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Sample records for erythropoiesis-stimulating agents esas

  1. Effect of Erythropoiesis-Stimulating Agent Policy Decisions

    Data.gov (United States)

    U.S. Department of Health & Human Services — Erythropoiesis-stimulating agents (ESAs) are used as a treatment for anemia in myelodysplastic syndromes (MDS) patients. In early 2007, the U.S. Food and Drug...

  2. Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-β superfamily inhibitors.

    Science.gov (United States)

    Mies, Anna; Platzbecker, Uwe

    2017-07-01

    Patients with lower-risk myelodysplastic syndromes (MDS) are mainly affected by chronic anemia and fatigue. Treatment strategies aim to improve anemia and quality of life, as well as iron overload due to red blood cell transfusion support. To promote proliferation and differentiation of erythropoiesis, erythropoiesis-stimulating agents (ESAs) such as erythropoietin (EPO) and mimetics are applied as first-line therapy in a large fraction of lower-risk MDS patients. In general, ESAs yield favorable responses in about half of the patients, although responses are often short-lived. In fact, many ESA-refractory patients harbor defects in late-stage erythropoiesis downstream of EPO action. Novel transforming growth factor (TGF)-β superfamily inhibitors sotatercept and luspatercept represent a promising approach to alleviate anemia by stimulating erythroid differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: Results from a randomized controlled trial (CONTRAST)

    NARCIS (Netherlands)

    N.C. van der Weerd (Neelke); C.H. den Hoedt (Claire); P.J. Blankestijn (Peter); M.L. Bots (Michiel); M.A. van den Dorpel (Marinus); R. Lévesque (Renée); A.H.A. Mazairac (Albert); M.J. Nubé (Menso); E. Lars Penne; P.M. ter Wee (Piet); M.P.C. Grooteman (Muriel)

    2014-01-01

    textabstractResistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this

  4. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST)

    NARCIS (Netherlands)

    Weerd, N.C. van der; Hoedt, C.H. den; Blankestijn, P.J.; Bots, M.L.; Dorpel, M.A. van den; Levesque, R.; Mazairac, A.H.; Nube, M.J.; Penne, E.L.; Wee, P.M. ter; Grooteman, M.P.; Hamersvelt, H.W. van; et al.,

    2014-01-01

    Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the

  5. Erythropoiesis stimulating agents and techniques: a challenge for doping analysts.

    Science.gov (United States)

    Jelkmann, W

    2009-01-01

    Recombinant human erythropoietin (rHuEPO) engineered in Chinese hamster ovary (CHO) cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected by isoelectric focusing (IEF) and immunoblotting of urine samples, because "EPO" is in reality a mixture of isoforms and the N-glycans of the recombinant products differ from those of the endogenous hormone. However, there is a plethora of novel erythropoiesis stimulating agents (ESAs). Since the originator Epoetins alfa and beta are no longer protected by patent in the European Union, rHuEPO biosimilars have entered the market. In addition, several companies in Asia, Africa and Latin America produce copied rHuEPOs for clinical purposes. While the amino acid sequence of all Epoetins is identical, the structure of their glycans differs depending on the mode of production. Some products contain more acidic and others more basic EPO isoforms. Epoetin delta is special, as it was engineered by homologous recombination in human fibrosarcoma cells (HT-1080), thus lacking N-glycolylneuraminic acid like native human EPO. ESAs under development include EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (Hematide(), CNTO 528) as well as non-peptidic EPO mimetics. Furthermore, preclinical respectively clinical trials have been performed with small orally active drugs that stimulate endogenous EPO production by activating the EPO promoter ("GATA-inhibitors": diazepane derivatives) or enhancer ("HIF-stabilizers": 2-oxoglutarate analogues). The prohibited direct EPO gene transfer may become a problem in sports only in the future.

  6. Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

    Directory of Open Access Journals (Sweden)

    Patrick Biggar

    2017-09-01

    Full Text Available Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

  7. Treatment with high dose of erythropoiesis-stimulating agents and mortality: analysis with a sequential Cox approach and a marginal structural model

    NARCIS (Netherlands)

    Suttorp, Marit M.; Hoekstra, Tiny; Mittelman, Moshe; Ott, Ilka; Krediet, Raymond T.; Dekker, Friedo W.; Putter, Hein

    2015-01-01

    Anemia-correction trials indicated higher mortality rates in chronic kidney disease patients assigned to higher hemoglobin targets. The safety of the high erythropoiesis-stimulating agent (ESA) doses that these patients received has therefore been questioned. However, no trial that directly compares

  8. Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis.

    Science.gov (United States)

    Rasche, Franz Maximilian; Ebert, Thomas; Beckmann, Julia; Busch, Volker; Barinka, Filip; Rasche, Wilma Gertrud; Lindner, Tom H; Schneider, Jochen G; Schiekofer, Stephan

    2017-06-01

    HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Effectiveness of Switch to Erythropoiesis-Stimulating Agent (ESA) Biosimilars versus Maintenance of ESA Originators in the Real-Life Setting: Matched-Control Study in Hemodialysis Patients.

