHANNYA

    Directory of Open Access Journals (Sweden)

    Bagus Addin Hutomo

    2017-02-01

    Full Text Available Abstrak ____________________________________________________________________ Telah dilakukan penelitian yang bertujuan untuk mengetahui pengaruh model active learning berbantuan media flash terhadap pemahaman konsep dan aktivitas belajar siswa pada tema kalor dan perpindahannya. Jenis penelitian ini yaitu quasi experiment dengan desain non-equivalent control group design. Sampel diambil dengan teknik purposive sampling. Sampel dalam penelitian ini adalah kelas VII C (kelas eksperimen dan VII A (kelas kontrol SMPN 1 Ungaran. Data diambil dengan metode tes (pemahaman konsep dan observasi (aktivitas belajar siswa.Hasil penelitian menunjukkan bahwa rata-rata pemahaman konsep (posttest kelas eksperimen (87,22 lebih tinggi dari kelas kontrol (75,83. Besarnya rata-rata aktivitas belajar siswa kelas eksperimen (83,90 juga lebih besar daripada kelas kontrol (76,28. Berdasarkan hasil penelitian dapat disimpulkan model active learning berbantuan media flash pada tema kalor dan perpindahannya berpengaruh positif terhadap pemahaman konsep siswa sebesar 54,06 % dengan nilai koefisen korelasi sebesar 0,74 (kategori kuat dan berpengaruh positif terhadap aktivitas belajar siswa sebesar 85,54 % dengan nilai koefisen korelasi sebesar 0,92 (kategori sangat kuat.   Abstract Studies have been conducted to determine the effect of active learning model of flash media aided the understanding of concepts and learning activities of students on the theme of heat and displacement. This type of research is a quasi-experimental design with non-equivalent control group design. The sample was taken by purposive sampling technique. The sample in this research is class VII C (experimental class and VII A (control group SMPN 1 Ungaran. Data taken with test method (understanding of the concept and observation (student activity. The results showed that the average understanding of the concept (posttest experimental class (87.22 higher than the control class (75.83. The average size

  12. FAKTOR-FAKTOR YANG MEMENGARUHI PRODUKSI GULA PTPN VII (PERSERO

    Directory of Open Access Journals (Sweden)

    Rizky Savitri

    2014-09-01

    Full Text Available ABSTRACTThis study aimed to analyze the influence of the level of sugar cane yield, labor, production process period, and supporting materials on the production of PTPN VII (Persero PG. Cinta Manis, as well as analyzing the elasticity of production and business scale  of PTPN VII (Persero PG. Cinta Manis. The method used to analyze the data were quantitative analysis of Cobb Douglas production function with ordinary least square method to observe variable influences of PG. Cinta Manis sugar production. Cobb Douglas estimation results indicate that the level of sugar cane yield, labor, production process period, and supporting materials affect sugar production in PTPN VII (Persero PG. Cinta Manis. Production elasticity of each production factor shows that the use of production factors is not yet optimal, while the production scale of the company is Increasing Return to Scale (IRTS in which the proportion of additional input will produce output with the larger proportion. Accordingly, company should utilize the factors of production optimally, improve the quality of human resources with various activities to improve skills, increase the productivity of land by having land intensification, and optimize milling period by improving the quality of machine.Keywords: PG. Cinta Manis, increasing return to scale, Cobb Douglas function, PTPN VIIABSTRAKPenelitian ini bertujuan menganalisis pengaruh tingkat rendemen, tenaga kerja, bahan pembantu dan lama lama giling terhadap produksi gula PTPN VII (Persero PG. Cinta Manis, sekaligus menganalisis elastisitas produksi dan skala usaha PTPN VII (Persero PG. Cinta Manis. Metode analisis data yang digunakan adalah  analisis kuantitatif. Analisis kuantitatif pada penelitian ini menggunakan fungsi produksi cobb douglas dengan metode ordinary least square untuk melihat pengaruh variabel-variabel yang telah ditentukan terhadap produksi gula PG. Cinta Manis. Hasil estimasi cobb douglas menunjukkan  bahwa tingkat

  13. Fokker D.VII

    Science.gov (United States)

    1923-01-01

    Fokker D.VII: The Fokker D.VII was one of the best fighter aircraft of World War I, and was the only weapon used by the Central Powers specifically mentioned in the Versailles Treaty. The Central Powers surrendered 142 at the close of the war, and the Fokker company sold even more to the U. S. Air Service. Several were flown at Langley Field, but this one was the sole example operated by the NACA.

  14. Lethal factor VII deficiency due to novel mutations in the F7 promoter: functional analysis reveals disruption of HNF4 binding site.

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Lopez, Estelle; Viart, Victoria; Chafa, Ouerdia; Tapon-Bretaudière, Jacqueline; Claustres, Mireille; Taulan, Magali

    2012-08-01

    Hereditary factor VII (FVII) deficiency is a rare autosomal recessive disorder. Deleterious mutations that prevent the synthesis of any amount of functional FVII have been associated with life-threatening haemorrhage in neonates. Here we report two infants, of Maghrebian origin, who suffered a fatal spontaneous cerebral haemorrhage. Investigation of the molecular basis for their severe FVII deficiency revealed novel mutations in a homozygous state within the F7 gene promoter: a single nucleotide substitution (c.-65G>C) and a 2bp deletion (c.-60_-59delTT). To determine whether these promoter variants were responsible for the FVII deficiency, computer-assisted sequence analyses were performed. The data predicted a disrupted binding of both HNF4 and COUP-TF transcription factors with each variant. Concordantly, experimental results revealed an altered HNF4-induced transactivation in the promoter mutated variants. The execution of functional tests is critical to ensuring a complete understanding of the effect of any promoter mutant on FVII deficiency. Only then can an accurate molecular diagnosis be made and further genetic counselling and prenatal diagnosis be offered.

  15. Activation of cerebellar lobules VI-VII during motor imagery but not during motor activation in unilateral cerebellar hypoplasia.

    Science.gov (United States)

    Habas, Christophe; Manto, Mario

    2014-01-01

    We report the case of a 25 year-old patient who underwent morphological and functional brain magnetic resonance imaging (fMRI) to investigate a left neocerebellar hypoplasia discovered incidentally. We compared brain activation during overt and covert finger movements, and haptic discrimination. The contralateral cerebellar hemisphere compensated for mental imagery of hand movements and haptic discrimination, but not for motor execution. Moreover, the resting-state functional connectivity did not show compensatory functional coherence between the right cerebellum and cerebral areas connected with the hypoplastic cerebellum. Our case illustrates for the first time that cerebellar compensatory recruitment is an active, specific process related to task complexity and under the control of executive networks.

  16. F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study.

    Science.gov (United States)

    Quintavalle, Gabriele; Riccardi, Federica; Rivolta, Gianna Franca; Martorana, Davide; Di Perna, Caterina; Percesepe, Antonio; Tagliaferri, Annarita

    2017-08-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:CF7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:CF7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi(2)=43.709, pF7 genotypic groups (Chi(2)=72.289, pF7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

  17. Characterisation of a large complex intragenic re-arrangement in the FVII gene (F7) avoiding misdiagnosis in inherited factor VII deficiency.

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Thorel, Delphine; Khau Van Kien, Philippe; Behar, Catherine; Romey, Marie-Catherine; Mugneret, Francine; Schved, Jean-François; Claustres, Mireille

    2007-08-01

    Inherited factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder mostly caused by point mutations. Large genomic re-arrangements at F7 locus could account for a fraction of mutant alleles that remain unidentified after DNA sequencing, because they escape conventional polymerase chain reaction (PCR)-based techniques. We report the first systematic screening of F7 for large re-arrangements, by semi-quantitative multiplex PCR of fluorescent fragments targeting the 9 exons and the promoter region. A well-characterised cohort of 43 unrelated patients either apparently homozygous for a F7 point mutation or carrying at least one unidentified F7 mutant allele participated in this study. Two large F7 re-arrangements were identified in two FVII-deficient pedigrees, including a discontinuous deletion involving two distinct portions of F7 whose proximal and distal end junctions were characterised. A simple and efficient method for the routine detection of gross alterations of F7, which accounted for 2.3% of mutant alleles in our sample, is now available in inherited FVII deficiency. This test should complement conventional PCR-based techniques not only in unsolved cases, but also where inheritance pattern analysis is not achievable.

  18. Dietary changes in fasting levels of factor VII coagulant activity (FVII:C) are accompanied by changes in factor VII protein and other vitamin K-dependent proteins

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Tholstrup, T; Marckmann, P

    1995-01-01

    each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1 + 2. FVII:C was significantly reduced on diet S compared with diet ML. This was accompanied...... by a decrease in FVII protein, F1 + 2 and the vitamin K-dependent proteins FII, FX, and protein C. In contrast, no changes were observed in triglycerides, FVII:C/FVII:Ag, albumin and CRP. Fibrinogen was increased on diet S compared with diet ML. Our findings suggest that the change in fasting FVII:C was part...... of a general change in concentrations of vitamin K-dependent proteins. Udgivelsesdato: 1995-Feb...

  19. Preface: STATPHYS-Kolkata VII

    Science.gov (United States)

    Bhattacharjee, Jayanta Kumar; Chakrabarti, Bikas K.; Inoue, Jun-Ichi; Sen, Parongama

    2011-04-01

    In the past two decades, a series of international conferences on Statistical Physics, going by the name Statphys Kolkata, have been organized in Kolkata (previously Calcutta) at roughly three-year intervals, the first one being held in 1992-93. The seventh of this series, Statphys Kolkata VII (http://www.saha.ac.in/cmp/stat.vii/index.php) was held from 26-30 November 2010. This meeting was organized as part of the Silver Jubilee Celebration of the Satyendra Nath Bose National Centre for Basic Sciences, Kolkata, in collaboration with the Saha Institute of Nuclear Physics, Kolkata. In Statphys Kolkata VII, a few topics of current interest such as Collective behavior and emergent phenomena, Systems far from equilibrium, Soft matter, and Quantum critical phenomena were given special emphasis, while various other issues of Statistical Physics were also addressed. We were happy to note that the conference attracted a large number of participants, and the talk and poster sessions generated a lot of discussions, arguments and collaborations. The articles appearing in this proceedings are based on the invited talks and selected poster presentations. We would like to thank the Journal of Physics Conference Series, IOP, for publishing the proceedings of the conference, and the referees for their prompt and active support. The proceedings of the earlier Statphys Kolkata conferences have appeared in Physica A, vol 384 (2007); Physica A, vol 346 (2005); Physica A, vol 318 (2003); Physica A, vol 270 (1999); Physica A, vol 224 (1996); and Physica A, vol 186 (1992). We would like to take this opportunity to thank all the members of the organizing committee (especially Dr Anjan Kumar Chandra for extensive all-round help), and acknowledge the Centre for Applied Mathematics and Computational Science (CAMCS, Saha Institute of Nuclear Physics, Kolkata) and Satyendra Nath Bose National Centre for Basic Sciences, Kolkata, for their financial support. Jayanta Kumar Bhattacharjee, Bikas K

  20. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Mayer, Stephan A; Brun, Nikolai C; Begtrup, Kamilla;

    2008-01-01

    patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability...... or death according to the modified Rankin scale 90 days after the stroke. RESULTS: Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26......% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P

  1. A high fat meal activates blood coagulation factor VII in rats

    DEFF Research Database (Denmark)

    Olsen, Aage K; Bladbjerg, Else M; Hansen, Axel K

    2002-01-01

    the LEW/Mol rat. We gavaged 3 mL of a fat emulsion (n = 42) or 3 mL isotonic glucose (n = 42). Blood was sampled by heart puncture 2, 4 and 6 h (n = 14/group at each time) after the fat/glucose load. Furthermore, blood was sampled from 16 untreated rats to determine the baseline levels. Triglyceride...

  2. Factor VII-activating protease: Mechanism and regulation of nucleosome release from dead cells

    NARCIS (Netherlands)

    F. Stephan

    2014-01-01

    Cell death is indispensable for tissue homeostasis and is a fundamental principle of inflammation and lymphocyte generation. Rapid removal and destruction of cellular corpses is critical and insufficient removal may lead to the release of cellular content into the environment. These immunogenic "hos

  3. Absence of in vitro Procoagulant Activity in Immunoglobulin Preparations due to Activated Coagulation Factors

    Science.gov (United States)

    Oviedo, Adriana E.; Bernardi, María E.; Guglielmone, Hugo A.; Vitali, María S.

    2015-01-01

    Summary Background Immunoglobulin (IG) products, including intravenous (IVIG) or subcutaneous (SCIG) immunoglobulins are considered safe and effective for medical therapy; however, a sudden and unexpected increase in thromboembolic events (TE) after administration of certain batches of IVIG products has been attributed to the presence of activated coagulation factors, mainly factor XIa. Our aims were to examine the presence of enduring procoagulant activity during the manufacturing process of IGs, with special focus on monitoring factor XIa, and to evaluate the presence of in vitro procoagulant activity attributed to coagulation factors in different lots of IVIG and SCIG. Methods Samples of different steps of IG purification, 19 lots of IVIG and 9 of SCIG were analyzed and compared with 1 commercial preparation of IVIG and 2 of SCIG, respectively. Factors II, VII, IX, XI and XIa and non-activated partial thromboplastin time (NAPTT) were assayed. Results The levels of factors II, VII, IX, X and XI were non-quantifiable once fraction II had been re-dissolved and in all analyzed lots of IVIG and SCIG. The level of factor XIa at that point was under the detection limits of the assay, and NAPTT yielded values greater than the control during the purification process. In SCIG, we detected higher concentrations of factor XIa in the commercial products, which reached values up to 5 times higher than the average amounts found in the 9 batches produced by UNC-Hemoderivados. Factor XIa in commercial IVIG reached levels slightly higher than those of the 19 batches produced by UNC-Hemoderivados. Conclusion IVIG and SCIG manufactured by UNC-Hemoderivados showed a lack of thrombogenic potential, as demonstrated not only by the laboratory data obtained in this study but also by the absence of any reports of TE registered by the post marketing pharmacovigilance department. PMID:26733772

  4. [Study of the polymorphism R353Q in the coagulation factor VII gene and the N700S in the thrombospondin-1 gene in young patients with acute myocardial infarction].

    Science.gov (United States)

    Valades-Mejía, María Guadalupe; Domínguez-López, María Lilia; Aceves-Chimal, José Luis; Miranda, Alfredo Leaños; Majluf-Cruz, Abraham; Isordia-Salas, Irma

    2014-01-01

    Antecedentes: el infarto agudo de miocardio es la principal causa de morbilidad y mortalidad en el mundo, y resulta de la combinación de factores modificables y genéticos. Se ha propuesto que el polimorfismo R353Q en el gen del factor VII de la coagulación representa un factor protector en contra del infarto agudo de miocardio, mientras que el polimorfismo N700S en el gen de la trombospondina-1 (TSP- 1) incrementa el riesgo; sin embargo, los resultados aún suscitan controversia. Objetivo: determinar la posible asociación de los polimorfismos R353Q y del N700S con el infarto agudo de miocardio en pacientes mexicanos menores de 45 años. Material y métodos: estudio de casos y controles que incluyó 252 pacientes con diagnóstico de infarto agudo de miocardio y 252 individuos aparentemente sanos sin antecedentes de enfermedad coronaria, pareados por edad y sexo. Los polimorfismos R353Q N700S se determinaron en todos los participantes por medio de PCR-RFLP. Resultados: no se observó diferencia estadística en la distribución genotípica del polimorfismo R353Q del FVII entre los grupos con infarto agudo de miocardio y el grupo control (p = 0.06). Se encontró una distribución genotípica similar del polimorfismo N700S en ambos grupos (p = 0.50). Se identificaron como factores de riesgo independiente para infarto agudo de miocardio: hipertensión arterial, diabetes mellitus, antecedentes heredofamiliares para enfermedad coronaria y dislipidemia. Conclusiones: los polimorfismos R353Q y N700S no representan un factor protector o de riesgo, respectivamente, para infarto agudo de miocardio en pacientes jóvenes mexicanos. Palabras clave: factor VII de la coagulación, trombospondina-1, infarto agudo de miocardio, polimorfismo.

  5. Intelsat VII planning and evolution

    Science.gov (United States)

    Nadkarni, P.; Neyret, P.; Allnutt, J.; Chidambaram, T.

    This paper describes the evolution of the Intelsat VII concept from among a number of spacecraft concepts considered in the planning process. The considerations of greatest importance in this evolution are examined, including the compatibility with small earth stations, available digital services and circuit multiplication techniques, schedule considerations, launch vehicle considerations, and operational flexibility. The roles of demand analysis and of architecture selection in the development of the Intelsat VII concept are addressed.

  6. Result of Rendezvous Docking Experiment of ETS.35zw .5zw .25mmVII

    Science.gov (United States)

    Kawano, Isao; Mokuno, Masaaki; Suzuki, Takashi; Koyama, Hiroshi; Kunugi, Makoto

    ETS VII is a test satellite to perform in-orbit demonstration of autonomous rendezvous docking (RVD) technology, which will be necessary for advanced space activities in the early 21st century. ETS VII performed three RVD experiment flights, and verified all technical items. ETS VII demonstrated first autonomous RVD between unmanned vehicles, and remote piloted rendezvous flight position accuracy at docking was about 1cm, and acceleration was less than 1.5mG (low impact docking). In the second RVD experiment flight, ETS VII detected attitude anomaly and executed disable abort for safety insurance. We present the results and evaluation of three RVD experiment flights in this paper.

  7. Ajateenistust alustab ka viis neidu

    Index Scriptorium Estoniae

    2013-01-01

    Tuleval nädalal alustab ajateenistust üle 1600 noormehe, lisaks alustab juulis Kuperjanovi jala­väepataljonis vabatahtlikuna ajateenistust ka viis neidu. Juulikuise teenistusse kutsumisega alustavad teenistust ajateenijad, kelle ametikoht eeldab 11-kuulist ajateenistust ehk autojuhid, erialaspet­sialistid, allohvitserid ja reservrühmaülemad

  8. Positivity VII (Zaanen Centennial Conference)

    CERN Document Server

    Pagter, Ben; Gaans, Onno; Veraar, Mark

    2016-01-01

    This book presents the proceedings of Positivity VII, held from 22-26 July 2013, in Leiden, the Netherlands. Positivity is the mathematical field concerned with ordered structures and their applications in the broadest sense of the word. A biyearly series of conferences is devoted to presenting the latest developments in this lively and growing discipline. The lectures at the conference covered a broad spectrum of topics, ranging from order-theoretic approaches to stochastic processes, positive solutions of evolution equations and positive operators on vector lattices, to order structures in the context of algebras of operators on Hilbert spaces. The contributions in the book reflect this variety and appeal to university researchers in functional analysis, operator theory, measure and integration theory and operator algebras. Positivity VII was also the Zaanen Centennial Conference to mark the 100th birth year of Adriaan Cornelis Zaanen, who held the chair of Analysis in Leiden for more than 25 years and was ...

  9. Adenovirus Core Protein pVII Is Translocated into the Nucleus by Multiple Import Receptor Pathways†

    Science.gov (United States)

    Wodrich, Harald; Cassany, Aurelia; D'Angelo, Maximiliano A.; Guan, Tinglu; Nemerow, Glen; Gerace, Larry

    2006-01-01

    Adenoviruses are nonenveloped viruses with an ∼36-kb double-stranded DNA genome that replicate in the nucleus. Protein VII, an abundant structural component of the adenovirus core that is strongly associated with adenovirus DNA, is imported into the nucleus contemporaneously with the adenovirus genome shortly after virus infection and may promote DNA import. In this study, we evaluated whether protein VII uses specific receptor-mediated mechanisms for import into the nucleus. We found that it contains potent nuclear localization signal (NLS) activity by transfection of cultured cells with protein VII fusion constructs and by microinjection of cells with recombinant protein VII fusions. We identified three NLS-containing regions in protein VII by deletion mapping and determined important NLS residues by site-specific mutagenesis. We found that recombinant protein VII and its NLS-containing domains strongly and specifically bind to importin α, importin β, importin 7, and transportin, which are among the most abundant cellular nuclear import receptors. Moreover, these receptors can mediate the nuclear import of protein VII fusions in vitro in permeabilized cells. Considered together, these data support the hypothesis that protein VII is a major NLS-containing adaptor for receptor-mediated import of adenovirus DNA and that multiple import pathways are utilized to promote efficient nuclear entry of the viral genome. PMID:16973564

  10. Adenovirus core protein pVII is translocated into the nucleus by multiple import receptor pathways.

    Science.gov (United States)

    Wodrich, Harald; Cassany, Aurelia; D'Angelo, Maximiliano A; Guan, Tinglu; Nemerow, Glen; Gerace, Larry

    2006-10-01

    Adenoviruses are nonenveloped viruses with an approximately 36-kb double-stranded DNA genome that replicate in the nucleus. Protein VII, an abundant structural component of the adenovirus core that is strongly associated with adenovirus DNA, is imported into the nucleus contemporaneously with the adenovirus genome shortly after virus infection and may promote DNA import. In this study, we evaluated whether protein VII uses specific receptor-mediated mechanisms for import into the nucleus. We found that it contains potent nuclear localization signal (NLS) activity by transfection of cultured cells with protein VII fusion constructs and by microinjection of cells with recombinant protein VII fusions. We identified three NLS-containing regions in protein VII by deletion mapping and determined important NLS residues by site-specific mutagenesis. We found that recombinant protein VII and its NLS-containing domains strongly and specifically bind to importin alpha, importin beta, importin 7, and transportin, which are among the most abundant cellular nuclear import receptors. Moreover, these receptors can mediate the nuclear import of protein VII fusions in vitro in permeabilized cells. Considered together, these data support the hypothesis that protein VII is a major NLS-containing adaptor for receptor-mediated import of adenovirus DNA and that multiple import pathways are utilized to promote efficient nuclear entry of the viral genome.

  11. Identification of two conserved aspartic acid residues required for DNA digestion by a novel thermophilic Exonuclease VII in Thermotoga maritima

    Science.gov (United States)

    Larrea, Andres A.; Pedroso, Ilene M.; Malhotra, Arun; Myers, Richard S.

    2008-01-01

    Exonuclease VII was first identified in 1974 as a DNA exonuclease that did not require any divalent cations for activity. Indeed, Escherichia coli ExoVII was identified in partially purified extracts in the presence of EDTA. ExoVII is comprised of two subunits (XseA and XseB) that are highly conserved and present in most sequenced prokaryotic genomes, but are not seen in eukaryotes. To better understand this exonuclease family, we have characterized an ExoVII homolog from Thermotoga maritima. Thermotoga maritima XseA/B homologs TM1768 and TM1769 were co-expressed and purified, and show robust nuclease activity at 80°C. This activity is magnesium dependent and is inhibited by phosphate ions, which distinguish it from E. coli ExoVII. Nevertheless, both E. coli and T. maritima ExoVII share a similar putative active site motif with two conserved aspartate residues in the large (XseA/TM1768) subunit. We show that these residues, Asp235 and Asp240, are essential for the nuclease activity of T. maritima ExoVII. We hypothesize that the ExoVII family of nucleases can be sub-divided into two sub-families based on EDTA resistance and that T. maritima ExoVII is the first member of the branch that is characterized by EDTA sensitivity and inhibition by phosphate. PMID:18812402

  12. Psychosocial factors underlying physical activity

    Directory of Open Access Journals (Sweden)

    Ji Cheng-Ye

    2007-09-01

    of physical activity on academic achievement and other factors beyond physical health; barriers of not having enough time and having too many assignments perceived to hinder frequent physical activity; and parental approval. More rigorous research on psychosocial determinants with close-ended items developed from these open-ended data and with larger sample sizes of students is necessary. Research with parents and school staff will be needed to understand the perceptions of these stakeholder groups key to creating the students' social environment.

  13. An effective treatment of severe intractable bleeding after valve repair by one single dose of activated recombinant factor VII

    NARCIS (Netherlands)

    Hendriks, HGD; van der Maaten, JMAA; de Wolf, J; Slooff, MJH; van der Meer, J; Waterbolk, T

    Excessive bleeding (>2 L) after cardiac surgery is encountered in 3% to 7% of patients (1), and necessitates reexploration in 3.6% (2) to 4.2% (3) of cases. A variety of hemostatic defects may contribute and are probably induced by cardiopulmonary bypass (CPB), i.e., impaired platelet function,

  14. The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade.

    Science.gov (United States)

    Xing, Elizabeth M; Knox, Van W; O'Donnell, Patricia A; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

    2013-06-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term.

  15. Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han pulation

    Indian Academy of Sciences (India)

    YI ZENG; LE ZHANG; ZHIPING HU; QIDONG YANG; MINGMING MA; BAOQIONG LIU; JIAN XIA; HONGWEI XU; YUNHA I LIU; XIAOPING DU

    2016-06-01

    Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linkedfunction and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genesare associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphismsfor CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 andrs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case–control study andin a family-based association study. Case–control analysis found no evidence of significant association. But family-basedassociation study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the ‘G’ allele of PZ rs2273971:haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z =1.882,P =0.049;Z =1.922,P =0.044; Z =1.826,P =0.047; Z =1.977,P =0.048, respectively). While, the A allele of PZ rs2273971, andfour haplotypes carrying or crossing the ‘A’ allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ andFVII genes, may confer protection against CH (Z =−1.882,P =0.049; Z =−2.000,P =0.045; Z =−2.319,P =0.020;Z =−2.002,P =0.045; Z =−2.015,P =0.043, respectively). This is a first family-based association study providing geneticevidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.

  16. Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case-control and a family-based association study in a Chinese Han population.

    Science.gov (United States)

    Zeng, Yi; Zhang, Le; Hu, Zhiping; Yang, Qidong; Ma, Mingming; Liu, Baoqiong; Xia, Jian; Xu, Hongwei; Liu, Yunhai; Du, Xiaoping

    2016-06-01

    Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case-control study and in a family-based association study. Case-control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the 'G' allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the 'A' allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z= -1.882, P = 0.049; Z= -2.000, P = 0.045; Z= -2.319, P = 0.020; Z= -2.002, P = 0.045; Z= -2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.

  17. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  18. The effects of long-term malathion or diazinon ingestion on the activity of hepatic synthesized clotting factors.

    Science.gov (United States)

    Lox, C D; Davis, J R

    1983-12-01

    Female Sprague-Dawley rats were placed on a drinking solution of 1 ppm Diazinon or malathion dissolved in water for 6 months. At the conclusion of the experiment liver tissue and plasma were examined. Clotting studies included the prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen, and factors II, V, VII, X, plus the platelet count. Hepatic morphology, basically hepatocyte degeneration, was altered by malathion while diazinon had no notable effect. Likewise, malathion prolonged both the PT and APTT, the only changes in clotting activity.

  19. Silence of Synaptotagmin VII inhibits release of dense core vesicles in PC12 cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Synaptotagmin VII (Syt VII), which has a higher Ca2+ affinity and slower disassembly kinetics with lipid than Syt I and Syt IX, was regarded as being uninvolved in synaptic vesicle (SV) exocytosis but instead possibly as a calcium sensor for the slower kinetic phase of dense core vesicles (DCVs) release. By using high temporal resolution capacitance and amperometry measurements, it was demonstrated that the knockdown of endogenous Syt VII attenuated the fusion of DCV with the plasma membrane, reduced the amplitude of the exocytotic burst of the Ca2+-triggered DCV release without affecting the slope of the sustained component, and blocked the fusion pore expansion. This suggests that Syt VII is the Ca2+ sensor of DCV fusion machinery and is an essential factor for the establishment and maintenance of the pool size of releasable DCVs in PC12 cells.

  20. Genetics Home Reference: mucopolysaccharidosis type VII

    Science.gov (United States)

    ... becomes cloudy, which can cause significant vision loss. People with MPS VII may also have recurrent ear infections and hearing loss. Affected individuals may have developmental delay and progressive intellectual disability, although intelligence is unaffected in some people with ...

  1. Activity factors of the Korean exposure factors handbook.

    Science.gov (United States)

    Jang, Jae-Yeon; Jo, Soo-Nam; Kim, So-Yeon; Lee, Kyung-Eun; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Exposure factors based on the Korean population are required for making appropriate risk assessment. It is expected that handbooks for exposure factors will be applied in many fields, as well as by health department risk assessors. The present article describes the development of an exposure factors handbook that specifically focuses on human activities in situations involving the possible risk of exposure to environmental contaminants. We define majour exposure factors that represent behavioral patterns for risk assessment, including time spent on routine activities, in different places, on using transportation, and engaged in activities related to water contact including swimming, bathing and washing. Duration of residence and employment are also defined. National survey data were used to identify recommended levels of exposure factors in terms of time spent on routine activities and period of residence and employment. An online survey was conducted with 2073 subjects who were selected using a stratified random sampling method in order to develop a list of exposure factors for the time spent in different places and in performing water-related activities. We provide the statistical distribution of the variables, and report reference levels of average exposure based on the reliable data in our exposure factors handbook.

  2. Coagulation factor VIII activity in diabetic patients

    Directory of Open Access Journals (Sweden)

    Nermina Babić

    2011-02-01

    Full Text Available Aim To examine coagulation factor VIII activity in plasma, as a risk factor for thrombosis, in the patients with diabetes mellitus (DM. Also, to assess its relationship with ibrinogen and fasting blood glucose concentrations and with body mass index. Methods The plasma coagulation factor VIII activity, plasma levels of ibrinogen and blood glucose concentrations were measured in 30 patients with DM type 1, 30 patients with DM type 2 and in 30 healthy subjects. Body weight and body height were also measured and BMI was calculated.Results The plasma factor VIII activity in patients with DM type 1 and patients with DM type 2 was signiicantly higher than the values measured in healthy subjects. There was no signiicant difference in the factor VIII activity between patients with DM type 1 and type 2. The concentrations of ibrinogen and blood glucose in both groups of patients were signiicantly higher than in the group of healthy subjects. Patients with DM type 2 had a signiicantly higher BMI compared to healthy subjects, as well as compared to patients with DM type 1. There was a signiicant positive correlation between plasma factor VIII activity and plasma level of ibrinogen and a signiicant negative correlation between factor VIII activity and BMI in patients with DM type 2. Conclusion Diabetic patients have the elevated plasma coagulation factor VIII activity and increased ibrinogen concentration thus an increased risk of thrombosis and vascular diseases.

  3. Extraction of Tc(VII) and Re(VII) on TRU resin

    Energy Technology Data Exchange (ETDEWEB)

    Guerin, Nicolas; Riopel, Remi; Kramer-Tremblay, Sheila [Canadian Nuclear Laboratories (CNL), Chalk River, ON (Canada). Radiobiology and Health Branch; De Silva, Nimal; Cornett, Jack [Ottawa Univ., ON (Canada). Dept. of Earth and Environmental Sciences; Dai, Xiongxin [China Institute for Radiation Protection, Beijing (China)

    2017-06-01

    TRU resin can be used to rapidly and selectively extract Tc(VII) and Re(VII). The retention capacity curves of Tc(VII) and Re(VII) for HNO{sub 3}, HCl, H{sub 2}SO{sub 4} and H{sub 3}PO{sub 4} solutions were studied and prepared. Tc(VII) and Re(VII) were simultaneously extracted in 2 M H{sub 2}SO{sub 4} and 1.5 M H{sub 3}PO{sub 4} and were effectively separated from Mo(VI) and Ru(III). Tc(VII) and Re(VII) remained strongly bonded to the resin even after washing using a large volume of 2 M H{sub 2}SO{sub 4} at a relatively high flow rate. Also, they were both completely eluted from the resin using 15 mL of near boiling water, an eluent directly compatible for ICP-MS instrument measurements.

  4. Biological and analytical variations of 16 parameters related to coagulation screening tests and the activity of coagulation factors.

    Science.gov (United States)

    Chen, Qian; Shou, Weiling; Wu, Wei; Guo, Ye; Zhang, Yujuan; Huang, Chunmei; Cui, Wei

    2015-04-01

    To accurately estimate longitudinal changes in individuals, it is important to take into consideration the biological variability of the measurement. The few studies available on the biological variations of coagulation parameters are mostly outdated. We confirmed the published results using modern, fully automated methods. Furthermore, we added data for additional coagulation parameters. At 8:00 am, 12:00 pm, and 4:00 pm on days 1, 3, and 5, venous blood was collected from 31 healthy volunteers. A total of 16 parameters related to coagulation screening tests as well as the activity of coagulation factors were analyzed; these included prothrombin time, fibrinogen (Fbg), activated partial thromboplastin time, thrombin time, international normalized ratio, prothrombin time activity, activated partial thromboplastin time ratio, fibrin(-ogen) degradation products, as well as the activity of factor II, factor V, factor VII, factor VIII, factor IX, and factor X. All intraindividual coefficients of variation (CVI) values for the parameters of the screening tests (except Fbg) were less than 5%. Conversely, the CVI values for the activity of coagulation factors were all greater than 5%. In addition, we calculated the reference change value to determine whether a significant difference exists between two test results from the same individual.

  5. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  6. Purification and characterization of adenovirus core protein VII: a histone-like protein that is critical for adenovirus core formation.

    Science.gov (United States)

    Sharma, Gaurav; Moria, Nithesh; Williams, Martin; Krishnarjuna, Bankala; Pouton, Colin W

    2017-07-01

    Adenovirus protein VII is a highly cationic core protein that forms a nucleosome-like structure in the adenovirus core by condensing DNA in combination with protein V and mu. It has been proposed that protein VII could condense DNA in a manner analogous to mammalian histones. Due to the lack of an expression and purification protocol, the interactions between protein VII and DNA are poorly understood. In this study we describe methods for the purification of biologically active recombinant protein VII using an E. coli expression system. We expressed a cleavable fusion of protein VII with thioredoxin and established methods for purification of this fusion protein in denatured form. We describe an efficient method for resolving the cleavage products to obtain pure protein VII using hydroxyapatite column chromatography. Mass spectroscopy data confirmed its mass and purity to be 19.4 kDa and >98 %, respectively. Purified recombinant protein VII spontaneously condensed dsDNA to form particles, as shown by dye exclusion assay, electrophoretic mobility shift assay and nuclease protection assay. Additionally, an in vitro bioluminescence assay revealed that protein VII can be used to enhance the transfection of mammalian cells with lipofectamine/DNA complexes. The availability of recombinant protein VII will facilitate future studies of the structure of the adenovirus core. Improved understanding of the structure and function of protein VII will be valuable in elucidating the mechanism of adenoviral DNA condensation, defining the morphology of the adenovirus core and establishing the mechanism by which adenoviral DNA enters the nucleus.

  7. The GAPS programme with HARPS-N at TNG. VII. Putting exoplanets in the stellar context: magnetic activity and asteroseismology of τ Bootis A

    Science.gov (United States)

    Borsa, F.; Scandariato, G.; Rainer, M.; Bignamini, A.; Maggio, A.; Poretti, E.; Lanza, A. F.; Di Mauro, M. P.; Benatti, S.; Biazzo, K.; Bonomo, A. S.; Damasso, M.; Esposito, M.; Gratton, R.; Affer, L.; Barbieri, M.; Boccato, C.; Claudi, R. U.; Cosentino, R.; Covino, E.; Desidera, S.; Fiorenzano, A. F. M.; Gandolfi, D.; Harutyunyan, A.; Maldonado, J.; Micela, G.; Molaro, P.; Molinari, E.; Pagano, I.; Pillitteri, I.; Piotto, G.; Shkolnik, E.; Silvotti, R.; Smareglia, R.; Southworth, J.; Sozzetti, A.; Stelzer, B.

    2015-06-01

    Aims: We observed the τ Boo system with the HARPS-N spectrograph to test a new observational strategy aimed at jointly studying asteroseismology, the planetary orbit, and star-planet magnetic interaction. Methods: We collected high-cadence observations on 11 nearly consecutive nights and for each night averaged the raw FITS files using a dedicated software. In this way we obtained spectra with a high signal-to-noise ratio, used to study the variation of the Ca ii H&K lines and to have radial velocity values free from stellar oscillations, without losing the oscillations information. We developed a dedicated software to build a new custom mask that we used to refine the radial velocity determination with the HARPS-N pipeline and perform the spectroscopic analysis. Results: We updated the planetary ephemeris and showed the acceleration caused by the stellar binary companion. Our results on the stellar activity variation suggest the presence of a high-latitude plage during the time span of our observations. The correlation between the chromospheric activity and the planetary orbital phase remains unclear. Solar-like oscillations are detected in the radial velocity time series: we estimated asteroseismic quantities and found that they agree well with theoretical predictions. Our stellar model yields an age of 0.9 ± 0.5 Gyr for τ Boo and further constrains the value of the stellar mass to 1.38 ± 0.05 M⊙. Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated on the island of La Palma by the Fundacion Galileo Galilei of the INAF at the Spanish Observatorio Roque de los Muchachos of the IAC in the frame of the program Global Architecture of the Planetary Systems (GAPS).Full Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/578/A64

  8. European Energy Law. Report VII

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, U.; Roggenkamp, M.M. (eds.)

    2010-04-15

    The European Energy Law Report VII presents in four parts an overview of the most important legal developments in the field of EU and national energy and climate change law as discussed at the 2009 European Energy Law Seminar. The first part examines recent developments in EU climate change regulation. It includes an overview of the revision of the EU Directive governing CO2 emissions trading and a more detailed analysis of the new allocation regime, including the auctioning of emission rights. This is followed by an analysis of the competitiveness of the new EU emissions trading Directive and recent developments in the US regarding emissions trading. The second part focuses on the energy liberalisation process and the Third Energy Package. Following an overview of recent developments in EU competition law and the impact of the Sector Inquiry on the energy sector, this part concentrates particularly on the new Internal Energy Market Directives and most particularly on the legality of the unbundling provisions. Subsequently, the focus is on the role of the TSOs. After an analysis of the need for an increased cooperation of the German TSOs, another chapter discusses the need for more consolidation in the European gas transmission market and the role of regulation therein. Is there a new role for nuclear energy? In order to secure long term energy supply, the focus turns again to nuclear energy. The third part of this report discusses two elements of nuclear liability. First, it analyses the issue of the possible privatisation of the nuclear sector and its impact on long term liability. Although the focus is on the UK nuclear sector, a comparison is made with some other regulatory regimes. Next, the role of nuclear energy is discussed as an instrument to reduce CO2 emissions and, more particularly as a means to reach the 20-20-20 targets. The question is raised whether the international rules on civil liability provide sufficient protection to victims of nuclear

  9. [Entomology of onchocerciasis in Soconusco, Chiapas, México. VII. Quantitative variations in the transmission of Onchocerca volvulus (Nematoda: Filaroiidea) according to human activity space].

    Science.gov (United States)

    Ortega Gutiérrez, M; Ramírez, A; Miranda, R

    1991-01-01

    In this research we tried to demonstrate differences in transmission intensities of onchocerciasis by Simulium ochraceum in the community of Golondrinas, Municipality of Acacoyagua in the Soconusco area of the state of Chiapas. Adult females of this species were captured in the center of the villages, the coffee plantation, and the corn bean planted plots, during 7 to 10 consecutive days of the months of June, August, November and December of 1983, and January, March, and May of 1984. Captures were made from 7:00 to 11:00 h, by two persons (a human bait and a collector) in each of the mentioned areas. Variations in densities of S. ochraceum were not statistically significant among the different areas, although there was a predominance in the center of the villages during all the time periods. There was not a statistical significance in the number of oviparous females, although again the center of 50 villages showed the highest percentages (43.5%), as compared to the coffee plantation (37.8%), and the corn-bean plots (33.8%). Regarding the ratio infection: infectivity, only the infective mosquitoes with L3 showed a statistical significance in the three types of areas, being highest in the center of the villages. Transmission potentials were: center of the village 28.5 L3/human/period; coffee plantation, 73 L3/human/period; corn-bean plot, 5.8 L3/human/period. We discuss the possibility that the differences in densities among the various areas might depend on the variations of the breeding sites, mobility or permanence of the individuals during the hours of greater activity of S. ochraceum, and the wind and light local conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Radiographic Evaluation of Bones and Joints in Mucopolysaccharidosis I and VII Dogs After Neonatal Gene Therapy

    Science.gov (United States)

    Herati, Ramin Sedaghat; Knox, Van W.; O’Donnell, Patricia; D’Angelo, Marina; Haskins, Mark E.; Ponder, Katherine P.

    2009-01-01

    Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes α-L-iduronidase and β-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs. PMID:18707908

  11. Synthesis of a novel organic-inorganic hybrid of polyaniline/titanium phosphate for Re(VII) removal.

    Science.gov (United States)

    Gao, Yang; Chen, Changlun; Chen, He; Zhang, Rui; Wang, Xiangke

    2015-05-21

    The organic-inorganic hybrid material of polyaniline/titanium(IV) (PANI/Ti(HPO4)2) was synthesized by an oxidative polymerization reaction. The PANI/Ti(HPO4)2 was applied to remove Re(VII). The size of Ti(HPO4)2 nanoplates has no obvious effect on the sorption capacity. The effects of various environmental factors (such as pH, extra anions (NO3(-) and MO4(2-)) and temperature) on Re(VII) sorption to PANI/Ti(HPO4)2 were investigated by batch experiments. The sorption kinetics followed a pseudo-second-order model. The nitrogen-containing functional groups of PANI promoted Re(VII) sorption. The PANI/Ti(HPO4)2 exhibited excellent maximum sorption capacity to Re(VII) (47.62 mg g(-1)), which was superior to that of PANI (10.75 mg g(-1)) and much higher than that of many other sorbents. The sorption isotherms of Re(VII) can be well fitted with the Langmuir model. Re(VII) sorption decreased with increasing solution pH at pH > 4.0, which implied that Re(VII) sorption on PANI/Ti(HPO4)2 might be attributed to the outer-sphere complexation between amine and imine groups on the surface of PANI/Ti(HPO4)2 and Re(VII). This study implies that the hybrid material of PANI/Ti(HPO4)2 can be regarded as a potential sorbent to remove Re(VII) and its analogues from large volumes of aqueous solutions.

  12. Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages

    Science.gov (United States)

    Copin, C.; Derudas, B.; Marx, N.

    2016-01-01

    Tissue factor (TF) is the initiator of the blood coagulation cascade after interaction with the activated factor VII (FVIIa). Moreover, the TF/FVIIa complex also activates intracellular signalling pathways leading to the production of inflammatory cytokines. The TF/FVIIa complex is inhibited by the tissue factor pathway inhibitor-1 (TFPI-1). Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that, together with PPARα and PPARβ/δ, controls macrophage functions. However, whether PPARγ activation modulates the expression of TFP1-1 in human macrophages is not known. Here we report that PPARγ activation increases the expression of TFPI-1 in human macrophages in vitro as well as in vivo in circulating peripheral blood mononuclear cells. The induction of TFPI-1 expression by PPARγ ligands, an effect shared by the activation of PPARα and PPARβ/δ, occurs also in proinflammatory M1 and in anti-inflammatory M2 polarized macrophages. As a functional consequence, treatment with PPARγ ligands significantly reduces the inflammatory response induced by FVIIa, as measured by variations in the IL-8, MMP-2, and MCP-1 expression. These data identify a novel role for PPARγ in the control of TF the pathway. PMID:28115923

  13. Unemployment as a factor of entrepreneurial activity

    Directory of Open Access Journals (Sweden)

    Sebastian Șipoș-Gug

    2012-12-01

    Full Text Available We aim to investigate the nature and direction of the relationship between unemployment and entrepreneurial activity. Our research, using monthly data from Romania (1991-2012, brings evidence to the hypothesis that the relationship is non-linear in regard to the temporal delay factor. From our data it would seem that unemployment and entrepreneurial activity are negatively related on the short term, and positively related on the long term. Based on these results, we propose that the two effects be treated separately, and we propose two predictive models of entrepreneurial activity based on unemployment that follow this distinction.