    Science.gov (United States)

    Minutolo, Roberto; Bolasco, Piergiorgio; Chiodini, Paolo; Sposini, Stefano; Borzumati, Maurizio; Abaterusso, Cataldo; Mele, Alessandra A; Santoro, Domenico; Canale, Valeria; Santoboni, Alberto; Filiberti, Oliviero; Fiorini, Fulvio; Mura, Carlo; Imperiali, Patrizio; Borrelli, Silvio; Russo, Luigi; De Nicola, Luca; Russo, Domenico

    2017-10-01

    In hemodialysis (HD), switching from erythropoiesis-stimulating agent (ESA) originators to biosimilars is associated with the need for doses approximately 10% higher, according to industry-driven studies. The aim of this study was to evaluate the efficacy on anemia control of switching from ESA originators to biosimilars in daily clinical practice. We retrospectively selected consecutive HD patients receiving stable intravenous ESA doses, and who had not been transfused in the previous 6 months, from 12 non-profit Italian centers. Patients switched from originators to biosimilars (n = 163) were matched with those maintained on ESA originators (n = 163) using a propensity score approach. The study duration was 24 weeks, and the primary endpoint was the mean dose difference (MDD), defined as the difference between the switch and control groups of ESA dose changes during the study (time-weighted average ESA dose minus baseline ESA dose). Age (70 ± 13 years), male sex (63%), diabetes (29%), history of cardiovascular disease (40%), body weight (68 ± 14 kg), vascular access (86% arteriovenous fistula), hemoglobin [Hb] (11.2 ± 0.9 g/dL) and ESA dose (8504 ± 6370 IU/week) were similar in the two groups. Hb remained unchanged during the study in both groups. Conversely, ESA dose remained unchanged in the control group and progressively increased in the switch group from week 8 to 24. The time-weighted average of the ESA dose was higher in the switch group than in the control group (10,503 ± 7389 vs. 7981 ± 5858 IU/week; p = 0.001), leading to a significant MDD of 2423 IU/week (95% confidence interval [CI] 1615-3321), corresponding to a 39.6% (95% CI 24.7-54.6) higher dose of biosimilars compared with originators. The time-weighted average of Hb was 0.2 g/dL lower in the switch group, with a more frequent ESA hyporesponsiveness (14.7 vs. 2.5%). Iron parameters and other resistance factors remained unchanged. In stable dialysis patients

  10. Effects of Erythropoiesis-stimulating Agents on Intestinal Flora in Peritoneal Fibrosis.

    Science.gov (United States)

    Bilici, Muammer; Oz, Ibrahim Ilker; Uygun Ilikhan, Sevil; Borazan, Ali

    2017-05-01

    This study aimed to investigate the effects of erythropoiesis-stimulating agents (ESAs) on intestinal flora in peritoneal fibrosis. Twenty-four Wistar albino rats were divided into 3 groups as the control group, which received 0.9% saline (3 mL/d) intraperitoneally; the chlorhexidine gluconate (CH) group, which received 3 mL/d injections of 0.1% CH intraperitoneally, and the ESA group, which received 3 mL/d injections of 0.1% CH intraperitoneally and epoetin beta (3 doses of 20 IU/kg/wk) subcutaneously. On the 21st day, the rats were sacrificed and the visceral peritoneum samples were obtained from left liver bowel. Blood samples were obtained from abdominal aorta and intestinal flora samples were obtained from transverse colon. Histopathologically, the CH, ESA, and control groups had peritoneal thickness of 135.4 ± 22.2 µm, 48.6 ± 12.8 µm, and 6.0 ± 2.3 µm, respectively. Escherichia coli was the predominant bacterium in the intestinal flora in the control group. Significant changes in microbial composition of intestinal flora towards Proteus species and Enterobacter species was seen among the groups (P flora among these groups were significantly different (P flora by a clinically significant amount in experimental peritoneal fibrosis. We consider that ESAs achieve this via regulating intestinal peristaltism.

  11. Basic analytical methods for identification of erythropoiesis-stimulating agents in doping control

    International Nuclear Information System (INIS)

    Postnikov, P V; Krotov, G I; Rodchenkov, G M; Efimova, Yu A

    2016-01-01

    The design of new erythropoiesis-stimulating agents for clinical use necessitates constant development of methods for detecting the abuse of these substances, which are prohibited under the World Anti-Doping Code and are included in the World Anti-Doping Agency (WADA) prohibited list. This review integrates and describes systematically the published data on the key methods currently used by WADA-accredited anti-doping laboratories around the world to detect the abuse of erythropoiesis-stimulating agents, including direct methods (various polyacrylamide gel electrophoresis techniques, enzyme-linked immunosorbent assay, membrane enzyme immunoassay and mass spectrometry) and indirect methods (athlete biological passport). Particular attention is given to promising approaches and investigations that can be used to control prohibited erythropoietins in the near future. The bibliography includes 122 references

  12. Drug Utilization Patterns and Costs of Erythropoiesis-Stimulating Agents in an Outpatient Setting in Greece.

    Science.gov (United States)

    Papachristos, Apostolos; Kani, Chara; Litsa, Panagiota; Valsami, Georgia; Souliotis, Kyriakos; Saridi, Maria; Markantonis, Sophia

    2016-05-01

    Anemia in the elderly is often related to a higher prevalence of chronic diseases such as chronic kidney failure, arthritis, and malignancy. Erythropoiesis-stimulating agents (ESAs) have been used for years to effectively treat anemia and when used appropriately can substantially improve the health status and quality of life of older adults. Following the 2008 recession in Greece, the government introduced ESA price control restrictions, but no prescribing restrictions, in an effort to reduce drug expenditure. ESA prescribing patterns and treatment costs were analyzed to determine inappropriate or appropriate use of these agents and related health care resources in Greece. A retrospective register-based drug utilization study was carried out using data from prescriptions dispensed at the public pharmacy of the largest social insurance fund (IKA-ETAM), for patients receiving ESAs over a six-month period. For each patient, demographic data, ESA dosage regimen, treatment indication and cost, prescriber specialty, and prescription origin were recorded. A total of 14,387 prescriptions from 6,074 patients (median age 74 years) were reviewed. A substantial number of patients (13.5%) were treated for off-label indications, for which the average cost per patient per indication was higher. ESA dosage/frequency of administration varied but was in accordance with recommendations. The percentage of patients who received innovator and biosimilar erythropoietin (EPO) was 88% and 12%, respectively. For the optimization of ESA utilization and the reduction of treatment costs, strict ESA prescription monitoring, development of registries, and criteria for off-label indications and biosimilar use in naive patients under the umbrella of risk-sharing agreements should be proposed.