  14. DEVELOPMENT OF ENDF/B-VII.1 AND ITS COVARIANCE COMPONENT

    Energy Technology Data Exchange (ETDEWEB)

    Herman, M.

    2010-04-30

    The US nuclear data community, coordinated by CSEWG, is preparing release of the ENDF/B-VII.1 library. This new release will address deficiencies identified in ENDF/B-VII.0, include improved evaluations for some 50-60 materials and provide covariances for more than 110 materials. The major players in this undertaking are LANL, BNL, ORNL, and LLNL. We summarize deficiencies in the ENDF/B-VII.0 and outline development of the new library. We concentrate on the BNL activities which aim in providing covariances for the materials important for the design of the innovative reactors. Finally we outline a futuristic approach, known as assimilation that tries to link nuclear reaction theory and integral experiments.

  15. Aspects of haemostatic function in healthy subjects with microalbuminuria--a potential atherosclerotic risk factor

    DEFF Research Database (Denmark)

    Jensen, J S; Myrup, B; Borch-Johnsen, K

    1995-01-01

    .6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors...

  16. The role of carrier number on the procoagulant activity of tissue factor in blood and plasma

    Science.gov (United States)

    Tormoen, G. W.; Rugonyi, S.; Gruber, A.; McCarty, O. J. T.

    2011-12-01

    Tissue factor (TF) is a transmembrane glycoprotein cofactor of activated blood coagulation factor VII (FVIIa) that is required for hemostatic thrombin generation at sites of blood vessel injury. Membrane-associated TF detected in circulating blood of healthy subjects, referred to as intravascular or circulating TF has been shown to contribute to experimental thrombus propagation at sites of localized vessel injury. Certain disease states, such as metastatic cancer, are associated with increased levels of intravascular TF and an elevated risk of venous thromboembolism. However, the physiological relevance of circulating TF to hemostasis or thrombosis, as well as cancer metastasis, is ill-defined. This study was designed to assess whether the spatial separation of intravascular TF carriers in blood, demonstrated with TF-inducible human monocytic cell line U937 or TF-coated polymer microspheres, affected procoagulant activity and hence thrombogenic potential. Experiments were performed to characterize the effects of TF-carrier number on the kinetics of clot formation in both open and closed systems. The procoagulant activity of TF carriers was found to correlate with spatial separation in both closed, well-mixed systems and open, flowing systems. TF carriers enhanced the amidolytic activity of FVIIa toward the chromogenic substrate, S-2366, as a function of carrier count. These results suggest that TF-initiated coagulation by circulating TF is kinetically limited by mass transport of TF-dependent coagulation factors to the TF-bearing surface, a constraint that may be unique to circulating TF. Spatial separation of circulating TF carriers is therefore a critical determinant of the procoagulant activity of circulating TF.

  17. Intelsat VII communications capabilities and performance

    Science.gov (United States)

    Abdel-Nabi, T.; Koh, E.; Kennedy, D.

    This paper describes the general characteristics of the Intelsat VII communications payload and analyzes the suitability of its design for digital transmission, for efficient incorporation of small earth stations into the Intelsat network, and for a relatively straightforward transition from the current Intelsat VA/VI configuration. An overview is presented of the comunications performance of the Intelsat VII satellite for the more important Intelsat digital and analog services, and earth stations standards. Specifically, the advantages, in terms of performance and capabilities, of the improved transponder linearity characteristics associated with the C-Band SSPA's and the K(u)-Band linearized TWTA's are addressed. The enhanced ability of this spacecraft to provide bandwidth where required from several possible orbital locations is discussed.

  18. VII International Congress of Engineering Physics

    Science.gov (United States)

    2015-01-01

    In the frame of the fortieth anniversary celebration of the Universidad Autónoma Metropolitana and the Physics Engineering career, the Division of Basic Science and Engineering and its Departments organized the "VII International Congress of Physics Engineering". The Congress was held from 24 to 28 November 2014 in Mexico City, Mexico. This congress is the first of its type in Latin America, and because of its international character, it gathers experts on physics engineering from Mexico and all over the globe. Since 1999, this event has shown research, articles, projects, technological developments and vanguard scientists. These activities aim to spread, promote, and share the knowledge of Physics Engineering. The topics of the Congress were: • Renewable energies engineering • Materials technology • Nanotechnology • Medical physics • Educational physics engineering • Nuclear engineering • High precision instrumentation • Atmospheric physics • Optical engineering • Physics history • Acoustics This event integrates lectures on top trending topics with pre-congress workshops, which are given by recognized scientists with an outstanding academic record. The lectures and workshops allow the exchange of experiences, and create and strengthen research networks. The Congress also encourages professional mobility among all universities and research centres from all countries. CIIF2014 Organizing and Editorial Committee Dr. Ernesto Rodrigo Vázquez Cerón Universidad Autónoma Metropolitana - Azcapotzalco ervc@correo.azc.uam.mx Dr. Luis Enrique Noreña Franco Universidad Autónoma Metropolitana - Azcapotzalco lnf@correo.azc.uam.mx Dr. Alberto Rubio Ponce Universidad Autónoma Metropolitana - Azcapotzalco arp@correo.azc.uam.mx Dr. Óscar Olvera Neria Universidad Autónoma Metropolitana - Azcapotzalco oon@correo.azc.uam.mx Professor Jaime Granados Samaniego Universidad Autónoma Metropolitana - Azcapotzalco jgs@correo.azc.uam.mx Dr. Roberto Tito Hern

  19. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  20. Anticancer Effects of Sinocrassulosides VI/VII from Silene viscidula on HeLa Cells

    Directory of Open Access Journals (Sweden)

    Hang Chen

    2017-01-01

    Full Text Available Natural products are becoming increasingly important in chemoprevention and for cancer therapy. Silene viscidula (S. viscidula, a traditional Chinese herb, has long been used as an anti-inflammatory and neuroleptic agent. However, the anticancer activity of S. viscidula has remained unclear. In this study, 16 compounds were extracted from S. viscidula. Among those compounds, sinocrassulosides VI/VII, an inseparable isomer mixture, possess the strongest inhibitory activity on HeLa cells with the IC50 value of 2.37 μM. Mechanism studies found that sinocrassulosides VI/VII downregulated the expression of cyclin D1 and decreased retinoblastoma (Rb phosphorylation, which arrested HeLa cells in the G1 phase. Also, sinocrassulosides VI/VII could induce senescence via the upregulation of p16 and a significant increase of β-galactosidase (β-gal staining. Our results suggest that sinocrassulosides VI/VII may be a new therapeutic potential agent for cervical cancer. In addition, we explored the structure-activity relationships of three groups of the configurational isomer with similar chemical structure from S. viscidula. We first demonstrated that the length of the ester chains linked to the carboxyl group of the glucuronic acid residue could affect the potent cytotoxicity. This finding will open new avenues for developing effective anticancer compounds by modifying the components derived from plants in nature.

  1. Anticancer Effects of Sinocrassulosides VI/VII from Silene viscidula on HeLa Cells.

    Science.gov (United States)

    Chen, Hang; Ma, Qian; Xu, Wei; Li, Wan-Ming; Yuan, De-Zheng; Wu, Jia-Mei; Li, Yu-Shan; Fang, Jin

    2017-01-01

    Natural products are becoming increasingly important in chemoprevention and for cancer therapy. Silene viscidula (S. viscidula), a traditional Chinese herb, has long been used as an anti-inflammatory and neuroleptic agent. However, the anticancer activity of S. viscidula has remained unclear. In this study, 16 compounds were extracted from S. viscidula. Among those compounds, sinocrassulosides VI/VII, an inseparable isomer mixture, possess the strongest inhibitory activity on HeLa cells with the IC50 value of 2.37 μM. Mechanism studies found that sinocrassulosides VI/VII downregulated the expression of cyclin D1 and decreased retinoblastoma (Rb) phosphorylation, which arrested HeLa cells in the G1 phase. Also, sinocrassulosides VI/VII could induce senescence via the upregulation of p16 and a significant increase of β-galactosidase (β-gal) staining. Our results suggest that sinocrassulosides VI/VII may be a new therapeutic potential agent for cervical cancer. In addition, we explored the structure-activity relationships of three groups of the configurational isomer with similar chemical structure from S. viscidula. We first demonstrated that the length of the ester chains linked to the carboxyl group of the glucuronic acid residue could affect the potent cytotoxicity. This finding will open new avenues for developing effective anticancer compounds by modifying the components derived from plants in nature.

  2. Quantitative clinical characteristics of 53 patients with MPS VII: a cross-sectional analysis.

    Science.gov (United States)

    Zielonka, Matthias; Garbade, Sven F; Kölker, Stefan; Hoffmann, Georg F; Ries, Markus

    2017-04-06

    The main purpose of the study was to provide quantitative data regarding survival and diagnostic delay. Mucopolysaccharidosis (MPS) type VII (OMIM 253220) is a progressive neurometabolic disorder caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS). Hard clinical end points have not been quantitatedMethods:We quantitatively analyzed published cases with MPS VII (N = 53/88 with sufficient data). Main outcome measures were onset of disease and survival. The role of biomarkers such as GUS residual enzyme activity and levels of storage material assessed as urinary excretion of glucosaminoglycans (GAG) as potential predictors of clinical outcomes were investigated. The analysis was conducted according to STROBE criteria. Median survival of the postnatally diagnosed population was 42 months. Median age of disease onset was the first day of life; median age at diagnosis was 11 months. Hydrops fetalis was frequent. Patients with residual GUS activity in fibroblasts more than 1.4% or urinary GAG excretion less than 602% of normal survived longer than patients with GUS enzyme activity below or GAG excretion above these thresholds. MPS VII has its disease onset prenatally. In the absence of a prenatal diagnosis, most cases are clinically apparent at birth. Our data corroborate a phenotype-biomarker association in MPS VII. The survival data characterize the natural history with important implications for therapeutic studies.Genet Med advance online publication 06 April 2017Genetics in Medicine (2017); doi:10.1038/gim.2017.10.

  3. Investigating the air oxidation of V(II) ions in a vanadium redox flow battery

    Science.gov (United States)

    Ngamsai, Kittima; Arpornwichanop, Amornchai

    2015-11-01

    The air oxidation of vanadium (V(II)) ions in a negative electrolyte reservoir is a major side reaction in a vanadium redox flow battery (VRB), which leads to electrolyte imbalance and self-discharge of the system during long-term operation. In this study, an 80% charged negative electrolyte solution is employed to investigate the mechanism and influential factors of the reaction in a negative-electrolyte reservoir. The results show that the air oxidation of V(II) ions occurs at the air-electrolyte solution interface area and leads to a concentration gradient of vanadium ions in the electrolyte solution and to the diffusion of V(II) and V(III) ions. The effect of the ratio of the electrolyte volume to the air-electrolyte solution interface area and the concentrations of vanadium and sulfuric acid in an electrolyte solution is investigated. A higher ratio of electrolyte volume to the air-electrolyte solution interface area results in a slower oxidation reaction rate. The high concentrations of vanadium and sulfuric acid solution also retard the air oxidation of V(II) ions. This information can be utilized to design an appropriate electrolyte reservoir for the VRB system and to prepare suitable ingredients for the electrolyte solution.

  4. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  5. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85...

  6. Physics and engineering design for Wendelstein VII-X

    Energy Technology Data Exchange (ETDEWEB)

    Beidler, C.; Grieger, G.; Herrnegger, F.; Harmeyer, E.; Kisslinger, J.; Lotz, W.; Maassberg, H.; Merkel, P.; Nuhrenberg, J.; Rau, F.; Sapper, J.; Sardei, F.; Scardovell, R.; Schluter, A.; Woblig, H. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-01-01

    This paper reports on the development of the future experiment Wendelstein VII-X. A helical advanced stellarator configuration has been chosen. The goals of W VII-X are to continue the development of the modular stellarator, to demonstrate the reactor capability of this stellarator line, and to achieve quasi-steady-state operation in a temperature regime > 5 keV.

  7. Re(VII) and Tc(VII) trioxo complexes stabilized by tridentate ligands and their potential use as radiopharmaceuticals

    NARCIS (Netherlands)

    Hahn, Eva M.; Casini, Angela; Kuehn, Fritz E.

    2014-01-01

    Tc(VII) and Re(VII) trioxo complexes are currently arousing interest because of their potential use as radiopharmaceuticals due to their hydrophilic character and stability in a biological environment. The radioactive isotopes Tc-99m and Re-188 are readily obtained from commercially available Mo-99/

  8. TEH võrgustik - viis aastat Eestis / Marika Kusnets

    Index Scriptorium Estoniae

    Kusnets, Marika

    2005-01-01

    Eestis on tervist edendavate haiglate (TEH) võrgustik tegutsenud juba viis aastat, sellega on liitunud 22 haiglat. Tänavust konverentsi peeti teemal "Tervise edendamine ja kvaliteedi tagamine haiglas: standardid ja praktika"

  9. TEH võrgustik - viis aastat Eestis / Marika Kusnets

    Index Scriptorium Estoniae

    Kusnets, Marika

    2005-01-01

    Eestis on tervist edendavate haiglate (TEH) võrgustik tegutsenud juba viis aastat, sellega on liitunud 22 haiglat. Tänavust konverentsi peeti teemal "Tervise edendamine ja kvaliteedi tagamine haiglas: standardid ja praktika"

  10. Settling Title VII Disputes: A Role for the Arbitrator

    Science.gov (United States)

    Owens, Stephen D.

    1976-01-01

    Selected arbitration cases illustrate the dilemma facing the arbitrator when employment practices that violate both the collective bargaining agreement and Title VII must be resolved. Problems in dealing with race and sex discrimination are discussed. (LBH)

  11. Meenutusi VII Riigikogu päevilt / Helle Ruusing

    Index Scriptorium Estoniae

    Ruusing, Helle, 1966-

    2003-01-01

    Katkendeid Riigikogu Kantselei 2002. aastal gümnaasiumiõpilastele korraldatud VII Riigikogu liikmete mälestuste kogumise võistlusele laekunud töödest. Eesti taasiseseisvumisaja esimese parlamendi, VII Riigikogu töökorraldust, töötingimusi Toompea lossis, tööd fraktsioonides ja komisjonides meenutavad Juhan Aare, Avo Kiir, Kalle Jürgenson, Kalev Raave, Ants Käärma, Paul-Olev Mõtsküla, Tiit Sinissaar, Peeter Lorents

  12. Marine Mammals, Coastal and River Issues. Alaska Sea Week Curriculum Series VII. Alaska Sea Grant Report 84-8.

    Science.gov (United States)

    Mickelson, Belle

    This curriculum guide is the last (Series VII) in a six-volume set that comprises the Sea Week Curriculum Series developed in Alaska. The guide lends itself to the sixth-grade curriculum but can be adapted to preschool, secondary, and adult education. Eight units contain 43 activities with worksheets that cover the following topics: (1) the values…

  13. Experimental evidence for competitive growth advantage of genotype VII over VI: implications for foot-and-mouth disease virus serotype A genotype turnover in nature.

    Science.gov (United States)

    Mohapatra, J K; Subramaniam, S; Singh, N K; Sanyal, A; Pattnaik, B

    2012-04-01

    In India, systematic genotype replacement has been observed for serotype A foot-and-mouth disease virus. After a decade of co-circulation of genotypes VI and VII, genotype VII emerged as the single dominant genotype since 2001. To derive possible explanations for such epochal evolution dynamics, in vitro intergenotype growth competition experiments involving both co- and superinfection regimes were conducted. Coinfection of BHK-21 cells demonstrated abrupt loss in the genotype VI viral load with commensurate increase in the load of genotype VII as measured by the genotype differentiating ELISA, RT-PCR and real-time RT-PCR. The superinfection dynamics was shaped by temporal spacing of infection, where the invading genotype VII took more number of passages than coinfection to eventually overtake the resident genotype VI. It was speculated that such superior replicative fitness of genotype VII could have been a possible factor for the ultimate dominance of genotype VII in nature. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Physical activity and cardiovascular disease risk factors among ...

    African Journals Online (AJOL)

    We assessed level physical activity and its relationship with CVD risk factors among ... Anthropometric measurements, blood pressure, fasting blood glucose and ... Conclusion: Physical activity energy expenditure was high in this population ...

  15. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in expos

  16. Beyond stopping the bleed: short-term episodic prophylaxis with recombinant activated factor FVII in haemophilia patients with inhibitors

    Science.gov (United States)

    Šalek, Silva Zupančić; Auerswald, Günter; Benson, Gary; Dolan, Gerry; Duffy, Anne; Hermans, Cedric; Jiménez-Yuste, Victor; Ljung, Rolf; Morfini, Massimo; Santagostino, Elena; Lambert, Thierry

    2017-01-01

    Preventing haemarthroses and arthropathy is a major challenge in patients with haemophilia and inhibitors, as treatment options are limited. One potential strategy is short-term episodic prophylaxis, which extends bypassing agent therapy beyond the resolution of bleeding to include the post-bleed inflammatory phase. At the 13th Zürich Haemophilia Forum, an expert panel reviewed the rationale behind this strategy, explored its current use with recombinant activated factor VII (rFVIIa) and considered treatment monitoring and optimisation. Two protocols are currently used for short-term episodic prophylaxis, both of which stipulate on-demand rFVIIa until resolution of bleeding, followed by daily dosing for ≥3 days to prevent re-bleeds. Short-term episodic prophylaxis should be individualised to optimise outcomes, perhaps through early treatment initiation or by combining rFVIIa with other treatments (e.g. factor VIII, tranexamic acid). Encouraging treatment compliance can also improve outcomes. Additionally, there is a need to develop objective clinical outcome measures, biomarkers and imaging protocols that can monitor treatment outcomes and joint disease in patients with inhibitors. A proactive approach incorporating a systematic package of care is needed. Currently, short-term episodic prophylaxis with rFVIIa may be an alternative treatment option to on-demand treatment for patients with inhibitors. PMID:26674816

  17. Ecological Factors Improving Efficiency of Business Activities

    Directory of Open Access Journals (Sweden)

    Kononova G. A.

    2015-01-01

    Full Text Available The economic importance of optimizing the environmental situation from the perspective of an entrepreneur are assessed in the article. The classification of administrative decisions taken in the course of the business activities is proposed. The authors identified a group of solutions directly providing optimization of environment external to the enterprise, solutions that have an indirect positive impact on the environment and solutions that improve ecology of industrial premises. The nature of economic effect of resulting solutions of various types is taken into account. Vectors of influence of working conditions on the economic results of business activities are described. The nature and strength of the impact of model management decisions results of business activities are defined. Key performance indicators of entrepreneurial activity are identified: employee productivity, the amount of revenue and profitability, solvency, staff stability, the competitiveness of enterprises. Grouping the costs of ecological parameters optimization of the production environment is proposed. Relationship between level of working conditions and socio-psychological climate in the collective enterprise is disclosed. The methods of motivation of entrepreneurs in solving of environmental, production problems are considered. The role of training entrepreneurs engaged of medium and small businesses are underlined especially. Thus, in the article the relationship between environmental and economic problems of entrepreneurial activity is investigated. Role and opportunities of entrepreneurs in solving these problems are defined and structured.

  18. Benchmarking ENDF/B-VII.0

    Science.gov (United States)

    van der Marck, Steven C.

    2006-12-01

    The new major release VII.0 of the ENDF/B nuclear data library has been tested extensively using benchmark calculations. These were based upon MCNP-4C3 continuous-energy Monte Carlo neutronics simulations, together with nuclear data processed using the code NJOY. Three types of benchmarks were used, viz., criticality safety benchmarks, (fusion) shielding benchmarks, and reference systems for which the effective delayed neutron fraction is reported. For criticality safety, more than 700 benchmarks from the International Handbook of Criticality Safety Benchmark Experiments were used. Benchmarks from all categories were used, ranging from low-enriched uranium, compound fuel, thermal spectrum ones (LEU-COMP-THERM), to mixed uranium-plutonium, metallic fuel, fast spectrum ones (MIX-MET-FAST). For fusion shielding many benchmarks were based on IAEA specifications for the Oktavian experiments (for Al, Co, Cr, Cu, LiF, Mn, Mo, Si, Ti, W, Zr), Fusion Neutronics Source in Japan (for Be, C, N, O, Fe, Pb), and Pulsed Sphere experiments at Lawrence Livermore National Laboratory (for 6Li, 7Li, Be, C, N, O, Mg, Al, Ti, Fe, Pb, D 2O, H 2O, concrete, polyethylene and teflon). For testing delayed neutron data more than thirty measurements in widely varying systems were used. Among these were measurements in the Tank Critical Assembly (TCA in Japan) and IPEN/MB-01 (Brazil), both with a thermal spectrum, and two cores in Masurca (France) and three cores in the Fast Critical Assembly (FCA, Japan), all with fast spectra. In criticality safety, many benchmarks were chosen from the category with a thermal spectrum, low-enriched uranium, compound fuel (LEU-COMP-THERM), because this is typical of most current-day reactors, and because these benchmarks were previously underpredicted by as much as 0.5% by most nuclear data libraries (such as ENDF/B-VI.8, JEFF-3.0). The calculated results presented here show that this underprediction is no longer there for ENDF/B-VII.0. The average over 257

  19. Clinical course of sly syndrome (mucopolysaccharidosis type VII)

    Science.gov (United States)

    Montaño, Adriana M; Lock-Hock, Ngu; Steiner, Robert D; Graham, Brett H; Szlago, Marina; Greenstein, Robert; Pineda, Mercedes; Gonzalez-Meneses, Antonio; Çoker, Mahmut; Bartholomew, Dennis; Sands, Mark S; Wang, Raymond; Giugliani, Roberto; Macaya, Alfons; Pastores, Gregory; Ketko, Anastasia K; Ezgü, Fatih; Tanaka, Akemi; Arash, Laila; Beck, Michael; Falk, Rena E; Bhattacharya, Kaustuv; Franco, José; White, Klane K; Mitchell, Grant A; Cimbalistiene, Loreta; Holtz, Max; Sly, William S

    2016-01-01

    Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients’ phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity

  20. Desain Pembelajaran Materi Belah Ketupat Menggunakan Kain Jumputan Palembang untuk Siswa Kelas VII

    Directory of Open Access Journals (Sweden)

    Fauziyah Fauziyah

    2016-06-01

    Full Text Available Desain pembelajaran materi belah ketupat menggunakan kain Jumputan Palembang untuk siswa kelas VII. Penelitian ini bertujuan untuk melihat bagaimana penggunaan kain Jumputan Palembang dalam membangun pemahaman siswa mengenai belah ketupat. Siswa akan membandingkan luas daerah dua buah kain Jumputan, merancang dan membuat belah ketupat kemudian menggunting serta menyusunnya kembali menjadi suatu bentuk baru, menentukan luas daerah belah ketupat, membandingkan keliling dua buah kain Jumputan dan menentukan keliling belah ketupat. Subjek penelitian ini adalah 30 siswa kelas VII SMP Pusri Palembang. Penelitian ini menggunakan design research yang terdiri dari tiga tahap : preparing for the experiment, experiment in the classroom (pilot experiment dan  teaching experiment, dan retrospective analysis. Pada tahap preparing for the experiment, beberapa aktifitas dibuat menggunakan pendekatan Pendidikan Matematika Realistik Indonesia (PMRI. Hasil dari penelitian menunjukkan kain Jumputan Palembang dapat digunakan sebagai starting point dalam pembelajaran belah ketupat untuk siswa kelas VII SMP.The design learning rhombus using kain Jumputan Palembang for VII grade students. This research aims to investigate how to use Kain Jumputan Palembang to build student’s understanding on rhombus. Students were required to comparing the area of two cloths, designing and making rhombus then reshaping to new shapes, determining the area of rhombus, comparing the perimeter of two cloths and determining the perimeter of rhombus. Subjects were 30 first grade students of SMP Pusri Palembang. The study used a design research method consisting of three stages : preparing for the experiment, experiment in the classroom (pilot experiment and teaching experiment, and retrospective analysis. During the preparing for the experiment stage, instructional activities was designing utilizing of Indonesian Realistic Mathematics Education (PMRI approach. The result of experiments

  1. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

    NARCIS (Netherlands)

    Planinsic, RM; van der Meer, J; Testa, G; Grande, L; Candela, A; Porte, RJ; Ghobrial, RM; Isoniemi, H; Schelde, PB; Erhardtsen, E; Klintmalm, G; Emre, S

    Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however there has been a limited

  2. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

    NARCIS (Netherlands)

    Planinsic, RM; van der Meer, J; Testa, G; Grande, L; Candela, A; Porte, RJ; Ghobrial, RM; Isoniemi, H; Schelde, PB; Erhardtsen, E; Klintmalm, G; Emre, S

    2005-01-01

    Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however there has been a limited a

  3. Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: A randomized controlled trial

    NARCIS (Netherlands)

    Mennen, L.; Maat, M. de; Meijer, G.; Zock, P.; Grobbee, D.; Kok, F.; Kluft, C.; Schouten, E.

    1998-01-01

    A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and investi

  4. Factors influencing beta-amylase activity in sorghum malt

    CSIR Research Space (South Africa)

    Taylor, JRN

    1993-09-01

    Full Text Available An investigation into factors influencing beta-amylase activity in sorghum malt confirmed that ungerminated sorghum grain exhibited essentially no beta-amylase activity. Malted sorghum had beta-amylase activity less than 25% of the level in barley...

  5. PENGARUH KETERAMPILAN MENGELOLA KELAS DAN GAYA MENGAJAR GURU TERHADAP KEAKTIFAN BELAJAR SISWA KELAS VII MATA PELAJARAN IPS TERPADU DI SMP NEGERI SE-KECAMATAN WEDUNG KABUPATEN DEMAK

    Directory of Open Access Journals (Sweden)

    Rifanah

    2014-06-01

    Full Text Available Tujuan Penelitian ini adalah mengetahui pengaruh keterampilan mengelola kelas, dan gaya mengajar guru terhadap keaktifan belajar siswa kelas VII SMP Negeri se-Kecamatan Wedung. Dalam penelitian ini populasi yang digunakan adalah seluruh siswa kelas VII SMP Negeri se-Kecamatan Wedung yang berjumlah 296 siswa. Penelitian ini menggunakan sampel yang berjumlah 81 sampel. Teknik pengambilan sampel menggunakan proportional random sampling. Variabel dalam penelitian ini adalah variabel bebas yaitu keterampilan mengelola kelas (XI, gaya mengajar guru (X2, dan keaktifan belajar siswa (Y sebagai variabel terikat. Metode pengumpulan data: dokumentasi dan angket. Metode analisis yaitu analisi deskriptif persentase. Hasil penelitian diperoleh persamaan regresi Y = 1,873+ 0,260 X1 + 0,670 X2. Secara deskriptif penelitian menunjukkan bahwa keterampilan mengelola kelas, dan gaya mengajar guru adalah baik. Pengaruh keterampilan mengelola kelas terhadap keaktifan belajar siswa sebesar 84,5%, gaya mengajar guru terhadap keaktifan belajar siswa sebesar 92,8%, pengarunya positif dan signifikan. Sedangkan pengaruh keterampilan mengelola kelas dan gaya mengajar guru secara bersama berpengaruh terhadap keaktifan belajar siswa sebesar 89,7% dan sisanya sebesar 10,3% dipengaruhi oleh faktor lain yang tidak diteliti. The purpose of this study was to determine the effect of classroom management skills, and the teaching style of teachers to students of class VII activity of SMP Wedung throughout the District. In this study population used is the entire Junior High School seventh grade students throughout the District Wedung totaling 296 students. This study used a sample of 81 samples. Sampling technique using proportional random sampling. The variable in this study is the independent variable classroom management skills (XI, the teacher's teaching style (X2, and the activity of student learning (Y as the dependent variable. Methods of data collection: documentation and

  6. Exonuclease VII is involved in "reckless" DNA degradation in UV-irradiated Escherichia coli.

    Science.gov (United States)

    Repar, Jelena; Briški, Nina; Buljubašić, Maja; Zahradka, Ksenija; Zahradka, Davor

    2013-01-20

    The recA mutants of Escherichia coli exhibit an abnormal DNA degradation that starts at sites of double-strand DNA breaks (DSBs), and is mediated by RecBCD exonuclease (ExoV). This "reckless" DNA degradation occurs spontaneously in exponentially growing recA cells, and is stimulated by DNA-damaging agents. We have previously found that the xonA and sbcD mutations, which inactivate exonuclease I (ExoI) and SbcCD nuclease, respectively, markedly suppress "reckless" DNA degradation in UV-irradiated recA cells. In the present work, we show that inactivation of exonuclease VII (ExoVII) by an xseA mutation contributes to attenuation of DNA degradation in UV-irradiated recA mutants. The xseA mutation itself has only a weak effect, however, it acts synergistically with the xonA or sbcD mutations in suppressing "reckless" DNA degradation. The quadruple xseA xonA sbcD recA mutants show no sign of DNA degradation during post-irradiation incubation, suggesting that ExoVII, together with ExoI and SbcCD, plays a crucial role in regulating RecBCD-catalyzed chromosome degradation. We propose that these nucleases act on DSBs to create blunt DNA ends, the preferred substrates for the RecBCD enzyme. In addition, our results show that in UV-irradiated recF recA(+) cells, the xseA, xonA, and sbcD mutations do not affect RecBCD-mediated DNA repair, suggesting that ExoVII, ExoI and SbcCD nucleases are not essential for the initial targeting of RecBCD to DSBs. It is possible that the DNA-blunting activity provided by ExoVII, ExoI and SbcCD is required for an exchange of RecBCD molecules on dsDNA ends during ongoing "reckless" DNA degradation.

  7. Contamination monitoring and control on ASML MS-VII 157-nm exposure tool

    Science.gov (United States)

    Okoroanyanwu, Uzodinma; Gronheid, Roel; Coenen, Jan; Hermans, Jan; Ronse, Kurt G.

    2004-05-01

    This paper presents results of monitoring and control of contaminants in an ASML MS-VII 157nm full-field exposure tool at IMEC, as verified lithographically in terms of field uniformity, lens transmission, CD uniformity, and scattered light. The daily contamination monitoring system utilizes in-line photo-ionization detector, oxygen and moisture analyzers, as well as chemiluminescent detector, and gas chromatograph that is coupled to a mass spectrometer. On a monthly basis, contamination monitoring was performed with thermal desorption-gas chromatographi/mass spectrometric techniques. The following four locations within the optical path of the MS-VII are monitored: source optic assembly, condenser lens optic, 1X relay station, and projection optics box. Contamination control is realized in the system with an on-board purge control unit, which is equipped with gas purifiers that remove contaminants such as H2O, O2, CO, CO2, hydrocarbons, H2, and sulfur compounds. All the observed contaminants have been trending within expected values and no contamination-related tool performance degradation has been observed. The excursions observed in the contaminant concentrations are coincident with tool downtime/maintenance events. Siloxane levels appear to be consistently below 50 ppt in all the monitored locations within the optical path of the tool, except on one occasion when it reached 90 ppt in the projection optics. Volatile organic compounds (VOCs) concentration within the MS-VII enclosure show a stable background level of around 10-25 ppb during weekends and levels of 45-60 ppb (during working days). VOCs concentration variations inside the MS-VII enclosure during the working days correlate well with activities inside the clean room. Air recirculation and low intake of fresh air inside the MS-VII tend to slow down the speed with which the VOCs levels decreases to stable background level, whenever there was a major upward excursion in their concentration. Average light

  8. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    XU; Jinping(徐进平); YE; Linbai(叶林柏)

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  9. Apollonius de Perge, Coniques tome 4, livres VI et VII

    CERN Document Server

    Rashed, Roshdi

    2009-01-01

    Book VI of the Konika is essentially devoted to the question of the identity and similarity of two conic sections, or two parts of conic sections. In Book VII Apollonius deals with the various relationships between the lengths of diameters and conjugate diameters. The results are applied to the exposition of a number of problems, as well as to some problems which Apollonius indicates will be demonstrated and solved in Book VIII, which was lost in Antiquity. Books VI and VII have only survived in an Arabic translation, and are presented here in a critical edition, together with a faithful trans

  10. Conciliar politics and administration in the reign of Henry VII

    OpenAIRE

    Ford, Lisa L.

    2001-01-01

    Since Elton's commentary on the absence of critical study of the early Tudor council in 1964, some progress has been made towards a wider, fuller, more detailed understanding of Henry VII's council and where it fits-or does not-into the development of council under the Tudors. However, the early Tudor council remains something of an enigma. Added to that is recent interest by late medieval historians in just how much power Henry VII exercised in the operation of his councils. W...

  11. [Factors influencing research activity of Andalusian nurses and improvement strategies].

    Science.gov (United States)

    López Alonso, Sergio R; Gálvez González, María; Amezcua, Manuel

    2013-04-01

    To identify factors influencing research activity of Andalusian nurses and to find improvement strategies. Qualitative research using SWOT analysis (weaknesses, threats, strengths, opportunities). Nurses were selected deliberately in eight groups according to predetermined criteria. Analysis included categorization and relationship of factors and strategies. 81 participants were included in groups of 7-12 range. 45 categories were identified with 212 factors: 12 weaknesses (50 factors), 10 strengths (44 factors), 12 threats (68 factors) and 11 opportunities (50 factors). In addition, 32 categories were identified with 53 strategies: 14 categories of W-T strategies (42 strategies), 3 categories of S-T strategies (11 strategies), 5 categories of W-O strategies (13 strategies) and 10 categories of S-O strategies (41 strategies). Nurses identified numerous factors, mainly threats. The strategies are focused on W-T but they also suggest many but weak 5-0 strategies due to the low potential of the opportunities and strengths perceived.

  12. Crystallographic B factor of critical residues at enzyme active site

    Institute of Scientific and Technical Information of China (English)

    张海龙; 宋时英; 林政炯

    1999-01-01

    Thirty-seven sets of crystallographic enzyme data were selected from Protein Data Bank (PDB, 1995). The average temperature factors (B) of the critical residues at the active site and the whole molecule of those enzymes were calculated respectively. The statistical results showed that the critical residues at the active site of most of the enzymes had lower B factors than did the whole molecules, indicating that in the crystalline state the critical residues at the active site of the natural enzymes possess more stable conformation than do the whole molecules. The flexibility of the active site during the unfolding by denaturing was also discussed.

  13. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  14. 40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Standard Bench Cycle (SBC) VII.... VII Appendix VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging durability... bench cycle (SBC) described in this appendix. 2. The SBC requires use of an aging bench with an...

  15. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions.

    Science.gov (United States)

    Mani, Helen; Hesse, Christian; Stratmann, Gertrud; Lindhoff-Last, Edelgard

    2013-01-01

    Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.

  16. Effect of warfarin on the kinetics of the vitamin K-dependent clotting factors in rats.

    Science.gov (United States)

    Vainieri, H; Wingard, L B

    1977-05-01

    The objectives of this study were to compare the time course of activities and rates of synthesis of activities for the separate clotting factors II, VII, IX, and X and to relate the rate of synthesis of activity of each factor to the plasma concentration of warfarin in individual rats after acute and chronic dosing with warfarin. Sequences of blood samples were obtained from each rat for 50 to 70 hours after an acute dose of warfarin or for 120 hours after a chronic loading dose plus 12-hour maintenance doses of warfarin and assayed for factor activities and warfarin concentration. The half-lives for degradation of factor activities ranged from 2.6 to 9.0 hours for the four factors. During periods of changing warfarin concentration (acute dosing) factor VII and X activities and rates of synthesis of activity showed large rapid changes, while factors II and IX responded more slowly. As the warfarin concentration diminished, the factor X rate of synthesis of activity appeared to exceed predrug values in all rats. During chronic dosing with warfarin the factor II activity and rate of synthesis of activity was depressed the most. The percent depression of the rate of synthesis of activity for each factor was related linearly to the logarithm of the plasma concentration of warfarin for the range 0 to 80% depression with acute dosing. However, this relationship was not suitable to explain the apparent overshoot in factor X rate of synthesis of activity.

  17. Expression of protooncogenes during lymphocyte activation by growth factors.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Yarilin, A A; Mazurenko, N N

    1997-09-01

    Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

  18. Physical Activity : The interplay between individual and neighbourhood factors

    NARCIS (Netherlands)

    M.A. Beenackers (Marielle)

    2013-01-01

    textabstractPhysical inactivity is among the most important and prevalent risk factors of many major diseases. Although the health benefits of regular exercise and a physically active lifestyle are well known, many people are still not active. Understanding why some population groups are physically

  19. Viis armastuslugu suurel ekraanil / Tristan Priimägi

    Index Scriptorium Estoniae

    Priimägi, Tristan, 1976-

    2008-01-01

    Viis näidet filmiajaloost, kus režissööri ja staari vahel on tunded : Roger Vadim ja Tema Naised, Werner Herzog ja Klaus Kinski, Federico Fellini ja Anita Ekberg, Quentin Tarantino ja Uma Thurman, Rainer Werner Fassbinder ja Mr/Mrs X

  20. Viis aastakümmet raamatukogunduse radadel / Anne Veinberg

    Index Scriptorium Estoniae

    Veinberg, Anne

    2008-01-01

    Arvustus: Kikas, Konrad. Verba volant, scripta manent : viis aastakümmet raamatukogunduse ja infoteaduse radadel = Verba volant, scripta manent : five decades on the field of librarianship and information science. - Tallinn : Tallinna Tehnikaülikooli Kirjastus, 2008. - 366 lk. : ill. portr. - (Tallinna Tehnikaülikooli Raamatukogu töid. A ; 5)

  1. Kasuperest viidi viis last ja algatati kriminaalmenetlus piinamises / Rasmus Rekand

    Index Scriptorium Estoniae

    Rekand, Rasmus

    2011-01-01

    Lugu asenduskodu teenust pakkuvast perekonnast, kelle hoole all oli lisaks pere enda 3 lapsele 6 võõrast last ning kuidas lastega mittehakkama saamine viis olukorrani, kus lapsed viidi kasupere juurest ära ja lisaks algatati uurimine keelatud võtete kasutamise kohta kasvatamistegevuses

  2. Viis armastuslugu suurel ekraanil / Tristan Priimägi

    Index Scriptorium Estoniae

    Priimägi, Tristan, 1976-

    2008-01-01

    Viis näidet filmiajaloost, kus režissööri ja staari vahel on tunded : Roger Vadim ja Tema Naised, Werner Herzog ja Klaus Kinski, Federico Fellini ja Anita Ekberg, Quentin Tarantino ja Uma Thurman, Rainer Werner Fassbinder ja Mr/Mrs X

  3. Enrico VII e l’Italia. Un primo bilancio

    Directory of Open Access Journals (Sweden)

    Gian Maria Varanini

    2014-06-01

    Full Text Available Il testo introduce i saggi pubblicati nel fasc. 1 (2014 di “Reti Medievali - Rivista”, traccia un sintetico bilancio delle ricerche recenti sulla spedizione di Enrico VII di Lussemburgo in Italia (1310-1313 e propone alcune questioni interpretative.

  4. Subjective Criteria in Employment Decisions Under Title VII

    Science.gov (United States)

    Stacy, Donald R.

    1976-01-01

    Since higher echelon jobs have been drawn into litigation under Title VII, subjective criteria have been employed. The legal ramifications of assessing noncognitive traits such as leadership, aggressiveness, and attitude are discussed. Available from: the University of Georgia School of Law, Athens, Georgia 30602. (LBH)

  5. Viis aastakümmet raamatukogunduse radadel / Anne Veinberg

    Index Scriptorium Estoniae

    Veinberg, Anne

    2008-01-01

    Arvustus: Kikas, Konrad. Verba volant, scripta manent : viis aastakümmet raamatukogunduse ja infoteaduse radadel = Verba volant, scripta manent : five decades on the field of librarianship and information science. - Tallinn : Tallinna Tehnikaülikooli Kirjastus, 2008. - 366 lk. : ill. portr. - (Tallinna Tehnikaülikooli Raamatukogu töid. A ; 5)

  6. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  7. Underground Test Area Subproject Phase I Data Analysis Task. Volume VII - Tritium Transport Model Documentation Package

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-12-01

    Volume VII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the tritium transport model documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  8. MOTIVATIONAL FACTORS FOR PHYSICAL ACTIVITY IN THE ELDERS

    Directory of Open Access Journals (Sweden)

    J. Parreira

    2015-04-01

    Full Text Available Nowadays the elderly population is well aware of the benefits of the practice of physical activity, which leads to an increasing demand for specialized physical activity programs in urban centers or recreational self-practice. However, people easily quit those programs or recreational self-practice and return to a sedentary lifestyle. A key factor to avoid this quittance is to keep them motivated to practice and stay in the programs.Objectives: This study aims to understand the motivational factors that lead older people to physical activity in order to improve existing programs so to better meet the needs of this population.

  9. Activated protein C resistance testing for factor V Leiden.

    Science.gov (United States)

    Kadauke, Stephan; Khor, Bernard; Van Cott, Elizabeth M

    2014-12-01

    Activated protein C resistance assays can detect factor V Leiden with high accuracy, depending on the method used. Factor Xa inhibitors such as rivaroxaban and direct thrombin inhibitors including dabigatran, argatroban, and bivalirudin can cause falsely normal results. Lupus anticoagulants can cause incorrect results in most current assays. Assays that include dilution into factor V-deficient plasma are needed to avoid interference from factor deficiencies or elevations, which can arise from a wide variety of conditions such as warfarin, liver dysfunction, or pregnancy. The pros and cons of the currently available assays are discussed. © 2014 Wiley Periodicals, Inc.

  10. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    activity/antigen ratios in samples classified as having VWD (activity classification power might interfere with the interpretation......INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...... glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD. AIM: To compare four automated VWF activity methods in a mixed population of patients referred for evaluation of bleeding tendency. METHODS: The analytical...

  11. Comparison of kaolin and tissue factor activated thromboelastography in haemophilia.

    Science.gov (United States)

    Young, G; Zhang, R; Miller, R; Yassin, D; Nugent, D J

    2010-05-01

    A limitation of bypassing agent therapy for haemophilia patients with inhibitors is the absence of a laboratory assay, which predicts the clinical response to treatment. Recent investigations have demonstrated the potential for thromboelastography to assess the effects of bypassing agent therapy in this patient population. While tissue factor activation has been used in several prior studies, a recent multicentre study failed to demonstrate an expected concentration-response effect of rFVIIa and called into question the tissue factor activation methods that have been employed. A comparison of kaolin to two concentrations of tissue factor as the activation method for thromboelastography was investigated in patients with haemophilia. We performed kaolin and tissue factor activated thromboelastography on blood from inhibitor and non-inhibitor patients with and without addition of rFVIIa and rFVIII. The results demonstrate that kaolin leads to a longer R, K and angle than the higher dilution of tissue factor (1:17 000) at baseline (no factor) and after addition of rFVIIa for both the inhibitor and non-inhibitor patients. Kaolin led to a longer R and K in comparison to a low dilution of tissue factor (1:42 000) following the addition of rFVIIa in the inhibitor patients. The longer R and K allows for better discrimination of the effects of rFVIIa thus making kaolin the most sensitive activation method in this setting. Thus kaolin activated thromboelastography should be considered an effective, perhaps the most effective, activator when utilizing thromboelastography to assess the effects of rFVIIa in haemophilia patients with inhibitors.

  12. Speciation analysis of Mn(II)/Mn(VII) using Fe3O4@ionic liquids-β-cyclodextrin polymer magnetic solid phase extraction coupled with ICP-OES.

    Science.gov (United States)

    Chen, Songqing; Qin, Xingxiu; Gu, Weixi; Zhu, Xiashi

    2016-12-01

    Ionic liquids-β-cyclodextrin polymer (ILs-β-CDCP) was attached on Fe3O4 nanoparticles to prepare magnetic solid phase extraction agent (Fe3O4@ILs-β-CDCP). The properties and morphology of Fe3O4@ILs-β-CDCP were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction(XRD), size distribution and magnetic analysis. A new method of magnetic solid phase extraction (MSPE) coupled to ICP-OES for the speciation of Mn(II)/Mn(VII) in water samples was established. The results showed that Mn(VII) and total manganese [Mn(II)+Mn(VII)] were quantitatively extracted after adjusting aqueous sample solution to pH 6.0 and 10.0, respectively. Mn(II) was calculated by subtraction of Mn(VII) from total manganese. Fe3O4@ILs-β-CDCP showed a higher adsorption capacity toward Mn(II) and Mn(VII). Several factors, such as the pH value, extraction temperature and sample volume, were optimized to achieve the best extraction efficiency. Moreover, the adsorption ability of Fe3O4@ILs-β-CDCP would not be significantly lower after reusing of 10 times. The accuracy of the developed method was confirmed by analyzing certified reference materials (GSB 07-1189-2000), and by spiking spring water, city water and lake water samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.

    2015-01-01

    Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective...

  14. Calidad de las actividades de la asignatura medicina general integral VII en los diferentes escenarios docentes

    Directory of Open Access Journals (Sweden)

    Maricel Felicia Castellanos González

    2012-06-01

    Full Text Available Fundamento: en el proceso de enseñanza-aprendizaje que se desarrolla en los diferentes escenarios docentes, se deben tener en cuenta los contenidos ya impartidos, para logar una integración entre los conocimientos teóricos con la práctica médica. Objetivo: evaluar los escenarios docentes según la calidad de las actividades desarrolladas en la asignatura medicina general integral VII, en el contexto del policlínico universitario. Método: se realizó una investigación cuanti-cualitativa según el cumplimiento de indicadores de calidad mediante la aplicación de una guía de observación en los escenarios docentes de la asignatura medicina general integral VII, en el policlínico universitario. Los escenarios docentes evaluados fueron: consultorios, vacunatorios, círculos infantiles, hogares maternos y consulta de planificación familiar. Resultados: el consultorio, el vacunatorio, la consulta de planificación familiar, la escuela y círculo infantil fueron evaluados de regular, solo obtuvieron categoría de bien el hogar materno y el escenario cuerpo de guardia. Las actividades docentes con mayores dificultades fueron: la vigilancia epidemiológica para la pesquisa de factores de riesgo, el control de foco para enfermedades transmisibles y la presentación del análisis de la situación de salud a la comunidad. Conclusiones: el nivel escenario docente en la asignatura medicina general integral VII, de forma general fue evaluado de regular, por tener: el escenario consultorio, el vacunatorio, consulta de planificación familiar, la escuela y círculo infantil evaluados de regular, el hogar materno y el escenario cuerpo de guardia evaluados de bien.

  15. Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential.

    Science.gov (United States)

    Anand, Sanjeev K; Gaba, Amit; Singh, Jaswant; Tikoo, Suresh K

    2014-02-01

    Viruses modulate the functions of mitochondria by translocating viral proteins to the mitochondria. Subcellular fractionation and sensitivity to proteinase K/Triton X-100 treatment of mitochondrial fractions of bovine adenovirus (BAdV)-3-infected/transfected cells suggested that core protein pVII localizes to the mitochondria and contains a functional mitochondrial localization signal. Moreover, mitochondrial localization of BAdV-3 pVII appears to help in the retention of mitochondrial Ca(2+), inducing a significant increase in the levels of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant effect on the levels of cytoplasmic Ca(2+) and reactive oxygen species production in the transfected cells. Consistent with these results, expression of pVII in transfected cells treated with staurosporine decreased significantly the activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by increasing mitochondrial Ca(2+) and ATP production.

  16. Heighten the Study on Factor Seven Activating Protease

    Institute of Scientific and Technical Information of China (English)

    贺石林; 陈方平; 张广森; 文志斌

    2008-01-01

    @@ Recent studies have showed that factor seven activating protease (FSAP) is a novel serine protease in human plasma. Immunoreactivity for FSAP has been observed in vascular endothelial cells,epithelial cells and macrophages but FSAP-specific mRNA expression only exists in the former two cells. FSAP has three epidermal growth factor (EGF) domains,a kringle domain and a serine protease domain.

  17. Physical activity and associated factors among students attending evening classes

    Directory of Open Access Journals (Sweden)

    Fabio Luis Ceschini

    2015-03-01

    Full Text Available The aim of this study was to describe the physical activity level and associated factors among students attending evening classes in public and private schools in a region of the city of São Paulo. The sample was composed of 1,844 adolescents of both sexes aged 15-20 years. Three public and private schools in the city of São Paulo were visited. Daily physical activity level was assessed through International Physical Activity Questionnaire that classifies physical activity level. Physical activity level was divided into insufficiently active (when subject reported less than 300 minutes of moderate to vigorous physical activities per week and physically active (when subject reported more than 300 minutes of moderate to vigorous physical activities per week. Information related to risk behavior such as smoking and alcohol consumption was collected. Data were analyzed using logistic regression with three levels of data input and p<.05 as significance level. The prevalence of physically active adolescents was 36.1%. Most active subjects were: A younger boys with low socioeconomic levels; B adolescents from private schools; C adolescents that do not smoke or drink alcoholic beverages; D those who do not attend formal exercise program; E those who go to school to perform physical activities on weekends. Adolescents attending evening classes tended to be insufficiently active. We believe that school structure, working hours, and distance from home and workplace to school and risk factor should explain these data. Intervention programs could significantly contribute to increase the physical activity level among adolescents.

  18. 40 CFR Appendix Vii to Part 266 - Health-Based Limits for Exclusion of Waste-Derived Residues*

    Science.gov (United States)

    2010-07-01

    ... Waste-Derived Residues* VII Appendix VII to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VII Appendix VII to Part 266—Health...

  19. Psychosocial factors associated with increased physical activity in insufficiently active adults with arthritis.

    Science.gov (United States)

    Peeters, G M E E Geeske; Brown, Wendy J; Burton, Nicola W

    2015-09-01

    Although physical activity can potentially reduce symptoms of arthritis, 50% of people with arthritis are insufficiently active. The aim was to identify psychosocial factors associated with increased physical activity in mid-age adults with arthritis who did not meet recommended physical activity levels. Longitudinal cohort study. Data were from 692 insufficiently active men and women (mean age 55 ± 6.6 years) with arthritis, who answered mailed surveys in 2007 and 2009 in the HABITAT study. Increased physical activity was defined as a change of ≥ 200 MET min/week in walking, moderate and vigorous activities from 2007 to 2009. Scale scores were used to measure psychosocial factors including intention, experiences, attitudes, efficacy, barriers, motivation, social support, and health professional advice. Associations between (1) 2007 psychosocial factors and (2) 2007-2009 improvement (≥ +1 standard deviation) in psychosocial factors and increased physical activity were examined with logistic regression models. Results were adjusted for education, body mass index, and self-rated health. Between 2007 and 2009, 296 participants (42.8%) increased their physical activity. Engagement, mastery and physical activity intention in 2007 were associated with this increase in physical activity (engagement OR = 1.11, 99% confidence interval (CI) = 1.05-1.17; mastery OR = 1.12, 99%CI = 1.02-1.22; physical activity intention OR = 1.29, 99%CI = 1.06-1.56). Improved scores for encouragement (OR = 2.07, CI = 1.07-4.01) and self-efficacy (OR =2 .27, CI = 1.30-3.97) were also significantly associated with increased physical activity. Positive physical activity experiences and intentions were predictors of increased physical activity among people with arthritis. Improved physical activity confidence and social support were associated with increased physical activity. It is important to consider these psychosocial factors when planning physical activity interventions for people with

  20. Factor H-related proteins determine complement-activating surfaces.

    Science.gov (United States)

    Józsi, Mihály; Tortajada, Agustin; Uzonyi, Barbara; Goicoechea de Jorge, Elena; Rodríguez de Córdoba, Santiago

    2015-06-01

    Complement factor H-related proteins (FHRs) are strongly associated with different diseases involving complement dysregulation, which suggests a major role for these proteins regulating complement activation. Because FHRs are evolutionarily and structurally related to complement inhibitor factor H (FH), the initial assumption was that the FHRs are also negative complement regulators. Whereas weak complement inhibiting activities were originally reported for these molecules, recent developments indicate that FHRs may enhance complement activation, with important implications for the role of these proteins in health and disease. We review these findings here, and propose that FHRs represent a complex set of surface recognition molecules that, by competing with FH, provide improved discrimination of self and non-self surfaces and play a central role in determining appropriate activation of the complement pathway.

  1. Factors Associated with Early Platelet Activation in Obese Children

    Science.gov (United States)

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  2. Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism.

    Science.gov (United States)

    Solomonson, Matthew; Setiaputra, Dheva; Makepeace, Karl A T; Lameignere, Emilie; Petrotchenko, Evgeniy V; Conrady, Deborah G; Bergeron, Julien R; Vuckovic, Marija; DiMaio, Frank; Borchers, Christoph H; Yip, Calvin K; Strynadka, Natalie C J

    2015-03-03

    Mycobacterium tuberculosis (Mtb) uses the ESX-1 type VII secretion system to export virulence proteins across its lipid-rich cell wall, which helps permeabilize the host's macrophage phagosomal membrane, facilitating the escape and cell-to-cell spread of Mtb. ESX-1 membranolytic activity depends on a set of specialized secreted Esp proteins, the structure and specific roles of which are not currently understood. Here, we report the X-ray and electron microscopic structures of the ESX-1-secreted EspB. We demonstrate that EspB adopts a PE/PPE-like fold that mediates oligomerization with apparent heptameric symmetry, generating a barrel-shaped structure with a central pore that we propose contributes to the macrophage killing functions of EspB. Our structural data also reveal unexpected direct interactions between the EspB bipartite secretion signal sequence elements that form a unified aromatic surface. These findings provide insight into how specialized proteins encoded within the ESX-1 locus are targeted for secretion, and for the first time indicate an oligomerization-dependent role for Esp virulence factors.

  3. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors.

    Science.gov (United States)

    Wright, Marilyn; Bryans, Angie; Gray, Kaylin; Skinner, Leah; Verhoeve, Amanda

    2013-01-01

    The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a "mixed methods" design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale-Adolescents, and the Amherst Health and Activity Study-Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  4. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors

    Directory of Open Access Journals (Sweden)

    Marilyn Wright

    2013-01-01

    Full Text Available The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a “mixed methods” design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale—Adolescents, and the Amherst Health and Activity Study—Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  5. Factors determining physical activity of Ukrainian students

    Directory of Open Access Journals (Sweden)

    Barbara Bergier

    2014-09-01

    Full Text Available [b]Objective[/b]. Scientific reports provide information concerning an insufficient level of physical activity of societies. The objective of the study is recognition of the level of physical activity among Ukrainian students, and factors which condition this activity: gender, place of residence, self-reported physical fitness, and the BMI. [b]Methods[/b]. The study was conducted in 2013 among 2,125 Ukrainian students using a long version of the International Physical Activity Questionnaire (IPAQ, supplemented with data concerning the respondents’ physical development. [b]Results[/b]. The results of the study showed that the mean total physical activity of students was 3.560 MET, and its highest percentage pertained to the area of activity in sports – 1.124 MET. Significantly higher statistically physical activity was observed among males than females. In males, the highest activity was related to participation in sports classes, while in females – engagement in household chores. It was found that males, compared to females, were significantly more physically active in such areas as occupational activity (education and sports activity, whereas females showed higher activity performing household chores. According to the place of residence, inhabitants of medium-size towns and rural areas obtained the most favourable results in activity, while the inhabitants of large cities the poorest. Self-reported physical fitness was significantly correlated with the results in physical activity obtained by the students. No relationship was found between the BMI and the level of student’s physical activity. [b]Conclusion[/b]. Considering the very large population of respondents, the results obtained may be considered as an up-to-date pattern of physical activity among Ukrainian students.

  6. Elevated plasma phospholipase A2 and platelet-activating factor acetylhydrolase activity in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yves Denizot

    2004-01-01

    Full Text Available This clinical study reports that blood levels of the pro-inflammatory mediator platelet-activating factor (PAF did not change in colorectal cancer patients. In contrast, plasma levels of two enzymatic activities, one implicated in PAF production (i.e. phospholipase A2 and one in PAF degradation (i.e. PAF acetylhydrolase activity were significantly elevated.

  7. The Geometrical Structure of the Tolman VII solution

    CERN Document Server

    Raghoonundun, Ambrish M

    2016-01-01

    The Tolman~VII solution, an exact analytic solution to the spherically symmetric, static Einstein equations with a perfect fluid source, has many characteristics that make it interesting for modelling high density physical astronomical objects. Here we supplement those characteristics with the geometrical tensors that this solution possess, and find that the Weyl, Riemann, and Ricci tensor components show unexpected mathematical behaviour that change depending on physically motivated parameters, even though the mass of the modelled objects is fixed. We show these features firstly through tensor components, and then through the scalars in the null tetrad formalism of Newmann and Penrose. The salient conclusion of this analysis is the intimate relationship between the Tolman~VII solution and the constant density Schwarzschild interior solution: the former being a straight forward generalization of the latter while eschewing the unphysical constant density.

  8. Experimental arterial thrombosis in genetically or diet induced hyperlipidemia in rats--role of vitamin K-dependent clotting factors and prevention by low-intensity oral anticoagulation.

    Science.gov (United States)

    De Curtis, A; D'Adamo, M C; Amore, C; Polishchuck, R; Castelnuovo, A D; Donati, M B; Iacoviello, L

    2001-12-01

    To investigate the relationship among lipids, coagulation and thrombosis in the absence of atherosclerosis, spontaneous or dietary-induced hyperlipidemic (FHL) rats were studied. FHL showed higher levels of coagulation factors VII, IX, X, VIII and XII and a shortening of the occlusion time (OT) of an artificial arterial prosthesis as compared with normolipidemic (FNL) animals. Damage of abdominal aorta of FHL was followed by increased fibrin deposition in the vascular intima as compared to FNL. After 5 months of cholesterol-rich diet FNL showed increased cholesterol, triglycerides and factor II, VII, IX, X, XII levels. A significant shortening of the OT and increased fibrin deposition was also observed. Two-month diet withdrawal restored the initial condition. Warfarin treatment, at a dose decreasing vitamin K-dependent factor to levels found in FNL, prolonged the OT and reduced fibrin deposition, without modifying F XII or changing lipid profile. An increase in the activated form of F VII was observed. In contrast, no difference was found in F VII clearance. High lipid levels favour the process of thrombus formation by increasing the activation of vitamin K-dependent coagulation factors. Low-dose warfarin treatment reverts the prothrombotic effect of hyperlipidemia.

  9. Cystine 186-cystine 209 disulfide bond is not essential for the procoagulant activity of tissue factor or for its de-encryption.

    Science.gov (United States)

    Kothari, Hema; Nayak, Ramesh C; Rao, L Vijaya Mohan; Pendurthi, Usha R

    2010-05-27

    Tissue factor (TF) on cell surfaces resides mostly in a cryptic state. It is not entirely clear how cryptic TF differs from procoagulantly active TF and how deencryption occurs. Here, we critically evaluated the importance of cystine 186-cystine 209 (Cys186-Cys209) bond formation for TF procoagulant activity and its de-encryption. Chinese hamster ovary cells transfected with TF(C186S), TF(C209S), or TF(C186S/C209S) expressed little procoagulant activity at the cell surface. TF monoclonal antibody and activated factor VII (FVIIa) binding studies showed that little TF protein was present at the cell surface in cells expressing mutant TF. Similar data were obtained in human umbilical vein endothelial cells (HUVECs) transduced to express TF(C186S), TF(C209S), or TF(C186S/C209S). Analysis of TF activity in HUVECs expressing similar levels of wild-type TF and TF(C186S/C209S) showed that TF mutant in the presence of saturating concentrations of FVIIa exhibited similar coagulant activity as that of wild-type TF. More importantly, treatment of HUVECs expressing TF(C186S/C209S) with HgCl(2) or ionomycin increased the cell-surface TF activity to the same extent as that of the wild-type TF. Our data provide clear evidence that TF lacking the Cys186-Cys209 bond is coagulantly active once it is complexed with FVIIa, and TF de-encryption does not require Cys186-Cys209 disulfide bond formation.

  10. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H;

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics...... tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results...... of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon...

  11. Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism.

    Science.gov (United States)

    Cantürk, Zeynep; Cetinarslan, Berrin; Tarkun, Ilhan; Cantürk, Nuh Zafer; Ozden, Meltem; Duman, Can

    2003-10-01

    Hypothyroidism has been associated with atherosclerosis. The mechanisms of atherosclerosis in patients with thyroid failure remain controversial. Hypofibrinolysis might be a risk factor for thromboembolic disease in subclinical hypothyroidism (SH). We measured fibrinolytic activity in patients with SH before and after levothyroxine (LT(4)) treatment and compared it to those of controls. We prospectively included 35 patients with SH and 30 healthy controls. We treated patients with LT(4) until almost 6 months after the euthyroid state has been achieved. We measured fibrinogen, D-dimer, antithrombin III (ATIII), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) activity, and factor VII. Clinical and anthropometric variables were recorded for both groups. We found increased levels of fibrinogen, PAI-1, and factor VII and decreased levels of ATIII activity in patients compared to control (p 0.05). At the end of the LT(4) treatment, significant decreases were determined in PAI-1 and factor VII (p < 0.05). In conclusion, our data suggest an important role of hypofibrinolytic and hypercoagulable state on the development of atherosclerosis in patients with SH and beneficial effects of LT(4 )treatment for decreasing the risk of atherosclerosis.

  12. CROSS SECTION EVALUATIONS FOR ENDF/B-VII.

    Energy Technology Data Exchange (ETDEWEB)

    HERMAN, M.; ROCHMAN, D.; OBLOZINSKY, P.

    2006-06-05

    This is the final report of the work performed under the LANL contract on neutron cross section evaluations for ENDF/B-VII (April 2005-May 2006). The purpose of the contract was to ensure seamless integration of the LANL neutron cross section evaluations in the new ENDF/B-VII library. The following work was performed: (1) LANL evaluated data files submitted for inclusion in ENDF/B-VII were checked and, when necessary, formal formatting errors were corrected. As a consequence, ENDF checking codes, run on all LANL files, do not report any errors that would rise concern. (2) LANL dosimetry evaluations for {sup 191}Ir and {sup 193}Ir were completed to match ENDF requirements for the general purpose library suitable for transport calculations. A set of covariances for both isotopes is included in the ENDF files. (3) Library of fission products was assembled and successfully tested with ENDF checking codes, processed with NJOY-99.125 and simple MCNP calculations. (4) KALMAN code has been integrated with the EMPIRE system to allow estimation of covariances based on the combination of measurements and model calculations. Covariances were produced for 155,157-Gd and also for 6 remaining isotopes of Gd.

  13. Impact of ENDF/B-VII.0 for AECL applications

    Energy Technology Data Exchange (ETDEWEB)

    Kozier, Ken S.; Altiparmakov, Dimitar V. [AECL - Chalk River Laboratories, Chalk River (Canada)

    2008-07-01

    This paper examines the impact of the new evaluated nuclear data library ENDF/B-VII.0 on selected reactor physics applications at AECL. The twin objectives are to provide feedback to the nuclear data community concerning the practical impact of their work and preliminary guidance to end-users. This work is based on comparison of the results of MCNP simulations with critical measurements involving both the ZED-2 zero power reactor and the MAPLE dedicated isotope production reactors at the Chalk River Laboratories. Significant improvement in the reactivity agreement with the measurements is obtained with ENDF/B-VII.0 for the specific ZED-2 measurements analysed; however, improvements associated with the thermal scattering law data for UO{sub 2} that had been observed initially were subsequently determined to be fortuitous, due to the inadvertent omission of the elastic neutron scattering component. Additionally, the net reactivity impact of major changes to the {sup 90}Zr and {sup 91}Zr capture cross sections with ENDF/B-VII.0 is examined in the MAPLE reactor context and found to be modest due primarily to the offsetting effects of the specific nuclides involved. (authors)

  14. The Education Innovator. Volume VII, No. 2

    Science.gov (United States)

    Schweitzer, Sherry, Ed.

    2009-01-01

    The purpose of the U.S. Department of Education's online newsletter "The Education Innovator" is to promote innovative practices in education; to offer features on promising programs and practices; to provide information on innovative research, schools, policies, and trends; and to keep readers informed of key Department priorities and activities.…

  15. Changes in CVD risk factors in the activity counseling trial

    Directory of Open Access Journals (Sweden)

    Meghan Baruth

    2011-01-01

    Full Text Available Meghan Baruth1, Sara Wilcox1, James F Sallis3, Abby C King4,5, Bess H Marcus6, Steven N Blair1,21Department of Exercise Science, 2Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Public Health Research Center, Columbia, SC, USA; 3Department of Psychology, San Diego State University, San Diego, CA, USA; 4Department of Health Research and Policy, 5Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; 6Behavioral and Social Sciences Section, Brown University Program in Public Health, Providence, RI, USAAbstract: Primary care facilities may be a natural setting for delivering interventions that focus on behaviors that improve cardiovascular disease (CVD risk factors. The purpose of this study was to examine the 24-month effects of the Activity Counseling Trial (ACT on CVD risk factors, to examine whether changes in CVD risk factors differed according to baseline risk factor status, and to examine whether changes in fitness were associated with changes in CVD risk factors. ACT was a 24-month multicenter randomized controlled trial to increase physical activity. Participants were 874 inactive men and women aged 35–74 years. Participants were randomly assigned to one of three arms that varied by level of counseling, intensity, and resource requirements. Because there were no significant differences in change over time between arms on any of the CVD risk factors examined, all arms were combined, and the effects of time, independent of arm, were examined separately for men and women. Time × Baseline risk factor status interactions examined whether changes in CVD risk factors differed according to baseline risk factor status. Significant improvements in total cholesterol, high-density lipoprotein cholesterol (HDL-C and low-density lipoprotein cholesterol, the ratio of total cholesterol to HDL-C, and triglycerides were seen in

  16. PENINGKATAN AKTIVITAS DAN HASIL BELAJAR MENGGUNAKAN METODE EKSPERIMEN PADA SISWA KELAS VII SMP NEGERI 1 PURBOLINGGO TAHUN PELAJARAN 2013/2014

    Directory of Open Access Journals (Sweden)

    Endang Kurniawati

    2014-03-01

    Full Text Available The purposeofthis studyis: to describethe use ofexperimental method sin enhancingthe activity oflearning physicsclass VII students of SMPN1Purbolinggoandto describethe use ofexperimentalmethodsin improvingstudentlearning outcomesphysicsclass VII SMP N 1 Purbolinggo.This study uses a Class Action Research and 4-cycle stages: planning, action, observation and reflection for further action. The study lasted 2 cycles each cycle consisting of 2 meetings. As the subjects in this study were VII.F grade students of SMP N 1 Purbolinggo of 40 people. Means of collecting data in the form of sheets of observations and tests. From the analysis and the results of this study concluded that the use of experimental methods in the learning process can improve the activity and student learning outcomes VII.F SMP N 1 Purbolinggo on the material and temperature measurements with an average of 11.56% increase in activity. Average learning outcomes increased by 55%. Thus it can be advisable for teachers to improve the activity and student learning outcomes using experimental methods.

  17. Factors Predicting Physical Activity Among Children With Special Needs

    Directory of Open Access Journals (Sweden)

    Shahram Yazdani, MD

    2013-07-01

    Full Text Available Introduction Obesity is especially prevalent among children with special needs. Both lack of physical activity and unhealthful eating are major contributing factors. The objective of our study was to investigate barriers to physical activity among these children. Methods We surveyed parents of the 171 children attending Vista Del Mar School in Los Angeles, a nonprofit school serving a socioeconomically diverse group of children with special needs from kindergarten through 12th grade. Parents were asked about their child’s and their own physical activity habits, barriers to their child’s exercise, and demographics. The response rate was 67%. Multivariate logistic regression was used to examine predictors of children being physically active at least 3 hours per week. Results Parents reported that 45% of the children were diagnosed with attention deficit hyperactivity disorder, 38% with autism, and 34% with learning disabilities; 47% of children and 56% of parents were physically active less than 3 hours per week. The top barriers to physical activity were reported as child’s lack of interest (43%, lack of developmentally appropriate programs (33%, too many behavioral problems (32%, and parents’ lack of time (29%. However, child’s lack of interest was the only parent-reported barrier independently associated with children’s physical activity. Meanwhile, children whose parents were physically active at least 3 hours per week were 4.2 times as likely to be physically active as children whose parents were less physically active (P = .01. Conclusion In this group of students with special needs, children’s physical activity was strongly associated with parental physical activity; parent-reported barriers may have had less direct effect. Further studies should examine the importance of parental physical activity among children with special needs.

  18. LPS-inducible factor(s) from activated macrophages mediates cytolysis of Naegleria fowleri amoebae

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, S.F.; Marciano-Cabral, F.

    1986-03-01

    Soluble cytolytic factors of macrophage origin have previously been described with respect to their tumoricidal activity. The purpose of this study was to investigate the mechanism and possible factor(s) responsible for cytolysis of the amoeba Naegleria fowleri by activated peritoneal macrophages from B6C3F1 mice. Macrophages or conditioned medium (CM) from macrophage cultures were incubated with /sup 3/H-Uridine labeled amoebae. Percent specific release of label served as an index of cytolysis. Bacille Calmette-Guerin (BCG) and Corynebacterium parvum macrophages demonstrated significant cytolysis of amoebae at 24 h with an effector to target ratio of 10:1. Treatment of macrophages with inhibitors of RNA or protein synthesis blocked amoebicidal activity. Interposition of a 1 ..mu..m pore membrane between macrophages and amoebae inhibited killing. Inhibition in the presence of the membrane was overcome by stimulating the macrophages with LPS. CM from SPS-stimulated, but not unstimulated, cultures of activated macrophages was cytotoxic for amoebae. The activity was heat sensitive and was recovered from ammonium sulfate precipitation of the CM. Results indicate that amoebicidal activity is mediated by a protein(s) of macrophage origin induced by target cell contact or stimulation with LPS.

  19. Potassium chloride-bearing ice VII and ice planet dynamics

    Science.gov (United States)

    Frank, Mark R.; Scott, Henry P.; Aarestad, Elizabeth; Prakapenka, Vitali B.

    2016-02-01

    Accurate modeling of planetary interiors requires that the pressure-volume-temperature (PVT) properties of phases present within the body be well understood. The high-pressure polymorphs of H2O have been studied extensively due to the abundance of ice phases in icy moons and, likely, vast number of extra-solar planetary bodies, with only select studies evaluating impurity-laden ices. In this study, ice formed from a 1.6 mol percent KCl-bearing aqueous solution was studied up to 32.89 ± 0.19 GPa and 625 K, and the incorporation of K+ and Cl- ionic impurities into the ice VII structure was documented. The compression data at 295 K were fit with a third order Birch-Murnaghan equation of state and yielded a bulk modulus (KT0), its pressure derivative (KT0‧), and zero pressure volume (V0) of 24.7 ± 0.9 GPa, 4.44 ± 0.09, and 39.2 ± 0.2 Å3, respectively. The impurity-laden ice was found to be 6-8% denser than ice VII formed from pure H2O. Thermal expansion coefficients were also determined for several isothermal compression curves at elevated temperatures, and a PVT equation of state was obtained. The melting curve of ice VII with incorporated K+ and Cl- was estimated by fitting experimental data up to 10.2 ± 0.4 GPa, where melting occurred at 625 K, to the Simon-Glatzel equation. The melting curve of this impurity-laden ice is systematically depressed relative to that of pure H2O by approximately 45 K and 80 K at 4 and 11 GPa, respectively. A portion of the K+ and Cl- contained within the ice VII structure was observed to exsolve with increasing temperature. This suggests that an internal differentiating process could concentrate a K-rich phase deep within H2O-rich planets, and we speculate that this could supply an additional source of heat through the radioactive decay of 40K. Our data illustrate ice VII can incorporate significant concentrations of K+ and Cl- and increasing the possibility of deep-sourced and solute-rich plumes in moderate to large sized H2O

  20. [Chemical tests with Marrubium species. Official data on Marubii herba in Pharmacopoeia Hungarica VII].

    Science.gov (United States)

    Telek, E; Tõth, L; Botz, L; Máthé, I

    1997-01-01

    About 40 species of the Marrubium genus (Lamiaceae) are known of which 2 species (M. vulgare L. and M. peregrinum L.) and one hybrid (M. x paniculatum Desr.) can be found as native plants in Hungary. The above-ground parts of M. vulgare L. are official in Hungarian Pharmacopoeia VII. Active substances in Marrubii herba are labdane-structured bitter materials. Although the presence of furanic labdane diterpenes in the plant is known, the pharmacopoeia gives only microscopic tests, qualitative tests (for other parts of the plant and foreign organic matter) for the bitter value of Marrubii herba. We have examined the main terpenoid substances isolated with column, gel and preparative layer chromatography. Structure elucidations were performed by means of UV, mass and NMR spectroscopy. We have compared the changes in terpenoid-type compounds (premarrubiin and marrubiin) in plants during the vegetation period; in different Marrubium species and in the different extractions of horehound by means of thin layer chromatography and densitometry. By reason of our results we propose qualitative and quantitative chemical tests for the paragraph of Marrubii herba in Pharmacopoeia Hungarica VII.

  1. The HI Chronicles of LITTLE THINGS BCDs: VII Zw 403’s External Gas Cloud

    Science.gov (United States)

    Ashley, Trisha L.; Simpson, Caroline E.; Elmegreen, Bruce; Johnson, Megan C.; Pokhrel, Nau Raj

    2017-01-01

    Blue compact dwarf (BCD) galaxies are characterized by their concentrated bursts of star formation. Yet, for many BCDs, it is unclear what has triggered this activity. VII Zw 403 is a well-known BCD that is relatively isolated from other galaxies. Using the high angular and velocity resolution Very Large Array (VLA) atomic hydrogen (HI) data from the LITTLE THINGS1 survey, we study the detailed kinematics and morphology of VII Zw 403’s HI gas. High sensitivity HI Green Bank Telescope (GBT) observations were also used to search the surrounding area for companion galaxies and extended HI emission, but they did not result in detections of either. The VLA data show a kinematically and morphologically disturbed HI disk. From the VLA HI data cubes, we have separated out most of the emission from what is likely an external gas cloud that is in the line of sight of the HI disk. This external gas cloud appears to be accreting onto the disk and could trigger a future burst of star formation. 1Local Irregulars That Trace Luminosity Extremes, The HI Nearby Galaxy Survey; https://science.nrao.edu/science/surveys/ littlethings

  2. Activating transcription factor 4 regulates osteoclast differentiation in mice

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L.; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G. David; Xiao, Guozhi

    2010-01-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4–/– bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4–/– BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity. PMID:20628199

  3. Activating transcription factor 4 regulates osteoclast differentiation in mice.

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G David; Xiao, Guozhi

    2010-08-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity.

  4. Platelet-activating factor in liver injury: A relational scope

    Institute of Scientific and Technical Information of China (English)

    Nikolaos P Karidis; Gregory Kouraklis; Stamatios E Theocharis

    2006-01-01

    The hepatocyte, the main cellular component of the liver, exhibits variable susceptibility to different types of injury induced by endogenous or exogenous factors.Hepatocellular dysfunction or death and regeneration are dependent upon the complicated interactions between numerous biologically active molecules. Plateletactivating factor (PAF) seems to play a pivotal role as the key mediator of liver injury in the clinical and experimental setting, as implied by the beneficial effects of its receptor antagonists. A comprehensive up-todate overview of the specific functional and regulatory properties of PAF in conditions associated with liver injury is attempted in this review.

  5. Factors related to physical activity: a study of adolescents.

    Science.gov (United States)

    Vilhjalmsson, R; Thorlindsson, T

    1998-09-01

    Although the consequences of physical activity have been carefully documented, less is known about its correlates, particularly among children and youth. Based on a representative national survey of 1131 Icelandic adolescents, the study examined various physical, psychological, social and demographic factors related to physical activity. Male sex, significant others' involvement in physical activity (father, friend and older brother), sociability, perceived importance of sport and of health improvement and satisfaction with mandatory gym classes in school, were all related to more involvement, whereas hours of paid work and TV-viewing were related to less. Furthermore, the data suggested that the influence of friend's participation in physical activity depends on his or her emotional significance. Influential others appeared to affect males and females in the same way. The meaning of the results and their implications for future research are discussed.

  6. VII Microquasar Workshop: Microquasars and Beyond

    Science.gov (United States)

    This workshop is the seventh of the series of conferences mainly devoted to Galactic black holes. The conference will cover all topics related to relativistic jet sources in the universe including microquasars, neutron stars, active galactic nuclei, and gamma-ray bursts. The results of the analysis of data from high energy missions (RXTE, Chandra, XMM-Newton, INTEGRAL, Swift, Suzaku, Agile) as well as from ground based observatories in the optical, infrared and radio bands will be presented. The emphasis will be on the formation and evolution of jets, and their relation to other accretion components. The broad context of the workshop will also allow researchers to present their results on the comparisons between microquasars, neutron stars, ultraluminous X-ray sources, active galactic nuclei and gamma-ray bursts. The workshop also intends to include presentations on recent missions (e.g. GLAST, ASTROSAT) and missions in preparation e.g. IXO concentrating on the prospects of black hole research with those missions. The program will be organized in sessions centered around a limited number of invited reviews, with contributed presentations and ample time for discussion. Young researchers will be encouraged to contribute.

  7. VII Latin American Congress on Biomedical Engineering

    CERN Document Server

    Bustamante, John; Sierra, Daniel

    2017-01-01

    This volume presents the proceedings of the CLAIB 2016, held in Bucaramanga, Santander, Colombia, 26, 27 & 28 October 2016. The proceedings, presented by the Regional Council of Biomedical Engineering for Latin America (CORAL), offer research findings, experiences and activities between institutions and universities to develop Bioengineering, Biomedical Engineering and related sciences. The conferences of the American Congress of Biomedical Engineering are sponsored by the International Federation for Medical and Biological Engineering (IFMBE), Society for Engineering in Biology and Medicine (EMBS) and the Pan American Health Organization (PAHO), among other organizations and international agencies to bring together scientists, academics and biomedical engineers in Latin America and other continents in an environment conducive to exchange and professional growth.

  8. Risk factors for glucose intolerance in active acromegaly

    Directory of Open Access Journals (Sweden)

    Kreze A.

    2001-01-01

    Full Text Available In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33% had diabetes mellitus and 2 (5%; 1-16% impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test. A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

  9. TALE factors poise promoters for activation by Hox proteins.

    Science.gov (United States)

    Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

    2014-01-27

    Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription.

  10. Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human.

    Science.gov (United States)

    Fukuda, Mitsunori; Ogata, Yukie; Saegusa, Chika; Kanno, Eiko; Mikoshiba, Katsuhiko

    2002-07-01

    Synaptotagmin VII (Syt VII) has been proposed to regulate several different types of Ca2+-dependent exocytosis, but its subcellular localization (lysosome or plasma membrane) and the number of alternative splicing isoforms of Syt VII (single or multiple forms) are matters of controversy. In the present study, we show by reverse transcriptase-PCR analysis that mouse Syt VII has one major isoform (Syt VIIalpha), the original Syt VII, and two minor isoforms (Syt VIIbeta and Syt VIIgamma), which contain unique insertions (of 44 and 116 amino acids respectively) in the spacer domain between the transmembrane and C2 domains of Syt VIIalpha. Similar results were obtained with respect to rat and human Syt VII mRNA expression. An antibody against the N-terminal domain of mouse Syt VII [anti-(Syt VII-N)], which specifically recognized recombinant Syt VII but not other Syt isoforms expressed in COS-7 cells, recognized two major, closely co-migrating bands (p58 and p60) and minor bands of approx. 65 kDa in mouse brain. Immunoaffinity purification of proteins that bind the anti-(Syt VII-N) antibody, and peptide sequence analysis revealed that: (i) the major p58 and p60 bands are identified as adenylate cyclase-associated protein 2; (ii) actin-binding protein is localized at the plasma membrane; and (iii) Syt VIIalpha (65 kDa) is the major Syt VII isoform, but with a much lower expression level than previously thought. It was also shown that FLAG-Syt VII-green-fluorescence-protein fusion protein stably expressed in PC12 cells is localized in the perinuclear region (co-localization with TGN38 protein, even after brefeldin A treatment) and in the tips of neurites (co-localization with Syt I), and not in the plasma membrane.

  11. Assessing the Subject General Medicine VII in the University Polyclinic Evaluación de la asignatura Medicina General Integral VII en el policlínico universitario

    Directory of Open Access Journals (Sweden)

    Cynthia Olivia Morales Pérez

    2012-06-01

    Full Text Available Background: the subject General Medicine VII is part of the guiding discipline in Medicine studies. It ensures that when Medicine Doctors obtain their degrees they have acquired all the knowledge that allows them to perform multiple tasks in health care services. Objective: to assess the subject General Medicine VII, in the university polyclinic as part of the educational process. Methods: we conducted a mixed research using quantitative and qualitative methods through a methodology that included the level of satisfaction of students, teachers, managers, and knowledge levels obtained by students. This methodology was applied in the fourth year of Medicine studies and in the four university polyclinics in the municipality of Cienfuegos, inserted into the new training model. Results: managers referred insufficient chances for exchanging with subordinates as well as for the profits of methodological activities, teachers were dissatisfied because of insufficient educational preparation and high work load and students reported difficulties with the availability and on-time delivery of textbooks, in addition to not having the necessary instrumentation for skills appropriation. Conclusions: we found that managers were dissatisfied with organizational and functional aspects, teachers with planning and implementation of the teaching process and students with the literature and the necessary tools while in teaching practice.Fundamento: la asignatura Medicina General Integral VII es parte de la disciplina rectora de la carrera de Medicina, que garantiza que una vez graduado el Médico General, posea conocimientos que le permitan desempeñar múltiples tareas en los servicios de atención médica. Objetivo: evaluar la asignatura Medicina General Integral VII en el policlínico universitario como parte del proceso docente educativo.

  12. Uudised : Baltimaade suurim, XII "Jazzkaar". VII rahvusvaheline koorifestival. Leipzigis improviseeriti edukalt

    Index Scriptorium Estoniae

    2001-01-01

    23.-29. apr. toimuvast festivalist "Jazzkaar 2001". VII rahvusvahelisest koorifestivalist "Tallinn "2001". 6. ja 7. apr. Leipzigis toimunud V rahvusvahelisest improvisatsioonikonkursist, kus osalesid ka eesti interpreedid

  13. Uudised : Baltimaade suurim, XII "Jazzkaar". VII rahvusvaheline koorifestival. Leipzigis improviseeriti edukalt

    Index Scriptorium Estoniae

    2001-01-01

    23.-29. apr. toimuvast festivalist "Jazzkaar 2001". VII rahvusvahelisest koorifestivalist "Tallinn "2001". 6. ja 7. apr. Leipzigis toimunud V rahvusvahelisest improvisatsioonikonkursist, kus osalesid ka eesti interpreedid

  14. Feedback activation of neurofibromin terminates growth factor-induced Ras activation

    OpenAIRE

    Hennig, Anne; Markwart, Robby; Wolff, Katharina; Schubert, Katja; Cui, Yan; Ian A Prior; Manuel A Esparza-Franco; Ladds, Graham; Rubio, Ignacio

    2016-01-01

    This is the final published version. It first appeared at http://biosignaling.biomedcentral.com/articles/10.1186/s12964-016-0128-z. Background Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleo...

  15. PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

    Directory of Open Access Journals (Sweden)

    Apri Dwi Astuti

    2012-10-01

    kriteria ketuntasan minimum (KKM � � Learning Independency is crucial for students. Additionality, learning independence helps students to be responsible and grows the willing of learning. The management of the use of pocket money creates a feeling of responsibility, commitment and discipline. The finale of this research to know learning independence and the use of pocket money influence the learning achievement in Economics subject on VII and VIII of SMP Semesta Boarding School in the Academic year of 2011/2012. The populations of this research are all VII and VIII grade studentsof SMP Semesta Boarding School. Learning Independency and The use of Pocket Money act as free variable, while students�learning achievement acts asbound variable. The data was gathered from interview, questionnaire and teacher�s documentation. The analysis of the data applies double regression linear analysis.Based on the double linear analysis simultaneously, it is revealed that Learning Independency and The use of Pocket Money influene� the learning achievement in Economics subject on VII and VIII until up to 51,3%. Partially, thev ariable of Learning Independency influence the learning achievement in Economics is 66,2% and The use of Pocket Money influene� the learning achievement in Economics is 62,5%.According to the result of the research above, it can be concluded that learning independence and the use of Pocket Money influence the learning independence and the use of pocket money influence the learning achievement of Econimics subject for VII and VIII grade of SMP Semesta Boarding School Semarang in the academic year of 2011/2012 on simultan and partially . Based on this research, hopefullythe, 1 School give a little change to student when they go home. 2 Parents observe give of pocket money by the students activity in the dormitory.3 student hopefully to progress their learning independency actually to the learning achievement that still under minimum criteria (KKM.

  16. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

    Science.gov (United States)

    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.