  13. Utilization Patterns of IV Iron and Erythropoiesis Stimulating Agents in Anemic Chronic Kidney Disease Patients: A Multihospital Study

    Directory of Open Access Journals (Sweden)

    Avani D. Joshi

    2012-01-01

    Full Text Available Intravenous (IV iron and Erythropoiesis Stimulating Agents (ESAs are recommended for anemia management in chronic kidney disease (CKD. This retrospective cohort study analyzed utilization patterns of IV iron and ESA in patients over 18 years of age admitted to University Health System Hospitals with a primary or secondary diagnosis of CKD between January 1, 2006 to December 31, 2008. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Only 8% (n = 6678 of CKD patients on ESA therapy received IV iron supplementation in university hospitals. Those receiving iron used significantly less amounts of ESAs. Patient demographics (age, race, primary payer, patient clinical conditions (admission status, severity of illness, dialysis status, and physician specialty were identified as predictors of IV iron use in CKD patients. Use of IV iron with ESAs was low despite recommendations from consensus guidelines. The low treatment rate of IV iron represents a gap in treatment practices and signals an opportunity for healthcare improvement in CKD anemic patients.

  14. Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate

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    Keitaro Yokoyama

    2017-05-01

    Discussion: It is suggested that not only iron load but also the erythropoiesis-stimulating agent dose reduction may be involved in ferritin elevation during ferric citrate hydrate treatment, resulting in a decrease of erythropoietin resistance index.

  15. Use of Erythropoietin-Stimulating Agents (ESA) in Patients With End-Stage Renal Failure Decided to Forego Dialysis: Palliative Perspective.

    Science.gov (United States)

    Cheng, Hon Wai Benjamin; Chan, Kwok Ying; Lau, Hoi To; Man, Ching Wah; Cheng, Suk Ching; Lam, Carman

    2017-05-01

    Normochromic normocytic anemia is a common complication in chronic kidney disease (CKD) and is associated with many adverse clinical consequences. Erythropoiesis-stimulating agents (ESAs) act to replace endogenous erythropoietin for patients with end-stage renal disease having anemia. Today, ESAs remain the main tool for treating anemia associated with CKD. In current practice, the use of ESA is not limited to the patients on renal replacement therapy but has extended to nondialysis patients under palliative care (PC). Current evidence on ESA usage in patients with CKD decided to forego dialysis often have to take reference from studies conducted in other groups of patients with CKD, including pre-dialysis patients and those on renal replacement therapy. There is paucity of studies targeting use of ESAs in renal PC patients. Small-scale retrospective study in renal PC patients had suggested clinical advantage of ESAs in terms of hemoglobin improvement, reduction in fatigue, and hospitalization rate. With the expected growth in elderly patients with CKD decided to forego dialysis and manage conservatively, there remains an urgent need to call for large-scale prospective trial in exploring efficacy of ESAs in this population, targeting on quality of life and symptoms improvement outcome. This article also reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for ESA in patients with CKD under renal PC.

  16. Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study.

    Directory of Open Access Journals (Sweden)

    Ylenia Ingrasciotta

    Full Text Available Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs.This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD and cancer patients in a Local Health Unit (LHU from Northern Italy.A retrospective cohort study was conducted during the years 2009-2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID with at least one hemoglobin measurement within one month prior to ID (baseline Hb value and another measurement between 2nd and 3rd month after ID (follow-up Hb value were identified. The strength of the consumption (as total number of defined daily dose (DDD dispensed during the follow-up divided by days of follow-up and the difference between follow-up and baseline Hb values [delta Hb (ΔHb] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ΔHb≤0 g/dl, responders (02 g/dl. A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID.Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7% with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in ΔHb as well as in frequency of non-responders, responders and highly responders among

  17. The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome.

    Science.gov (United States)

    Silverberg, Donald S

    2011-11-01

    Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) excessive cytokine production in CHF, which can cause both depression of erythropoietin production in the kidney and depression of erythropoietin response in the bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. It appears that iron deficiency is very common in CHF and is rarely recognized or treated. The iron deficiency can cause a thrombocytosis that might contribute to cardiovascular complications in both CHF and CKD and is reversible with iron treatment. Thus, attempts to control this anemia in CHF will have to take into consideration both the use of both Erythropoiesis Stimulating Agents (ESA) such as EPO and oral and, probably more importantly, intravenous (IV) iron. Many studies of anemia in CHF with ESA and oral or IV iron and even with IV iron without ESA have shown a positive effect on hospitalization, New York Heart Association functional class, cardiac and renal function, quality of life, exercise capacity and reduced Beta Natriuretic Peptide and have not demonstrated an increase in cardiovascular damage related to the therapy. However, adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed and are currently being carried out.

  18. Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study

    OpenAIRE

    Castillo Nieves; García-García Patricia; Rivero Antonio; Jiménez-Sosa Alejandro; Macía Manuel; Getino María; Méndez María; García-Pérez Javier; Navarro-González Juan F

    2012-01-01

    Abstract Background Predialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE). Methods Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialy...

  19. ErythropoieSIS stimulating agent (ESA use is increased following missed dialysis sessions

    Directory of Open Access Journals (Sweden)

    T. Christopher Bond

    2012-06-01

    Missed session episodes result in significant increases in ESA utilization in the post-miss period, and also in total monthly ESA use. Such increases should be considered in any assessment of impact of missed sessions: both clinical and economic.

  20. Healthcare resource utilization for anemia management: current practice with erythropoiesis-stimulating agents and the impact of converting to once-monthly C.E.R.A.

    Science.gov (United States)

    Saueressig, Ulrich; Kwan, Jonathan T C; De Cock, Erwin; Sapède, Claudine

    2008-01-01

    Background andMethods: A prospective, observational study in 12 German and UK dialysis centers which quantified personnel time for anemia treatment using erythropoiesis-stimulating agents (ESAs). Tasks directly observable were measured through the time-and-motion method; time for non-observable tasks was estimated by healthcare staff. Using activity-based costing methods, time was converted into monetary units. Modeling was used to estimate potential time and cost savings using once-monthly C.E.R.A., a continuous erythropoietin receptor activator. For current ESAs in Germany and the UK, respectively: mean observed time was 1.67 and 2.67 min/patient/administration, corresponding to 31 and 42 days/year/center/100 patients; mean total time/center/100 patients/year was estimated at 79 and 95 days, equivalent to EUR 17,031 and GBP 18,739. Assuming 100% once-monthly C.E.R.A. uptake, the observed time/patient/year may decrease by 79 and 84% in Germany and the UK, respectively, compared with traditional ESAs. Conversion to once-monthly C.E.R.A. may offer the potential to reduce time spent on ESA administration in hemodialysis centers. Copyright 2008 S. Karger AG, Basel.

  1. Budget impact analysis on erythropoiesis-stimulating agents use for the management of chemotherapy-induced anaemia in Greece.

    Science.gov (United States)

    Nikolaidi, Eleftheria; Hatzikou, Magdalini; Geitona, Mary

    2013-07-16

    Chemotherapy-induced anaemia is a common and significant complication of chemotherapy treatment. Blood transfusion and administration of Erythropoiesis-Stimulating Agents (ESAs) either alone or in combination with iron are the most widely used therapeutic options. In Greece, ESAs are among the top ten therapeutic groups with the highest pharmaceutical expenditure, since they are fully reimbursed by social security funds. The objective of the study is to determine potential cost savings related with the use of biosimilar over originator ESAs for the management of the newly diagnosed chemotherapy-induced anemic patients. A budget impact analysis has been carried through the elaboration of national epidemiological, clinical and economic data. Epidemiological data derived from WHO (GLOBOCAN) and the European Cancer Anaemia Survey. Clinical data reflect oncology patients' disease management. ESAs consumption was based on data from the biggest social security fund (IKA). The administration of ESAs under different dosing schemes and time periods has been estimated by separating them in originators and biosimilars as well as by classifying anaemic patients in responders and non-responders. Cost analysis is based on newly diagnosed patients' alternative treatment scenarios. Treatment costs and prices are used in 2012 values. The Social Security Funds's perspective was undertaken. Based on the annual incidence rates, 2.551 newly diagnosed chemotherapy-induced anemic patients are expected to be treated with ESAs. Average cost of treatment on originators ESAs for responders is €2.887 for the 15-week ESAs treatment and €5.019 for non-responders, while on biosimilars €2.623 and €4.009 respectively. Treatment cost on biosimilars is 10.1% lower than originators for responders and 25.2% for non-responders. Budget impact estimates show that treating anemic patients with originator ESAs was estimated at €10.084.800 compared to €8.460.119 when biosimilar ESAs were used

  2. Implications of a Reduction in the Hemoglobin Target in Erythropoiesis-Stimulating Agent-Treated Hemodialysis Patients

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    Timothy V. Nguyen

    2011-11-01

    Full Text Available Background: Patients treated with erythropoiesis-stimulating agents (ESAs to a hemoglobin (Hb level >12.0 g/dl have increased risk of multiple complications, including death. The optimal Hb target for ESA use has not been established. We hypothesized that reducing the target Hb would prevent levels >12 g/dl and lead to significant cost savings. Methods: Our target Hb range was reduced to 9–11 g/dl from 10–12 g/dl. Thirty-five chronic hemodialysis (HD patients received erythropoietin (EPO and intravenous iron from January to December 2009. Data analysis included: Hb level, EPO dose, transferrin saturation and ferritin levels. EPO was administered via subcutaneous injection weekly or twice weekly. Results: The mean monthly Hb level changed from 11.2 to 10.6 g/dl. The percentages of patients with mean Hb >10.0, 12.0 and 13.0 g/dl were 82 ± 6.5, 10 ± 5.6 and 1.8 ± 1.9%, respectively. Weekly EPO dose decreased from 9,500 to 5,600 units, a 40% reduction per dose per patient and costs. The savings exceeded USD 60,000 per year for 35 patients. More than 80% of patients had transferrin saturation >20% and ferritin >200 ng/ml throughout the entire period. Conclusions: Lowering the target Hb range to 9–11 g/dl in HD patients achieved quality anemia management, avoided values >12.0 g/dl and resulted in cost savings. A minimal reduction in quality of life and no change in cardiovascular morbidity or mortality would be expected. The study has important implications in the new American bundled reimbursement model.

  3. Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: results from a randomized controlled trial (CONTRAST.

    Directory of Open Access Journals (Sweden)

    Neelke C van der Weerd

    Full Text Available Resistance to erythropoiesis stimulating agents (ESA is common in patients undergoing chronic hemodialysis (HD treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF. In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556, the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit. The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [-0.024 to 0.081]; P = 0.29. Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (-2.52% [-4.72 to -0.31]; P = 0.02 and -49 ng/mL [-103 to 4]; P = 0.06 respectively, although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [-0.4 to 14.5]; P = 0.06. In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.ClinicalTrials.gov NCT00205556.

  4. The long-term effect of erythropoiesis stimulating agents given to preterm infants. A proton magnetic resonance spectroscopy study on neurometabolites in early childhood

    International Nuclear Information System (INIS)

    Gasparovic, Charles; Caprihan, Arvind; Yeo, Ronald A.; Phillips, John; Lowe, Jean R.; Ohls, Robin K.; Campbell, Richard

    2018-01-01

    Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS). We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4-6 years of age. Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children (500-1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho), combined creatine and phosphocreatine, and combined glutamate and glutamine. No significant (P≤0.5) group differences were observed for any metabolite level. Significant age-related increases in white-matter tNAA and Cho were observed, as well as a trend for increased gray-matter tNAA. Neither prematurity nor neonatal ESA treatment was associated with differences in brain metabolite levels in the children of this study at a significance level of 0.05. These findings suggest that earlier differences that might have existed had normalized by 4-6 years of age or were too small to be statistically significant in the current sample. (orig.)