  17. Factors affecting perceived change in physical activity in pregnancy.

    Science.gov (United States)

    Merkx, Astrid; Ausems, Marlein; Budé, Luc; de Vries, Raymond; Nieuwenhuijze, Marianne J

    2017-08-01

    reduction of physical activity (PA) during pregnancy is common but undesirable, as it is associated with negative outcomes, including excessive gestational weight gain. Our objective was to explore changes in five types of activity that occurred during pregnancy and the behavioural determinants of the reported changes in PA. we performed a secondary analysis of a cross sectional survey that was constructed using the ASE-Model - an approach to identifying the factors that drive behaviour change that focuses on Attitude, Social influence, and self-Efficacy. 455 healthy pregnant women of all gestational ages, receiving prenatal care from midwifery practices in the Netherlands. more than half of our respondents reported a reduction in their PA during pregnancy. The largest reduction occurred in sports and brief rigorous activities, but other types of PA were reduced as well. Reduction of PA was more likely in women who considered themselves as active before pregnancy, women who experienced pregnancy-related barriers, women who were advised to reduce their PA, and multiparous women. Fewer than 5% increased their PA. Motivation to engage in PA was positively associated with enjoying PA. all pregnant women should be informed about the positive effects of staying active and should be encouraged to engage in, or to continue, moderately intensive activities like walking, biking or swimming. Our findings concerning the predictors of PA reduction can be used to develop an evidence-based intervention aimed at encouraging healthy PA during pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Modulation of topoisomerase activities by tumor necrosis factor.

    Science.gov (United States)

    Baloch, Z; Cohen, S; Fresa, K; Coffman, F D

    1995-01-01

    A number of chemotherapeutic agents which inhibit the DNA topoisomerases markedly potentiate cell death mediated by tumor necrosis factor, suggesting a role for these enzymes in the TNF cytotoxic mechanism. To investigate this possibility, topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition and returned to baseline levels within 1 and 2 hr, respectively. The increases in both topoisomerase activities were blocked by H-7 (but not H-8) and similar increases were seen following PMA addition. However, concentrations of H-7 which blocked the increased topoisomerase activities had no effect on TNF cytotoxicity nor on the enhancement of TNF cytotoxicity by topoisomerase inhibitors. Thus, in these cells topoisomerase activities are directly modified by TNF during the initial phases of a cytotoxic response. However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities.

  19. Pengembangan Vaksin Inaktif Tetelo Genotipe VII Isolat Lokal pada Kondisi Laboratorium. (DEVELOPMENT OF TETELO INACTIVATED VACCINE GENOTYPE VII LOCAL ISOLATE IN LABORATORY CONDITION

    Directory of Open Access Journals (Sweden)

    Risa Indriani

    2016-11-01

    Full Text Available Tetelo/Newcastle disease (ND inactive vaccine of genotipe VII virus local isolate have been developedin laboratory condition and compared with commercial ND vaccine. A total of 200 commercial layer chickenat 4 weeks age were divided into four groups, that were (1 vaccinated with ND genotype VII Indonesia/GTT/11, (2 vaccinated with commercial ND vaccine genotype VII, (3 vaccinated with commercial genotypeVI and (4 unvaccinated as control group. After two weeks post vaccination, 10 chicken from each groupwere sellected randomly and challenged with 105 EID50 per 0,1 mL of ND virus genotype VII Indonesian/GTT/11 by intramuscular. Chicken were observed, and swab were collected from oropharyngeal and cloacaat 2, 5, 7, 12 and 14 days post challenge. The result of this study showed inactived vaccine genotype VIIIndonesia/GTT/11 can induced a good antibody titer response to vaccinated chicken with mean titer 7.30log2 and CI 6.3 to 7.8, while commercial ND vaccine genotipe VII was 5.30 log2 with CI 3.8-6.7, andcommercial genotype VI was 4.8 log2 with CI 4.1-5.4. The level of protection which determined by noclinical signs, mortality and viral shedding showed 100% protection in chicken vaccinated with Indonesia/GTT/11 and commercial genotype VII were 100%, compared with control chicken, and vaccined commercialND vaccine genotype VII, compared with control chicken. While in chicken vaccinated commercial NDvaccine genotype VI showed viral shedding on day two post challenge, but there were no clinical sign andmortality. Based on this results, Indonesia/GTT/11 genotype VII ND vaccine could be used as an alternativeND vaccine to protect chicken from infection of ND virus genotype VII in the field.

  20. Time-activity relationships to VOC personal exposure factors

    Science.gov (United States)

    Edwards, Rufus D.; Schweizer, Christian; Llacqua, Vito; Lai, Hak Kan; Jantunen, Matti; Bayer-Oglesby, Lucy; Künzli, Nino

    Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and α-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, m- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in

  1. Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

    Science.gov (United States)

    Christiansen, Cory; Moore, Charity; Schenkman, Margaret; Kluger, Benzi; Kohrt, Wendy; Delitto, Anthony; Berman, Brian; Hall, Deborah; Josbeno, Deborah; Poon, Cynthia; Robichaud, Julie; Wellington, Toby; Jain, Samay; Comella, Cynthia; Corcos, Daniel; Melanson, Ed

    2017-04-01

    Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

  2. Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor.

    Science.gov (United States)

    Noga, O; Peiser, M; Altenähr, M; Knieling, H; Wanner, R; Hanf, G; Grosse, R; Suttorp, N

    2007-11-01

    Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well. The aim of this study was to investigate the influence of neurotrophins on DC function. Monocyte-derived dendritic cells were generated from allergic and non-allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull-down assays. DCs were incubated with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL-4, IL-6, IL-10, IL-12p70, TNF-alpha and TGF-beta. Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand-specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL-6, while for healthy subjects a significantly higher amount of IL-10 was found. These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor-dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T-helper type 2 response.

  3. Stellarator Wendelstein VII-AS; Physics and engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sapper, J.; Renner, H. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-01-01

    The advanced stellarator Wendelstein VII-AS is a medium-sized experimental machine with the following properties and aims: a broadly optimized magnetic configuration with improved plasma equilibrium and smaller neoclassical transport losses compared to classical stellarators; operation with net-current-free plasma; field generation with a modular set of coils instead of the conventional helix/toroidal field coil; system; and good access for plasma heating methods, e.g., neutral beam injection, electron cyclotron heating, and ion cyclotron heating. The physics characteristics and the engineering design of the experiment as well as results from the initial operation period are reported.

  4. [Activated protein C resistance and factor V Leiden: clinical interest].

    Science.gov (United States)

    Guermazi, S; Znazen, R

    2011-10-01

    Activated protein C resistance (APCR) is a coagulation abnormality often linked to FV Leiden mutation, a single nucleotide G1691A substitution resulting in arginine 506→glutamine missense factor V mutation. FV Leiden has a frequency of 20 to 30% in groups of patients with venous thrombosis while it is of 4 to 10% in normal subjects. FV Leiden is considered as a weak risk factor of thrombosis except in homozygote. FV Leiden is implicated in deep venous thrombosis occurrence. Duration of oral anticoagulant treatment is six months in patients developing a first venous thrombosis except in patients with combined defects or a clinical context suggesting a high risk of severe relapse. Detection of APCR by coagulation methods is often used in first intention with a high specificity if plasmas tested are diluted in factor V deficient plasma. Genotyping study is essential to establish the heterozygote or homozygote statute and certain teams perform it directly. Nevertheless, APCR not related to FV Leiden could be an independent thrombosis risk factor. APCR and FV Leiden are included in laboratory investigations of thrombophilic markers in patients less than 50 years with venous thrombosis. In arterial thrombosis, FV Leiden implication is weak or absent. FV Leiden increases the risk of thrombosis in other situations as in patients with cancer. An association with recurrent miscarriages and other vasculoplacental complications is also reported in many studies but the data concerning the efficacy of antithrombotic treatment to prevent recurrence are currently insufficient. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  5. The dust covering factor in active galactic nuclei

    CERN Document Server

    Stalevski, Marko; Ueda, Yoshihiro; Lira, Paulina; Fritz, Jacopo; Baes, Maarten

    2016-01-01

    The primary source of emission of active galactic nuclei (AGN), the accretion disk, is surrounded by an optically and geometrically thick dusty structure ("the so-called dusty torus"). The infrared radiation emitted by the dust is nothing but a reprocessed fraction of the accretion disk emission, so the ratio of the torus to the AGN luminosity ($L_{\\text{torus}}/L_{\\text{AGN}}$) should correspond to the fraction of the sky obscured by dust, i.e. the covering factor. We undertook a critical investigation of the $L_{\\text{torus}}/L_{\\text{AGN}}$ as the dust covering factor proxy. Using state-of-the-art 3D Monte Carlo radiative transfer code, we calculated a grid of SEDs emitted by the clumpy two-phase dusty structure. With this grid of SEDs, we studied the relation between $L_{\\text{torus}}/L_{\\text{AGN}}$ and the dust covering factor for different parameters of the torus. We found that in case of type 1 AGNs the torus anisotropy makes $L_{\\text{torus}}/L_{\\text{AGN}}$ underestimate low covering factors and ove...

  6. Effects of basic fibroblast growth factor on superoxide dismutase activity and malondialdehyde content in the rat brain following intracerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Hongqiao Wei; Juen Huang; Junjie Huang; Bing Li; Qianming Li

    2008-01-01

    BACKGROUND: Studies have confirmed that basic fibroblast growth factor (bFGF) promotes neuronal survival and neurite outgrowth. OBJECTIVE: To compare and verify the effects of bFGF on superoxide dismutase activity and malondialdehyde content in rat brain tissues surrounding a hemorrhagic lesion, as well as the hippocampus at the hemorrhagic side. DESIGN, TIME AND SETTING: The randomized, controlled, neurobiological study was performed at the Science Experimental Center and Research Laboratory, Guangxi Medical University, China, from September to December 2006. MATERIALS: Ninety-two adult, healthy, Wistar rats of equal gender were used to establish intraeerebral hemorrhage by infusing type VII collagenase into the left internal capsule. Type Ⅶ collagenase (Sigma, USA), superoxide dismutase and malondialdehyde kits (Jiancheng, China), and bFGF (Institute of Bioengineering, Ji'nan University, China) were used for this study. METHODS: Ninety successfully lesioned rats were equally and randomly divided into three groups. Rats in the bFGF group were intramuscularly injected daily with bFGF (8μg/kg). Rats in the saline control group received an equal volume of saline. The rats in the model group did not receive other interventions. Superoxide dismutase activity was measured using the xanthine oxidase method. Malondialdehyde contents were detected using the thiobarbituric acid method. MAIN OUTCOME MEASURES: At 1, 3, and 7 days following intracerebral hemorrhage, superoxide dismutase and malondialdehyde were determined in the brain tissue surrounding the hematoma and in the hippocampus in the affected hemisphere. RESULTS: In brain tissue surrounding the hematoma, superoxide dismutase activity was significantly increased in the bFGF group at 3 and 7 days after intracerebral hemorrhage compared with the saline control group, whereas malondialdehyde content was significantly decreased (P 0.05). CONCLUSION: Increased superoxide dismutase activity and decreased

  7. Enhanced imaging of DNA via active quality factor control

    Science.gov (United States)

    Humphris, A. D. L.; Round, A. N.; Miles, M. J.

    2001-10-01

    Adsorption processes at single molecule level are of fundamental importance for the understanding and development of biomaterials. Atomic force microscopy (AFM) has played a critical role in this field due to its high resolution and ability to image in a liquid environment. We present a method that improves the dynamic force sensitivity and the resolution of a conventional AFM. This is achieved via a positive feedback loop that enhances the effective quality factor of the cantilever in a liquid environment to values in excess of 300, compared to a nominal value of ˜1. This active quality factor enhancement has been used to image DNA and an increase in the height of the molecule observed.

  8. Report of material and equipment section`s activities at New York Shipbuilding Corporation during fabrication of AXC 167 1/2 starting May 18, 1951. Part 7, Section 1: Paragraphs 1--14

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, J.R.

    1954-02-28

    This document provides Part VII, Section I, Paragraphs 1 through 16 and Part VII, Section II of the Material and Equipment Section`s activities during the fabrication of reactor components and vessels at the New York Shipbuilding Corporation.

  9. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity.

    Science.gov (United States)

    Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun; Wang, Wei; Liu, Jing; Liu, Wei; Pan, Shaokun; Xie, Youhua

    2016-09-16

    Endogenous viral elements (EVE) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital for viral gene expression and replication. We previously identified in the budgerigar genome two EVEs that contain the full-length genome of an ancient budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2 Cp were active in several human and chicken cell lines. A region from nt -85 to -11 in eBHBV1 Cp was critical for the promoter activity. Bioinformatic analysis revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous transcription factor, at nt -64 to -50 in eBHBV1 Cp. The NF-Y core binding site (ATTGG, nt -58 to -54) was essential for eBHBV1 Cp activity. The same results were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y (NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated the promoter activity. Finally, the NF-Y core binding site is conserved in the Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses. Interestingly, a putative and functionally important NF-Y core binding site is located at nt -21 to -17 in the Cp of human hepatitis B virus. In conclusion, our findings have pinpointed an evolutionary conserved and functionally critical NF-Y binding element in the Cps of avihepadnaviruses.

  10. Pengembangan Perangkat Pembelajaran Strategi IDEAL Problem Solving Berbantuan Puzzquare Materi Luas Daerah Segiempat Kelas VII

    Directory of Open Access Journals (Sweden)

    Eny Susiana

    2011-12-01

    Full Text Available This research is classified as the developmental research. It develops learning materials using IDEAL problem solving strategy supported by Puzzquare for quadrilateral area for grade VII. The goals of this research are the development of learning materials using IDEAL problem solving strategy supported by Puzzquare is valid and learning process using that materials is effective. The development of learning materials on this research used 4-D model (Thiagarajan, Semmel and Semmel: (1 Define, (2 Design, (3 Develop, and (4 Disseminate. The developed learning-materials are (1 syllabus (2 lesson plan, (3 handbook, (4 student activity sheet, and (5 problem solving ability test. Keyword: The Development of Learning Material, IDEAL Problem Solving, Puzzquare

  11. Methods for Processing ENDF/B-VII with NJOY

    Science.gov (United States)

    MacFarlane, R. E.; Kahler, A. C.

    2010-12-01

    The NJOY Nuclear Data Processing System is widely used to convert evaluations in the Evaluated Nuclear Data Files (ENDF) format into forms useful for practical applications such as fission and fusion reactor analysis, stockpile stewardship calculations, criticality safety, radiation shielding, nuclear waste management, nuclear medicine procedures, and more. This paper provides a description of the system's capabilities, summary descriptions of the methods used, and information on how to use the code to process the modern evaluated nuclear data files from ENDF/B-VII. It begins with the generation of pointwise libraries, including reaction and resonance reconstruction, Doppler broadening, radiation heating and damage, thermal scattering data, unresolved resonance data, and gas production. It then reviews the production of libraries for the continuous-energy Monte Carlo code MCNP, multigroup neutron, photon, and particle cross sections and matrices, and photon interaction data. The generation of uncertainty information for ENDF data is discussed, including new capabilities for calculating covariances of resonance data, angular distributions, energy distributions, and radioactive nuclide production. NJOY's ability to prepare thermal scattering data evaluations for bound moderators (which was used during the preparation of the ENDF/B-VII library) is described. The strong plotting capabilities of NJOY are summarized. Many examples of black&white and color Postscript plots are included throughout the paper. The capabilities of NJOY to output multigroup data in several different formats to suit various applications is reviewed. Finally, a section is included that summarizes the history of the development of the NJOY system over the last 37 years.

  12. Delayed presentation of traumatic facial nerve (CN VII) paralysis.

    Science.gov (United States)

    Napoli, Anthony M; Panagos, Peter

    2005-11-01

    Facial nerve paralysis (Cranial Nerve VII, CN VII) can be a disfiguring disorder with profound impact upon the patient. The etiology of facial nerve paralysis may be congenital, iatrogenic, or result from neoplasm, infection, trauma, or toxic exposure. In the emergency department, the most common cause of unilateral facial paralysis is Bell's palsy, also known as idiopathic facial paralysis (IFP). We report a case of delayed presentation of unilateral facial nerve paralysis 3 days after sustaining a traumatic head injury. Re-evaluation and imaging of this patient revealed a full facial paralysis and temporal bone fracture extending into the facial canal. Because cranial nerve injuries occur in approximately 5-10% of head-injured patients, a good history and physical examination is important to differentiate IFP from another etiology. Newer generation high-resolution computed tomography (CT) scans are commonly demonstrating these fractures. An understanding of this complication, appropriate patient follow-up, and early involvement of the Otolaryngologist is important in management of these patients. The mechanism as well as the timing of facial nerve paralysis will determine the proper evaluation, consultation, and management for the patient. Patients with total or immediate paralysis as well as those with poorly prognostic audiogram results are good candidates for surgical repair.

  13. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    Science.gov (United States)

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  14. Factor XI and contact activation as targets for antithrombotic therapy.

    Science.gov (United States)

    Gailani, D; Bane, C E; Gruber, A

    2015-08-01

    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa (FXa) or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and FX. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that place them at unacceptable risk for hemorrhage. Studies in animals demonstrate that components of the plasma contact activation system contribute to experimentally induced thrombosis, despite playing little or no role in hemostasis. Attention has focused on FXII, the zymogen of a protease (FXIIa) that initiates contact activation when blood is exposed to foreign surfaces, and FXI, the zymogen of the protease FXIa, which links contact activation to the thrombin generation mechanism. In the case of FXI, epidemiologic data indicate this protein contributes to stroke and venous thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial showing that reduction of FXI may be more effective than low molecular weight heparin at preventing venous thrombosis during knee replacement surgery provides proof of concept for the premise that an antithrombotic effect can be uncoupled from an anticoagulant effect in humans by targeting components of contact activation. Here, we review data on the role of FXI and FXII in thrombosis and results of preclinical and human trials for therapies targeting these proteins.

  15. Role of PDI in regulating tissue factor: FVIIa activity.

    Science.gov (United States)

    Popescu, Narcis I; Lupu, Cristina; Lupu, Florea

    2010-04-01

    Cell exposed tissue factor (TF) is generally in a low procoagulant ("cryptic") state, and requires an activation step (decryption) to exhibit its full procoagulant potential. Recent data suggest that TF decryption may be regulated by the redox environment through the oxidoreductase activity of protein disulfide isomerase (PDI). In this article we review PDI contribution to different models of TF decryption, namely the disulfide switch model and the phosphatidylserine dynamics, and hypothesize on PDI contribution to TF self-association and association with lipid domains. Experimental evidence debate the disulfide switch model of TF decryption and its regulation by PDI. More recently we showed that PDI oxidoreductase activity regulates the phosphatidylserine equilibrium at the plasma membrane. Interestingly, PDI reductase activity could maintain TF in the reduced monomeric form, while also maintaining low exposure of PS, both states correlated with low procoagulant function. In contrast, PDI inhibition or oxidants may promote the adverse effects with a net increase in coagulation. The relative contribution of disulfide isomerization and PS exposure needs to be further analyzed to understand the redox control of TF procoagulant function. For the moment however TF regulation remains cryptic.

  16. Title VII Funding and Physician Practice in Rural or Low-Income Areas

    Science.gov (United States)

    Krist, Alex H.; Johnson, Robert E.; Callahan, David; Woolf, Steven H.; Marsland, David

    2005-01-01

    Whether Title VII funding enhances physician supply in underserved areas has not clearly been established. The purpose was to determine the relation between Title VII funding in medical school, residency, or both, and the number of family physicians practicing in rural or low-income communities. A retrospective cross sectional analysis was carried…

  17. 15 CFR Appendix Vii to Subpart P... - Areas To Be Avoided Boundary Coordinates

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Areas To Be Avoided Boundary Coordinates VII Appendix VII to Subpart P of Part 922 Commerce and Foreign Trade Regulations Relating to... Avoided Boundary Coordinates In The Vicinity of the Florida Keys Point Latitude Longitude 1 25°45.00′N...

  18. 20 CFR 211.12 - Compensation credited for title VII benefits.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compensation credited for title VII benefits... RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.12 Compensation credited for title VII benefits... as compensation only for the month in which the employee first filed an application for benefits...

  19. Thioredoxin interacting protein inhibits hypoxia-inducible factor transcriptional activity

    Science.gov (United States)

    Farrell, Michael R; Rogers, Lynette K; Liu, Yusen; Welty, Stephen E; Tipple, Trent E

    2010-01-01

    Vascular endothelial growth factor (VEGF) is required for proper lung development and is transcriptionally regulated in alveolar epithelial cells by hypoxia inducible factor (HIF). Previous findings in a newborn mouse model of bronchopulmonary dysplasia (BPD) suggest that thioredoxin interacting protein (Txnip) is a novel regulator of VEGF expression. The present studies were designed to test the hypothesis that Txnip negatively regulates VEGF through effects on HIF-mediated gene expression. To test this hypothesis, we first examined the levels of VEGF and Txnip protein in the lungs of 1 day-old newborn and E19 embryos and detected a significant inverse correlation. To elucidate the mechanisms underlying this relationship, we studied the effects of Txnip overexpression on HIF-mediated transcription using murine lung epithelial (MLE-12) cells. Overexpression of Txnip inhibited HIF-mediated reporter activity in both hypoxia and room air. Suppression of HIF activity by Txnip appeared to be independent of the ability of Txnip to bind to thioredoxin. Thus, our studies support a model in which Txnip is a potentially critical regulator of HIF-mediated gene transcription in the murine lung. Alterations in Txnip expression could alter lung VEGF expression in prematurely born human infants and contribute to the development of BPD. PMID:20692333

  20. IDENTIFICATION OF CRITICAL SSCM ACTIVITIES THROUGH CONFIRMATORY FACTOR ANALYSIS

    Directory of Open Access Journals (Sweden)

    V. Narasimham

    2013-06-01

    Full Text Available As a developing country, economic and environmental performance has to be balanced in India. Green supply chain management (GSCM is emerging as an important proactive approach for Indian enterprises for improving environmental performance of processes and products in accordance with the requirements of environmental regulations. This study examines the consistency approaches by confirmatory factor analysis that determines the construct validity, convergent validity,construct reliability and internal consistency of the items of Sustainable supply chain management (SSCM requirements. This study examines the consistency approaches by Confirmatory factor analysis that determines the adoption and implementation of Sustainable supply chain management activities in small & medium scale industries. The requirements include Management commitment, customer coordination, sustainable design & production, green procurement and eco logistics for sustainable supply chains. This study suggested that the five factor model with eighteen items of the sustainable supply chain design had a good fit. Further, the study showed a valid and reliable measurement to identify critical items among the requirements of sustainable supply chains.

  1. Factors associated with Spanish older people's membership in political organizations: the role of active aging activities.

    Science.gov (United States)

    Serrat, Rodrigo; Villar, Feliciano; Celdrán, Montserrat

    2015-09-01

    This study explores older people's membership in political organizations by using data from the Survey on older people 2010, carried out by Spain's National Institute for older people and social services. The objectives were to describe the extent of this kind of participation among Spaniards aged 65 and over, and to analyze the factors that are associated with it. Results show that only slightly less than 7 % of the sample belonged to a political organization. To analyze the factors related to this membership, a set of models of multivariate analyses were run, including socioeconomic resources and participation in other types of active aging activity (participation in leisure, learning, and productive activities). Educational level, leisure activities, learning activities, and only volunteering in the case of productive activities were found to be associated with membership in political organizations. Results provide partial support for the socioeconomic resources model and suggest that engagement in leisure activities, learning activities, and volunteering might have an enhancing effect on membership in political organizations.

  2. Arabidopsis sigma factor binding proteins are activators of the WRKY33 transcription factor in plant defense.

    Science.gov (United States)

    Lai, Zhibing; Li, Ying; Wang, Fei; Cheng, Yuan; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2011-10-01

    Necrotrophic pathogens are important plant pathogens that cause many devastating plant diseases. Despite their impact, our understanding of the plant defense response to necrotrophic pathogens is limited. The WRKY33 transcription factor is important for plant resistance to necrotrophic pathogens; therefore, elucidation of its functions will enhance our understanding of plant immunity to necrotrophic pathogens. Here, we report the identification of two WRKY33-interacting proteins, nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2, which also interact with plastid-encoded plastid RNA polymerase SIGMA FACTOR1. Both SIB1 and SIB2 contain an N-terminal chloroplast targeting signal and a putative nuclear localization signal, suggesting that they are dual targeted. Bimolecular fluorescence complementation indicates that WRKY33 interacts with SIBs in the nucleus of plant cells. Both SIB1 and SIB2 contain a short VQ motif that is important for interaction with WRKY33. The two VQ motif-containing proteins recognize the C-terminal WRKY domain and stimulate the DNA binding activity of WRKY33. Like WRKY33, both SIB1 and SIB2 are rapidly and strongly induced by the necrotrophic pathogen Botrytis cinerea. Resistance to B. cinerea is compromised in the sib1 and sib2 mutants but enhanced in SIB1-overexpressing transgenic plants. These results suggest that dual-targeted SIB1 and SIB2 function as activators of WRKY33 in plant defense against necrotrophic pathogens.

  3. Risk factors of falls in community dwelling active elderly.

    Science.gov (United States)

    Tuunainen, Eeva; Rasku, Jyrki; Jäntti, Pirkko; Pyykkö, Ilmari

    2014-02-01

    To search for measures to describe and relate to accidental falls in community dwelling elderly. A EuroQol EQ-5D questionnaire based on a patient's otoneurological case history provided a general health related quality of life measure, a fall history for the last 3 months and force platform measures for 96 active elderly from a pensioner organization. On average, the elderly experienced 0.3 falls over the preceding three months. A fall was seen to cause a significant deterioration in the quality of life and vertigo and caused fear of falling. The postural instability correlated with falls. Vertigo was present among 42% and was most commonly characterized as episodic and rotatory in factorial analysis items relating to vertigo correlated to falls and balance complaints. Four factors were identified and three of these correlated with falls. Vestibular failure correlated to a fall occurring when a person was rising up; Movement intolerance correlated with falls due to slips and trips, and Near-syncope factor correlated to falls for other reasons. In posturography, the variable measuring critical time describing the memory based "closed loop" control of postural stability carried a risk for accidental fall with an odds ratio of 6. The variable measuring zero crossing velocity showed a high rate of velocity change around the neutral position of stance. Vertigo and poor postural stability were the major reasons for falls in the active elderly. In ageing, postural control is shifted towards open loop control (visual, proprioception, exteroception and vestibular) instead of closed loop control and is a factor that contributes to a fall. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Coagulation Factor Xa inhibits cancer cell migration via Protease-activated receptor-1 activation

    NARCIS (Netherlands)

    Borensztajn, Keren; Bijlsma, Maarten F.; Reitsma, Pieter H.; Peppelenbosch, Maikel R.; Spek, C. Arnold

    2009-01-01

    Cell migration is critically important in (patho) physiological processes. The metastatic potential of cancer cells partly depends on activation of the coagulation cascade. The aim of the present study was to determine whether coagulation factor X (FXa) can regulate the migration and invasion of can

  5. Associations between Socio-Motivational Factors, Physical Education Activity Levels and Physical Activity Behavior among Youth

    Science.gov (United States)

    Ning, Weihong; Gao, Zan; Lodewyk, Ken

    2012-01-01

    This study examined the relationships between established socio-motivational factors and children's physical activity levels daily and during physical education classes. A total of 307 middle school students (149 boys, 158 girls) from a suburban public school in the Southern United States participated in this study. Participants completed…

  6. Arenavirus nucleoproteins prevent activation of nuclear factor kappa B.

    Science.gov (United States)

    Rodrigo, W W Shanaka I; Ortiz-Riaño, Emilio; Pythoud, Christelle; Kunz, Stefan; de la Torre, Juan C; Martínez-Sobrido, Luis

    2012-08-01

    Arenaviruses include several causative agents of hemorrhagic fever (HF) disease in humans that are associated with high morbidity and significant mortality. Morbidity and lethality associated with HF arenaviruses are believed to involve the dysregulation of the host innate immune and inflammatory responses that leads to impaired development of protective and efficient immunity. The molecular mechanisms underlying this dysregulation are not completely understood, but it is suggested that viral infection leads to disruption of early host defenses and contributes to arenavirus pathogenesis in humans. We demonstrate in the accompanying paper that the prototype member in the family, lymphocytic choriomeningitis virus (LCMV), disables the host innate defense by interfering with type I interferon (IFN-I) production through inhibition of the interferon regulatory factor 3 (IRF3) activation pathway and that the viral nucleoprotein (NP) alone is responsible for this inhibitory effect (C. Pythoud, W. W. Rodrigo, G. Pasqual, S. Rothenberger, L. Martínez-Sobrido, J. C. de la Torre, and S. Kunz, J. Virol. 86:7728-7738, 2012). In this report, we show that LCMV-NP, as well as NPs encoded by representative members of both Old World (OW) and New World (NW) arenaviruses, also inhibits the nuclear translocation and transcriptional activity of the nuclear factor kappa B (NF-κB). Similar to the situation previously reported for IRF3, Tacaribe virus NP (TCRV-NP) does not inhibit NF-κB nuclear translocation and transcriptional activity to levels comparable to those seen with other members in the family. Altogether, our findings demonstrate that arenavirus infection inhibits NF-κB-dependent innate immune and inflammatory responses, possibly playing a key role in the pathogenesis and virulence of arenavirus.

  7. Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.

    Science.gov (United States)

    Liang, Hai Po H; Kerschen, Edward J; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; Jia, Shuang; Hessner, Martin J; Toso, Raffaella; Rezaie, Alireza R; Fernández, José A; Camire, Rodney M; Ruf, Wolfram; Griffin, John H; Weiler, Hartmut

    2015-11-19

    The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylococcus aureus sepsis, we demonstrate marked disease stage-specific effects of the anticoagulant and cell signaling functions of aPC. aPC resistance of factor (f)V due to the R506Q Leiden mutation protected against detrimental anticoagulant effects of aPC therapy but also abrogated the anti-inflammatory and mortality-reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. We found that procofactor V (cleaved by aPC at R506) and protein S were necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The anti-inflammatory cofactor function of fV involved the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities did not involve proteolysis of activated coagulation factors Va and VIIIa. These findings reveal a novel biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of fV are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection.

  8. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  9. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

    Directory of Open Access Journals (Sweden)

    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  10. Coagulation Factor IX concentrate: method of preparation and assessment of potential in vivo thrombogenicity in animal models.

    Science.gov (United States)

    Menache, D; Behre, H E; Orthner, C L; Nunez, H; Anderson, H D; Triantaphyllopoulos, D C; Kosow, D P

    1984-12-01

    Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)-Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX) that is essentially free of prothrombin, factor VII, and factor X. Factor IX specific activity is at least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts of factors II, VII, and X are less than 5 units each per 100 units of factor IX. The concentrate is essentially free of activated clotting factors and contains no added heparin. In the rabbit stasis model, a dose of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the DEAE-Sephadex eluate from which the concentrate was derived. Infusion of 200 factor IX U/kg did not induce DIC in the nonstasis rabbit model, whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in this model. Several factor IX lots were found to have shortened nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic in both animal models. These data indicate that coagulation factor IX concentrate is less thrombogenic than factor IX complex.

  11. [Antifibrillatory activity of dipeptide antagonist of nerve growth factor].

    Science.gov (United States)

    Kryzhanovskiĭ, S A; Stoliarchuk, V N; Vititnova, M B; Tsorin, I B; Pekel'dina, E S; Gudasheva, T A

    2012-01-01

    In experiments on anesthetized rats were assessed antifibrillatoty action of dipeptide GK-1. This compound is the fragment of fourth loop of nerve growth factor (NGF) and manifests antagonistic activity in respect to TrkA receptor, that specified for NGF. It is shown that this compound is able to significantly increase the threshold of electrical fibrillation of the heart and its effectiveness is not inferior to the reference antiarrhythmics I and III class on Vaughan Williams classification. However, unlike the latter, antifibrillatory action of dipeptide GK-1 was delayed and realized within 40-60 minutes after its administration. It is discussed possible mechanisms underlying antifibrillatory action of dipeptide GK-1, that, to some extent, may be associated with its ability to change the reactivity of beta-adrenergic structures of the heart.

  12. Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKKε.

    Science.gov (United States)

    Pythoud, Christelle; Rodrigo, W W Shanaka I; Pasqual, Giulia; Rothenberger, Sylvia; Martínez-Sobrido, Luis; de la Torre, Juan Carlos; Kunz, Stefan

    2012-08-01

    Arenaviruses perturb innate antiviral defense by blocking induction of type I interferon (IFN) production. Accordingly, the arenavirus nucleoprotein (NP) was shown to block activation and nuclear translocation of interferon regulatory factor 3 (IRF3) in response to virus infection. Here, we sought to identify cellular factors involved in innate antiviral signaling targeted by arenavirus NP. Consistent with previous studies, infection with the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) prevented phosphorylation of IRF3 in response to infection with Sendai virus, a strong inducer of the retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling (MAVS) pathway of innate antiviral signaling. Using a combination of coimmunoprecipitation and confocal microscopy, we found that LCMV NP associates with the IκB kinase (IKK)-related kinase IKKε but that, rather unexpectedly, LCMV NP did not bind to the closely related TANK-binding kinase 1 (TBK-1). The NP-IKKε interaction was highly conserved among arenaviruses from different clades. In LCMV-infected cells, IKKε colocalized with NP but not with MAVS located on the outer membrane of mitochondria. LCMV NP bound the kinase domain (KD) of IKKε (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation. Together, our data identify IKKε as a novel target of arenavirus NP. Engagement of NP seems to sequester IKKε in an inactive complex. Considering the important functions of IKKε in innate antiviral immunity and other cellular processes, the NP-IKKε interaction likely plays a crucial role in arenavirus-host interaction.

  13. Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice.

    Science.gov (United States)

    Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

    2017-01-01

    Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5(-/-)) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5(-/-) mice were less aggressive than ATF5(+/+) mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5(-/-) mice and wild type littermates. ATF5(-/-) mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5(-/-) mice displayed reduced social interaction in the Crawley's social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5(-/-) mice compared with wild type. In addition, we demonstrated that ATF5(-/-) mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5(-/-) mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5(-/-) mice may be a unique animal model of some psychiatric disorders.

  14. Transcription factor PIF4 controls the thermosensory activation of flowering

    KAUST Repository

    Kumar, S. Vinod

    2012-03-21

    Plant growth and development are strongly affected by small differences in temperature. Current climate change has already altered global plant phenology and distribution, and projected increases in temperature pose a significant challenge to agriculture. Despite the important role of temperature on plant development, the underlying pathways are unknown. It has previously been shown that thermal acceleration of flowering is dependent on the florigen, FLOWERING LOCUS T (FT). How this occurs is, however, not understood, because the major pathway known to upregulate FT, the photoperiod pathway, is not required for thermal acceleration of flowering. Here we demonstrate a direct mechanism by which increasing temperature causes the bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) to activate FT. Our findings provide a new understanding of how plants control their timing of reproduction in response to temperature. Flowering time is an important trait in crops as well as affecting the life cycles of pollinator species. A molecular understanding of how temperature affects flowering will be important for mitigating the effects of climate change. © 2012 Macmillan Publishers Limited. All rights reserved.

  15. Observations on the nucleation of ice VII in compressed water

    Science.gov (United States)

    Stafford, Samuel J. P.; Chapman, David J.; Bland, Simon N.; Eakins, Daniel E.

    2017-01-01

    Water can freeze upon multiple shock compression, but the window material determines the pressure of the phase transition. Several plate impact experiments were conducted with liquid targets on a single-stage gas gun, diagnosed simultaneously using photonic doppler velocimetry (PDV) and high speed imaging through the water. The experiments investigated why silica windows instigate freezing above 2.5 GPa whilst sapphire windows do not until 7 GPa. We find that the nucleation of ice occurs on the surfaces of windows and can be affected by the surface coating suggesting the surface energy of fused silica, likely due to hydroxyl groups, encourages nucleation of ice VII crystallites. Aluminium coatings prevent nucleation and sapphire surfaces do not nucleate until approximately 6.5 GPa. This is believed to be the threshold pressure for the homogeneous nucleation of water.

  16. PSYCHOLOGICAL FACTORS OF LABOR ACTIVITY OF ELDERLY MAN

    Directory of Open Access Journals (Sweden)

    Lyusova O.V.

    2016-04-01

    Full Text Available In modern Russian society occurred deformation traditions of respect and maintain the credibility of the elderly, and the socio-economic situation has deteriorated. An important condition to characterize the elderly is related to labor activity. expressed doubts surrounding their professionalism and high-quality and modern education. In society there are negative stereotypes about the elderly: Edil accusations of conservatism, the inability to take risks, tolerance for young. Old age pensioners perceived themselves as age losses, shrinking circle of social contacts, there is social exclusion, significant interpersonal contacts become strained. The psychological diagnosis of labor socialization of older employees 40 people participated. Conducted an empirical study it possible to identify the factors of labor activity in old age: the age and state of health; desire to raise the level of material well-being, the need to work, enthusiasm labor process, achievement motivation, the need for communication with the team; desire for samooaktualizatsii, positive self-esteem, internal locus of control. Working pensioners have high situational anxiety, adequate to the achievement of the objectives, an adequate assessment of its internal and external quality, high life satisfaction, motivation tends to focus on the process and result, reflexivity, subjectivity, have no fear of being rejected, is well adapted to society. Workers older people have average values of introversion, neuroticism, psychoticism.

  17. Platelet-Activating Factor Induces Th17 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Anne-Marie Drolet

    2011-01-01

    Full Text Available Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.

  18. Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects

    DEFF Research Database (Denmark)

    Vanschoonbeek, Kristof; Feijge, Marion A H; Saris, Wim H M;

    2007-01-01

    determined partly the interindividual variation in thrombin generation, of which prothrombin and triacylglycerol concentrations were the main determinants. In both healthy subjects and diabetes patients, high triacylglycerol concentrations (>1.69 mmol/L) at baseline were closely linked to a strong fish oil......-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil....

  19. Complement factor B activation in patients with preeclampsia.

    Science.gov (United States)

    Velickovic, Ivan; Dalloul, Mudar; Wong, Karen A; Bakare, Olufunke; Schweis, Franz; Garala, Maya; Alam, Amit; Medranda, Giorgio; Lekovic, Jovana; Shuaib, Waqas; Tedjasukmana, Andreas; Little, Perry; Hanono, Daniel; Wijetilaka, Ruvini; Weedon, Jeremy; Lin, Jun; Toledano, Roulhac d'Arby; Zhang, Ming

    2015-06-01

    Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African-American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann-Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African-American patients' results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African-American patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2009-02-27

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  1. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  2. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive permane

  3. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  4. 99Tc(VII) Retardation, Reduction, and Redox Rate Scaling in Naturally Reduced Sediments

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yuanyuan; Liu, Chongxuan; Kukkadapu, Ravi K.; McKinley, James P.; Zachara, John M.; Plymale, Andrew E.; Miller, Micah D.; Varga, Tamas; Resch, Charles T.

    2015-10-15

    Abstract: An experimental and modeling study was conducted to investigate pertechnetate (Tc(VII)) retardation, reduction, and rate scaling in three sediments from Ringold formation at U.S. Department of Energy’s Hanford site, where 99Tc is a major contaminant in groundwater. Tc(VII) was reduced in all the sediments in both batch reactors and diffusion columns, with a faster rate in a sediment containing a higher concentration of HCl-extractable Fe(II). Tc(VII) migration in the diffusion columns was reductively retarded with retardation degrees correlated with Tc(VII) reduction rates. The reduction rates were faster in the diffusion columns than those in the batch reactors, apparently influenced by the spatial distribution of redox-reactive minerals along transport paths that supplied Tc(VII). X-ray computed tomography and autoradiography were performed to identify the spatial locations of Tc(VII) reduction and transport paths in the sediments, and results generally confirmed the newly found behavior of reaction rate changes from batch to column. The results from this study implied that Tc(VII) migration can be reductively retarded at Hanford site with a retardation degree dependent on reactive Fe(II) content and its distribution in sediments. This study also demonstrated that an effective reaction rate may be faster in transport systems than that in well-mixed reactors.

  5. Factoring - financial instrument supporting the current activity of an enterprise

    Directory of Open Access Journals (Sweden)

    Dorota Czerwińska-Kayzer

    2009-01-01

    Full Text Available Small and medium enterprises have a difficult access to classic financial sources. Therefore the factoring could be a financial instrument supporting effective management of the liabilities. Factoring improves the financial situation of a company, first of all financial liquidity. Moreover, factoring improves structure of financial statement and creates a possibility of risk transfer of debtor insolvency on factor.

  6. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Directory of Open Access Journals (Sweden)

    Pangburn Heather A

    2005-09-01

    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  7. The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects

    DEFF Research Database (Denmark)

    Jepsen, S; Hansen, A B

    1994-01-01

    The purpose of the study was to evaluate whether the infusion of N-acetylcysteine decreased the measurement of prothrombin time and activated partial thromboplastin time (APTT) in healthy persons. N-acetylcysteine was administered intraveneously 10 mg kg-1 as a loading dose and then at a rate of 10...... mg kg-1 h-1 for 32 h in six male subjects. The intrinsic, extrinsic and common pathway of coagulation were monitored with activated partial thromboplastin time (APTT), and prothrombin time, respectively. In addition, the extrinsic coagulation pathway was monitored with the clotting activity of single...... factors II, VII, and X. No effect on the intrinsic coagulation pathway was observed. There was a significant and rapid decrease in prothrombin time. Coagulation factors II, VII and X, the three components of prothrombin time, decreased significantly to different degrees. We conclude that infusion of N...

  8. Clinical and Epidemiological behavior of Acute Dentoalveolar Abscess in Patients of the Health Area VII in Cienfuegos

    Directory of Open Access Journals (Sweden)

    Ana Belkys Hernández Millán

    2015-02-01

    Full Text Available Background: acute dentoalveolar abscess is a dental emergency and one of the major condition affecting the population; however, there are few studies on the subject. Objective: to describe the clinical and epidemiological characteristics of acute dentoalveolar abscess in patients of the health area VII in Cienfuegos. Methods: a descriptive study was conducted from January to December 2013 in the Health Area VII, Cienfuegos. The universe consisted of 672 patients and the sample included 374 individuals selected by simple random sampling. Primary data recording and data collection was obtained from medical records prior informed consent of the patients. The main variables were age, sex, pulp irritating agents. Results: females were more affected with 55, 35% and the 19-34 year age group with 33.69%. The main pulp irritator was microbial, 59.36%. Among the iatrogenic factors, the remains of decayed tissues were significant with 32.35%. Conclusions: there is a high number of patients with acute dentoalveolar abscess, thus, as a dental emergency, the dentist should know the characteristics and factors that develop the disease to promote a comprehensive job in terms of health promotion, prevention, treatment and rehabilitation of affected patients.

  9. Immunomodulator CD200 promotes neurotrophic activity by interacting with and activating the fibroblast growth factor receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Bjornsdottir, Halla; Christensen, Claus;

    2016-01-01

    in the suppression of microglia activation. We for the first time demonstrated that CD200 can interact with and transduce signaling through activation of the fibroblast growth factor receptor (FGFR), thereby inducing neuritogenesis and promoting neuronal survival in primary neurons. CD200-induced FGFR...... phosphorylation was abrogated by CD200R, whereas FGF2-induced FGFR activation was inhibited by CD200. We also identified a sequence motif located in the first Ig-like module of CD200, likely representing the minimal CD200 binding site for FGFR. The FGFR binding motif overlaps with the CD200R binding site......, suggesting that they can compete for CD200 binding in cells that express both receptors. We propose that CD200 in neurons functions as a ligand of FGFR....