  5. Retrospective review of hemoglobin and/or hematocrit levels with occurrence of thrombosis in cancer patients treated with erythropoiesis stimulating agents.

    Science.gov (United States)

    Fullmer, Amber C; Miller, Rickey

    2009-09-01

    No data exists that directly compares hemoglobin and hematocrit levels between cancer patients with and without occurrence of thrombosis during treatment with erythropoiesis stimulating agents (ESAs). To determine the association of hemoglobin and hematocrit levels with the occurrence of thrombosis in cancer patients treated with ESAs. A retrospective case-control study approved by the Institutional Review Board was conducted on cancer patients billed for epoetin or darbepoetin between 1 July 2002 and 30 June 2007. Cases were defined as patients billed for thrombosis while controls were defined as patients not billed for thrombosis. Sixteen patients had an occurrence of thrombosis (cases) and were matched to 16 patients that did not have an occurrence of thrombosis (controls) based on age, sex, and cancer type. The mean peak hemoglobin levels for cases and controls were 12.6 +/- 1.2 g/dL versus 12.6 +/- 1.4 g/dL (p = 0.9). The mean peak hematocrit levels for cases and controls were 37.3 +/- 3.8% versus 37.9 +/- 4.3% (p = 0.8). For the 16/586 (2.7%) patients with thrombosis, the mean hemoglobin and hematocrit at time of thrombosis were 9.6 +/- 1.0 g/dL and 28.9 +/- 3.1%. A significant identifiable risk factor for thrombosis between the cases and controls was history of thrombosis 31.3% versus 0% (p = 0.04). There was no statistical difference in peak hemoglobin and hematocrit levels between patients with thrombosis and those without thrombosis. Further study is warranted to determine if these levels are true risk factors for thrombosis.

  6. Influence of erythropoiesis stimulation on 54Mn distribution in rats

    International Nuclear Information System (INIS)

    Ziecik, A.

    1976-01-01

    The experiments were carried out on animals in which erythropoiesis was stimulated. The rats were anaemized by blood letting or they received subcutaneous injections of erythropoietic filtrate of anaemized sheep plasma. The investigations demonstated that enhanced 54 Mn incorporation into the erytrocytes and bone marrow is induced by stimulation of the erythropoiesis process, whereas the raised 54 Mn level in the plasma of anaemized rats is associated with blood loss and not with erythropoiesis. (author)

  7. Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study

    Directory of Open Access Journals (Sweden)

    Castillo Nieves

    2012-07-01

    Full Text Available Abstract Background Predialysis hemoglobin (Hb may overestimate the true erithropoiesis-stimulating agents (ESA requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE. Methods Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialysis Hb is proposed. During 18 months follow-up, CVE, hospitalizations and mortality were collected. Results After dialysis, Hb cocentration rise by 6.1 ± 5.6%. Using postdialysis Hb, the weight-adjusted ESA dosage would be lower respect to the prescription using predialysis Hb: 104 ± 120 vs 128 ± 124 U/kg/week (P P = 0.001. The prediction model is: Postdialysis Hb (g/dL = 1.636 + 0.871 x predialysis Hb* (g/dL + 0.099 x UF rate** (mL/kg/h - 0.39 for women***. [R2 = 0.74; *P P = 0.001; ***P = 0.03. Conclusions Postdialysis Hb can be a better reflect of the real Hb level in hemodialysis patients. Using postdialysis Hb would avoid the use of inappropriately high ESA doses. The prediction of postdialysis Hb with an adjusted model would help us to identify those patients at risk for ESA overdosification.

  8. Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study.

    Science.gov (United States)

    Castillo, Nieves; García-García, Patricia; Rivero, Antonio; Jiménez-Sosa, Alejandro; Macía, Manuel; Getino, María Adela; Méndez, María Luisa; García-Pérez, Javier; Navarro-González, Juan F

    2012-07-16

    Predialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requirements. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE). Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialysis Hb is proposed. During 18 months follow-up, CVE, hospitalizations and mortality were collected. After dialysis, Hb concentration rise by 6.1 ± 5.6%. Using postdialysis Hb, the weight-adjusted ESA dosage would be lower respect to the prescription using predialysis Hb: 104 ± 120 vs 128 ± 124 U/kg/week (P < 0.001). Using predialysis Hb, 40.2% of subjects had a Hb level above 12 g/dL, whereas this percent increased to 70.1% using postdialysis Hb. During the follow-up, 15 patients had a CVE, without differences in Hb levels respect to subjects without CVE. However, patients with CVE had received higher ESA doses: 186 ± 180 vs 111 ± 98 U/Kg/week (P = 0.001). The prediction model is: Postdialysis Hb (g/dL) = 1.636 + 0.871 x predialysis Hb* (g/dL) + 0.099 x UF rate** (mL/kg/h) - 0.39 for women***. [R2 = 0.74; *P < 0,001; **P = 0.001; ***P = 0.03). Postdialysis Hb can be a better reflect of the real Hb level in hemodialysis patients. Using postdialysis Hb would avoid the use of inappropriately high ESA doses. The prediction of postdialysis Hb with an adjusted model would help us to identify those patients at risk for ESA overdosification.

  9. [Erythropoiesis and functional characteristics in bone marrow erythroblastic islets during stimulated adn inhibited erythropoiesis].

    Science.gov (United States)

    Rassokhin, A G; Kruglov, D G; Zakharov, Iu M

    2000-01-01

    When erythropiesis is stimulated (acute blood loss) or inhibited (posttransfusion polycythemia), there are early changes in the cytochemical values of erythroblastic islets (EI): in the levels of acid and neutral glucoconjugates and in the activity of nonspecific esterase. A close correlation has been found between the erythropoiesis in EI and its functional characteristics. It is concluded that central macrophages play the key role in the modulation of EI erythropoiesis. It is suggested that EI macrophages are involved in the provision of bioenergetic and reparative processes in EI.

  10. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

    International Nuclear Information System (INIS)

    Gong, Xue-Lian; Gu, Xiao-Lei; Chen, Yong-Chun; Zhu, Hai; Xia, Zhen-Na; Li, Jian-Zhong; Lu, Guo-Cai

    2016-01-01

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical

  11. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xue-Lian; Gu, Xiao-Lei [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Chen, Yong-Chun [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Department of Pharmacy, No.422 Hospital, Zhanjiang 524005 (China); Zhu, Hai; Xia, Zhen-Na [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China); Li, Jian-Zhong, E-mail: lijianzhong1234@hotmail.com [Department of Biochemical Pharmacy, Second Military Medical University, Shanghai 200433 (China); Lu, Guo-Cai, E-mail: newdrug@smmu.edu.cn [Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433 (China)

    2016-09-15

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical

  12. Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

    Science.gov (United States)

    Noronha, Vanita; Joshi, Amit; Patil, Vijay Maruti; Banavali, Shripad D; Gupta, Sudeep; Parikh, Purvish M; Marfatia, Shalaka; Punatar, Sachin; More, Sucheta; Goud, Supriya; Nakti, Dipti; Prabhash, Kumar

    2018-04-01

    We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) 10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia. © 2017 John Wiley & Sons Australia, Ltd.

  13. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to make more red blood ... NHLBI is funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision ...

  15. Stimulation and inhibition of erythropoiesis in donors and hematopoietic effect in irradiated recipient

    Energy Technology Data Exchange (ETDEWEB)

    Ninkov, V; Piletic, O; Stepanovic, D [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia); Belgrade Univ. (Yugoslavia). Inst. of Histology)

    1976-03-01

    Regeneration dynamics in bone marrow and spleen was studied in rats after irradiation of 800 R and transfusion of bone marrow cells from donors treated in different ways. Priority of the microenvironment of the recipient or of the information obtained in cell donors with respect to further hematopoietic cell differentiation was studied in irradiated recipients. Rats irradiated with 800 R were used as recipients in the experiments. The donors of marrow cells were the rats with stimulated or inhibited erythropoiesis. Stimulation of erythropoiesis was induced by bleeding and experimental polycythemia was provoked by packed erythrocytes. According to our results, it can be concluded that the processes of postirradiation hematopoiesis after transplantation of the bone marrow cells depend on the number and proliferative state of both donors and recipient stem cells, and microenvironment, not excluding the information introduced with the donor cell transplant.

  16. ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD Patients, But Not with Iron Storage.

    Directory of Open Access Journals (Sweden)

    Takahiro Kuragano

    Full Text Available It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA is associated with adverse events in patients on maintenance hemodialysis (MHD. However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.We measured serum ferritin, hemoglobin (Hb, and transferrin saturation (TSAT levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI.A significant correlation (p280; however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280 and a high ferritin level (≥100 ng/mL was significantly greater (hazard ratio [HR], 2.09, P = 0.033 than that for patients with a high ERI and a low ferritin (<100 ng/mL level.Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.

  17. Balancing ESA and iron therapy in a prospective payment environment.

    Science.gov (United States)

    Aronoff, George R; Gaweda, Adam E

    2014-02-01

    Ever since the introduction of EPO, ESAs and iron dosing have been driven by financial incentives. When ESAs were a profit center for providers, large doses were used. With ESAs becoming a cost center, a new trend has appeared, gradually replacing their use with iron to achieve the same therapeutic effect at lower cost. This financially driven approach, treating ESAs and iron as alternatives, is not consistent with human physiology where these agents act in a complementary manner. It is likely that we are still giving unnecessarily large doses of ESAs and iron, relative to what our patients' true needs are. Although we have highlighted the economic drivers of this outcome, many other factors play a role. These include our lack of understanding of the complex interplay of the anemia of chronic disease, inflammation, poor nutrition, blood loss through dialysis, ESAs and iron deficiency. We propose that physiology-driven modeling may provide some insight into the interactions between erythropoiesis and ferrokinetics. This insight can then be used to derive new, physiologically compatible dosing guidelines for ESAs and iron.

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... vegetables. Foods rich in vitamin C, such as oranges, strawberries, and tomatoes, may help increase your absorption ... deficiency anemia, your doctor may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to ...

  19. The role of erythropoietin stimulating agents in anemic patients with heart failure: solved and unresolved questions

    Directory of Open Access Journals (Sweden)

    Palazzuoli A

    2014-08-01

    Full Text Available Alberto Palazzuoli, Gaetano Ruocco, Marco Pellegrini, Carmelo De Gori, Gabriele Del Castillo, Nicola Giordano, Ranuccio NutiDepartment of Internal Medicine and Metabolic Diseases, Cardiology Section, Le Scotte Hospital, University of Siena, Siena, ItalyAbstract: Anemia is a common finding in congestive heart failure (CHF and is associated with an increased mortality and morbidity. Several conditions can cause depression of erythroid progenitor cells: reduction of iron absorption and reuptake, decreased bone marrow activity, reduced endogenous erythropoietin production, and chronic inflammatory state. Anemia’s etiology in CHF is complex and partially understood; it involves several systems including impaired hemodynamic condition, reduced kidney and bone perfusion, increased inflammatory activity, and neurohormonal overdrive. The use of erythropoiesis stimulating agents (ESAs such as erythropoietin and its derivatives is recently debated; the last interventional trial seems to demonstrate a neutral or negative effect in the active arm with darbepoetin treatment. The current data is opposite to many single blind studies and previous meta-analysis showing an improvement in quality of life, New York Heart Association class, and exercise tolerance using ESA therapy. These contrasting data raise several concerns regarding the target of hemoglobin levels needing intervention, the exact anemia classification and categorization, and the standardization of hematocrit cutoffs. Some cardiac and systemic conditions (ie, hypertension, atrial fibrillation, prothrombotic status may predispose to adverse events, and ESA administration should be avoided. To prevent the negative effects, high-dosage and chronic administration should be avoided. Clarification of these items could probably identify patients that may benefit from additional iron or ESA treatment. In this review, we discuss the interventional trials made in anemic heart failure patients, the

  20. [Experimental study of the relationships between activation of erythropoiesis and hematotoxicity of some antitumoral agents (author's transl)].