  10. Oxidatively fragmented phosphatidylcholines activate human neutrophils through the receptor for platelet-activating factor.

    Science.gov (United States)

    Smiley, P L; Stremler, K E; Prescott, S M; Zimmerman, G A; McIntyre, T M

    1991-06-15

    Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) activates neutrophils (polymorphonuclear leukocytes, PMN) through a receptor that specifically recognizes short sn-2 residues. We oxidized synthetic [2-arachidonoyl]phosphatidylcholine to fragment and shorten the sn-2 residue, and then examined the phospholipid products for the ability to stimulate PMN. 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine was fragmented by ozonolysis to 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine. This phospholipid activated human neutrophils at submicromolar concentrations, and is effects were inhibited by specific PAF receptor antagonists WEB2086, L659,989, and CV3988. 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine next was fragmented by an uncontrolled free radical-catalyzed reaction: it was treated with soybean lipoxygenase to form its sn-2 15-hydroperoxy derivative (which did not activate neutrophils) and then allowed to oxidize under air. The secondary oxidation resulted in the formation of numerous fragmented phospholipids (Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11095-11103), some of which activated PMN. Hydrolysis of sn-2 residues with phospholipase A2 destroyed biologic activity, as did hydrolysis with PAF acetylhydrolase. PAF acetylhydrolase is specific for short or intermediate length sn-2 residues and does not hydrolyze the starting material (Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11095-11103). Neutrophil activation was completely blocked by L659,989, a specific PAF receptor antagonist. We conclude that diacylphosphatidylcholines containing an sn-2 polyunsaturated fatty acyl residue can be oxidatively fragmented to species with sn-2 residues short enough to activate the PAF receptor of neutrophils. This suggests a new mechanism for the appearance of biologically active phospholipids, and shows

  11. Stimulation of Leishmania tropica protein kinase CK2 activities by platelet-activating factor (PAF).

    Science.gov (United States)

    Dutra, Patricia M L; Vieira, Danielle P; Meyer-Fernandes, Jose R; Silva-Neto, Mario A C; Lopes, Angela H

    2009-09-01

    Leishmania tropica is one of the causative agents of cutaneous leishmaniasis. Platelet-activating factor (PAF) is a phospholipid mediator in diverse biological and pathophysiological processes. Here we show that PAF promoted a three-fold increase on ecto-protein kinase and a three-fold increase on the secreted kinase activity of L. tropica live promastigotes. When casein was added to the reaction medium, along with PAF, there was a four-fold increase on the ecto-kinase activity. When live L. tropica promastigotes were pre-incubated for 30 min in the presence of PAF-plus casein, a six-fold increase on the secreted kinase activity was observed. Also, a protein released from L. tropica promastigotes reacted with polyclonal antibodies for the mammalian CK2 alpha catalytic subunit. Furthermore, in vitro mouse macrophage infection by L. tropica was doubled when promastigotes were pre-treated for 2 h with PAF. Similar results were obtained when the interaction was performed in the presence of purified CK2 or casein. TBB and DRB, CK2 inhibitors, reversed PAF enhancement of macrophage infection by L. tropica. WEB 2086, a competitive PAF antagonist, reversed all PAF effects here described. This study shows for the first time that PAF promotes the activation of two isoforms of CK2, secreted and membrane-bound, correlating these activities to infection of mouse macrophages.

  12. Technological organization of the first Neanderthal societies in the Cantabrian region. Interpreting the lithic industry and fauna from the lowermost levels (V, VI and VII of Lezetxiki cave

    Directory of Open Access Journals (Sweden)

    Talía LAZUÉN

    2012-07-01

    Full Text Available This article studies the technological organization of the first Neanderthal societies that inhabited the Cantabrian region. We use the information provided by the lithic industry excavated in the three lowermost levels (V, VI and VII of Lezetxiki cave. We also explore the other related evidences, especially those inferred from faunal remains. The analysis and explanation of the technical activities fits in a general perspective centered in the production-management-function subsystem.

  13. Technological organization of the first Neanderthal societies in the Cantabrian region. Interpreting the lithic industry and fauna from the lowermost levels (V, VI and VII) of Lezetxiki cave

    OpenAIRE

    Talía LAZUÉN; Altuna, Jesús

    2011-01-01

    This article studies the technological organization of the first Neanderthal societies that inhabited the Cantabrian region. We use the information provided by the lithic industry excavated in the three lowermost levels (V, VI and VII) of Lezetxiki cave. We also explore the other related evidences, especially those inferred from faunal remains. The analysis and explanation of the technical activities fits in a general perspective centered in the production-management-function subsystem. En...

  14. Factors influencing quality of life in patients with active tuberculosis

    Directory of Open Access Journals (Sweden)

    Cox Victoria C

    2004-10-01

    Full Text Available Abstract Background With effective treatment strategies, the focus of tuberculosis (TB management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. Methods English, Cantonese, and Punjabi-speaking subjects with active TB who were receiving treatment were eligible for recruitment into the study. Gender-based focus group sessions were conducted for the inner city participants but individual interviews were conducted for those who came to the main TB clinic or were hospitalized. Facilitators used open-ended questions and participants were asked to discuss their experiences of being diagnosed with tuberculosis, what impact it had on their lives, issues around adherence to anti-TB medications and information pertaining to their experience with side effects to these medications. All data were audio-recorded, transcribed verbatim, and analyzed using constant comparative analysis. Results 39 patients with active TB participated. The mean age was 46.2 years (SD 18.4 and 62% were male. Most were Canadian-born being either Caucasian or Aboriginal. Four themes emerged from the focus groups and interviews. The first describes issues related to the diagnosis of tuberculosis and sub-themes were identified as 'symptoms', 'health care provision', and 'emotional impact'. The second theme discusses TB medication factors and the sub-themes identified were 'adverse effects', 'ease of administration', and 'adherence'. The third theme describes social support and functioning issues for the individuals with TB. The fourth theme describes health behavior issues for the individuals with TB and the identified sub-themes were "behavior modification" and "TB knowledge." Conclusion Despite the ability to

  15. Influence of Environmental Factors on Feammox Activity in Soil Environments

    Science.gov (United States)

    Huang, S.; Jaffe, P. R.

    2015-12-01

    The oxidation of ammonium (NH4+) under iron reducing conditions, referred to as Feammox, has been described in recent years by several investigators. The environmental characteristics in which the Feammox process occurs need to be understood in order to determine its contribution to the nitrogen cycle. In this study, a total of 66 locations were selected covering 4 different types of soils/sediments: wetland soils (W), river sediments (R), forest soils (F), and paddy soils (P) from several locations in central New Jersey, at Tims Branch at Savannah River in South Carolina, both in the Unities States, and at several locations in the Guangdong province in China. Though soil chemical analyses, serial culturing experiments, analysis of microbial communities, and using a canonical correspondence analysis, the occurrence of the Feammox reaction and the presence of Acidimicrobiaceae bacterium A6, which plays a key role in the Feammox process(1), were found in 17 samples. Analyses showed that the soil pH, as well as its Fe(III) and NH4+ content were the most important factors controlling the distribution of these Feammox microorganisms. Based on the results, soils in the subtropical forests and soils that are near agricultural areas could be Feammox hotspot. Under the conditions that favor the presence and activity of Feammox microorganisms and their oxidation of NH4+, denitrification bacteria were also active. However, the presence of nitrous oxide (N2O) reducers was limited under these conditions, implying that at locations where the Feammox process is active, conditions are favoring a higher ratio of N2O: N2 as the nitrogen (N) end products. Incubations of soils where the presence of Acidimicrobiaceae bacterium A6 was detected, were conducted for 120 days under two different DO levels (DO ammonia-oxidizing bacteria and anammox bacteria) decreased, while in the incubations with DO = 0.8~1.0 mg/L the opposite trend was observed. References Huang S., and Jaffé P.R., 2015

  16. Activation of coagulation in chronic urticaria in relation to disease severity and activity.

    Science.gov (United States)

    Farres, M N; Refaat, M; Melek, N A; Ahmed, E E; Shamseldine, M G; Arafa, N A

    2015-01-01

    The pathogenesis of chronic urticaria is incompletely understood. There is growing interest in the role of the coagulation cascade in chronic urticaria. We aimed to assess the possible activation of the coagulation cascade in chronic spontaneous urticaria (CSU) in relation to disease severity and activity. This study was conducted on 30 patients with active CSU and 30 apparently healthy individuals as controls. Patients with acute urticaria, physical urticaria, or any form of urticaria other than spontaneous urticaria were excluded. Plasma levels of D-dimer and activated factor VII (FVIIa) were measured by ELISA at baseline for all recruited patients and controls. In addition, they were measured for CSU patients after complete disease remission. Plasma levels of D-dimer and FVIIa were significantly higher among patients with active CSU than among healthy controls. D-dimer levels were lowest among patients with grade 1 severity and highest among those with grade 4 severity. Factor VIIa levels did not differ significantly according to disease severity grades. After complete disease remission, there was a significant dramatic drop in levels of D-dimer and FVIIa among patients. We conclude that activation of the coagulation cascade occurs in CSU, and we demonstrate the novel finding that activated factor VII levels are significantly reduced after medical therapy, confirming the implication of the extrinsic pathway activation in CSU. Future controlled studies may investigate the role of anticoagulant therapy in refractory chronic urticaria. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  17. Physical activity in the prevention and amelioration of osteoporosis in women : interaction of mechanical, hormonal and dietary factors.

    Science.gov (United States)

    Borer, Katarina T

    2005-01-01

    Osteoporosis is a serious health problem that diminishes quality of life and levies a financial burden on those who fear and experience bone fractures. Physical activity as a way to prevent osteoporosis is based on evidence that it can regulate bone maintenance and stimulate bone formation including the accumulation of mineral, in addition to strengthening muscles, improving balance, and thus reducing the overall risk of falls and fractures. Currently, our understanding of how to use exercise effectively in the prevention of osteoporosis is incomplete. It is uncertain whether exercise will help accumulate more overall peak bone mass during childhood, adolescence and young adulthood. Also, the consistent effectiveness of exercise to increase bone mass, or at least arrest the loss of bone mass after menopause, is also in question. Within this framework, section 1 introduces mechanical characteristics of bones to assist the reader in understanding their responses to physical activity. Section 2 reviews hormonal, nutritional and mechanical factors necessary for the growth of bones in length, width and mineral content that produce peak bone mass in the course of childhood and adolescence using a large sample of healthy Caucasian girls and female adolescents for reference. Effectiveness of exercise is evaluated throughout using absolute changes in bone with the underlying assumption that useful exercise should produce changes that approximate or exceed the absolute magnitude of bone parameters in a healthy reference population. Physical activity increases growth in width and mineral content of bones in girls and adolescent females, particularly when it is initiated before puberty, carried out in volumes and at intensities seen in athletes, and accompanied by adequate caloric and calcium intakes. Similar increases are seen in young women following the termination of statural growth in response to athletic training, but not to more limited levels of physical activity

  18. Neutron Thermal Cross Sections, Westcott Factors, Resonance Integrals, Maxwellian Averaged Cross Sections and Astrophysical Reaction Rates Calculated from the ENDF/B-VII.1, JEFF-3.1.2, JENDL-4.0, ROSFOND-2010, CENDL-3.1 and EAF-2010 Evaluated Data Libraries

    Science.gov (United States)

    Pritychenko, B.; Mughabghab, S. F.

    2012-12-01

    We present calculations of neutron thermal cross sections, Westcott factors, resonance integrals, Maxwellian-averaged cross sections and astrophysical reaction rates for 843 ENDF materials using data from the major evaluated nuclear libraries and European activation file. Extensive analysis of newly-evaluated neutron reaction cross sections, neutron covariances, and improvements in data processing techniques motivated us to calculate nuclear industry and neutron physics quantities, produce s-process Maxwellian-averaged cross sections and astrophysical reaction rates, systematically calculate uncertainties, and provide additional insights on currently available neutron-induced reaction data. Nuclear reaction calculations are discussed and new results are presented. Due to space limitations, the present paper contains only calculated Maxwellian-averaged cross sections and their uncertainties. The complete data sets for all results are published in the Brookhaven National Laboratory report.

  19. Neutron Thermal Cross Sections, Westcott Factors, Resonance Integrals, Maxwellian Averaged Cross Sections and Astrophysical Reaction Rates Calculated from the ENDF/B-VII.1, JEFF-3.1.2, JENDL-4.0, ROSFOND-2010, CENDL-3.1 and EAF-2010 Evaluated Data Libraries

    Energy Technology Data Exchange (ETDEWEB)

    Pritychenko, B. [National Nuclear Data Center, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Mughabghab, S.F. [National Nuclear Data Center, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States)

    2012-12-15

    We present calculations of neutron thermal cross sections, Westcott factors, resonance integrals, Maxwellian-averaged cross sections and astrophysical reaction rates for 843 ENDF materials using data from the major evaluated nuclear libraries and European activation file. Extensive analysis of newly-evaluated neutron reaction cross sections, neutron covariances, and improvements in data processing techniques motivated us to calculate nuclear industry and neutron physics quantities, produce s-process Maxwellian-averaged cross sections and astrophysical reaction rates, systematically calculate uncertainties, and provide additional insights on currently available neutron-induced reaction data. Nuclear reaction calculations are discussed and new results are presented. Due to space limitations, the present paper contains only calculated Maxwellian-averaged cross sections and their uncertainties. The complete data sets for all results are published in the Brookhaven National Laboratory report.

  20. Final Report: Stability of U (VII) and Tc (VII) Reducing Microbial Communities To Environmental Perturbation

    Energy Technology Data Exchange (ETDEWEB)

    Istok, Jonathan D

    2008-07-07

    'Bioimmobilization' of redox-sensitive metals and radionuclides is being investigated as a way to remediate contaminated groundwater and sediments. In this approach, growth-limiting substrates are added to stimulate the activity of targeted groups of indigenous microorganisms and create conditions favorable for the microbially-mediated precipitation ('bioimmobilization') of targeted contaminants. This project investigated a fundamentally new approach for modeling this process that couples thermodynamic descriptions for microbial growth with associated geochemical reactions. In this approach, a synthetic microbial community is defined as a collection of defined microbial groups; each with a growth equation derived from bioenergetic principles. The growth equations and standard-state free energy yields are appended to a thermodynamic database for geochemical reactions and the combined equations are solved simultaneously to predict the effect of added substrates on microbial biomass, community composition, and system geochemistry. This approach, with a single set of thermodynamic parameters (one for each growth equation), was used to predict the results of laboratory and field bioimmobilization experiments at two geochemically diverse research sites. Predicted effects of ethanol or acetate addition on uranium and technetium solubility, major ion geochemistry, mineralogy, microbial biomass and community composition were in general agreement with experimental observations although the available experimental data precluded rigorous model testing. Model simulations provide insight into the long-standing difficulty in transferring experimental results from the laboratory to the field and from one field site to the next, especially if the form, concentration, or delivery of growth substrate is varied from one experiment to the next. Although originally developed for use in better understanding bioimmobilization of uranium and technetium via reductive

  1. ICSBEP Criticality Benchmark Eigenvalues with ENDF/B-VII.1 Cross Sections

    Energy Technology Data Exchange (ETDEWEB)

    Kahler, Albert C. III [Los Alamos National Laboratory; MacFarlane, Robert [Los Alamos National Laboratory

    2012-06-28

    We review MCNP eigenvalue calculations from a suite of International Criticality Safety Benchmark Evaluation Project (ICSBEP) Handbook evaluations with the recently distributed ENDF/B-VII.1 cross section library.

  2. Design and engineering aspects of the main components for the Wendelstein VII-AS stellarator experiment

    Energy Technology Data Exchange (ETDEWEB)

    Mathis, R.; Sapper, J. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-02-01

    In this paper the design of the essential components of the newly constructed Wendelstein VII-AS stellarator experiment at Garching are described, and the first technical and experimental results are reported. (orig.).

  3. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: Efficacy of vaccination

    Science.gov (United States)

    Here we describe the characterization a virulent genotype VII Newcastle disease virus (NDV) from Venezuela and evaluate the efficacy of heterologous genotype commercial vaccination under field and controlled rearing conditions. Biological pathotyping and molecular analysis were applied. Results sh...

  4. Genome-wide signatures of transcription factor activity: connecting transcription factors, disease, and small molecules.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    Full Text Available Identifying transcription factors (TF involved in producing a genome-wide transcriptional profile is an essential step in building mechanistic model that can explain observed gene expression data. We developed a statistical framework for constructing genome-wide signatures of TF activity, and for using such signatures in the analysis of gene expression data produced by complex transcriptional regulatory programs. Our framework integrates ChIP-seq data and appropriately matched gene expression profiles to identify True REGulatory (TREG TF-gene interactions. It provides genome-wide quantification of the likelihood of regulatory TF-gene interaction that can be used to either identify regulated genes, or as genome-wide signature of TF activity. To effectively use ChIP-seq data, we introduce a novel statistical model that integrates information from all binding "peaks" within 2 Mb window around a gene's transcription start site (TSS, and provides gene-level binding scores and probabilities of regulatory interaction. In the second step we integrate these binding scores and regulatory probabilities with gene expression data to assess the likelihood of True REGulatory (TREG TF-gene interactions. We demonstrate the advantages of TREG framework in identifying genes regulated by two TFs with widely different distribution of functional binding events (ERα and E2f1. We also show that TREG signatures of TF activity vastly improve our ability to detect involvement of ERα in producing complex diseases-related transcriptional profiles. Through a large study of disease-related transcriptional signatures and transcriptional signatures of drug activity, we demonstrate that increase in statistical power associated with the use of TREG signatures makes the crucial difference in identifying key targets for treatment, and drugs to use for treatment. All methods are implemented in an open-source R package treg. The package also contains all data used in the analysis

  5. Mechanism of surface-mediated activation of bovine Factor XII and prekallikrein.

    Science.gov (United States)

    Sugo, T; Ohno, Y; Shimada, T; Kato, H; Iwanaga, S

    1983-01-01

    The mechanism of kaolin-mediated activation of bovine Factor XII was studied in the presence of prekallikrein and HMW kininogen. The activated enzymes were assayed using fluorogenic peptides, Boc-Glu (OBzl)-Gly-Arg-4-methylcoumaryl-7-amide (MCA) for Factor XIIa and Z-Phe-Arg-MCA for plasma kallikrein. The rates of activation of the zymogens were separately measured by blocking either of the active enzymes with specific inhibitors, corn inhibitor for Factor XIIa (Ki = 6.7 nM) and Trasylol for plasma kallikrein (Ki = 3.9 nM). The result was as follows: (1) At the early stage of the activation reaction, kallikrein activity was first generated after short lag time, and then Factor XIIa activity was generated with a sigmoidal curve. In the presence of corn inhibitor, the activation of prekallikrein was observed, but in the presence of Trasylol, the activation of Factor XII was not observed. In the presence of high concentration of Ala-Phe-Arg-Ch2Cl, which inactivates immediately both of the active enzymes, the cleavage of a single chain prekallikrein into the two chain form by Factor XII was shown by SDS-PAGE, using nonlabelled and tritiated prekallikrein. (2) The incubation of Factor XII alone in a quartz cuvette or in the presence of kaolin and HMW kininogen did not result in the activation of Factor XII. The concave upward curve due to an autocatalytic activation was not observed even after the addition of Factor XIIa to Factor XII preparation. Moreover, no structural change of Factor XII during the incubation with kaolin and HMW kininogen was shown by SDS-PAGE, using 3H-Factor XII. (3) The rates of activation of prekallikrein by Factor XII and by Factor XIIa were approximately the same at higher concentration of prekallikrein. However, at lower concentration of prekallikrein the rate of activation of prekallikrein by Factor XII was shown to be a sigmoidal curve and slower than that by Factor XIIa. These results indicate that the activation of bovine Factor XII is

  6. Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants.

    Science.gov (United States)

    Jantan, I; Rafi, I A A; Jalil, J

    2005-01-01

    Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).

  7. The Trigeminal (V) and Facial (VII) Cranial Nerves: Head and Face Sensation and Movement

    OpenAIRE

    Sanders, Richard D.

    2010-01-01

    There are close functional and anatomical relationships between cranial nerves V and VII in both their sensory and motor divisions. Sensation on the face is innervated by the trigeminal nerves (V) as are the muscles of mastication, but the muscles of facial expression are innervated mainly by the facial nerve (VII) as is the sensation of taste. This article briefly reviews the anatomy of these cranial nerves, disorders of these nerves that are of particular importance to psychiatry, and some ...

  8. Partial agonism through a zinc-Ion switch constructed between transmembrane domains III and VII in the tachykinin NK(1) receptor

    DEFF Research Database (Denmark)

    Holst, B; Elling, C E; Schwartz, T W

    2000-01-01

    Partly due to lack of detailed knowledge of the molecular recognition of ligands the structural basis for partial versus full agonism is not known. In the beta(2)-adrenergic receptor the agonist binding site has previously been structurally and functionally exchanged with an activating metal......-ion site located between AspIII:08-or a His residue introduced at this position in transmembrane domain (TM)-III-and a Cys residue substituted for AsnVII:06 in TM-VII. Here, this interhelical, bidentate metal-ion site is without loss of Zn(2+) affinity transferred to the tachykinin NK(1) receptor....... In contrast to the similarly mutated beta(2)-adrenergic receptor, signal transduction-i.e., inositol phosphate turnover-could be stimulated by both Zn(2+) and by the natural agonist, Substance P in the mutated NK(1) receptor. The metal-ion acted as a 25% partial agonist through binding to the bidentate zinc...

  9. Onset of ice VII phase during ps laser pulse propagation through liquid water

    Science.gov (United States)

    Kumar, V. Rakesh; Kiran, P. Prem

    2017-01-01

    Water dominantly present in liquid state on earth gets transformed to crystalline polymorphs under different dynamic loading conditions. Out of different crystalline phases discovered till date, ice VII is observed to be stable over wide pressure (2-63 GPa) and temperature (>273 K) ranges. The formation of ice VII crystalline structure has been vastly reported during high pressure static compression using diamond anvil cell and propagation of high energy (>50 mJ/pulse) nanosecond laser pulse induced dynamic high pressures through liquid water. We present the onset of ice VII phase at low threshold of 2 mJ/pulse during 30 ps (532 nm, 10 Hz) laser pulse induced shock propagating through liquid water. Role of input pulse energy on the evolution of Stoke's and anti-Stoke's Raman shift of the dominant A1g mode of ice VII, filamentation, free-electrons, plasma shielding is presented. The H-bond network rearrangement, electron ion energy transfer time coinciding with the excitation pulse duration supported by the filamentation and plasma shielding of the ps laser pulses reduced the threshold of ice VII structure formation. Filamentation and the plasma shielding have shown the localized creation and sustenance of ice VII structure in liquid water over 3 mm length and 50 μm area of cross-section.

  10. Energy levels and radiative rates for transitions in Ti VII

    CERN Document Server

    Aggarwal, KM

    2013-01-01

    We report calculations of energy levels, radiative rates, oscillator strengths and line strengths for transitions among the lowest 231 levels of Ti VII. The general-purpose relativistic atomic structure package ({\\sc grasp}) and flexible atomic code ({\\sc fac}) are adopted for the calculations. Radiative rates, oscillator strengths and line strengths are provided for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions among the 231 levels, although calculations have been performed for a much larger number of levels (159,162). In addition, lifetimes for all 231 levels are listed. Comparisons are made with existing results and the accuracy of the data is assessed. In particular, the most recent calculations reported by Singh {\\em et al} [Can J. Phys. {\\bf 90} (2012) 833] are found to be unreliable, with discrepancies for energy levels of up to 1 Ryd and for radiative rates of up to five orders of magnitude for several transitions, particularly the we...

  11. Collagen VII plays a dual role in wound healing.

    Science.gov (United States)

    Nyström, Alexander; Velati, Daniela; Mittapalli, Venugopal R; Fritsch, Anja; Kern, Johannes S; Bruckner-Tuderman, Leena

    2013-08-01

    Although a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds.

  12. Evaluación de la asignatura Medicina General Integral VII en el policlínico universitario

    Directory of Open Access Journals (Sweden)

    Cynthia Olivia Morales Pérez

    2012-06-01

    Full Text Available Background: the subject General Medicine VII is part of the guiding discipline in Medicine studies. It ensures that when Medicine Doctors obtain their degrees they have acquired all the knowledge that allows them to perform multiple tasks in health care services. Objective: to assess the subject General Medicine VII, in the university polyclinic as part of the educational process. Methods: we conducted a mixed research using quantitative and qualitative methods through a methodology that included the level of satisfaction of students, teachers, managers, and knowledge levels obtained by students. This methodology was applied in the fourth year of Medicine studies and in the four university polyclinics in the municipality of Cienfuegos, inserted into the new training model. Results: managers referred insufficient chances for exchanging with subordinates as well as for the profits of methodological activities, teachers were dissatisfied because of insufficient educational preparation and high work load and students reported difficulties with the availability and on-time delivery of textbooks, in addition to not having the necessary instrumentation for skills appropriation. Conclusions: we found that managers were dissatisfied with organizational and functional aspects, teachers with planning and implementation of the teaching process and students with the literature and the necessary tools while in teaching practice.

  13. State support as factor of increase of innovative activity of industrial enterprises

    Directory of Open Access Journals (Sweden)

    N.N. Bondarenko

    2011-10-01

    Full Text Available The article is devoted research of factors of increase of innovative activity of enterprise, the indexes of innovative activity of industrial enterprises are analysed in Ukraine, the necessity of creation of attractive terms is grounded for development of innovative activity and increase of innovative activity of management subjects at state level, the forms of state support as factor of increase of innovative activity of industrial enterprises are considered.

  14. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  15. Technetium (VII) fixation in synthetic oxides under aerobic conditions; Fijacion de tecnecio (VII) en oxidos sinteticos en condiciones aerobicas

    Energy Technology Data Exchange (ETDEWEB)

    Arizpe M, L. G. [Instituto Tecnologico de Toluca, Av. Tecnologico s/n, Fraccionamiento La Virgen, 52149 Metepec, Estado de Mexico (Mexico); Badillo A, V. E., E-mail: letygame_06@hotmail.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2012-10-15

    The retention of fission products as the technetium in different materials to observe the behavior of anionic species, present in the spent fuel, is of vital importance in the evaluation of the safety of a radioactive waste storage. The radionuclide {sup 99}Tc is one of the fission products of long half life of 2.11 X 10{sup 5} years, which could be liberated in the underground waters that surround to a geologic warehouse of high level wastes, in the chemical form TcO{sub 4}{sup -}, which prevails in aerated solutions since is extremely soluble. In this work was evaluated the use of synthetic oxides as potential adsorbents of the radioactive technetium and to study the importance of the superficial properties of these solids in the radionuclide migration. Two synthetic oxides were studied, the titanium and aluminium oxide. The results demonstrate that the retention of Tc (VII) under aerobic conditions of the solution is worthless in the interval of studied ph of 4 at 9 for both solids; however when the ph of the solution diminishes to ph values of 3, important kD are obtained in the case of the titanium oxide, what shows the importance of the surface properties of these oxides to interpret the radionuclide retention. (Author)

  16. Factor XI and Contact Activation as Targets for Antithrombotic Therapy

    OpenAIRE

    Gailani, David; Bane, Charles E.; Gruber, Andras

    2015-01-01

    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa, or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and factor X. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that ...

  17. A novel family VII esterase with industrial potential from compost metagenomic library

    Directory of Open Access Journals (Sweden)

    Oh Tae-Kwang

    2011-05-01

    Full Text Available Abstract Background Among the vast microbial genomic resources now available, most microbes are unculturable in the laboratory. A culture-independent metagenomic approach is a novel technique that circumvents this culture limitation. For the screening of novel lipolytic enzymes, a metagenomic library was constructed from compost, and the clone of estCS2 was selected for lipolytic properties on a tributyrin-containing medium. Results The estCS2 sequence encodes a protein of 570 amino acid residues, with a predicted molecular mass of 63 kDa, and based on amino acid identity it most closely matches (45% the carboxylesterase from Haliangium ochraceum DSM 14365. EstCS2 belong to family VII, according to the lipolytic enzyme classification proposed by Arpigny and Jaeger, and it retains the catalytic triad Ser245-Glu363-His466 that is typical of an α/β hydrolase. The Ser245 residue in the catalytic triad of EstCS2 is located in the consensus active site motif GXSXG. The EstCS2 exhibits strong activity toward p-nitrophenyl caproate (C6, and it is stable up to 60°C with an optimal enzymatic activity at 55°C. The maximal activity is observed at pH 9, and it remains active between pH 6-10. EstCS2 shows remarkable stability in up to 50% (v/v dimethyl sulfoxide (DMSO or dimethylformamide (DMF. The enzyme has the ability to cleave sterically hindered esters of tertiary alcohol, as well as to degrade polyurethanes, which are widely used in various industries. Conclusions The high stability of EstCS2 in organic solvents and its activity towards esters of ketoprofen and tertiary alcohols, and in polyurethane suggests that it has potential uses for many applications in biotransformation and bioremediation.

  18. In silico dissection of Type VII Secretion System components across bacteria: New directions towards functional characterization

    Indian Academy of Sciences (India)

    Chandrani Das; Tarini Shankar Ghosh; Sharmila S Mande

    2016-03-01

    Type VII Secretion System (T7SS) is one of the factors involved in virulence of Mycobacteriun tuberculosis H37Rv. Numerous research efforts have been made in the last decade towards characterizing the components of this secretion system. An extensive genome-wide analysis through compilation of isolated information is required to obtain a global view of diverse characteristics and pathogenicity-related aspects of this machinery. The present study suggests that differences in structural components (of T7SS) between Actinobacteria and Firmicutes, observed earlier in a few organisms, is indeed a global trend. A few hitherto uncharacterized T7SS-like clusters have been identified in the pathogenic bacteria Enterococcus faecalis, Saccharomonospora viridis, Streptococcus equi, Streptococcuss gordonii and Streptococcus sanguinis. Experimental verification of these clusters can shed lights on their role in bacterial pathogenesis. Similarly, verification of the identified variants of T7SS clusters consisting additional membrane components may help in unraveling new mechanism of protein translocation through T7SS. A database of various components of T7SS has been developed to facilitate easy access and interpretation of T7SS related data.

  19. Tumour necrosis factor production and natural killer cell activity in peripheral blood during treatment with recombinant tumour necrosis factor

    OpenAIRE

    Männel, Daniela N.; Kist, A.; Ho, A D; Räth, U.; Reichardt, P; Wiedenmann, B; Schlick, E.; Kirchner, H.

    1989-01-01

    Tumour necrosis factor (TNF) has been found to be an important immunomodulator. Among other functions TNF activates natural killer (NK) cells and stimulates monocytes/macrophages in an autocrine fashion. TNF production and NK activity in peripheral blood mononuclear cells were determined in a clinical phase I study in which recombinant human (rh) TNF was administered as a continuous infusion weekly for a period of 8 weeks. Even though TNF production and NK activity were significantly reduced ...

  20. Physical Activity among Older People and Related Factors

    Science.gov (United States)

    Persson, Ann; While, Alison

    2012-01-01

    Objective: To investigate the duration, intensity and type of physical activity undertaken by people aged 60 years and over in relation to their reported levels of participation in social activities and their perceptions of their neighbourhood. Design: A cross-sectional questionnaire survey of older people attending two luncheon and eight social…

  1. Building gene expression signatures indicative of transcription factor activation to predict AOP modulation

    Science.gov (United States)

    Building gene expression signatures indicative of transcription factor activation to predict AOP modulation Adverse outcome pathways (AOPs) are a framework for predicting quantitative relationships between molecular initiatin...

  2. Physics and Algorithm Enhancements for a Validated MCNP/X Monte Carlo Simulation Tool, Phase VII

    Energy Technology Data Exchange (ETDEWEB)

    McKinney, Gregg W [Los Alamos National Laboratory

    2012-07-17

    Currently the US lacks an end-to-end (i.e., source-to-detector) radiation transport simulation code with predictive capability for the broad range of DHS nuclear material detection applications. For example, gaps in the physics, along with inadequate analysis algorithms, make it difficult for Monte Carlo simulations to provide a comprehensive evaluation, design, and optimization of proposed interrogation systems. With the development and implementation of several key physics and algorithm enhancements, along with needed improvements in evaluated data and benchmark measurements, the MCNP/X Monte Carlo codes will provide designers, operators, and systems analysts with a validated tool for developing state-of-the-art active and passive detection systems. This project is currently in its seventh year (Phase VII). This presentation will review thirty enhancements that have been implemented in MCNPX over the last 3 years and were included in the 2011 release of version 2.7.0. These improvements include 12 physics enhancements, 4 source enhancements, 8 tally enhancements, and 6 other enhancements. Examples and results will be provided for each of these features. The presentation will also discuss the eight enhancements that will be migrated into MCNP6 over the upcoming year.

  3. The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection

    Science.gov (United States)

    Kelesidis, Theodoros; Papakonstantinou, Vasiliki; Detopoulou, Paraskevi; Fragopoulou, Elizabeth; Chini, Maria; Lazanas, Marios C.; Antonopoulou, Smaragdi

    2016-01-01

    With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients. PMID:26616844

  4. Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban.

    Science.gov (United States)

    Noguchi, Kengo; Morishima, Yoshiyuki; Takahashi, Shinichi; Ishihara, Hiroaki; Shibano, Toshiro; Murata, Mitsuru

    2015-03-01

    Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral anticoagulant is less subject to drug-food and drug-drug interaction than existing vitamin K antagonists. Although this profile of edoxaban suggests it is well suited for clinical use, it is not clear whether genetic variations of factor X influence the activity of edoxaban. Our aim was to investigate a possible impact of single-nucleotide polymorphisms (SNPs) in the factor X gene on the functions of factor X and the activity of edoxaban. Two nonsynonymous SNPs within mature factor X, Ala152Thr and Gly192Arg, were selected as possible candidates that might affect the functions of FXa and the activity of edoxaban. We measured catalytic activities of wild type and mutant FXas in a chromogenic assay using S-2222 and coagulation times including prothrombin time (PT) and activated partial thrombin time (aPTT) of plasma-containing recombinant FXs in the presence and absence of edoxaban. Michaelis-Menten kinetic parameters of FXas, Km and Vmax values, PT and aPTT were not influenced by either mutation indicating these mutations do not affect the FXa catalytic and coagulation activities. The Ki values of edoxaban for the FXas and the concentrations of edoxaban required to double PT and aPTT were not different between wild type and mutated FXas indicating that both mutations have little impact on the activity of edoxaban. In conclusion, these data suggest that edoxaban has little interpatient variability stemming from SNPs in the factor X gene.

  5. Factors affecting teachers' participation in professional learning activities

    NARCIS (Netherlands)

    Kwakman, C.H.E.

    2003-01-01

    This paper describes two studies into teacher workplace learning. The first study aimed at developing a definition of teacher learning at the workplace and at exploring factors that may affect teacher learning at the workplace. Based on a conceptualization of teacher workplace learning as

  6. Active von Willebrand factor in thrombotic thrombocytopenic purpura and malaria

    NARCIS (Netherlands)

    Groot, E.

    2009-01-01

    Thrombotic thrombocytopenic purpura (TTP) and malaria are two diseases of distinct origin. TTP is a rare disorder caused by a deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13. Malaria is a poverty-related disease caused by protozoan parasites from the genus Plasmodium. TTP an

  7. Key factors governing alkaline pretreatment of waste activated sludge

    Institute of Scientific and Technical Information of China (English)

    Xianli Shi; Li Deng; Fangfang Sun; Jieyu Liang; Xu Deng

    2015-01-01

    Alkaline pretreatment is an effective technology to disintegrate sewage sludge, where alkali dosage and sludge concentration are two important factors. pH value or alkali concentration is usually adjusted in order to deter-mine a proper dosage of alkali. Our work has found that this is not a good strategy. A new parameter, the ratio of alkali to sludge (Ra/s), is more sensitive in controlling the alkali dosage. The sludge concentration Cs and reten-tion time t are two other important factors to consider. The validity of these arguments is confirmed with model-ing and experiments. The individual effect of Ra/s, Cs and t was studied separately. Then the combined effect of these three factors was evaluated. The sludge disintegration degree of 44.7%was achieved with the optimized factors. Furthermore, an alkaline-microwave combined pretreatment process was carried out under these optimized conditions. A high disintegration degree of 62.3%was achieved while the energy consumption of microwave was much lower than previously reported.

  8. A MATHEMATICAL MODEL FOR ASSESSING THE FACTORING ACTIVITY

    Directory of Open Access Journals (Sweden)

    Madalina Radoi

    2013-11-01

    Full Text Available Originally–being over 4,000 years old–factoring was first used in the fertile territory of old Mesopotamia at a time when the famous Code of Hammurabi was drawn up. However, many years passed until the British colonists started to use it on a large scale at a time when the metropolis would pay them sums of money for the merchandise that colonists sent to the old continent until they collected the invoices.In Romania factoring started to play a major role in financial operations for it led to the increase of liquidities on the market.According to the Romanian legislation, factoring is a contract concluded between a party known as “the client”, which supplies merchandise or provides services, and a banking institution or specialized financial institution known as “the factor”, whereby the latter ensures the financing source, collects the receivables and protects credit risks, while the client assigns to the factor the receivables resulting from the sale of goods or the provision of services to third parties.

  9. Situational and Personality Factors: Interactive Effects on Attitude - Active Consistency

    Science.gov (United States)

    Albrecht, Stan L.; Warner, Lyle G.

    1975-01-01

    An examination of the combined effect of a situational factor, disclosure, and two personality variables, "need for approval" and "inner-other directedness" on attitude - action relationships with respect to marijuana related attitudes and behavior of college students. Subjects with different personality characteristics were found to respond…

  10. Factors influencing quality of life in patients with active tuberculosis

    OpenAIRE

    Cox Victoria C; Marra Fawziah; Marra Carlo A; Palepu Anita; FitzGerald J Mark

    2004-01-01

    Abstract Background With effective treatment strategies, the focus of tuberculosis (TB) management has shifted from the prevention of mortality to the avoidance of morbidity. As such, there should be an increased focus on quality of life (QoL) experienced by individuals being treated for TB. The objective of our study was to identify areas of QoL that are affected by active TB using focus groups and individual interviews. Methods English, Cantonese, and Punjabi-speaking subjects with active T...

  11. Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3.

    Science.gov (United States)

    St Germain, Carly; Niknejad, Nima; Ma, Laurie; Garbuio, Kyla; Hai, Tsonwin; Dimitroulakos, Jim

    2010-07-01

    The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3) as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogen-activated protein kinase (MAPK) pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38) resulted in decreased ATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/- murine embryonic fibroblasts (MEFs) were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin's cytotoxic effects.

  12. Differential requirement of the epidermal growth factor receptor for G protein-mediated activation of transcription factors by lysophosphatidic acid

    Directory of Open Access Journals (Sweden)

    Dent Paul

    2010-01-01

    Full Text Available Abstract Background The role of the epidermal growth factor receptor (EGFR and other receptor tyrosine kinases (RTKs in provoking biological actions of G protein-coupled receptors (GPCRs has been one of the most disputed subjects in the field of GPCR signal transduction. The purpose of the current study is to identify EGFR-mediated mechanisms involved in activation of G protein cascades and the downstream transcription factors by lysophosphatidic acid (LPA. Results In ovarian cancer cells highly responsive to LPA, activation of AP-1 by LPA was suppressed by inhibition of EGFR, an effect that could be reversed by co-stimulation of another receptor tyrosine kinase c-Met with hepatocyte growth factor, indicating that LPA-mediated activation of AP-1 requires activity of a RTK, not necessarily EGFR. Induction of AP-1 components by LPA lied downstream of Gi, G12/13, and Gq. Activation of the effectors of Gi, but not Gq or G12/13 was sensitive to inhibition of EGFR. In contrast, LPA stimulated another prominent transcription factor NF-κB via the Gq-PKC pathway in an EGFR-independent manner. Consistent with the importance of Gi-elicited signals in a plethora of biological processes, LPA-induced cytokine production, cell proliferation, migration and invasion require intact EGFR. Conclusions An RTK activity is required for activation of the AP-1 transcription factor and other Gi-dependent cellular responses to LPA. In contrast, activation of G12/13, Gq and Gq-elicited NF-κB by LPA is independent of such an input. These results provide a novel insight into the role of RTK in GPCR signal transduction and biological functions.

  13. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-02

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  14. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Directory of Open Access Journals (Sweden)

    C.S. Bitencourt

    2012-03-01

    Full Text Available Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP activity in male Wistar rats (180 ± 10 g after altering their thyroid hormone levels by treatment with triiodothyronine (T3, propylthiouracil (PTU or thyroidectomy. T3 and thyroxine (T4 levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg. Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01. In contrast, increased factor B concentration and activity (32% were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  15. Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

    Science.gov (United States)

    Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

    2016-12-06

    Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

  16. Recombinant coagulation factor VIIa labelled with the fac-99 mTc(CO)3-core: synthesis and in vitro evaluation of a putative new radiopharmaceutical for imaging in acute bleeding lesion

    DEFF Research Database (Denmark)

    Madsen, Jacob; Christensen, Jesper B.; Olsen, Ole H.

    2011-01-01

    Coagulation in blood is initiated when coagulation factor VII (FVII) binds to exposed TF and is activated to FVIIa, and the TF/ FVIIa complex may therefore provide a marker of vascular injury potentially applicable in diagnostic imaging of acute gastrointestinal (GI) bleeding. Methods: Recombinan...... for stabilizing the 99mTc(CO)3 1-ligand structure in FVIIa were identified. Conclusion: Radiolabelled rFVIIa derivatives may represent a novel tool for the diagnosis of acute gastrointestinal bleeding lesions....

  17. Reversal of established bone pathology in MPS VII mice following lentiviral-mediated gene therapy.

    Science.gov (United States)

    Derrick-Roberts, Ainslie L K; Panir, Kavita; Pyragius, Carmen E; Zarrinkalam, Krystyna H; Atkins, Gerald J; Byers, Sharon

    2016-11-01

    Severe, progressive skeletal dysplasia is a major symptom of multiple mucopolysaccharidoses (MPS) types. While a gene therapy approach initiated at birth has been shown to prevent the development of bone pathology in different animal models of MPS, the capacity to correct developed bone disease is unknown. In this study, ex vivo micro-computed tomography was used to demonstrate that bone mass and architecture of murine MPS VII L5 vertebrae were within the normal range at 1month of age but by 2months of age were significantly different to normal. The difference between normal and MPS VII BV/TV increased with age reaching a maximal difference at approximately 4months of age. In mature MPS VII bone BV/TV is increased (51.5% versus 21.5% in normal mice) due to an increase in trabecular number (6.2permm versus 3.8permm in normal mice). The total number of osteoclasts in the metaphysis of MPS VII mice was decreased, as was the percentage of osteoclasts attached to bone. MPS VII osteoblasts produced significantly more osteoprotegerin (OPG) than normal osteoblasts and supported the production of fewer osteoclasts from spleen precursor cells than normal osteoblasts in a co-culture system. In contrast, the formation of osteoclasts from MPS VII spleen monocytes was similar to normal in vitro, when exogenous RANKL and m-CSF was added to the culture medium. Administration of murine β-glucuronidase to MPS VII mice at 4months of age, when bone disease was fully manifested, using lentiviral gene delivery resulted in a doubling of osteoclast numbers and a significant increase in attachment capacity (68% versus 29.4% in untreated MPS VII animals). Bone mineral volume rapidly decreased by 39% after gene therapy and fell within the normal range by 6months of age. Collectively, these results indicate that lentiviral-mediated gene therapy is effective in reversing established skeletal pathology in murine MPS VII. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway.