    Science.gov (United States)

    Pannacciulli, I; Bogliolo, G; Massa, G; Ronco, D; Fresco, G; Saviane, A; Dolcino, G; Celle, G

    1975-01-01

    The changes in the blood toxicity of some antitumoral chemotherapeutic agents in the presence of erythropoiesis activation by bleeding are evaluated. The general toxicity seems to be unaffected but the damage to erythropoiesis proved, in absolute terms, to be more severe in the bled animals. The recovery of hematopoiesis was slower after some drug than others. These results are discussed in the light of present knowledge of hematopoietic kinetics and of the relationships between antiblastic drugs and staminal hematopoietic compartments.

  1. Individualized Anemia Management Reduces Hemoglobin Variability in Hemodialysis Patients

    OpenAIRE

    Gaweda, Adam E.; Aronoff, George R.; Jacobs, Alfred A.; Rai, Shesh N.; Brier, Michael E.

    2013-01-01

    One-size-fits-all protocol-based approaches to anemia management with erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of hemoglobin variability. In this single-center, double-blind, randomized controlled trial, we tested the hypothesis that individualized dosing of ESA improves hemoglobin variability over a standard population-based approach. We enrolled 62 hemodialysis patients and followed them over a 12-month period. Patients were randomly assigned to receive ESA ...

  2. The approval process for biosimilar erythropoiesis-stimulating agents.

    Science.gov (United States)

    Wish, Jay B

    2014-09-05

    A biosimilar drug or follow-on biologic drug is defined by the Public Health Service Act as a product that is "highly similar to the reference product notwithstanding minor differences in clinically active components and there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity and potency of the product." The advantage of biosimilar drugs is that they are significantly less expensive than the reference products, allowing for increased accessibility and cost savings. Recognizing these advantages, the US Congress passed the Biologics Price Competition and Innovation Act in 2009 as part of health care reform. The Biologics Price Competition and Innovation Act allows sponsors of biosimilar agents to seek approval by showing structural and functional similarity to the reference agent, with the extent of required clinical studies to be determined on the basis of the degree of biosimilarity with the reference product. The goal is to bring biosimilar agents to the market more efficiently while still protecting the safety of the public. The European Union has had such a process in place for a number of years. Two biosimilar epoetin agents have been approved in the European Union since 2007, and their companies are conducting trials to seek approval in the United States, because Amgen's patent protection for epoetin alfa expires in 2014. Trials completed for European Union approval of both agents showed similar efficacy and safety to the reference epoetin alfa. As with all biologics, immunogenicity concerns may persist because of the fragility of the manufacturing process and the worldwide experience with pure red cell aplasia as a result of epoetin therapy. The uptake of biosimilar epoetins after approval in the United States will depend on the balance of cost advantage against safety concerns. Competition in the marketplace will likely decrease the cost of the reference agent as well. Copyright

  3. Comparison of Dosage Requirement of Erythropoietin Stimulating Agent (ESA in Maintenance of Hemoglobin Concentration in patients undergoing twice weekly versus thrice weekly Hemodialysis in Pakistani Population

    Directory of Open Access Journals (Sweden)

    Osama Kunwer Naveed

    2018-03-01

    Full Text Available Anemia is one of the major complications of patients with chronic kidney disease (CKD undergoing hemodialysis (HD and is associated with left ventricular hypertrophy and also increases morbidity and mortality. Anemia in patients with CKD can be due to two major reasons; iron deficiency or erythropoietin insufficiency. Erythropoietin Stimulating Agent (ESAs administration is the mainstay in treating anemia if the patient is iron sufficient. However, higher doses of ESAs have been associated with increased cerebrovascular and cardiovascular events. We conducted this study to see how much erythropoietin is required in our setting in iron sufficient patients to maintain hemoglobin(Hb  level and the effect of dialysis frequency on ESA doses.  Methods and Findings: A cross-sectional study was conducted at the Department of Nephrology at Ziauddin University Hospital. Patients’ charts were reviewed for Hb levels and doses of ESA to maintain Hb between 10-12 mg/dl. Patients were excluded if they had iron deficiency, malignancy, were on immunosuppressive agents, had renal transplant, and with Hb >12 mg/dl or <10 mg/dl and their ferritin levels, transferrin saturation, hemoglobin concentration, frequency of hemodialysis and ESA dosage were monitored. We also compared these variables between patients undergoing hemodialysis thrice weekly with those undergoing hemodialysis twice a week. A total of 105 patients were analyzed. 24 were excluded as they did not match the inclusion criteria. 81 patients were included in the study. 36 (44.4% were males and 45 (55.6% were females. Mean age of the patient was 56.47 ± 11.72 years. The average dose of ESA was 106.91 ± 61.47 for patients undergoing hemodialysis thrice weekly and 183.94 ± 116.71 for patients undergoing hemodialysis twice a week. Significant difference was found to exist between dosage of patients undergoing thrice weekly dialysis versus twice weekly dialysis(p=<0.001.  Our study has limitations

  4. High dose ESAs are associated with high iPTH levels in hemodialysis patients with end-stage kidney disease: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Lan eChen