    Science.gov (United States)

    Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A; Johnson, Jeffrey A

    2013-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H(2)O(2) induced cell death.

  19. Relation of physical activity to cardiovascular disease mortality and the influence of cardiometabolic risk factors.

    Science.gov (United States)

    Reddigan, Jacinta I; Ardern, Chris I; Riddell, Michael C; Kuk, Jennifer L

    2011-11-15

    Physical activity can improve several metabolic risk factors associated with cardiovascular disease (CVD) and is associated with a lower risk of CVD mortality. We sought to evaluate the extent to which metabolic risk factors mediate the association between physical activity and CVD mortality and whether physical activity provides protective effects against CVD mortality in healthy adults and those with metabolic risk factors. A sample of 10,261 adults from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up 13.4 ± 3.9 years) was used. Physical activity was assessed by questionnaire and classified into inactive, light, and moderate/vigorous activity categories. Metabolic risk factors (dyslipidemia, type 2 diabetes mellitus, obesity, hypertension, inflammation, and insulin resistance) were categorized using clinical thresholds. After adjusting for basic confounders, engaging in light or moderate/vigorous physical activity was associated with a lower risk of CVD mortality (p activity remained at lower risk of CVD mortality. In addition, physical activity provided protective effects for CVD mortality in healthy subjects and those with metabolic risk factors in isolation or in clusters. In conclusion, physical activity was associated with a lower risk of CVD mortality independent of traditional and inflammatory risk factors. Taken together these results suggest that physical activity may protect against CVD mortality regardless of the presence of metabolic risk factors.

  20. Expression and Activation of STAT Transcription Factors in Breast Cancer

    Science.gov (United States)

    1998-05-08

    clinicians. J~, 273: 577-585, 1995. 183 Hundertmark 5, Buhler H, Rudolf M, Weitzel HK, Ragosch V: Inhibition of 11 beta-hydroxysteroid dehydrogenase...activated protein kinase through a Jakl-dependent pathway. Mol. Cell. Bioi., 17:3833-40, 1997. Stewart JF, Rubens RO, King RJ, Minton MJ, Steiner R

  1. Physical activity and cardiovascular risk factors in children

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Riddoch, Chris; Kriemler, Susi

    2011-01-01

    A number of recent systematic reviews have resulted in changes in international recommendations for children's participation in physical activity (PA) for health. The World Health Authority (WHO) has recently released new recommendations. The WHO still recommends 60 min of moderate to vigorous ph...

  2. No evidence for a putative involvement of platelet-activating factor in systemic lupus erythematosus without active nephritis

    Directory of Open Access Journals (Sweden)

    Yves Denizot

    2003-01-01

    Full Text Available Background: Platelet-activating factor (PAF seems to be implicated in systemic lupus erythematosus (SLE patients with associated renal diseases.Aims: In this study, we ensured the role of PAF in SLE patients without renal complications.

  3. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    Science.gov (United States)

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

  4. Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents

    DEFF Research Database (Denmark)

    Ekelund, Ulf; Luan, Jian'an; Sherar, Lauren B

    2012-01-01

    Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children.......Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children....

  5. Activating Transcription Factor 3 (ATF3 and the Nervous System

    Directory of Open Access Journals (Sweden)

    Patrick Norval Anderson

    2012-02-01

    Full Text Available It has been recognised for over a century that the ability of axons to regenerate in peripheral nerves is fundamentally greater than that of axons in the brain, spinal cord or optic nerves [early literature was reviewed in (Ramon y Cajal, 1928]. One factor that contributes to the successful regeneration of the axons in peripheral nerves is the complex cell body response the neurons show to axotomy. That transcription factors must play an important role in enabling neurons to regrow their axons is implicit to the observation that several hundred genes are regulated in neurons during axonal regeneration (Costigan et al., 2002; Boeshore et al., 2004. In addition, similarly large numbers of genes are regulated in the non-neuronal cells present in injured peripheral nerves [especially Schwann cells (Barrette et al., 2010] and CNS tissue. Of the transcription factors that regulate these changes in gene expression, the function of c-jun is best understood but ATF-3 (also known as LRF-1, LRG-21, CRG-5 and TI-241 is also upregulated in most of the neurons (Fig. 1 and Schwann cells that express c-jun. Indeed, ATF-3 has become a standard marker for neurons axotomised by peripheral nerve injury (Tsuzuki et al., 2001; Yamanaka et al., 2005; Yano et al., 2008; Linda et al., 2011 and its expression by injured neurons is closely correlated with a regenerative response. None the less, surprisingly little is known about the functions of ATF3 in neurons or glia within the injured nervous system, especially when compared with those of its potential binding partner, c-Jun.

  6. Factor B structure provides insights into activation of the central protease of the complement system

    NARCIS (Netherlands)

    Milder, F.J.; Gomes, L.; Schouten, A.; Janssen, B.J.C.; Huizinga, E.G.; Romijn, R.A.; Hemrika, W.; Roos, A; Daha, M.R.; Gros, P.

    2007-01-01

    Factor B is the central protease of the complement system of immune defense. Here, we present the crystal structure of human factor B at 2.3-A° resolution, which reveals how the five-domain proenzyme is kept securely inactive. The canonical activation helix of the Von Willebrand factor A (VWA) domai

  7. Technetium (VII) Co-precipitation with Framework Aluminosilicates

    Energy Technology Data Exchange (ETDEWEB)

    Harsh, James B. [Washington State Univ., Pullman, WA (United States); Dickson, Johnbull Otah [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Pierce, Eric M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bargar, John [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-07-13

    Technetium-99 (99Tc), a long-lived radionuclide, is one of the most widespread contaminants within the Hanford subsurface. At some depths, it is only extractable with strong acids, suggesting incorporation into a solid phase. We hypothesized that Tc may have coprecipitated with feldspathoid aluminosilicates under waste tanks that had leaked caustic solutions into the vadose zone. Our objectives were to determine if Tc could be incorporated into the feldspathoids cancrinite and sodalite and under what conditions coprecipitation could occur. Our hypothesis was that sodalite was more likely to incorporate and retain Tc. Our approach was to use known methods of feldspathoid formation in solutions resembling those in Hanford waste tanks contacting sediments in terms of major ion (Na, NO3, OH, Al(OH)4, and Si(OH)4 concentrations. In some cases, Al and Si were supplied from zeolite. We used perrhenate (ReO4) as a surrogate for pertechnetate (TcO4) to avoid the radioactivity. The major findings of this study were 1) ReO4 could be incorporated into either sodalite or cancrinite but the concentration in the solid was < 1% of the competing ion Cl, NO3, or NO2. 2) The small amount of ReO4 incorporated was not exchangeable with NO3 or NO2. 3) In sodalite, NO3 was highly preferred over ReO4 but significant Re-sodalite was formed when the mole fraction in solution (Re/Re+N) exceeded 0.8. 4) A nonlinear relation between the unit cell parameter and amount of Re incorporated suggested that a separate Re-sodalite phase was formed rather than a solid solution. 5) We determined that sodalite preference for sodalite in the presence of different anions increased with the ionic size of the competing anion: Cl < CO3 < NO3 < SO4 < MnO4 < WO4 and significant incorporation did not occur unless the difference in anion radii was less than 12%. 6) Re(VII) was not significantly reduced to Re(IV) under the conditions of this experiment and Re appeared to be a good surrogate for Tc under oxidizing

  8. Aortic Root Dilatation in Mucopolysaccharidosis I–VII

    Directory of Open Access Journals (Sweden)

    Meena Bolourchi

    2016-11-01

    Full Text Available The prevalence of aortic root dilatation (ARD in mucopolysaccharidosis (MPS is not well documented. We investigated aortic root measurements in 34 MPS patients at the Children’s Hospital of Orange County (CHOC. The diagnosis, treatment status, age, gender, height, weight and aortic root parameters (aortic valve annulus (AVA, sinuses of Valsalva (SoV, and sinotubular junction (STJ were extracted by retrospective chart review and echocardiographic measurements. Descriptive statistics, ANOVA, and paired post-hoc t-tests were used to summarize the aortic dimensions. Exact binomial 95% confidence intervals (CIs were constructed for ARD, defined as a z-score greater than 2 at the SoV. The patient age ranged from 3.4–25.9 years (mean 13.3 ± 6.1, the height from 0.87–1.62 meters (mean 1.24 ± 0.21, and the weight from 14.1–84.5 kg (mean 34.4 ± 18.0. The prevalence of dilation at the AVA was 41% (14/34; 95% CI: 25%–59%; at the SoV was 35% (12/34; 95% CI: 20%–54%; and at the STJ was 30% (9/30; 95% CI: 15%–49%. The highest prevalence of ARD was in MPS IVa (87.5%. There was no significant difference between mean z-scores of MPS patients who received treatment with hematopoietic stem cell transplantation (HSCT or enzyme replacement therapy (ERT vs. untreated MPS patients at the AVA (z = 1.9 ± 2.5 vs. z = 1.5 ± 2.4; p = 0.62, SoV (z = 1.2 ± 1.6 vs. z = 1.3 ± 2.2; p = 0.79, or STJ (z = 1.0 ± 1.8 vs. z = 1.2 ± 1.6; p = 0.83. The prevalence of ARD was 35% in our cohort of MPS I–VII patients. Thus, we recommend screening for ARD on a routine basis in this patient population.

  9. Aortic Root Dilatation in Mucopolysaccharidosis I-VII.

    Science.gov (United States)

    Bolourchi, Meena; Renella, Pierangelo; Wang, Raymond Y

    2016-11-29

    The prevalence of aortic root dilatation (ARD) in mucopolysaccharidosis (MPS) is not well documented. We investigated aortic root measurements in 34 MPS patients at the Children's Hospital of Orange County (CHOC). The diagnosis, treatment status, age, gender, height, weight and aortic root parameters (aortic valve annulus (AVA), sinuses of Valsalva (SoV), and sinotubular junction (STJ)) were extracted by retrospective chart review and echocardiographic measurements. Descriptive statistics, ANOVA, and paired post-hoc t-tests were used to summarize the aortic dimensions. Exact binomial 95% confidence intervals (CIs) were constructed for ARD, defined as a z-score greater than 2 at the SoV. The patient age ranged from 3.4-25.9 years (mean 13.3 ± 6.1), the height from 0.87-1.62 meters (mean 1.24 ± 0.21), and the weight from 14.1-84.5 kg (mean 34.4 ± 18.0). The prevalence of dilation at the AVA was 41% (14/34; 95% CI: 25%-59%); at the SoV was 35% (12/34; 95% CI: 20%-54%); and at the STJ was 30% (9/30; 95% CI: 15%-49%). The highest prevalence of ARD was in MPS IVa (87.5%). There was no significant difference between mean z-scores of MPS patients who received treatment with hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT) vs. untreated MPS patients at the AVA (z = 1.9 ± 2.5 vs. z = 1.5 ± 2.4; p = 0.62), SoV (z = 1.2 ± 1.6 vs. z = 1.3 ± 2.2; p = 0.79), or STJ (z = 1.0 ± 1.8 vs. z = 1.2 ± 1.6; p = 0.83). The prevalence of ARD was 35% in our cohort of MPS I-VII patients. Thus, we recommend screening for ARD on a routine basis in this patient population.

  10. Aortic Root Dilatation in Mucopolysaccharidosis I–VII

    Science.gov (United States)

    Bolourchi, Meena; Renella, Pierangelo; Wang, Raymond Y.

    2016-01-01

    The prevalence of aortic root dilatation (ARD) in mucopolysaccharidosis (MPS) is not well documented. We investigated aortic root measurements in 34 MPS patients at the Children’s Hospital of Orange County (CHOC). The diagnosis, treatment status, age, gender, height, weight and aortic root parameters (aortic valve annulus (AVA), sinuses of Valsalva (SoV), and sinotubular junction (STJ)) were extracted by retrospective chart review and echocardiographic measurements. Descriptive statistics, ANOVA, and paired post-hoc t-tests were used to summarize the aortic dimensions. Exact binomial 95% confidence intervals (CIs) were constructed for ARD, defined as a z-score greater than 2 at the SoV. The patient age ranged from 3.4–25.9 years (mean 13.3 ± 6.1), the height from 0.87–1.62 meters (mean 1.24 ± 0.21), and the weight from 14.1–84.5 kg (mean 34.4 ± 18.0). The prevalence of dilation at the AVA was 41% (14/34; 95% CI: 25%–59%); at the SoV was 35% (12/34; 95% CI: 20%–54%); and at the STJ was 30% (9/30; 95% CI: 15%–49%). The highest prevalence of ARD was in MPS IVa (87.5%). There was no significant difference between mean z-scores of MPS patients who received treatment with hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT) vs. untreated MPS patients at the AVA (z = 1.9 ± 2.5 vs. z = 1.5 ± 2.4; p = 0.62), SoV (z = 1.2 ± 1.6 vs. z = 1.3 ± 2.2; p = 0.79), or STJ (z = 1.0 ± 1.8 vs. z = 1.2 ± 1.6; p = 0.83). The prevalence of ARD was 35% in our cohort of MPS I–VII patients. Thus, we recommend screening for ARD on a routine basis in this patient population. PMID:27916847

  11. Role of HMW kininogen in surface-mediated activation of Factor XII.

    Science.gov (United States)

    Shimada, T; Sugo, T; Kato, H; Iwanaga, S

    1983-01-01

    We have shown that bovine HMW kininogen remarkably accelerates the activation of Factor XII and prekallikrein in the presence of kaolin, adsorbing on kaolin through the fragment 1.2 region and forming a complex with prekallikrein through the light chain region (Sugo et al., 1980; Ikari et al., 1981). The present study was undertaken to examine the role of HMW kininogen in the activation of Factor XII and prekallikrein with other negatively-charged surfaces. The activation system used here was as follows; (1) Activation of prekallikrein by Factor XII, (2) Activation of Factor XII by plasma kallikrein and (3) Activation of prekallikrein by Factor XIIa. Among a variety of foreign surfaces, amylose sulfate and sulfatide were the most efficient in the activation reaction of Factor XII and prekallikrein. Bovene HMW kininogen accelerated all the three reactions triggered by these surfaces. However, the accelerating effect of HMW kininogen on the activation of Factor XII by plasma kallikrein was very weak, when amylose sulfate or sulfatide was used as surface. The three reactions were highly dependent on the amounts of HMW kininogen and surfaces contained in the reaction mixtures. Excess amount of them inhibited these reactions. Among the various fragments, which were prepared from HMW kininogen digests with plasma and urinary kallikreins (Sugo et al., 1980), a large fragment consisting of fragment 1.2 and light chain accelerated the reactions. Thus both fragment 1.2 and the light chain region in HMW kininogen were essential for these activation reactions.

  12. THE TIME FACTOR IN MARITIME TRANSPORT AND PORT LOGISTICS ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Florin NICOLAE

    2016-06-01

    Full Text Available Execution of the carriage contract requires compliance to all the conditions in it, by all those involved in the transport. Main obligations incumbent upon the vessel, and obviously, to other transporters, who must provide transportation according to deadlines and safety. Contract compliance is certifying transport participants about their seriousness and an appropriate market quotation. Therefore, present work pragmatically sets schematics reference time associated implementation of the carriage contract. Also, are demonstrated relationships established between maritime transport “players” and sequence of activities related to the operation of the vessel in port. The authors propose a set of concepts and terms whose utility is established to solve practical problems in this area of activity.

  13. Are intestinal helminths risk factors for developing active tuberculosis?

    DEFF Research Database (Denmark)

    Elias, Daniel; Mengistu, Getahun; Akuffo, Hannah

    2006-01-01

    OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy...... household contacts were tested for intestinal helminths using direct microscopy and the formol-ether concentration techniques. Three consecutive stool samples were examined before the start of TB chemotherapy. Sputum microscopy was done using the sodium hypochlorite concentration techniques. Participants...... were also tested for HIV by commercial sandwich enzyme linked immunosorbent assay. RESULTS: The study population consisted of 230 smear-positive TB patients and 510 healthy household contacts. The prevalence of intestinal helminths was 71% in patients and 36% in controls. HIV seroprevalence...

  14. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI

    Science.gov (United States)

    Puy, Cristina; Tucker, Erik I.; Ivanov, Ivan S.; Gailani, David; Smith, Stephanie A.; Morrissey, James H.; Gruber, András; McCarty, Owen J. T.

    2016-01-01

    Introduction Factor (F) XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa) promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα), in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP) derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin. Methods and Results Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma. Conclusions Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP. PMID:27764259

  15. Microwave assisted synthesis of novel tetrazole/sulfonamide derivatives based on octahydroacridine, xanthene and chromene skeletons as inhibitors of the carbonic anhydrases isoforms I, II, IV and VII.

    Science.gov (United States)

    Esirden, İbrahim; Tanç, Muhammet; Supuran, Claudiu T; Kaya, Muharrem

    2017-01-01

    The synthesis of novel tetrazole/sulfonamide derivatives based on octahydroacridine, xanthene and chromene scaffold by using microwave (MW) assisted techniques is reported in this study. These synthesized hybrid compounds were assayed for the inhibition of carbonic anhydrase (CA, EC 4.2.1.1). The inhibitory activities were determined against three cytosolic human isoforms (hCA I, II and VII) and one membrane-associated (hCA IV) isoform. Some of the newly synthesized sulfonamides showed micromolar to nanomolar inhibitory activity against these enzymes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

    DEFF Research Database (Denmark)

    Bosch, Jaime; Thabut, Dominique; Albillos, Agustín;

    2008-01-01

    A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal...... events, were comparable between groups. CONCLUSION: Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do...

  17. Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis.

    Science.gov (United States)

    Hsueh, W; Caplan, M S; Sun, X; Tan, X; MacKendrick, W; Gonzalez-Crussi, F

    1994-01-01

    The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood. We have established several animal models of NEC by using a combination of various stimuli and stress, including endotoxin, PAF, TNF, and hypoxia. We discuss the mechanism of their actions and the possible roles of these factors in the pathogenesis of human NEC.

  18. Physical activity, and physical activity related to sports, leisure and occupational activity as risk factors for ALS: A systematic review.

    Science.gov (United States)

    Lacorte, Eleonora; Ferrigno, Luigina; Leoncini, Emanuele; Corbo, Massimo; Boccia, Stefania; Vanacore, Nicola

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem neurodegenerative disease due to an interaction between environmental and genetic factors. This systematic review aims at gathering all available evidence on the association between physical activity (PA) and the risk of ALS. Relevant literature published up to January 2015 was gathered through structured searches on Medline, The Cochrane Library, and the ISI Web of Science databases. Studies considering any type of PA as the main exposure and a diagnosis of ALS or motor neuron disease were selected. Data were extracted in standardized forms, and the quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Bibliographic searches yielded 3168 records. Nineteen case control studies and 7 cohort studies met the inclusion criteria, and were included in the analysis. Evidence on cumulative measures of PA as a risk factor for ALS remain inconclusive. However, cohort studies report a significantly higher number of cases of ALS in professional soccer and American football players, and a slightly increased risk of ALS in varsity athletes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Giving children a voice: Exploring qualitative perspectives on factors influencing recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine

    2017-01-01

    Facilitators and barriers to recess physical activity are not well understood. To date, research on recess physical activity has predominantly focused on quantitative measures typically focusing on a narrow set of predefined factors, often constructed by adults. To really understand the factors...... affecting recess physical activity it is crucial to observe and listen to children to know how they engage in and perceive recess physical activity. The aim of this paper was to gain knowledge on children’s perceptions and experiences of factors influencing their physical activity behaviour during recess...... 11–12-year-old children. The socio-ecological model was used as the overall theoretical framework. Twelve factors were identified as influencing the children’s recess physical activity: bodily self-esteem and ability; gender; gendered school culture; peer influence; conflicts and exclusion; space...

  20. The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate.

    Directory of Open Access Journals (Sweden)

    TyAnna L Lovato

    Full Text Available Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2 is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer. Since Tinman, Pannier and MEF2 are evolutionarily conserved from Drosophila to vertebrates, and since their vertebrate homologs can convert mouse fibroblast cells to cardiomyocytes in different activator cocktails, we tested whether over-expression of these three factors in vivo could ectopically activate known cardiac marker genes. We found that mesodermal over-expression of Tinman and Pannier resulted in approximately 20% of embryos with ectopic Hand and Sulphonylurea receptor (Sur expression. By adding MEF2 alongside Tinman and Pannier, a dramatic expansion in the expression of Hand and Sur was observed in almost all embryos analyzed. Two additional cardiac markers were also expanded in their expression. Our results demonstrate the ability to initiate ectopic cardiac fate in vivo by the combination of only three members of the conserved Drosophila cardiac transcription network, and provide an opportunity for this genetic model system to be used to dissect the mechanisms of cardiac specification.

  1. [Risk factors in police activities: operational criticism in surveillance programs].

    Science.gov (United States)

    Ciprani, Fabrizio; Moroni, Maria; Conte, Giovanni

    2014-01-01

    The planning of specific health surveillance programs for police officers is extremely complex due to difficulty in predictability and variety of occupational hazards. Even in the case of conventional occupational risk factors clearly identified by current regulations, particular working conditions may require specific assessment to effectively identify and quantify the risk of occupational exposure. An extensive program of health surveillance, aimed at promoting overall health and effectiveness of the operators, would be really desirable, in order to help better address a number of risks that cannot be easily predicted. The progressive increase in the average age of the working population and the increasing prevalence of chronic degenerative diseases, may also suggest the need for health surveillance procedures designed to verify continued unqualified suitability to police service, providing for the identification of diversified suitability profiles in relation to age and state of health: accordingly, in regard to our field of interest, there is a close link between medico-legal eligibility and occupational medicine.

  2. THE FACTORS THAT INFLUENCE THE ACTIVITY OF ECONOMIC ENTITIES

    Directory of Open Access Journals (Sweden)

    SINTEA(ANGHEL LUCICA

    2014-02-01

    Full Text Available In the current situation many experts and ordinary people are asking themselves: Where is the economy heading? How can we counteract the disruptive factors? Which strategies must be employed? How should the risks be properly assessed in order to diminish them to the lowest level? What measures should be taken to improve the situation? This requires a necessary economic and financial analysis, based on the data from the financial statements, the discovery and application of risk assessment methods and the detection of procedures to mitigate this risk. It is also necessary to draw a comparison between the expected results of a rational and scientific research, and those obtained through empirical processes by means of marketing.

  3. [Family factors influence active commuting to school in Spanish children].

    Science.gov (United States)

    Rodríguez-López, Carlos; Villa-González, Emilio; Pérez-López, Isaac J; Delgado-Fernández, Manuel; Ruiz, Jonatan R; Chillón, Palma

    2013-01-01

    Introducción: El desplazamiento activo al colegio contribuye a aumentar los niveles de actividad física en niños. Los factores familiares pueden determinar dicho comportamiento. Objetivo: El objetivo fue analizar la asociación de la actividad laboral y el desplazamiento al trabajo de los padres con el modo de desplazamiento de sus hijos. Método: Participaron 721 familias de 4 colegios de la provincia de Granada. Las familias completaron un cuestionario sobre el modo de desplazamiento de sus hijos, la actividad laboral y el modo de desplazamiento de los padres, y la distancia y tiempo del trayecto al colegio de sus hijos. Las asociaciones entre la actividad laboral de las familias y modo de desplazamiento al trabajo con el desplazamiento activo al colegio de sus hijos se estudiaron con regresión logística binaria ajustando por distancia al colegio y edad de los hijos. Resultados: Los niños cuyos padres y madres no trabajaban eran más propensos a ir de forma activa al colegio que aquellos donde ambos trabajaban (p = 0,023; OR: 2,67; 95% IC: 1,14-6,23). Los niños cuyos padres y madres se desplazaban de forma activa al trabajo eran más propensos a ir de forma activa al colegio que aquellos donde ambos padres se desplazaban de forma pasiva al trabajo (p = 0,014; OR: 6,30; 95% IC: 1,45-27,26). Conclusión: Los factores familiares estaban relacionados con el modo de desplazamiento de los niños al colegio: en familias con desempleo y en familias con empleo donde los padres se desplazan al trabajo de forma activa, los hijos parecen ser más activos.

  4. Chondroitin 6-Sulfate as a Novel Biomarker for Mucopolysaccharidosis IVA and VII.

    Science.gov (United States)

    Shimada, Tsutomu; Tomatsu, Shunji; Yasuda, Eriko; Mason, Robert W; Mackenzie, William G; Shibata, Yuniko; Kubaski, Francyne; Giugliani, Roberto; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji; Orii, Tadao

    2014-01-01

    Chondroitin 6-sulfate (C6S), a glycosaminoglycan (GAG), is distributed mainly in the growth plates, aorta, and cornea; however, the physiological function of C6S is not fully understood. One of the limitations is that no rapid, accurate quantitative method to measure C6S has been established. Mucopolysaccharidosis IVA and VII (MPS IVA and VII) are caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase and β-D-glucuronidase, respectively, resulting in accumulation of C6S and other GAG(s). While levels of keratan sulfate (KS), heparan sulfate, and dermatan sulfate in samples from MPS patients are well described, this is the first report of quantitative analysis of C6S levels in samples from MPS IVA and VII patients.We developed a method to digest polymeric C6S and measure resultant disaccharides using liquid chromatography-tandem mass spectrometry (LC-MS/MS). C6S levels were measured in the blood from control subjects and patients with MPS IVA and VII aged from 0 to 58 years of age. We also assayed KS levels in the same samples for comparison with C6S.Levels of C6S in the blood decreased with age and were significantly elevated in patients with MPS IVA and VII, compared with age-matched controls. Levels of KS in patients with MPS IVA were also higher than those in age-matched controls, although differences were less pronounced than with C6S. Combining KS and C6S data, discriminated patients with MPS IVA from age-matched control subjects were better than either C6S or KS levels alone.In conclusion, this first report showing that blood levels of C6S are quantitatively evaluated in patients with MPS IVA and VII indicates that C6S could be a useful biomarker for these metabolic disorders.

  5. WRKY Transcription Factors Involved in Activation of SA Biosynthesis Genes

    Directory of Open Access Journals (Sweden)

    Bol John F

    2011-05-01

    Full Text Available Abstract Background Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR. The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA. An important step in SA biosynthesis in Arabidopsis is the conversion of chorismate to isochorismate through the action of isochorismate synthase, encoded by the ICS1 gene. Also AVRPPHB SUSCEPTIBLE 3 (PBS3 plays an important role in SA metabolism, as pbs3 mutants accumulate drastically reduced levels of SA-glucoside, a putative storage form of SA. Bioinformatics analysis previously performed by us identified WRKY28 and WRKY46 as possible regulators of ICS1 and PBS3. Results Expression studies with ICS1 promoter::β-glucuronidase (GUS genes in Arabidopsis thaliana protoplasts cotransfected with 35S::WRKY28 showed that over expression of WRKY28 resulted in a strong increase in GUS expression. Moreover, qRT-PCR analyses indicated that the endogenous ICS1 and PBS3 genes were highly expressed in protoplasts overexpressing WRKY28 or WRKY46, respectively. Electrophoretic mobility shift assays indentified potential WRKY28 binding sites in the ICS1 promoter, positioned -445 and -460 base pairs upstream of the transcription start site. Mutation of these sites in protoplast transactivation assays showed that these binding sites are functionally important for activation of the ICS1 promoter. Chromatin immunoprecipitation assays with haemagglutinin-epitope-tagged WRKY28 showed that the region of the ICS1 promoter containing the binding sites at -445 and -460 was highly enriched in the immunoprecipitated DNA. Conclusions The results obtained here confirm results from our multiple microarray co-expression analyses indicating that WRKY28 and WRKY46 are transcriptional activators of ICS1 and PBS3, respectively, and support this in silico screening as a powerful tool for identifying new components of stress

  6. Activation of the Nuclear Factor E2-Related Factor 2/Antioxidant Response Element Pathway Is Neuroprotective after Spinal Cord Injury

    Science.gov (United States)

    Wang, Xiaoliang; de Rivero Vaccari, Juan Pablo; Wang, Handong; Diaz, Paulo; German, Ramon; Marcillo, Alex E.

    2012-01-01

    Abstract The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI. PMID:21806470

  7. Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury.

    Science.gov (United States)

    Wang, Xiaoliang; de Rivero Vaccari, Juan Pablo; Wang, Handong; Diaz, Paulo; German, Ramon; Marcillo, Alex E; Keane, Robert W

    2012-03-20

    The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. Female Fischer rats were subjected to mild thoracic SCI (T8) using the New York University injury device. As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI.

  8. Specific features of domestic banks activity in the factoring services market

    OpenAIRE

    Trygub Olena V.

    2014-01-01

    The article analyses specific features of formation and development of the domestic factoring market. In the result of the study the article establishes that development of factoring in Ukraine took place due to active participation of banking institutions in this process and nowadays they are leaders in the domestic factoring services market due to possessing significant competitive advantages if compared with non-banking companies that specialise in factoring. The article detects that nowad...

  9. Dove sta andando l'analisi musicale? Riflessioni sul VII EuroMac

    Directory of Open Access Journals (Sweden)

    Mario Baroni

    2014-01-01

    Full Text Available Come tutti i lettori della Rivista ormai sapranno, si è svolto a Roma dal 29 settembre al 2 ottobre di quest’anno, presso il Conservatorio di S. Cecilia, il settimo convegno europeo di analisi musicale (VII European Music Analysis Conference ossia VII EuroMac. Nel convegno, organizzato dal GATM e diretto da Giorgio Sanguinetti, sono state presentate 197 relazioni e svolti otto laboratori. Tutti i materiali sono stati riassunti in un volume (Programme and Abstract Book, Iter Edizioni di Subiaco curato da Egidio Pozzi e Antonio Cascelli.

  10. Specific features of domestic banks activity in the factoring services market

    Directory of Open Access Journals (Sweden)

    Trygub Olena V.

    2014-01-01

    Full Text Available The article analyses specific features of formation and development of the domestic factoring market. In the result of the study the article establishes that development of factoring in Ukraine took place due to active participation of banking institutions in this process and nowadays they are leaders in the domestic factoring services market due to possessing significant competitive advantages if compared with non-banking companies that specialise in factoring. The article detects that nowadays the banks are not only offerers of factoring services and finance factoring operations of other market participants, but also take an active part in establishment of factoring branches and are consumers of factoring services. In order to accelerate development of international factoring in Ukraine, the article offers such forms of state support of banks, which render factoring services to domestic exporters. The article recommends to focus banks’ attention, under modern conditions that are characterised with volatility of financial markets, on factoring servicing of those clients, whom they have long business relations with, without jeopardising themselves through provision of factoring services to a big number of small debtors. The article provides schemes of banks’ co-operation in the sphere of “non-classic” factoring with accredited factoring companies.

  11. Heat Shock Factor-1 and Nuclear Factor-kappaB Are Systemically Activated in Human Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Derek A O’Reilly

    2006-03-01

    Full Text Available Context :Nuclear factor-kappa B (NFkappaB is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1 transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis. Objective :To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome. Patients :Twenty-four patients with acute pancreatitis and 12 healthy controls. Main outcome measures :Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS, APACHE II scores and final Atlanta designations of severity were also determined. Results: Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004. However, there was no significant difference between those with mild and severe disease (P=0.685. Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053. Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036. Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019 and APACHE II score (r=-0.47, P=0.026. Conclusions: Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis

  12. ESEA Title VII Bilingual/Bicultural Education Program; Programa de Educacion Bilingue/Bicultural 1975-1976.

    Science.gov (United States)

    Milwaukee Public Schools, WI. Dept. of Educational Research and Program Assessment.

    This is the annual evaluation report of the Title VII components of the Milwaukee Bilingual/Bicultural Education Program funded by Title I and Title VII of the Elementary and Secondary Education Act of 1967 and the Milwaukee Public Schools. The results of the 1975-76 assessment of pupil progress toward achievement of the program's academic and…

  13. Vascular endothelial growth factor activities on osteoarthritic chondrocytes.

    Science.gov (United States)

    Pulsatelli, L; Dolzani, P; Silvestri, T; Frizziero, L; Facchini, A; Meliconi, R

    2005-01-01

    Evaluation of the role of VEGF in cartilage pathophysiology. VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids. VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation. VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.

  14. Transforming Growth Factor-β Signaling Pathway Activation in Keratoconus

    Science.gov (United States)

    ENGLER, CHRISTOPH; CHAKRAVARTI, SHUKTI; DOYLE, JEFFERSON; EBERHART, CHARLES G.; MENG, HUAN; STARK, WALTER J.; KELLIHER, CLARE; JUN, ALBERT S.

    2011-01-01

    PURPOSE To assess the presence of transforming growth factor-β (TGFβ) pathway markers in the epithelium of keratoconus patient corneas. DESIGN Retrospective, comparative case series of laboratory specimens. METHODS Immunohistochemistry results for TGFβ2, total TGFβ, mothers against decacentaplegic homolog (Smad) 2, and phosphorylated Smad2 was performed on formalin-fixed, paraffin-embedded sections of keratoconus patient corneas and normal corneas from human autopsy eyes. Keratoconus patient corneas were divided in two groups, depending on their severity based on keratometer readings and pachymetry. Autopsy controls were age-matched with the keratoconus cases. Immunohistochemistry signal quantification was performed using automated software. Real-time reverse-transcriptase polymerase chain reaction was performed on total ribonucleic acid of epithelium of keratoconus patient corneas and autopsy control corneas. RESULTS Immunohistochemistry quantification showed a significant increase in mean signal in the group of severe keratoconus cases compared with normal corneas for TGFβ2 and phosphorylated Smad2 (P keratoconus cases versus the autopsy controls. Reverse-transcriptase polymerase chain reaction exhibited elevated messenger ribonucleic acid levels of Smad2 and TGFβ2 in severe keratoconus corneal epithelium. CONCLUSIONS This work shows increased TGFβ pathway markers in severe keratoconus cases and provides the rationale for investigating TGFβ signaling further in the pathophysiology of keratoconus. PMID:21310385

  15. Brain-derived neurotrophic factor and epidermal growth factor activate neuronal m-calpain via mitogen-activated protein kinase-dependent phosphorylation.

    Science.gov (United States)

    Zadran, Sohila; Jourdi, Hussam; Rostamiani, Karoline; Qin, Qingyu; Bi, Xiaoning; Baudry, Michel

    2010-01-20

    Calpain is a calcium-dependent protease that plays a significant role in synaptic plasticity, cell motility, and neurodegeneration. Two major calpain isoforms are present in brain, with mu-calpain (calpain1) requiring micromolar calcium concentrations for activation and m-calpain (calpain2) needing millimolar concentrations. Recent studies in fibroblasts indicate that epidermal growth factor (EGF) can activate m-calpain independently of calcium via mitogen-activated protein kinase (MAPK)-mediated phosphorylation. In neurons, MAPK is activated by both brain-derived neurotrophic factor (BDNF) and EGF. We therefore examined whether these growth factors could activate m-calpain by MAPK-dependent phosphorylation using cultured primary neurons and HEK-TrkB cells, both of which express BDNF and EGF receptors. Calpain activation was monitored by quantitative analysis of spectrin degradation and by a fluorescence resonance energy transfer (FRET)-based assay, which assessed the truncation of a calpain-specific peptide flanked by the FRET fluorophore pair DABCYL and EDANS. In both cell types, BDNF and EGF rapidly elicited calpain activation, which was completely blocked by MAPK and calpain inhibitors. BDNF stimulated m-calpain but not mu-calpain serine phosphorylation, an effect also blocked by MAPK inhibitors. Remarkably, BDNF- and EGF-induced calpain activation was preferentially localized in dendrites and dendritic spines of hippocampal neurons and was associated with actin polymerization, which was prevented by calpain inhibition. Our results indicate that, in cultured neurons, both BDNF and EGF activate m-calpain by MAPK-mediated phosphorylation. These results strongly support a role for calpain in synaptic plasticity and may explain why m-calpain, although widely expressed in CNS, requires nonphysiological calcium levels for activation.

  16. Factors Associated with High Levels of Physical Activity among Adults with Intellectual Disability

    Science.gov (United States)

    Temple, Viviene A.

    2009-01-01

    The aim was to identify factors associated with physical activity participation among active (i.e. more than or equal to 10 000 steps per day) individuals with intellectual disability. Staff at day program and supported employment organizations were asked to identify individuals they believed were physically active. To verify participants were…

  17. T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

    NARCIS (Netherlands)

    van Riemsdijk, I C; Baan, C C; Loonen, E H; Knoop, C J; Navarro Betonico, G; Niesters, H G; Zietse, R; Weimar, W

    2001-01-01

    BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in im

  18. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders;

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic propert...

  19. Cisplatin Induces Cytotoxicity through the Mitogen-Activated Protein Kinase Pathways ana Activating Transcription Factor 3

    Directory of Open Access Journals (Sweden)

    Carly St. Germain

    2010-07-01

    Full Text Available The mechanisms underlying the proapoptotic effect of the chemotherapeutic agent, cisplatin, are largely undefined. Understanding the mechanisms regulating cisplatin cytotoxicity may uncover strategies to enhance the efficacy of this important therapeutic agent. This study evaluates the role of activating transcription factor 3 (ATF3 as a mediator of cisplatin-induced cytotoxicity. Cytotoxic doses of cisplatin and carboplatin treatments consistently induced ATF3 expression in five tumor-derived cell lines. Characterization of this induction revealed a p53, BRCA1, and integrated stress response-independent mechanism, all previously implicated in stress-mediated ATF3 induction. Analysis of mitogenactivated protein kinase (MAPK pathway involvement in ATF3 induction by cisplatin revealed a MAPK-dependent mechanism. Cisplatin treatment combined with specific inhibitors to each MAPK pathway (c-Jun N-terminal kinase, extracellularsignal-regulated kinase, and p38 resulted in decreasedATF3 induction at the protein level. MAPK pathway inhibition led to decreased ATF3 messenger RNA expression and reduced cytotoxic effects of cisplatin as measured by the 3-(4,5-dimethylthiazol-2-ylF2,5-diphenyltetrazolium bromide cell viability assay. In A549 lung carcinoma cells, targeting ATF3 with specific small hairpin RNA also attenuated the cytotoxic effects of cisplatin. Similarly, ATF3-/murine embryonic fibroblasts (MEFs were shown to be less sensitive to cisplatin-induced cytotoxicity compared with ATF3+/+ MEFs. This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin’s cytotoxic effects.

  20. Predicting involvement in prison gang activity: street gang membership, social and psychological factors.

    Science.gov (United States)

    Wood, Jane L; Alleyne, Emma; Mozova, Katarina; James, Mark

    2014-06-01

    The aim of this study was to examine whether street gang membership, psychological factors, and social factors such as preprison experiences could predict young offenders' involvement in prison gang activity. Data were collected via individual interviews with 188 young offenders held in a Young Offenders Institution in the United Kingdom. Results showed that psychological factors such as the value individuals attached to social status, a social dominance orientation, and antiauthority attitudes were important in predicting young offenders' involvement in prison gang activity. Further important predictors included preimprisonment events such as levels of threat, levels of individual delinquency, and levels of involvement in group crime. Longer current sentences also predicted involvement in prison gang activity. However, street gang membership was not an important predictor of involvement in prison gang activity. These findings have implications for identifying prisoners involved in prison gang activity and for considering the role of psychological factors and group processes in gang research.

  1. Sexual activity and cardiac risk: is depression a contributing factor?

    Science.gov (United States)

    Roose, S P; Seidman, S N

    2000-07-20

    There is a well-documented association between depression, ischemic heart disease, and cardiovascular mortality. This association has a number of dimensions including: (1) depressed patients have a higher than expected rate of sudden cardiovascular death; (2) over the course of a lifetime, patients with depression develop symptomatic and fatal ischemic heart disease at a higher rate compared with a nondepressed group; and (3) depression after myocardial infarction (MI) is associated with increased cardiac mortality. Depression is also associated with sexual dysfunction, particularly erectile dysfunction. If depression is the primary illness, then erectile dysfunction can be considered a symptom of the depressive illness. However, if the erectile dysfunction is primary, men may develop a depressive syndrome in reaction to the loss of sexual function. Regardless of whether erectile dysfunction is a symptom of depression or depression is a consequence of erectile dysfunction, these conditions are frequently comorbid. Thus, the patient with ischemic heart disease who is depressed is more likely to have erectile difficulties. An attempt by this patient to engage in sexual activity is therefore more likely to be unsuccessful and, given the increase in cardiac mortality associated with depression, it may result in a serious cardiac event.

  2. Association of Coagulation and Inflammation Related Genes and Factor VIIc Levels with Stroke: The Cardiovascular Health Study

    Science.gov (United States)

    Zakai, Neil A.; Lange, Leslie; Longstreth, W.T.; O’Meara, Ellen S.; Kelley, Joanna L; Fornage, Myriam; Nikerson, Debbie; Cushman, Mary; Reiner, Alexander P.

    2010-01-01

    Background Thrombosis and inflammation are critical in stroke etiology, but associations of coagulation and inflammation gene variants with stroke, and particularly factor VII levels are inconclusive. Objectives To test the associations between 736 single nucleotide polymorphisms (SNP) between tagging haplotype patterns of 130 coagulation and inflammation genes, and stroke events in the 5,888 participants ≥ 65 of the observational Cardiovascular Health Study cohort. Patients /Methods: With 16 years of follow-up, age and sex-adjusted Cox models were used to estimate associations of SNPs and factor VIIc levels with future stroke. Results 815 strokes occurred in 5,255 genotyped participants without baseline stroke (748 ischemic strokes, 586 among whites). Among whites, 6 SNPs were associated with stroke with a nominal p HABP2 gene); rs3138055 (NFKB1A) and rs4648004 (NFKB1). Two of these SNPs were associated with factor VIIc levels (units = percent activity): rs6046 (β = −18.5, p = 2.38 × 10−83) and rs3093261 (β = 2.99, p = 3.93 × 10−6). Adjusting for age, sex, race, and cardiovascular risk factors, the association of factor VIIc quintiles (Q) with stroke were (HR: 95% CI): Q1 (reference); Q2 (1.4; 1.1, 1.9); Q3 (1.1; 0.8, 1.5); Q4 (1.5; 1.1, 2.0); Q5 (1.6; 1.2, 2.2). Associations between SNPs and stroke were independent of factor VIIc levels. Conclusions Variation in factor VII-related genes and factor VIIc levels were associated with risk of incident ischemic stroke in this elderly cohort, suggesting a potential causal role for factor VII in stroke etiology. PMID:21114618

  3. Increasing Physical Activity Decreases Hepatic Fat and Metabolic Risk Factors.

    Science.gov (United States)

    Alderete, Tanya L; Gyllenhammer, Lauren E; Byrd-Williams, Courtney E; Spruijt-Metz, Donna; Goran, Michael I; Davis, Jaimie N

    2012-04-01

    This study assessed the changes in time spent in moderate to vigorous physical activity (MVPA) on fat depots, insulin action, and inflammation. Longitudinal data were generated from 66 Hispanic adolescents (15.6±1.1 yr; BMI percentile 97.1±3.0) who participated in a 16-wk nutrition or nutrition+exercise intervention. There were no effects of the intervention on PA, but there were inter-individual changes in PA. For purposes of this analysis, all intervention groups were combined to assess how changes in PA during 16 wk affected changes in adiposity, insulin action, and markers of inflammation. MVPA was assessed by 7-day accelerometry, total body fat via DXA, liver fat by MRI, and insulin, glucose and HOMA-IR via a fasting blood draw. A repeated measures ANCOVA was used to assess the effect of MVPA on fat depots, insulin action, and inflammatory markers. Sixty-two percent of participants increased MVPA (mean increase, 19.7±16.5 min/day) and 38% decreased MVPA (mean decrease, 10.7±10.1 min/day). Those who increased MVPA by as little as 20 min per day over 16 wk, compared to those who decreased MVPA, had significant reductions in liver fat (-13% vs. +3%; P=0.01), leptin levels (-18% vs. +4%; P=0.02), and fasting insulin (-23% vs. +5%; P=0.05). These findings indicate that a modest increase in MVPA can improve metabolic health in sedentary overweight Hispanic adolescents.

  4. A correction factor to f-chart predictions of active solar fraction in active-passive heating systems

    Science.gov (United States)

    Evans, B. L.; Beckman, W. A.; Duffie, J. A.; Mitchell, J. W.; Klein, S. A.

    1983-11-01

    The extent to which a passive system degrades the performance of an active solar space heating system was investigated, and a correction factor to account for these interactions was developed. The transient system simulation program TRNSYS is used to simulate the hour-by-hour performance of combined active-passive (hybrid) space heating systems in order to compare the active system performance with simplified design method predictions. The TRNSYS simulations were compared to results obtained using the simplified design calculations of the f-Chart method. Comparisons of TRNSYS and f-Chart were used to establish the accuracy of the f-Charts for active systems. A correlation was then developed to correct the monthly loads input into the f-Chart method to account for controller deadbands in both hybrid and active only buildings. A general correction factor was generated to be applied to the f-Chart method to produce more accurate and useful results for hybrid systems.

  5. Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients.

    Science.gov (United States)

    Molino, Daniela; De Santo, Natale G; Marotta, Rosa; Anastasio, Pietro; Mosavat, Mahrokh; De Lucia, Domenico

    2004-09-01

    Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition

  6. An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

    Science.gov (United States)

    Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

    2015-04-01

    Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Pengaruh Penggunaan Lembar Kerja Peserta Didik Berbasis Pendekatan Ilmiah Terhadap Aktivitas dan Hasil Belajar IPA Biologi Kelas VII Peserta Didik SMP Negeri 2 Watampone

    Directory of Open Access Journals (Sweden)

    Marsa Marsa

    2016-04-01

    tinggi.Kata kunci: LKPD berbasis pendekatan ilmiah, aktivitas belajar  dan hasil belajar.ABSTRACTEducational paradigm requires a change in the teacher-centered learning to a student-centered learning. Learning to use the Student Worksheet based learning scientific approach is learner-centered. Student Worksheet-based scientific approach is student work sheet that contains instructions for implementing the learning activities to be performed by the students by applying scientific approach through stages observe, ask, collect data, associate and communicate. This study aims to (1 determine the activities to learn science Biology of seventh grade students at SMP Negeri 2 Watampone taught using LKPD-based scientific approach, (2 determine learning outcomes IPA Biology of seventh grade students at SMP Negeri 2 Watampone taught by using LKPD-based scientific approach, and (3 the effect of the use of LKPD scientific approach based on learning outcomes of science Biology of seventh grade students at SMP Negeri 2 Watampone. This study is peneltian pre-experimental design with one group pretest-posttest design. Subjects were students of class VII second semester of academic year 2015/2016, ie a total of 24 students VIIa class as a class experiment without a control class. Data were analyzed using descriptive statistics. The results showed that (1 the learning activities of students taught using a scientific approach based LKPD are in a very active category, (2 the learning outcomes of students after being taught to use a scientific approach based LKPD reach an average value of 83.13 with a standard deviation of 9.143 and (3 Increase the ability of students after being taught by learning to use a scientific approach based LKPD are at higher classification.Keywords: LKPD-based scientific approach, learning activities and learning outcomes.

  8. Intrapersonal, behavioral, and environmental factors associated with meeting recommended physical activity among rural Latino youth.

    Science.gov (United States)

    Perry, Cynthia K; Saelens, Brian E; Thompson, Beti

    2011-11-01

    This study aimed to identify intrapersonal, behavioral, and environmental factors associated with engaging in recommended levels of physical activity among rural Latino middle school youth. Data were from an anonymous survey of 773 Latino youth (51% female) about level of and barriers and motivators to physical activity, risk behaviors, and park use. Logistic regression models identified factors correlated with meeting recommended levels of physical activity (5 days or more 3 60 min/day). Thirty-four percent of girls and 41% of boys reported meeting this physical activity recommendation. Participation in an organized after school activity (p physical education (PE) classes 5 days a week (p physical activity level. Making PE available 5 days a week and creating opportunities for organized after school physical activity programs may increase the number of rural Latino middle school youth who meet recommended physical activity level.

  9. FUNDAMENTALS OF AMHARIC (REVISED), UNITS IV-VII (LESSONS 16-35).

    Science.gov (United States)

    BARTON, DONALD K.; AND OTHERS

    THIS IS THE SECOND OF A THREE-VOLUME COURSE IN BASIC AMHARIC. FOLLOWING THE SAME FORMAT AS THE FIRST VOLUME, EACH LESSON IN UNITS IV-VII CONTAINS A DIALOG, GRAMMATICAL NOTES, PATTERN DRILLS, EXERCISES, AND A VOCABULARY LIST. ENGLISH-AMHARIC AND AMHARIC-ENGLISH GLOSSARIES ARE APPENDED. THIS COURSE WILL PREPARE THE STUDENT TO PERFORM AT A…

  10. Vittorio De Sica viis meistritööd / Aare Ermel

    Index Scriptorium Estoniae

    Ermel, Aare, 1957-2013

    2008-01-01

    DVD-st "Vittorio De Sica Masterpiece Collection", kus on peal itaalia filmirežissööri Vittorio De Sica viis teost: "Jalgratavargad" ("Ladri di biciclette", 1948), "Ime Milanos" ("Miraclo a milano", 1951), "Umberto D." (1952), "Eile täna, homme" ("Ieri, oggi, domani", 1963), "Ajatu filmikunst" ("Cinema senza tempo: Cosi e la vita", 2001)

  11. Dos Idiomas, Un Mundo. Dual Language Project. Title VII Biennial Evaluation Report, 1995-97.

    Science.gov (United States)

    Ernest, Harishini M.; Gonzalez, Rosa M.

    This is an evaluation of the first 2 years of a 5-year comprehensive Bilingual Education grant funded by Title VII Part A of the Improving America's Schools Act of 1994 in the Austin Independent School District (AISD) (Texas). The grant awarded to the AISD funds a program of Developmental Bilingual Education at two elementary schools where more…

  12. Presidendi teenetemärgi pälvis viis spordiinimest

    Index Scriptorium Estoniae

    2008-01-01

    Vt. ka Linnaleht : Tartu 7. veebr., lk. 7. Eesti riigile osutatud teenete eest pälvisid president Toomas Hendrik Ilveselt teenetemärgi viis spordieluga seotud inimest: jalgpallikoondise ekstreenerid Jelle Goes ja Arno Pijpers, kergejõustikutreener Vésteinn Hafsteinsson, sõudetreener Tatjana Jaanson ning spordielu edendaja Nora Kutti. Juuresoleval fotol Jelle Goes

  13. 78 FR 36011 - Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing

    Science.gov (United States)

    2013-06-14

    ... ADMINISTRATION Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing AGENCY: U.S... Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National Ombudsman is issuing this notice to announce the location, date and time of the Regional Small Business Regulatory Fairness hearing...

  14. MERLIN and VLA Observations of VII Zw 19: Distant Cousin of M82

    Science.gov (United States)

    Beck, Sara C.; Garrington, S. T.; Turner, Jean L.; Van Dyk, Schuyler D.

    2004-10-01

    We have observed the starburst dwarf galaxy VII Zw 19 at subarcsecond resolution with MERLIN and MERLIN+European VLBI Network (EVN) at 18 cm, with MERLIN at 6 cm, and with the Very Large Array (VLA) in the A configuration at 6 and 2 cm. The galaxy is detected at all VLA wavelengths and is resolved. It is also resolved at 18 cm by MERLIN but is not detected by the EVN or by MERLIN at 6 cm. VII Zw 19 has a complex structure of nonthermal radio emission at 18 cm extended over ~1200-1800 pc (4"-6"). That the EVN did not detect this emission indicates that there are no obvious point sources that could be radio supernovae. The 2 cm emission, predominantly thermal free-free emission, has a markedly different spatial distribution from the nonthermal emission. The radio colors show that the galaxy contains numerous supernova remnants, as well as many young H II regions, many of which are optically thick at 6 cm. Two extended regions of 2 cm emission have little 18 cm flux and are probably emission from young star clusters. VII Zw 19 resembles M82 in its radio and infrared spectrum, but the starburst region in VII Zw 19 is twice the size of the one in M82 and twice as luminous.

  15. Vittorio De Sica viis meistritööd / Aare Ermel

    Index Scriptorium Estoniae

    Ermel, Aare, 1957-2013

    2008-01-01

    DVD-st "Vittorio De Sica Masterpiece Collection", kus on peal itaalia filmirežissööri Vittorio De Sica viis teost: "Jalgratavargad" ("Ladri di biciclette", 1948), "Ime Milanos" ("Miraclo a milano", 1951), "Umberto D." (1952), "Eile täna, homme" ("Ieri, oggi, domani", 1963), "Ajatu filmikunst" ("Cinema senza tempo: Cosi e la vita", 2001)

  16. VVER-440 and VVER-1000 reactor dosimetry benchmark - BUGLE-96 versus ALPAN VII.0

    Energy Technology Data Exchange (ETDEWEB)

    Duo, J. I. [Radiation Engineering and Analysis, Westinghouse Electric Company LLC, 1000 Westinghouse Dr., Cranberry Township, PA 16066 (United States)

    2011-07-01

    Document available in abstract form only, full text of document follows: Analytical results of the vodo-vodyanoi energetichesky reactor-(VVER-) 440 and VVER-1000 reactor dosimetry benchmarks developed from engineering mockups at the Nuclear Research Inst. Rez LR-0 reactor are discussed. These benchmarks provide accurate determination of radiation field parameters in the vicinity and over the thickness of the reactor pressure vessel. Measurements are compared to calculated results with two sets of tools: TORT discrete ordinates code and BUGLE-96 cross-section library versus the newly Westinghouse-developed RAPTOR-M3G and ALPAN VII.0. The parallel code RAPTOR-M3G enables detailed neutron distributions in energy and space in reduced computational time. ALPAN VII.0 cross-section library is based on ENDF/B-VII.0 and is designed for reactor dosimetry applications. It uses a unique broad group structure to enhance resolution in thermal-neutron-energy range compared to other analogous libraries. The comparison of fast neutron (E > 0.5 MeV) results shows good agreement (within 10%) between BUGLE-96 and ALPAN VII.O libraries. Furthermore, the results compare well with analogous results of participants of the REDOS program (2005). Finally, the analytical results for fast neutrons agree within 15% with the measurements, for most locations in all three mockups. In general, however, the analytical results underestimate the attenuation through the reactor pressure vessel thickness compared to the measurements. (authors)

  17. Structural studies on metal-containing enzymes. T4 endonuclease VII and D. gigas formate dehydrogenase

    NARCIS (Netherlands)

    Raaijmakers, H.C.A.

    2001-01-01

    Many biological processes require metal ions, and many of these metal-ion functions involve metalloproteins. The metal ions in metalloproteins are often critical to the protein's function, structure, or stability. This thesis focuses on two of these proteins, bacteriophage T4 endonuclease VII (EndoV

  18. Presidendi teenetemärgi pälvis viis spordiinimest

    Index Scriptorium Estoniae

    2008-01-01

    Vt. ka Linnaleht : Tartu 7. veebr., lk. 7. Eesti riigile osutatud teenete eest pälvisid president Toomas Hendrik Ilveselt teenetemärgi viis spordieluga seotud inimest: jalgpallikoondise ekstreenerid Jelle Goes ja Arno Pijpers, kergejõustikutreener Vésteinn Hafsteinsson, sõudetreener Tatjana Jaanson ning spordielu edendaja Nora Kutti. Juuresoleval fotol Jelle Goes

  19. Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors.

    Science.gov (United States)

    Kulkarni, Kiran; Yang, Jing; Zhang, Ziguo; Barford, David

    2011-07-15

    DOCK (dedicator of cytokinesis) guanine nucleotide exchange factors (GEFs) activate the Rho-family GTPases Rac and Cdc42 to control cell migration, morphogenesis, and phagocytosis. The DOCK A and B subfamilies activate Rac, whereas the DOCK D subfamily activates Cdc42. Nucleotide exchange is catalyzed by a conserved DHR2 domain (DOCK(DHR2)). Although the molecular basis for DOCK(DHR2)-mediated GTPase activation has been elucidated through structures of a DOCK9(DHR2)-Cdc42 complex, the factors determining recognition of specific GTPases are unknown. To understand the molecular basis for DOCK-GTPase specificity, we have determined the crystal structure of DOCK2(DHR2) in complex with Rac1. DOCK2(DHR2) and DOCK9(DHR2) exhibit similar tertiary structures and homodimer interfaces and share a conserved GTPase-activating mechanism. Multiple structural differences between DOCK2(DHR2) and DOCK9(DHR2) account for their selectivity toward Rac1 and Cdc42. Key determinants of selectivity of Cdc42 and Rac for their cognate DOCK(DHR2) are a Phe or Trp residue within β3 (residue 56) and the ability of DOCK proteins to exploit differences in the GEF-induced conformational changes of switch 1 dependent on a divergent residue at position 27. DOCK proteins, therefore, differ from DH-PH GEFs that select their cognate GTPases through recognition of structural differences within the β2/β3 strands.

  20. High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Naghi Momeni

    2012-01-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.

  1. Penerapan Model Pembelajaran Treffinger dengan Bantuan Media Audio Visual Untuk Meningkatkan Aktivitas dan Hasil Belajar IPA Terpadu pada Siswa Kelas VII SMP Frater Makassar

    Directory of Open Access Journals (Sweden)

    Nur Indah Sari

    2016-08-01

    Full Text Available Penelitian ini adalah  jenis Penelitian Tindakan Kelas (Classroom Action Research yang bertujuan untuk meningkatkan hasil belajar siswa pada pembelajaran IPA Terpadu melalui penerapan model pembelajaran Treffinger dengan bantuan media audio visual pada materi ekosistem siswa kelas VII SMP FRATER Makassar. Teknik pengumpulan data dilakukan dengan observasi aktivitas belajar siswa dan evaluasi pada setiap akhir siklus. Data yang terkumpul dianalisis dengan menggunakan analisis statistik deskriptif dan dilengkapi dengan tabel frekuensi dan presentase. Dari hasil kegiatan pembelajaran yang telah dilakukan terjadi peningkatan hasil belajar siswa, siklus I sebanyak 14 orang dengan presentase 37,83%, sedangkan pada siklus II sebanyak 32 orang dengan persentase 86,48%. dan terjadi peningkatan aktivitas belajar siswa, Semangat siswa dalam mengikuti pembelajaran IPA Terpadu pada siklus I 50,15% dan  meningkat pada siklus II menjadi 80,05%. Hasil penelitian ini menunjukkan bahwa penerapan model pembelajaran Treffinger dengan bantuan media audio visual dapat meningkatkan hasil belajar IPA Terpadu pada materi ekosistem pada siswa kelas VII A SMP FRATER Makassar.Kata kunci: model pembelajaran treffinger, hasil belajar, ipa terpadu.ABSTRACTThis study is classroom action research study that aims to increase activity and study results of Integrated Science of  student by using Treffinger model with audio visual media on ecosystem material of Class VII Student at SMP Frater Makassar. Data collection used in this study was observation and achievement test in the end of every cycle. Analytical data by using descriptive statistical analysis include the frequency tables and percentages. The results of this study indicate that: Treffinger  model with audio visual media showed a positive tendency from 14 students with 37,83% in cycle I and improve to 32 students with 86,48% in cycle II and showed a positive tendency on student’s activity in study. Student

  2. Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression.

    Science.gov (United States)

    Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression Exposure to many drugs and environmentally-relevant chemicals can cause adverse outcomes. These adverse outcomes, such as cancer, have been linked to mol...

  3. Factors Influencing the Introduction of Physical Activity Interventions in Primary Health Care: a Qualitative Study

    NARCIS (Netherlands)

    Huijg, J.M.; Zouwe, N. van der; Crone, M.R.; Verheijden, M.W.; Middelkoop, B.J.C.; Gebhardt, W.A.

    2015-01-01

    Background: The introduction of efficacious physical activity (PA) interventions in routine primary health care (PHC) is a complex process. Understanding factors influencing the process can enhance the development of successful introduction strategies. Purpose: The aim of this qualitative study was

  4. Children's perceptions of weight, obesity, nutrition, physical activity and related health and socio-behavioural factors

    National Research Council Canada - National Science Library

    Economos, Christina D; Bakun, Peter J; Herzog, Julia Bloom; Dolan, Peter R; Lynskey, Vanessa M; Markow, Dana; Sharma, Shanti; Nelson, Miriam E

    .... An online survey was conducted with children to capture their perceptions of weight, overweight, nutrition, physical activity and related socio-behavioural factors. Within the USA. US children (n 1224) aged 8-18 years...

  5. Factors associated with physical activity among young adults with a disability.

    Science.gov (United States)

    Saebu, M; Sørensen, M

    2011-10-01

    The purpose of this study was to examine: (1) total physical activity and (2) the relative importance of functioning and disability, environmental and personal factors for total physical activity among young adults with a disability. The International Classification of Functioning, Disability and Health developed by the World Health Organization was used as a structural framework for a cross-sectional survey, based on a questionnaire. The population studied was 327 young adults (age 18-30) with a disability who were members of interest organizations for persons with disabilities. Using an adapted version of the self-administered short form of International Physical Activity Questionnaire (IPAQ), the sample reported some differences in physical activity related to the type and the onset of disability. Linear regression analyses revealed that personal factors demonstrated more power in explaining the variance in physical activity than both the environmental factors and factors related to functioning and disability. As for the able-bodied, intrinsic motivation and identity as an active person were the factors most strongly associated with physical activity behavior. This should have important consequences for how professionals try to motivate people with disabilities for physical activity, and how they plan and implement rehabilitation.

  6. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Licarete Emilia

    2012-04-01

    Full Text Available Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA, but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50, Crohn's disease (CD, n = 50, ulcerative colitis (UC, n = 50, bullous pemphigoid (BP, n = 76, and pemphigus vulgaris (PV, n = 42 and healthy donors (n = 245. Results By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005, allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%, 2 CD (4%; 95% CI: 0%-9.43%, 8 UC (16%; 95% CI: 5.8%-26%, 2 BP (2.63%; 95% CI: 0%-6.23%, and 4 PV (9.52%; 95% CI: 0%-18.4% patients as well as from 4 (1.63%; 95% CI: 0%-3.21% healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Conclusions Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should

  7. Identification of platelet-activating factor acetylhydrolase II in human skin.

    Science.gov (United States)

    Marques, Mariangela; Pei, Yong; Southall, Michael D; Johnston, John M; Arai, Hiroyuki; Aoki, Junken; Inoue, Takao; Seltmann, Holger; Zouboulis, Christos C; Travers, Jeffrey B

    2002-10-01

    Platelet-activating factor acetylhydrolases are a family of specialized phospholipase A2 enzymes. They serve an anti-inflammatory function by converting the proinflammatory autocoid, PAF, into biologically inactive lyso-PAF, by the removal of the sn-2 acetyl group of this glycerophospholipid. Similarly, platelet-activating factor acetylhydrolases can also degrade oxidatively modified sn-2 polyunsaturated-fatty-acid-containing phospholipids, which are toxic to cells. Platelet-activating factor acetylhydrolase II is a recently cloned member of this family of specialized phospholipases. Consistent with a potential role of this intracellular enzyme in protecting membrane phospholipids against oxidative stress, platelet-activating factor acetylhydrolase II has been shown to translocate from cytosol to membranes in response to pro-oxidative stressors, and overexpression of this enzyme decreases the cytotoxic effects of these agents. The objective of this study was to assess whether platelet-activating factor acetylhydrolase II is involved in protecting skin against oxidative stress. Platelet-activating factor acetylhydrolase II protein was demonstrated in human skin by immunohistochemistry, with the highest levels of the enzyme found in sebaceous glands and lesser amounts in epidermal keratinocytes. Treatment of epidermal cells with t-butylhydroperoxide or ultraviolet B radiation resulted in platelet-activating factor acetylhydrolase II translocation from cytosol to membranes. To assess the role of this enzyme in epidermal function, a recombinant retroviral strategy was used to overexpress platelet-activating factor acetylhydrolase II in the human keratinocyte-derived cell line HaCaT. Overexpression of platelet-activating factor acetylhydrolase II protected HaCaT cells against apop tosis induced by oxidative stressors t-butylhydroperoxide and ultraviolet B radiation. Similar levels of apoptosis, however, were seen in both control and platelet-activating-factor

  8. Dietary and Physical Activity/Inactivity Factors Associated with Obesity in School-Aged Children123

    OpenAIRE

    Perez-Rodriguez, Marcela; Melendez, Guillermo; Nieto, Claudia; Aranda, Marisol; Pfeffer, Frania

    2012-01-01

    Diet and physical activity (PA) are essential components of nutritional status. Adequate nutrition and an active lifestyle are key factors during childhood, because food habits track into adulthood. Children spend more time in school than in any other environment away from home. Studying the diet factors and patterns of PA that affect obesity risk in children during school hours and the complete school day can help identify opportunities to lower this risk. We directly measured the time child...

  9. Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon.

    OpenAIRE

    1995-01-01

    Full-scale transcriptional activation of the mouse Gbp genes by gamma interferon (IFN-gamma) requires protein synthesis in embryonic fibroblasts. Although the Gbp-1 and Gbp-2 promoters contain binding sites for transcription factors Stat1 and IFN regulatory factor 1 (IRF-1), deletion analysis revealed that the Stat1 binding site is dispensable for IFN-gamma inducibility of Gbp promoter constructs in transfected fibroblasts. However, activation of the mouse Gbp promoter by IFN-gamma requires t...

  10. Giving children a voice: Exploring qualitative perspectives on factors influencing recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine

    2017-01-01

    11–12-year-old children. The socio-ecological model was used as the overall theoretical framework. Twelve factors were identified as influencing the children’s recess physical activity: bodily self-esteem and ability; gender; gendered school culture; peer influence; conflicts and exclusion; space...... of actions addressing factors from different layers in the socio-ecological model to increase recess physical activity....

  11. Factors That Influence Exercise Among Adults With Arthritis in Three Activity Levels

    OpenAIRE

    Der Ananian, Cheryl; Wilcox, Sara; Saunders, Ruth; Watkins, Ken; Evans, Alexandra

    2006-01-01

    Introduction Recent public health objectives emphasize the importance of exercise for reducing disability among people with arthritis. Despite the documented benefits of exercise, people with arthritis are less active than those without arthritis. The purpose of this study was to examine the factors that influence exercise participation among insufficiently active individuals with arthritis and to compare these factors with those identified by nonexercisers and regular exercisers with arthrit...

  12. Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

    Science.gov (United States)

    Konturek, S J; Dembinski, A; Konturek, P J; Warzecha, Z; Jaworek, J; Gustaw, P; Tomaszewska, R; Stachura, J

    1992-01-01

    The importance of platelet activating factor in acute pancreatitis was examined by determining the tissue content of endogenous platelet activating factor and the protective effects of TCV-309, a highly selective platelet activating factor blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine fold increase in tissue level of platelet activating factor and 165% rise in plasma amylase as well as histological evidence of acute pancreatitis. Such infusion of caerulein in chronic pancreatic fistula rats caused a marked increase in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in the first hour of infusion followed by a decline in protein output to 15-20 mg/30 minutes in the following hours of the experiment. Exogenous platelet activating factor (50 micrograms/kg) injected ip produced similar alterations in weight, protein content, blood flow, and histology of the pancreas but the increment in serum amylase was significantly smaller and pancreatic secretion was reduced below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or platelet activating factor administration significantly reduced the biochemical and morphological alterations caused by caerulein and abolished those induced by exogenous platelet activating factor. These results indicate that platelet activating factor plays an important role in the pathogenesis of acute pancreatitis probably by reducing the blood flow and increasing vascular permeability in the pancreas. PMID:1385272

  13. Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Stephan Niebler

    2015-01-01

    Full Text Available The transcription factor AP-2ε (activating enhancer-binding protein epsilon is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4 strongly correlated with that of AP-2ε suggesting that hypoxia might represent an external regulator of AP-2ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1, the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2ε, siRNA against HIF1α led to a significantly reduced expression rate of AP-2ε. Additionally, we detected a significant upregulation of the AP-2ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.

  14. Oxygen Sensing via the Ethylene Response Transcription Factor RAP2.12 Affects Plant Metabolism and Performance under Both Normoxia and Hypoxia1[OPEN

    Science.gov (United States)

    Paul, Melanie Verena; Iyer, Srignanakshi; Lehmann, Martin

    2016-01-01

    Subgroup-VII-ethylene-response-factor (ERF-VII) transcription factors are involved in the regulation of hypoxic gene expression and regulated by proteasome-mediated proteolysis via the oxygen-dependent branch of the N-end-rule pathway. While research into ERF-VII mainly focused on their role to regulate anoxic gene expression, little is known on the impact of this oxygen-sensing system in regulating plant metabolism and growth. By comparing Arabidopsis (Arabidopsis thaliana) plants overexpressing N-end-rule-sensitive and insensitive forms of the ERF-VII-factor RAP2.12, we provide evidence that oxygen-dependent RAP2.12 stability regulates central metabolic processes to sustain growth, development, and anoxic resistance of plants. (1) Under normoxia, overexpression of N-end-rule-insensitive Δ13RAP2.12 led to increased activities of fermentative enzymes and increased accumulation of fermentation products, which were accompanied by decreased adenylate energy states and starch levels, and impaired plant growth and development, indicating a role of oxygen-regulated RAP2.12 degradation to prevent aerobic fermentation. (2) In Δ13RAP2.12-overexpressing plants, decreased carbohydrate reserves also led to a decrease in anoxic resistance, which was prevented by external Suc supply. (3) Overexpression of Δ13RAP2.12 led to decreased respiration rates, changes in the levels of tricarboxylic acid cycle intermediates, and accumulation of a large number of amino acids, including Ala and γ-amino butyric acid, indicating a role of oxygen-regulated RAP2.12 abundance in controlling the flux-modus of the tricarboxylic acid cycle. (4) The increase in amino acids was accompanied by increased levels of immune-regulatory metabolites. These results show that oxygen-sensing, mediating RAP2.12 degradation is indispensable to optimize metabolic performance, plant growth, and development under both normoxic and hypoxic conditions. PMID:27372243

  15. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  16. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...

  17. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    Science.gov (United States)

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  18. Social Cognitive Factors Associated with Physical Activity in Elementary School Girls

    Science.gov (United States)

    Bean, Melanie K.; Miller, Sara; Mazzeo, Suzanne E.; Fries, Elizabeth A.

    2012-01-01

    Objective: To examine social cognitive factors associated with physical activity (PA) among preadolescent girls. Method: Social cognitive theory was used to examine PA in girls (N = 90; 71% African American) participating in Girls on the Run. Multiple regressions explored factors associated with PA at posttesting and 3-month follow-up. Results:…

  19. Root hair deformation activity of nodulation factor and their fate on Vicia sativa.

    NARCIS (Netherlands)

    Heidstra, R.; Geurts, R.; Franssen, H.; Spaink, H.P.; Kammen, van A.; Bisseling, T.

    1994-01-01

    We used a semiquantitative root hair deformation assay for Vicia sativa (vetch) to study the activity of Rhizobium leguminosarum bv viciae nodulation (Nod) factors. Five to 10 min of Nod factor-root interaction appears to be sufficient to induce root hair deformation. The first deformation is visibl

  20. Nuclear Factor-κB: Activation and Regulation during Toll-like Receptor Signaling

    Institute of Scientific and Technical Information of China (English)

    Ruaidhrí J. Carmody; Youhai H. Chen

    2007-01-01

    Toll-like receptors (TLRs) recognize distinct microbial components to initiate the innate and adaptive immune responses. TLR activation culminates in the expression of appropriate pro-inflammatory and immunomodulatory factors to meet pathogenic challenges. The transcription factor NF-κB is the master regulator of all TLR-induced responses and its activation is the pivotal event in TLR-mediated activation of the innate immune response. Many of the key molecular events required for TLR-induced NF-κB activation have been elucidated. However, much remain to be learned about the ability of TLRs to generate pathogen-specific responses using a limited number of transcription factors. This review will focus on our current understanding of NF-κB activation by TLRs and potential mechanisms for achieving a signal-specific response through NF-κB.

  1. Inferring yeast cell cycle regulators and interactions using transcription factor activities

    Directory of Open Access Journals (Sweden)

    Galbraith Simon J

    2005-06-01

    Full Text Available Abstract Background Since transcription factors are often regulated at the post-transcriptional level, their activities, rather than expression levels may provide valuable information for investigating functions and their interactions. The recently developed Network Component Analysis (NCA and its generalized form (gNCA provide a robust framework for deducing the transcription factor activities (TFAs from various types of DNA microarray data and transcription factor-gene connectivity. The goal of this work is to demonstrate the utility of TFAs in inferring transcription factor functions and interactions in Saccharomyces cerevisiae cell cycle regulation. Results Using gNCA, we determined 74 TFAs from both wild type and fkh1 fkh2 deletion mutant microarray data encompassing 1529 ORFs. We hypothesized that transcription factors participating in the cell cycle regulation exhibit cyclic activity profiles. This hypothesis was supported by the TFA profiles of known cell cycle factors and was used as a basis to uncover other potential cell cycle factors. By combining the results from both cluster analysis and periodicity analysis, we recovered nearly 90% of the known cell cycle regulators, and identified 5 putative cell cycle-related transcription factors (Dal81, Hap2, Hir2, Mss11, and Rlm1. In addition, by analyzing expression data from transcription factor knockout strains, we determined 3 verified (Ace2, Ndd1, and Swi5 and 4 putative interaction partners (Cha4, Hap2, Fhl1, and Rts2 of the forkhead transcription factors. Sensitivity of TFAs to connectivity errors was determined to provide confidence level of these predictions. Conclusion By subjecting TFA profiles to analyses based upon physiological signatures we were able to identify cell cycle related transcription factors consistent with current literature, transcription factors with potential cell cycle dependent roles, and interactions between transcription factors.

  2. Inhibition of the TEF/TEAD transcription factor activity by nuclear calcium and distinct kinase pathways.

    Science.gov (United States)

    Thompson, M; Andrade, V A; Andrade, S J; Pusl, T; Ortega, J M; Goes, A M; Leite, M F

    2003-02-07

    Transcription enhancer factor (TEF/TEAD) is a family of four transcription factors that share a common TEA-DNA binding domain and are involved in similar cellular functions, such as cell differentiation and proliferation. All adult tissues express at least one of the four TEAD genes, so this family of transcription factors may be of widespread importance, yet little is known about their regulation. Here we examine the factors that regulate TEAD activity in CHO cells. RT-PCR indicated the presence of TEAD-1, TEAD-3, and both isoforms of TEAD-4, but not TEAD-2. Quantitative measurements showed that TEAD-4 is most abundant, followed by TEAD-3, then TEAD-1. We examined the relative effects of nuclear and cytosolic Ca(2+) on TEAD activity, since TEAD proteins are localized to the nucleus and since free Ca(2+) within the nucleus selectively regulates transcription in some systems. Chelation of nuclear but not cytosolic Ca(2+) increased TEAD activity two times above control. Inhibition of mitogen-activated protein kinase (MAPK) also increased TEAD activity, while cAMP decreased TEAD activity, and protein kinase C had no effect. Together, these results show that nuclear Ca(2+), MAPK, and cAMP each negatively regulate the activity of the TEAD transcription factor.

  3. Genetic diversity of the genotype VII Newcastle disease virus: identification of a novel VIIj sub-genotype.

    Science.gov (United States)

    Xue, Cong; Cong, Yanlong; Yin, Renfu; Sun, Yixue; Ding, Chan; Yu, Shengqing; Liu, Xiufan; Hu, Shunlin; Qian, Jing; Yuan, Qianliang; Yang, Mingxi; Wang, Chunfeng; Ding, Zhuang

    2017-02-01

    Newcastle disease (ND) is a highly contagious disease of poultry caused by Newcastle disease virus (NDV). Multiple genotypes of NDV have been circulating worldwide and NDV is continuously evolving, resulting into more diversity. Of multiple viral genotypes, VII is particularly important given that it had been associated with most recent ND outbreaks worldwide. In this study, an epidemiological investigation performed in northeastern China during 2014-2015 showed that 11 genotype VII isolates amounted to 55 percent in a total number of NDV isolates. Therefore, to evaluate the genetic diversity worldwide and epidemiological distribution in China of genotype VII NDV, a phylogenetic analysis based on the 1255 complete F gene sequences showed that VII is the most predominant genotype worldwide. A further detailed characterization on genotype VII was conducted based on the 477 complete F gene sequences from 11 isolates and 466 reference viruses available in GenBank. The results demonstrated that VII can be further divided into 8 sub-genotypes (VIIb, VIId-VIIj), indicating its complex genetic diversity. It is worthy of note that the isolation rate of VIIj is increasing recently. It emphasizes the necessity to pay close attention to the epidemiological dynamic of genotype VII NDV and highlights the importance of vaccination program.

  4. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.

    Science.gov (United States)

    Mutoh, Shingo; Sobhany, Mack; Moore, Rick; Perera, Lalith; Pedersen, Lee; Sueyoshi, Tatsuya; Negishi, Masahiko

    2013-05-07

    Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.

  5. Comparing citrated native, kaolin-activated, and tissue factor-activated samples and determining intraindividual variability for feline thromboelastography.

    Science.gov (United States)

    Banerjee, Amrita; Blois, Shauna L; Wood, R Darren

    2011-11-01

    Thromboelastography (TEG) is a point-of-care whole blood test of hemostasis. While TEG is becoming more widely used in veterinary medicine, few studies describe the use of TEG in cats. The objectives of the current study were to: 1) document the range of TEG variables produced in healthy cats using 3 sample types (citrated native, kaolin-activated, and tissue factor-activated), and 2) determine if there was a significant difference between 2 separate samples obtained from individual healthy cats on the same day. Jugular venipuncture was performed in 20 cats, and citrated blood collected for TEG. TEG analysis was performed on citrated native, kaolin-activated, and tissue factor-activated blood for each sample. Two hours later, the procedure was repeated from the opposite jugular vein, yielding a total of 120 analyses. Reaction time (R), alpha angle (α), kappa value (κ), and maximum amplitude (MA) were recorded from each tracing. No significant differences were found between TEG tracings from the first and second venipuncture samples. Significant differences were found between sample types for R, α, κ, and MA. Means for citrated native/kaolin-activated/tissue factor-activated methods were R = 4.1/3.7/0.6 min; κ = 2.5/1.8/2.2 min; α = 59.9/65.1/70.4 degrees; MA = 47.4/49.9/44.7 mm. A limitation of this study was the small number of cats used. Thromboelastography analysis may be a suitable method of evaluating hemostasis in cats.

  6. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...... control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we...

  7. Comparison of Some Cardiovascular Risk Factors between Active and Sedentary Elderly Men

    Directory of Open Access Journals (Sweden)

    H. Najafgholizadeh

    2017-04-01

    Full Text Available Background: One of the major problems threatening the world’s people are cardiovascular diseases, accounting for 30% of the deaths. The factors exposing people to this danger are called risk factors. Objective: This study aimed to compare the cardiovascular risk factors and C-reactive protein between active and sedentary elderly men. Methods: The study was a descriptive comparison of two groups that were conducted in Rasht city in 2015. The subjects of this study consist of 30 active elderly men and 30 sedentary elderly men who were selected non-randomly and purposefully. Inclusion criteria of research for active subjects were have regular physical activity at least six months and don’t use cigarette and pills that affect profile lipids and inclusion criteria for sedentary subjects were don’t have regular physical activity and also don’t use cigarette and pills that affect profile lipids. The measured cardiovascular risk factors of subjects include fasting blood sugar (FBS, triglyceride (TG, total cholesterol (TC, highdensity lipoprotein (HDL, low-density lipoprotein (LDL, very low-density lipoprotein (VLDL, glycated haemoglobinA1c (HbA1c, and C-reactive protein (CRP. The statistical methods used for data analysis are Kolmogorov-Smirnov test, t-student, and U Mann-Whitney with significance level less than 0.05. Findings: The t-student exam shows that cardiovascular risk factors, including FBS, TG, TC, HDL, VLDL, HbA1c, and CRP, in active elderly men are lower than sedentary elderly men. This difference is also statistically significant (P≤0/01. Conclusion: The study showed that cardiovascular risk factors in active elderly men are less than sedentary ones. However, 80% of active elderly men had still at least one or several cardiovascular risk factors.

  8. Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, Niels Juel

    1993-01-01

    In order to describe the relation between snoring, cardiovascular risk factors, metabolic factors and sympathetitic activity, 804 70-year-old males and females were classified according to snoring habits and life-style factors (alcohol and tobacco consumption), blood pressure, body mass index (BMI....... Self-reported snoring was associated with gender (males showed higher prevalence than females, p ... with tobacco consumption (p = 0.08). No associations were found between snoring and fasting glucose, plasma lipids, plasma epinephrine or in the use of antihypertensive medication. In multivariate analysis, with forced entry of gender, BMI, physical activity, alcohol and tobacco consumption, the relation...

  9. Factors Involved in Iranian Women Heads of Household's Health Promotion Activities: A Grounded Theory Study.

    Science.gov (United States)

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh

    2013-01-01

    We aimed to explore and describe the factors involved in Iranian women heads of household's health promotion activities. Grounded theory was used as the method. Sixteen women heads of household were recruited. Data were generated by semi structured interviews. Our findings indicated that remainder of resources (money, time and energy) alongside perceived severity of health risk were two main factors whereas women's personal and socio-economic characteristics were two contextual factors involved in these women's health promotion activities. To help these women improve their health status, we recommended that the government, non-governmental organizations and health care professionals provide them with required resources and increase their knowledge by holding training sessions.

  10. Testing the Youth Physical Activity Promotion Model: Fatness and Fitness as Enabling Factors

    Science.gov (United States)

    Chen, Senlin; Welk, Gregory J.; Joens-Matre, Roxane R.

    2014-01-01

    As the prevalence of childhood obesity increases, it is important to examine possible differences in psychosocial correlates of physical activity between normal weight and overweight children. The study examined fatness (weight status) and (aerobic) fitness as Enabling factors related to youth physical activity within the Youth Physical Activity…

  11. Factors of physical activity among Chinese children and adolescents : A systematic review

    NARCIS (Netherlands)

    Lu, Congchao; Stolk, Ronald P.; Sauer, Pieter J. J.; Sijtsma, Anna; Wiersma, Rikstje; Huang, Guowei; Corpeleijn, Eva

    2017-01-01

    Background: Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this

  12. PAK1 negatively regulates the activity of the Rho exchange factor NET1.

    Science.gov (United States)

    Alberts, Arthur S; Qin, Huajun; Carr, Heather S; Frost, Jeffrey A

    2005-04-01

    Rho family small G-protein activity is controlled by guanine nucleotide exchange factors that stimulate the release of GDP, thus allowing GTP binding. Once activated, Rho proteins control cell signaling through interactions with downstream effector proteins, leading to changes in cytoskeletal organization and gene expression. The ability of Rho family members to modulate the activity of other Rho proteins is also intrinsic to these processes. In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner. Furthermore, coexpression of constitutively active PAK1 inhibits the ability of NET1 to stimulate actin polymerization only when serines 152 and 153 are present. These data provide a novel mechanism for the control of RhoA activity by Rac1 through the PAK-dependent phosphorylation of NET1 to reduce its activity as a guanine nucleotide exchange factor.

  13. Testing the Youth Physical Activity Promotion Model: Fatness and Fitness as Enabling Factors

    Science.gov (United States)

    Chen, Senlin; Welk, Gregory J.; Joens-Matre, Roxane R.

    2014-01-01

    As the prevalence of childhood obesity increases, it is important to examine possible differences in psychosocial correlates of physical activity between normal weight and overweight children. The study examined fatness (weight status) and (aerobic) fitness as Enabling factors related to youth physical activity within the Youth Physical Activity…

  14. Factors that Limit and Enable Preschool-Aged Children's Physical Activity on Child Care Centre Playgrounds

    Science.gov (United States)

    Coleman, Bianca; Dyment, Janet E.

    2013-01-01

    The incidence of childhood obesity amongst preschool-aged children has increased dramatically in recent years and can be attributed, in part, to a lack of physical activity amongst children in this age group. This study explores the social factors that stand to limit and/or enable children's physical activity opportunities in outdoor settings in…

  15. Association between Social and Environmental Factors and Physical Activity Opportunities in Middle Schools

    Science.gov (United States)

    Xu, Furong; Chepyator-Thomson, Jepkorir; Liu, Wenhao; Schmidlein, Robert

    2010-01-01

    School-based physical activity (PA) interventions impact children's PA involvement and thus opportunities and associated factors for the promotion of physical activity in children need to be examined. The purpose of this study was to examine physical education teachers' perceptions of PA opportunities available to students at the middle school…

  16. Physical and Psychosocial Factors Associated With Physical Activity in Patients With Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hartman, Jorine E.; Boezen, H. Marike; de Greef, Mathieu H.; ten Hacken, Nick H.

    2013-01-01

    Objectives: To assess physical activity and sitting time in patients with chronic obstructive pulmonary disease (COPD) and to investigate which physical and psychosocial factors are associated with physical activity and sitting time. Design: Cross-sectional study. Setting: Patients were recruited at

  17. Platelet-activating factor acetylhydrolase and haemophagocytosis in the sepsis syndrome

    Directory of Open Access Journals (Sweden)

    Franck Trimoreau

    2000-01-01

    Full Text Available Sepsis syndrome (SS is associated with depressed PAF acetylhydrolase, the enzyme responsible for the degradation of platelet activating factor. PAF acetylhydrolase is in a large part produced by macrophages, whose inadequate activation with haemophagocytosis is frequent in patients with SS.

  18. Tead proteins activate the Foxa2 enhancer in the node in cooperation with a second factor.

    Science.gov (United States)

    Sawada, Atsushi; Nishizaki, Yuriko; Sato, Hiroko; Yada, Yukari; Nakayama, Rika; Yamamoto, Shinji; Nishioka, Noriyuki; Kondoh, Hisato; Sasaki, Hiroshi

    2005-11-01

    The cell population and the activity of the organizer change during the course of development. We addressed the mechanism of mouse node development via an analysis of the node/notochord enhancer (NE) of Foxa2. We first identified the core element (CE) of the enhancer, which in multimeric form drives gene expression in the node. The CE was activated in Wnt/beta-catenin-treated P19 cells with a time lag, and this activation was dependent on two separate sequence motifs within the CE. These same motifs were also required for enhancer activity in transgenic embryos. We identified the Tead family of transcription factors as binding proteins for the 3' motif. Teads and their co-factor YAP65 activated the CE in P19 cells, and binding of Tead to CE was essential for enhancer activity. Inhibition of Tead activity by repressor-modified Tead compromised NE enhancer activation and notochord development in transgenic mouse embryos. Furthermore, manipulation of Tead activity in zebrafish embryos led to altered expression of foxa2 in the embryonic shield. These results suggest that Tead activates the Foxa2 enhancer core element in the mouse node in cooperation with a second factor that binds to the 5' element, and that a similar mechanism also operates in the zebrafish shield.

  19. Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells.

    Science.gov (United States)

    Kurosawa, Mie; Oda, Masataka; Domon, Hisanori; Saitoh, Issei; Hayasaki, Haruaki; Terao, Yutaka

    2016-02-01

    Streptococcus pyogenes produces molecules that inhibit the function of human immune system, thus allowing the pathogen to grow and spread in tissues. It is known that S. pyogenes CAMP factor increases erythrocytosis induced by Staphylococcus aureus β-hemolysin. However, the effects of CAMP factor for immune cells are unclear. In this study, we investigated the effects of CAMP factor to macrophages. Western blotting analysis demonstrated that all examined strains expressed CAMP factor protein. In the presence of calcium or magnesium ion, CAMP factor was significantly released in the supernatant. In addition, both culture supernatant from S. pyogenes strain SSI-9 and recombinant CAMP factor dose-dependently induced vacuolation in RAW 264.7 cells, but the culture supernatant from Δcfa isogenic mutant strain did not. CAMP factor formed oligomers in RAW 264.7 cells in a time-dependent manner. CAMP factor suppressed cell proliferation via G2 phase cell cycle arrest without inducing cell death. Furthermore, CAMP factor reduced the uptake of S. pyogenes and phagocytic activity indicator by RAW 264.7 cells. These results suggest that CAMP factor works as a macrophage dysfunction factor. Therefore, we conclude that CAMP factor allows S. pyogenes to escape the host immune system, and contribute to the spread of streptococcal infection.

  20. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

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    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  1. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation

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    Rosenbaum Susann

    2012-10-01

    Full Text Available Abstract Background It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2 pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS. The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. Findings Transcript levels of known Nrf2 target genes, UGT1A1 (encoding glucuronosyltransferase 1 family, polypeptide A1, HO-1 (encoding heme oxygenase 1, NQO1 (encoding NAD(PH dehydrogenase, quinone 1, GPX1 (encoding glutathione peroxidase, PRDX6 (encoding peroxiredoxin 6, TXNRD1 (encoding thioredoxin reductase 1, and SOD (encoding superoxide dismutase, in the liver are significantly elevated (between 1.7 and 3.1 fold in lactating sows compared to non-lactating sows. The inflammatory state in the liver was evidenced by the finding that transcript levels of genes encoding acute phase proteins, namely haptoglobin (HP, fibrinogen γ (FGG, complement factor B (CFB, C-reactive protein (CRP and lipopolysaccharide-binding protein (LBP, were significantly higher (2 to 8.7 fold in lactating compared to non-lactating sows. Conclusions The results of the present study indicate that the Nrf2 pathway in the liver of sows is activated during lactation. The activation of Nrf2 pathway during lactation in sows might be interpreted as a physiologic means to counteract the inflammatory process and to protect the liver against damage induced by inflammatory signals and ROS.

  2. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  3. Objectively measured physical activity in Brazilians with visual impairment: description and associated factors.

    Science.gov (United States)

    Barbosa Porcellis da Silva, Rafael; Marques, Alexandre Carriconde; Reichert, Felipe Fossati

    2017-05-19

    Low level of physical activity is a serious health issue in individuals with visual impairment. Few studies have objectively measured physical activity in this population group, particularly outside high-income countries. The aim of this study was to describe physical activity measured by accelerometry and its associated factors in Brazilian adults with visual impairment. In a cross-sectional design, 90 adults (18-95 years old) answered a questionnaire and wore an accelerometer for at least 3 days (including one weekend day) to measure physical activity (min/day). Sixty percent of the individuals practiced at least 30 min/day of moderate-to-vigorous physical activity. Individuals who were blind were less active, spent more time in sedentary activities and spent less time in moderate and vigorous activities than those with low vision. Individuals who walked mainly without any assistance were more active, spent less time in sedentary activities and spent more time in light and moderate activities than those who walked with a long cane or sighted guide. Our data highlight factors associated with lower levels of physical activity in people with visual impairment. These factors, such as being blind and walking without assistance should be tackled in interventions to increase physical activity levels among visual impairment individuals. Implications for Rehabilitation Physical inactivity worldwide is a serious health issue in people with visual impairments and specialized institutions and public policies must work to increase physical activity level of this population. Those with lower visual acuity and walking with any aid are at a higher risk of having low levels of physical activity. The association between visual response profile, living for less than 11 years with visual impairment and PA levels deserves further investigations Findings of the present study provide reliable data to support rehabilitation programs, observing the need of taking special attention to

  4. Change of Coagulation Factor Ⅷ and Antithrombin Ⅲ Activity in Bank-Stored Blood

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank-stored blood can be used to replenish antithrombin Ⅲ, while bank-stored blood in one day can be used to replenish FⅧ.

  5. PENINGKATAN KEMAMPUAN BERCERITA DENGAN MENGGUNAKAN MEDIA GAMBAR BAGI SISWA KELAS VII A SMP BHAYANGKARI KARANGPANDAN KABUPATEN KARANGANYAR SEMESTER GASAL TAHUN PELAJARAN 2009/2010

    Directory of Open Access Journals (Sweden)

    Sukidi Sukidi

    2016-07-01

    Full Text Available Classroom action research was conducted with the aim of: 1. To enhance the learning process for students tell the class VII A junior Bhayangkari Karangpandan, 2. To improve the ability to tell the students of class VII A junior Bhayangkari Karangpandan. Execution carried out in two cycles, each cycle consisting of four (4 steps of activities, namely planning, action, observation and reflection. Prior to the first cycle begins with the initial research activities to find out the condition of the subjects. Based on preliminary research results compiled in the form of research, planning learning implementation plan. First cycle of action as an effort to improve the conditions stated lack of or low on the initial research. Activity Cycle II, the efforts to repair/ improvement of a state which is still less in the first cycle. The result of study shows that low-ability students to tell based on initial research, one of which caused no/ not use the GCC appropriate learning media to achieve the expected competencies. In this study, the actions taken to improve the process and learning outcomes using instructional media telling picture. After doing the action over the past two cycles, the results showed that by using media images as well the ability to tell the students can be improved.

  6. UPAYA MENINGKATKAN AKTIVITAS DAN HASIL BELAJAR BIOLOGI MELALUI METODE INKUIRI YANG MENGGUNAKAN KOMIK BIOLOGI SISWA KELAS VII A MTs NEGERI METRO TAHUN PELAJARAN 2011/2012

    Directory of Open Access Journals (Sweden)

    Hesty Wahyuningsih

    2013-05-01

    Full Text Available The purposes of this research were (1 to improve students’ learning activity by using inquiry method with biology comics for the students of VII A MTs Negeri Metro (2 to improve students’ achievement in learning biology by using inquiry method with biology comics for the students of VII A MTs Negeri Metro. The results of this research were (1 learning through inquiry method which uses biology comics can improve students’ activity during the learning process. From the data of observation, the students achievements increase from cycle I to cycle II (from 46.6% to 55.28%, it means that the increasing is about 8.68% (2 learning through inquiry method which uses biology comics can improve students’ activity during the learning process, the students achievements increase from cycle II to cycle III (from 60% to 76.7%, it means that the increasing is about 16, 7%.   Kata kunci: metode inkuiri, media komik biologi, aktivitas belajar, hasil belajar biologi

  7. Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation

    Directory of Open Access Journals (Sweden)

    Das Sulagna

    2010-10-01

    Full Text Available Abstract Background Activation of microglia, the resident macrophages of the central nervous system (CNS, is the hallmark of neuroinflammation in neurodegenerative diseases and other pathological conditions associated with CNS infection. The activation of microglia is often associated with bystander neuronal death. Nuclear factor-κB (NF-κB is one of the important transcription factors known to be associated with microglial activation which upregulates the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (Cox-2 and other pro-inflammatory cytokines. Recent studies have focused on the role of Krüppel-like factor 4 (Klf4, one of the zinc-finger transcription factors, in mediating inflammation. However, these studies were limited to peripheral system and its role in CNS is not understood. Our studies focused on the possible role of Klf4 in mediating CNS inflammation. Methods For in vitro studies, mouse microglial BV-2 cell lines were treated with 500 ng/ml Salmonella enterica lipopolysacchride (LPS. Brain tissues were isolated from BALB/c mice administered with 5 mg/kg body weight of LPS. Expressions of Klf4, Cox-2, iNOS and pNF-κB were evaluated using western blotting, quantitative real time PCR, and reverse transcriptase polymerase chain reactions (RT-PCRs. Klf4 knockdown was carried out using SiRNA specific for Klf4 mRNA and luciferase assays and electromobility shift assay (EMSA were performed to study the interaction of Klf4 to iNOS promoter elements in vitro. Co-immunoprecipitation of Klf4 and pNF-κB was done in order to study a possible interaction between the two transcription factors. Results LPS stimulation increased Klf4 expression in microglial cells in a time- and dose-dependent manner. Knockdown of Klf4 resulted in decreased levels of the pro-inflammatory cytokines TNF-α, MCP-1 and IL-6, along with a significant decrease in iNOS and Cox-2 expression. NO production also decreased as a result of Klf4 knockdown

  8. THE EXTERNAL FACTORS OF STUDENTS’ INVOLVEMENT IN SPEAKING ACTIVITY AT SMP PROGRESIF BUMI SHALAWAT

    Directory of Open Access Journals (Sweden)

    M.A. Nurul Haikal

    2016-07-01

    Full Text Available This research is conducted to know what factors that influence the students’ involvement in speaking activity in order to practice their speaking skill and what strategies that the teacher used to encourage those external factors. This research uses descriptive qualitative method. There are two instruments used for this research, namely, class observation and interview. Based on the results of class observation and interview, the researcher concludes that teacher factor gives the greatest impact on students’ involvement and the appropriate strategies can support those external factors.

  9. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  10. [Dependence of EGF receptor and STAT factor activation on redox of A431 cells].

    Science.gov (United States)

    Gonchar, I V; Burova, E B; Dorosh, V N; Gamaleĭ, I A; Nikol'skiĭ, N N

    2003-01-01

    Reactive oxygen species (ROS) were established to play an important role in cellular signaling as second messengers by integrating different pathways. Recently, we showed that EGF initiated a rapid tyrosine phosphorylation of both EGF-receptor and STAT factors with simultaneous increase in the intracellular ROS level. Now, we have investigated the effect of intracellular red-ox state on EGF- and H2O2-induced activation of EGF receptor, STAT1 and STAT3. We demonstrated that the pretreatment of A431 cells with antioxidant N-acetyl-L-cysteine (NAC) partly reduced the level of EGF-induced phosphorylation of proteins under investigation. Besides, H2O2-induced activation of EGF receptor, and STAT factors was fully prevented by NAC pretreatment. The inhibition of ROS generation by DPI declined EGF-dependent activation of EGF receptor and STAT factors to basal level. Our results demonstrate the essential role of cellular red-ox status in the modulation of EGF-mediated activation of receptor and STAT factors. We have postulated that EGF-induced ROS generation is a very important initial event promoting physiological activation of EGF receptor and subsequent STAT factor activation.

  11. The translation initiation factor 3f (eIF3f exhibits a deubiquitinase activity regulating Notch activation.

    Directory of Open Access Journals (Sweden)

    Julien Moretti

    Full Text Available Activation of the mammalian Notch receptor after ligand binding relies on a succession of events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by the gamma-secretase, giving rise to a soluble, transcriptionally active molecule. The Notch1 receptor was proposed to be monoubiquitinated before its gamma-secretase cleavage; the targeted lysine has been localized to its submembrane domain. Investigating how this step might be regulated by a deubiquitinase (DUB activity will provide new insight for understanding Notch receptor activation and downstream signaling. An immunofluorescence-based screening of an shRNA library allowed us to identify eIF3f, previously known as one of the subunits of the translation initiation factor eIF3, as a DUB targeting the activated Notch receptor. We show that eIF3f has an intrinsic DUB activity. Knocking down eIF3f leads to an accumulation of monoubiquitinated forms of activated Notch, an effect counteracted by murine WT eIF3f but not by a catalytically inactive mutant. We also show that eIF3f is recruited to activated Notch on endocytic vesicles by the putative E3 ubiquitin ligase Deltex1, which serves as a bridging factor. Finally, catalytically inactive forms of eIF3f as well as shRNAs targeting eIF3f repress Notch activation in a coculture assay, showing that eIF3f is a new positive regulator of the Notch pathway. Our results support two new and provocative conclusions: (1 The activated form of Notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. (2 The enzyme accounting for this deubiquitinase activity is eIF3f, known so far as a translation initiation factor. These data improve our knowledge of Notch signaling but also open new avenues of research on the Zomes family and the translation initiation factors.

  12. A New Microsphere-Based Immunoassay for Measuring the Activity of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Tsai Chueh-Jen

    2010-01-01

    Full Text Available Abstract There are several traditional and well-developed methods for analyzing the activity of transcription factors, such as EMSA, enzyme-linked immunosorbent assay, and reporter gene activity assays. All of these methods have their own distinct disadvantages, but none can analyze the changes in transcription factors in the few cells that are cultured in the wells of 96-well titer plates. Thus, a new microsphere-based immunoassay to measure the activity of transcription factors (MIA-TF was developed. In MIA-TF, NeutrAvidin-labeled microspheres were used as the solid phase to capture biotin-labeled double-strand DNA fragments which contain certain transcription factor binding elements. The activity of transcription factors was detected by immunoassay using a transcription factor-specific antibody to monitor the binding with the DNA probe. Next, analysis was performed by flow cytometry. The targets hypoxia-inducible factor-1α (HIF-1α and nuclear factor-kappa B (NF-κB were applied and detected in this MIA-TF method; the results that we obtained demonstrated that this method could be used to monitor the changes of NF-κB or HIF within 50 or 100 ng of nuclear extract. Furthermore, MIA-TF could detect the changes in NF-κB or HIF in cells that were cultured in wells of a 96-well plate without purification of the nuclear protein, an important consideration for applying this method to high-throughput assays in the future. The development of MIA-TF would support further progress in clinical analysis and drug screening systems. Overall, MIA-TF is a method with high potential to detect the activity of transcription factors.

  13. Phase Relations and Properties of Salty ices VI and VII: Implications for Solar System Ices

    Science.gov (United States)

    Daniel, I.; Manning, C. E.

    2008-12-01

    Ice VI and ice VII may be important in the interiors of Europa, Ganymede, Callisto and Titan. Oceans and interior pore waters in these bodies likely contain dissolved salts. To address the role of salt on ice VI and ice VII, we investigated phase equilibria in the system H2O -NaCl at 1 molal (5.5 wt%) NaCl in an externally heated diamond-anvil cell. Phase identifications were made by optical microscopy combined with Raman spectroscopy. Experiments were conducted at 22-150°C and up to 5 GPa by allowing the cell to thermally equilibrate at a given temperature and then varying pressure isothermally while observing phase changes. The liquidus curves of ice VI and ice VII in a 5.5 wt% NaCl solution were determined. Melting was observed from 22 to 80°C (ice VI) and from 35 to 150°C (ice VII). Both melting curves are steeper than the respective NaCl-free curves, indicating that the freezing-point depression at this bulk composition increases with pressure. The intersection of the two liquidus curves indicates that VI-VII-liquid triple point is shifted toward lower T and higher P relative to pure H2O. The 5.5 wt% NaCl bulk composition crystallizes into a single solid phase of NaCl-bearing ice VI or ice VII solid solution over the investigated T range (the subscript 'ss' indicates solid solution). Large single crystals of ice VIss or ice VIIss can also be grown by slow compression of the cell from near-liquidus conditions to the solidus. Raman spectra of these crystals clearly show zoning in these crystals. The zoning persists for days at 22°C, indicating relatively slow Na+ and Cl- diffusivity. The large depression of the freezing point in a 1 molal NaCl solution has important implications for the oceans and interiors of the icy satellites of Jupiter and Saturn. Salty fluids may remain stable to much greater depth than expected. This would promote extensive hydrothermal metamorphism of the silicate interiors. If not limited to ice VI and VII, this behavior may suppress

  14. Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation

    NARCIS (Netherlands)

    Borensztajn, Keren; Stiekema, Jurrieen; Nijmeijer, Sebastiaan; Reitsmalf, Pieter H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    Coagulation proteases have been suggested to play a role in the pathogenesis of tissue remodeling and fibrosis. We therefore assessed the proinflammatory and fibroproliferative effects of coagulation protease factor (F)Xa. We show that FXa elicits a signaling response in C2C12 and NIH3T3

  15. Plant NAC-type transcription factor proteins contain a NARD domain for repression of transcriptional activation.

    Science.gov (United States)

    Hao, Yu-Jun; Song, Qing-Xin; Chen, Hao-Wei; Zou, Hong-Feng; Wei, Wei; Kang, Xu-Sheng; Ma, Biao; Zhang, Wan-Ke; Zhang, Jin-Song; Chen, Shou-Yi

    2010-10-01

    Plant-specific transcription factor NAC proteins play essential roles in many biological processes such as development, senescence, morphogenesis, and stress signal transduction pathways. In the NAC family, some members function as transcription activators while others act as repressors. In the present study we found that though the full-length GmNAC20 from soybean did not have transcriptional activation activity, the carboxy-terminal activation domain of GmNAC20 had high transcriptional activation activity in the yeast assay system. Deletion experiments revealed an active repression domain with 35 amino acids, named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain. NARD can reduce the transcriptional activation ability of diverse transcription factors when fused to either the amino-terminal or the carboxy-terminal of the transcription factors. NARD-like sequences are also present in other NAC family members and they are functional repression domain when fused to VP16 in plant protoplast assay system. Mutation analysis of conserved amino acid residues in NARD showed that the hydrophobic LVFY motif may partially contribute to the repression function. It is hypothesized that the interactions between the repression domain NARD and the carboxy-terminal activation domain may finally determine the ability of NAC family proteins to regulate downstream gene expressions.

  16. The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

    Science.gov (United States)

    Zhang, Qian; Doucet, Michele; Tomlinson, Ryan E; Han, Xiaobin; Quarles, L Darryl; Collins, Michael T; Clemens, Thomas L

    2016-01-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 (FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α (HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1α mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-1α and FGF23 were co-localized in spindle-shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-1α protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-1α expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-1α inhibitors decreased HIF-1α and FGF23 protein accumulation and inhibited HIF-1α-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-1α consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-1α inhibitor. These results show for the first time that HIF-1α is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-1α activity in TIO contributes to the aberrant FGF23 production in these patients. PMID:27468359

  17. Gastrointestinal growth factors and hormones have divergent effects on Akt activation

    Science.gov (United States)

    Berna, Marc J.; Tapia, Jose A.; Sancho, Veronica; Thill, Michelle; Pace, Andrea; Hoffmann, K. Martin; Gonzalez-Fernandez, Lauro; Jensen, Robert T.

    2009-01-01

    Akt is a central regulator of apoptosis, cell growth and survival. Growth factors and some G-protein-coupled receptors (GPCR) regulate Akt. Whereas growth-factor activation of Akt has been extensively studied, the regulation of Akt by GPCR's, especially gastrointestinal hormones/neurotransmitters, remains unclear. To address this area, in this study the effects of GI growth factors and hormones/neurotransmitters were investigate in rat pancreatic acinar cells which are high responsive to these agents. Pancreatic acini expressed Akt and 5 of 7 known pancreatic growth-factors stimulate Akt phosphorylation (T308, S473) and translocation. These effects are mediated by p85 phosphorylation and activation of PI3K. GI hormones increasing intracellular cAMP had similar effects. However, GI-hormones/neurotransmitters[CCK, bombesin,carbachol] activating phospholipase C (PLC) inhibited basal and growth-factor-stimulated Akt activation. Detailed studies with CCK, which has both physiological and pathophysiological effects on pancreatic acinar cells at different concentrations, demonstrated CCK has a biphasic effect: at low concentrations(pM) stimulating Akt by a Src-dependent mechanism and at higher concentrations(nM) inhibited basal and stimulated Akt translocation, phosphorylation and activation, by de-phosphorylating p85 resulting in decreasing PI3K activity. This effect required activation of both limbs of the PLC-pathway and a protein tyrosine phosphatase, but was not mediated by p44/42 MAPK, Src or activation of a serine phosphatase. Akt inhibition by CCK was also found in vivo and in Panc-1 cancer cells where it inhibited serum-mediated rescue from apoptosis. These results demonstrate that GI growth factors as well as gastrointestinal hormones/neurotransmitters with different cellular basis of action can all regulate Akt phosphorylation in pancreatic acinar cells. This regulation is complex with phospholipase C agents such as CCK, because both stimulatory and inhibitory

  18. The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7).

    OpenAIRE

    Bagheri-Yarmand, R.; Kourbali, Y; Mabilat, C; Morère, J. F.; Martin, A; Lu, H; Soria, C; Jozefonvicz, J; Crépin, M

    1998-01-01

    Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of t...

  19. Finding strategic communication & diverse leadership in the ancient world: The case of Queen Cleopatra VII, the last pharaoh of Egypt

    Directory of Open Access Journals (Sweden)

    Shannon A. Bowen

    2016-12-01

    Full Text Available The reign of Queen Cleopatra VII of Egypt offers a rare historical glimpse into ancient communication activities and how communication was used by the world’s last pharaoh. This historical research reveals how Cleopatra used public relations and strategic communication activities to advance both her reign as a lone woman sovereign and the interests of the Egyptian empire. Cleopatra was perhaps the first woman sovereign in history to rule alone for a period of over a decade. Her leadership showed skilled use of public communication and diplomacy with which she forestalled the fall of Egypt to Rome. A grounded theory approach allowed data to emerge naturally, surrounding communication activities, and then for a theoretical framework to be imposed that could explain the common themes in that data. This research compares Cleopatra’s activities with public relations theory using the classic four models of public relations to classify public communication. Findings show that Cleopatra used research in asymmetrical public relations and symmetrical relationship building, also including public diplomacy, public information, and press agentry/pseudo-event mastery. Careful examination of literature sources led to the conclusion that Cleopatra was a truly advanced, research-based, relationship-focused, and international policy-oriented lone woman ruler who was a supremely strategic communicator.

  20. Validation of MCNP6 Version 1.0 with the ENDF/B-VII.1 Cross Section Library for Plutonium Metals, Oxides, and Solutions on the High Performance Computing Platform Moonlight

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Bryan Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gough, Sean T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-12-05

    This report documents a validation of the MCNP6 Version 1.0 computer code on the high performance computing platform Moonlight, for operations at Los Alamos National Laboratory (LANL) that involve plutonium metals, oxides, and solutions. The validation is conducted using the ENDF/B-VII.1 continuous energy group cross section library at room temperature. The results are for use by nuclear criticality safety personnel in performing analysis and evaluation of various facility activities involving plutonium materials.

  1. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  2. Identifying factors hampering physical activity in longstanding rheumatoid arthritis: what is the role of glucocorticoid therapy?

    Science.gov (United States)

    van der Goes, M C; Hoes, J N; Cramer, M J; van der Veen, M J; van der Werf, J H; Bijlsma, J W J; Jacobs, J W G

    2014-01-01

    To identify factors hampering the level of physical activity in longstanding rheumatoid arthritis (RA) patients, and to evaluate the effects of glucocorticoid therapy on physical activity. Patient characteristics, disease characteristics and cardiovascular parameters were recorded in 170 patients, who participated in a study about glucose metabolism in longstanding RA treated with or without glucocorticoids. Disease activity scores (DAS28) were calculated and x-rays of hands and feet were taken and scored according to the Sharp van der Heijde score (SHS). Participants completed the health assessment questionnaire and short questionnaire to assess health-enhancing physical activity (SQUASH), which reflect physical disability and physical activity, respectively. Adherence rates to recommendations on physical activity were calculated, and patients were categorised as fully adhering, insufficiently adhering (adherence on less than the recommended number of days per week) or inactive (adherence on none of the days). Forty-four percent of the patients showed adherence to the recommended minimum level of physical activity, and 22% were classified as inactive. Higher DAS28 and SHS, glucocorticoid therapy, and presence of cardiovascular risk factors were associated with lower total SQUASH physical activity scores univariately. In a multivariate model, higher age, higher body mass index (BMI), higher DAS28, and higher SHS negatively influenced the score significantly; cardiovascular risk factors and glucocorticoid therapy were no longer significantly influencing physical activity. Physical activity in longstanding RA is hampered by higher age, higher BMI, higher disease activity, and more radiographic joint damage. Glucocorticoid therapy was not identified as independent risk factor in multivariate analyses.

  3. Using avian radar to examine relationships among avian activity, bird strikes, and meteorological factors

    Science.gov (United States)

    Coates, Peter S.; Casazza, Michael L.; Halstead, Brian J.; Fleskes, Joseph P.; Laughlin, James A.

    2011-01-01

    Radar systems designed to detect avian activity at airfields are useful in understanding factors that influence the risk of bird and aircraft collisions (bird strikes). We used an avian radar system to measure avian activity at Beale Air Force Base, California, USA, during 2008 and 2009. We conducted a 2-part analysis to examine relationships among avian activity, bird strikes, and meteorological and time-dependent factors. We found that avian activity around the airfield was greater at times when bird strikes occurred than on average using a permutation resampling technique. Second, we developed generalized linear mixed models of an avian activity index (AAI). Variation in AAI was first explained by seasons that were based on average migration dates of birds at the study area. We then modeled AAI by those seasons to further explain variation by meteorological factors and daily light levels within a 24-hour period. In general, avian activity increased with decreased temperature, wind, visibility, precipitation, and increased humidity and cloud cover. These effects differed by season. For example, during the spring bird migration period, most avian activity occurred before sunrise at twilight hours on clear days with low winds, whereas during fall migration, substantial activity occurred after sunrise, and birds generally were more active at lower temperatures. We report parameter estimates (i.e., constants and coefficients) averaged across models and a relatively simple calculation for safety officers and wildlife managers to predict AAI and the relative risk of bird strike based on time, date, and meteorological values. We validated model predictability and assessed model fit. These analyses will be useful for general inference of avian activity and risk assessment efforts. Further investigation and ongoing data collection will refine these inference models and improve our understanding of factors that influence avian activity, which is necessary to inform

  4. Nuclear factor-κB p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    Liang-Liang Yu; Hong-Gang Yu; Jie-Ping Yu; He-Sheng Luo; Xi-Ming Xu; Jun-Hua Li

    2004-01-01

    AIM: Activation of transcription factor nuclear factor-κB (NF-κB) has been shown to play a role in cell proliferation,apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-κB was constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-κB in colorectal tumorigenesis, and furthermore, to determine the association of RelA expression with tumor cell apoptosis and the expression of Bcl-2 and Bcl-xL.METHODS: Paraffin sections of normal epithelial, adenomatous and adenocarcinoma tissues were analysed immunohistochemically for expression of RelA, Bcl-2 and Bcl-xL proteins.Electrophoretic mobility shift assay (EMSA) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The mRNA expressions of Bcl-2 and Bcl-xL were determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method.RESULTS: The activity of NF-κB was significantly higher in adenocarcinoma tissue in comparison with that in adenomatous and normal epithelial tissues. The apoptotic index (AI)significantly decreased in the transition from adenoma to adenocarcinoma. Meanwhile, the expressions of Bcl-2 and Bcl-xL protein and their mRNAs were significantly higher in adenocarcinoma tissues than that in adenomatous and normal epithelial tissues.CONCLUSION: NF-κB may inhibit apoptosis via enhancing the expression of the apoptosis genes Bcl-2 and BCl-xL. And the increased expression of RelA/nuclear factor-κB plays an important rote in the pathogenesis of colorectal carcinoma.

  5. Inactivation of staphylococcal virulence factors using a light-activated antimicrobial agent

    Directory of Open Access Journals (Sweden)

    Wilson Michael

    2009-10-01

    Full Text Available Abstract Background One of the limitations of antibiotic therapy is that even after successful killing of the infecting microorganism, virulence factors may still be present and cause significant damage to the host. Light-activated antimicrobials show potential for the treatment of topical infections; therefore if these agents can also inactivate microbial virulence factors, this would represent an advantage over conventional antibiotic therapy. Staphylococcus aureus produces a wide range of virulence factors that contribute to its success as a pathogen by facilitating colonisation and destruction of host tissues. Results In this study, the ability of the light-activated antimicrobial agent methylene blue in combination with laser light of 665 nm to inactivate staphylococcal virulence factors was assessed. A number of proteinaceous virulence factors were exposed to laser light in the presence of methylene blue and their biological activities re-determined. The activities of V8 protease, α-haemolysin and sphingomyelinase were shown to be inhibited in a dose-dependent manner by exposure to laser light in the presence of methylene blue. Conclusion These results suggest that photodynamic therapy could reduce the harmful impact of preformed virulence factors on the host.

  6. Female reproductive factors are associated with objectively measured physical activity in middle-aged women

    Science.gov (United States)

    Kulmala, Janne; Aukee, Pauliina; Hakonen, Harto; Kujala, Urho M.; Lowe, Dawn A.; Kovanen, Vuokko; Tammelin, Tuija; Sipilä, Sarianna

    2017-01-01

    Physical activity improves health and may delay the onset of several chronic diseases. For women in particular, the rate of these diseases accelerates at middle age; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population. In this study, we focused on determinants that are unique to the female sex, such as childbearing and menopause. The main objective was to characterize the level of physical activity and differences between active and inactive middle-aged Finnish women. In addition, we examined the association of physical activity with female reproductive factors at midlife. The study population consisted of 647 women aged 48 to 55 years who participated in our Estrogenic Regulation of Muscle Apoptosis (ERMA) study during the period from 2015 to 2016. Physical activity was measured objectively using hip-worn accelerometers for seven consecutive days. The outcome measures included the amounts of light intensity physical activity and moderate to vigorous intensity physical activity accumulated in bouts of at least 10 minutes (MVPA10). MVPA10 was used to determine whether women were placed in the active (≥150 min/week) or inactive (pelvic floor dysfunction as independent variables. We found that a large portion (61%) of Finnish middle-aged women did not meet the physical activity recommendations of 150 minutes of MVPA10 per week. In the studied cohort, 78% of women experienced menopausal symptoms, and 54% exhibited pelvic floor dysfunction. Perceived menopausal symptoms were associated with greater light physical activity. Perceived pelvic floor dysfunction was associated with lower MVPA10. According to the fully adjusted multiple linear regression models, reproductive factors explained 6.0% of the variation of MVPA10 and 7.5% of the variation of light physical activity. The results increase our knowledge of the factors related to physical activity participation among middle-aged women and

  7. Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E

    2016-09-01

    The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.

  8. Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation

    DEFF Research Database (Denmark)

    Hauge, Camilla; Antal, Torben L; Hirschberg, Daniel

    2007-01-01

    investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within...... the kinase domain, promoting zipper-like association of the tail with the kinase domain, serving to stabilize the HM in its kinase-activating binding site. We present a molecular model for allosteric activation of AGC kinases by the turn motif phosphate via HM-mediated stabilization of the alphaC helix. In S......6K and MSK, the turn motif phosphate thereby also protects the HM from dephosphorylation. Our results suggest that the mechanism described is a key feature in activation of upto 26 human AGC kinases....

  9. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  10. Sociocultural factors relating to Tongans' and Indigenous Fijians' patterns of eating, physical activity and body size.

    Science.gov (United States)

    Mavoa, Helen M; McCabe, Marita

    2008-01-01

    This paper reviews literature between 1974 and 2007 that addresses the impact of sociocultural factors on reported patterns of eating, physical activity (activity) and body size of Tongans and indigenous Fijians (Fijians) in their countries of origin. There have been changes in diet (more imported and fewer traditional foods), activity (reduced, especially in urban settings), residence (rural-urban shift) and body size (increased obesity and at a younger age). The prevalence of overweight/obesity in Tongans and Fijians has increased rapidly over the last two decades and remains among the highest in the world (>80% in Tonga; >40% in Fiji), with more females reported to be obese than males. The few studies that investigated sociocultural influences on patterns of eating, activity and/or body size in this population have examined the impact of hierarchical organisation, rank and status (sex, seniority), values (respect, care, co-operation) and/or role expectations. It is important to examine how sociocultural factors influence eating, activity and body size in order to i) establish factors that promote or protect against obesity, ii) inform culturally-appropriate interventions to promote healthy lifestyles and body size, and iii) halt the obesity epidemic, especially in cultural groups with a high prevalence of obesity. There is an urgent need for more systematic investigations of key sociocultural factors, whilst taking into account the complex interplay between sociocultural factors, behaviours and other influences (historical; socioeconomic; policy; external global influences; physical environment).

  11. Roscovitine in combination with calcium ionophore induces oocyte activation through reduction of M-phase promoting factor activity in mice.

    Science.gov (United States)

    Iba, Tomomi; Yano, Yuya; Umeno, Mayumi; Hinokio, Kenji; Kuwahara, Akira; Irahara, Minoru; Yamano, Shuji; Yasui, Toshiyuki

    2012-11-01

    The aim of the present study was to determine oocyte activation and change in M-phase promoting factor (MPF) activity induced by treatment with calcium ionophore and roscovitine in comparison with those induced by treatment with roscovitine alone and treatment with calcium ionophore and puromycin in mice. Freshly ovulated oocytes obtained from 6-8-week-old mice were divided into five groups (no activation treatment; 5 μM calcium ionophore A23187; 50 μM roscovitine; 5 μM calcium ionophore and 10 μg/ml puromycin; and 5 μM calcium ionophore and 50 μM roscovitine) and were incubated for 6 h. Oocyte activation, assessed by morphological changes, and changes in MPF activity in the five groups at 0, 2, 4 and 6 h of incubation were examined. Activated oocytes were defined as oocytes with at least one pronucleus. Oocytes treated with roscovitine alone were not activated during the 6-h incubation period. All of the oocytes in the calcium ionophore with puromycin group and in the calcium ionophore with roscovitine group were activated. The percentage activity of MPF in oocytes treated with roscovitine alone was decreased after 2 h and increased after 4 h of incubation. The percentage activity of MPF in oocytes treated with calcium ionophore and roscovitine was significantly decreased with suppression of MPF activity being maintained for 6 h, and this change was similar to that in oocytes treated with calcium ionophore and puromycin. Roscovitine with calcium ionophore is effective for induction of oocyte activation through suppression of MPF activity in mice.

  12. Sp3 controls fibroblast growth factor receptor 4 gene activity during myogenic differentiation.

    Science.gov (United States)

    Cavanaugh, Eric; DiMario, Joseph X

    2017-03-27

    Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling is a critical component in the regulation of myoblast proliferation and differentiation. The transient FGFR4 gene expression during the transition from proliferating myoblasts to differentiated myotubes indicates that FGFR4 regulates this critical phase of myogenesis. The Specificity Protein (SP) family of transcription factors controls FGFR family member gene activity. We sought to determine if members of the Sp family regulate mouse FGFR4 gene activity during myogenic differentiation. RT-PCR and western blot analysis of FGFR4 mRNA and protein revealed transient expression over 72h, with peak expression between 24 and 36h after addition of differentiation medium to C2C12 myogenic cultures. Sp3 also displayed a transient expression pattern with peak expression occurring after 6h of differentiation. We cloned a 1527bp fragment of the mouse FGFR4 promoter into a luciferase reporter. This FGFR4 promoter contains eight putative Sp binding sites and directed luciferase gene activity comparable to native FGFR4 expression. Overexpression of Sp1 and Sp3 showed that Sp1 repressed FGFR4 gene activity, and Sp3 activated FGFR4 gene activity during myogenic differentiation. Mutational analyses of multiple Sp binding sites within the FGFR4 promoter revealed that three of these sites were transcriptionally active. Electromobility shift assays and chromatin immunoprecipitation of the area containing the activator sites showed that Sp3 bound to this promoter location.

  13. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  14. Factors Related to Meeting Physical Activity Guidelines in Active College Students: A Social Cognitive Perspective

    Science.gov (United States)

    Farren, G. L.; Zhang, T.; Martin, S. B.; Thomas, K. T.

    2017-01-01

    Objective: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). Participants: Three hundred ninety-six college students participated in this study in the summer 2013. Methods: Students completed online questionnaires that assessed physical activity…

  15. Factors Related to Meeting Physical Activity Guidelines in Active College Students: A Social Cognitive Perspective

    Science.gov (United States)

    Farren, G. L.; Zhang, T.; Martin, S. B.; Thomas, K. T.

    2017-01-01

    Objective: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). Participants: Three hundred ninety-six college students participated in this study in the summer 2013. Methods: Students completed online questionnaires that assessed physical activity…

  16. Factors Associated with Physical Activity among Macedonian Adolescents in Albanian Ethnic Community

    Science.gov (United States)

    GONTAREV, Seryozha; KALAC, Ruzdija; AMETI, Vullnet; REDJEPI, Agim

    2016-01-01

    Background: The purpose of this study was to determine the relationship of demographic, psychological, social and environmental factors with physical activity and to determine whether indicators of physical activity differ by gender among Macedonian adolescents from Albanian ethnic community from 11 to 14 yr (N = 886). Methods: Research were conducted in 2014 in several primary schools randomly selected from Tetovo and Gostivar region of the R. Macedonia. Students completed a questionnaire which examined their level of participation in physical activity and sedentary behavior along with a number of potential correlates. Hierarchical regression was used to explore the relationship between hypothesised factors and physical activity. Results: The boys unlike the girls showed significantly higher levels of physical activity (P=0.001). Respondents of both genders who perceive greater benefits from the physical activity (P=0.010). They have more confidence in their abilities (P=0.001), enjoy more in the physical activities (P=0.016), perceive greater social support from friends (P=0.008) and parents (P=0.001) and have higher levels of physical activity. Conclusions: The results indicate the importance of developing a national plan and program to promote physical activity in order to help young people to change unhealthy lifestyle habits and increase the physical activity, thus improving their health. PMID:27252917

  17. Type VII Secretion Systems in Gram-Positive Bacteria

    NARCIS (Netherlands)

    Bottai, Daria; Gröschel, Matthias I.; Brosch, Roland; Bagnoli, Fabio; Rappuoli, Rino

    2017-01-01

    Bacterial secretion systems are sophisticated molecular machines that fulfil a wide range of important functions, which reach from export/secretion of essential proteins or virulence factors to the implication in conjugation processes. In contrast to the widely distributed Sec and Twin Arginine

  18. Energy Optimization And Calculation Of Dose Absorption Enhancement Factor In Photon Activation Therapy

    Directory of Open Access Journals (Sweden)

    Hassan Ranjbar

    2010-06-01

    Full Text Available Introduction: Secondary radiation such as photoelectrons, Auger electrons and characteristic radiations cause a local boost in dose for a tumor when irradiated with an external X-ray beam after being loaded with elements capable of activating the tumor, e.g.; I and Gd. Materials and Methods:  In this investigation, the MCNPX code was used for simulation and calculation of dose enhancement factor for a tumor loaded with activating elements. The designed model comprised the X-ray source, phantom (target tissue and loaded tumor with activating agent, detector, interactions modeling and results. The source was defined as monochromatic and plane surface situated at 50 cm (z = 50. Phantom geometry was a 10 × 10 × 10 cm3 cube centered at (0, 0, 0 with a 2.2 × 2.2 × 2.2 cm3 cubic tumor with a center located at 3 cm depth inside the phantom Results: Dose enhancement factor and optimum energy in radiotherapy are evaluated using the photon activation therapy method. Result show that the dose enhancement factor increases with activating concentration in the tumor. The maximum dose enhancement factor for iodine in the tumor occurs for photons in the energy range of 50-60 keV. Dose uniformity is less for lower energy photons within the activated region inside the tumor. Results indicate that the dose enhancement factor varies linearly with the activating concentration agent. Discussion and Conclusion: In this study, the obtained results point out a considerable enhancement in dose in the presence of activating agents in the tumor regions.

  19. Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

    NARCIS (Netherlands)

    Vorobyev, Artem; Ujiie, Hideyuki; Recke, Andreas; Buijsrogge, Jacqueline J. A.; Jonkman, Marcel F.; Pas, Hendrikus; Iwata, Hiroaki; Hashimoto, Takashi; Kim, Soo-Chan; Kim, Jong Hoon; Groves, Richard; Samavedam, Unni; Gupta, Yask; Schmidt, Enno; Zillikens, Detlef; Shimizu, Hiroshi; Ludwig, Ralf J.

    Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease of the skin and mucous membranes, characterized by autoantibodies against type VII collagen (COL7), a major component of anchoring fibrils. Different clinical EBA phenotypes are described, including mechanobullous and

  20. Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

    NARCIS (Netherlands)

    Vorobyev, Artem; Ujiie, Hideyuki; Recke, Andreas; Buijsrogge, Jacqueline J. A.; Jonkman, Marcel F.; Pas, Hendrikus; Iwata, Hiroaki; Hashimoto, Takashi; Kim, Soo-Chan; Kim, Jong Hoon; Groves, Richard; Samavedam, Unni; Gupta, Yask; Schmidt, Enno; Zillikens, Detlef; Shimizu, Hiroshi; Ludwig, Ralf J.

    2015-01-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease of the skin and mucous membranes, characterized by autoantibodies against type VII collagen (COL7), a major component of anchoring fibrils. Different clinical EBA phenotypes are described, including mechanobullous and inflamma