    2015-11-01

    Full Text Available Objective: Anemia and secondary hyperparathyroidism are the two most common complications associated with chronic kidney disease (CKD. Erythropoiesis-stimulating agents (ESAs are widely used in the management of anemia in hemodialysis patients. A reverse correlation has been established between hyperparathyroidism and hemoglobin levels. The aim of this retrospective study is to evaluate the relationship of high dose ESAs and hyperparathyroidism in hemodialysis patients with anemia. Methods: A total of 240 uremic patients maintained on regular hemodialysis were enrolled into this study. Among them, 142 patients were treated with Epiao® (epoetin-alfa and 98 patients were treated with Recormon® (epoetin-beta. The target hemoglobin concentration was 110-130 g/L. Laboratory measurements including hemoglobin, calcium, phosphorus, albumin, intact-parathyroid hormone (iPTH, serum ferritin and transferrin saturation were collected. Results: Hemoglobin concentration increased as iPTH level decreased by stratification. However, no significant association between anemia and calcium or phosphorus level was found. Patients with iPTH levels within 150-300 pg/mL had the highest levels of hemoglobin, serum ferritin and transferrin saturation. Patients treated with Recormon and Epiao had similar hemoglobin concentrations. However, the dose of Recormon for anemia treatment was significantly less than that the dose of Epiao (P<0.05. The level of iPTH in the Recormon group was significantly lower than in the Epiao group. In patients with hemoglobin levels between 110-130 g/L (P<0.05, iPTH level was found to be significantly lower in patients treated with lower doses of ESAs than in patients treated with higher doses of ESAs, no matter which ESA was used (Recormon or Epiao, P<0.05. Conclusions: The dose of ESAs might be positively associated with iPTH level, suggesting that a reasonable hemoglobin target can be achieved by using the lowest possible ESA dose.

  5. Does Erythropoietin Cause Hemoglobin Variability- Is It ‘Normal’?

    OpenAIRE

    Gupta, Ashwani K; David, Waseem

    2014-01-01

    Hemoglobin variability (Hb-var) in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA) and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients no...

  6. Stress Erythropoiesis Model Systems.

    Science.gov (United States)

    Bennett, Laura F; Liao, Chang; Paulson, Robert F

    2018-01-01

    Bone marrow steady-state erythropoiesis maintains erythroid homeostasis throughout life. This process constantly generates new erythrocytes to replace the senescent erythrocytes that are removed by macrophages in the spleen. In contrast, anemic or hypoxic stress induces a physiological response designed to increase oxygen delivery to the tissues. Stress erythropoiesis is a key component of this response. It is best understood in mice where it is extramedullary occurring in the adult spleen and liver and in the fetal liver during development. Stress erythropoiesis utilizes progenitor cells and signals that are distinct from bone marrow steady-state erythropoiesis. Because of that observation many genes may play a role in stress erythropoiesis despite having no effect on steady-state erythropoiesis. In this chapter, we will discuss in vivo and in vitro techniques to study stress erythropoiesis in mice and how the in vitro culture system can be extended to study human stress erythropoiesis.

  7. Macrophages support splenic erythropoiesis in 4T1 tumor-bearing mice.

    Directory of Open Access Journals (Sweden)

    Min Liu

    Full Text Available Anemia is a common complication of cancer; a role of spleen in tumor-stress erythropoiesis has been suggested. However, the molecular mechanisms involved in the splenic erythropoiesis following tumor maintenance remain poorly understood. Here we show that tumor development blocks medullar erythropoiesis by granulocyte colony-stimulating factor (G-CSF and then causes anemia in murine 4T1 breast tumor-bearing mice. Meanwhile, tumor-stress promotes splenic erythropoiesis. Splenectomy worsened tumor-induced anemia, and reduced tumor volume and tumor weight, indicating the essential role of spleen in tumor-stress erythropoiesis and tumor growth. Tumor progression of these mice led to increased amounts of bone morphogenetic protein 4 (BMP4 in spleen. The in vivo role of macrophages in splenic erythropoiesis under tumor-stress conditions was investigated. Macrophage depletion by injecting liposomal clodronate decreased the expression of BMP4, inhibited splenic erythropoiesis, aggravated the tumor-induced anemia and suppressed tumor growth. Our results provide insight that macrophages and BMP4 are positive regulators of splenic erythropoiesis in tumor pathological situations. These findings reveal that during the tumor-stress period, the microenvironment of the spleen is undergoing changes, which contributes to adopt a stress erythropoietic fate and supports the expansion and differentiation of stress erythroid progenitors, thereby replenishing red blood cells and promoting tumor growth.

  8. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism.

    Science.gov (United States)

    Das, K C; Mukherjee, M; Sarkar, T K; Dash, R J; Rastogi, G K

    1975-02-01

    remaining 13 it was above the normal range. Erythrokinetic studies also provided evidences of increased erythropoietic activity in the bone marrow. It is postulated that thyroid hormones stimulate erythropoiesis, sometimes leading to erythrocytosis provided there is no deficiency of hemopoietic nutrients. Stimulation of erythropoiesis by thryoid hormones appears to be mediated through erythropoietin.

  9. Simplifying anemia management in hemodialysis patients: ESAs administered at longer dosing intervals can enhance opportunities to provide patient-focused care.

    Science.gov (United States)

    Schiller, Brigitte; Besarab, Anatole

    2011-08-01

    To review issues and challenges in caring for hemodialysis patients with anemia of chronic kidney disease, specifically focusing on the effects of longer erythropoiesis-stimulating agent (ESA) dosing intervals on processes of care. PubMed searches were performed limited to the last 10 years to February 2011, focusing on articles in English that were 'clinical trials,' assessed processes of care, measured associations of hemoglobin (Hb) with outcomes, and explored/analyzed extended dosing intervals of ESAs in hemodialysis patients and recommendations for increasing the quality of care of these patients. Some limitations included the fact that a meta-analysis was not conducted; many studies were associative and therefore unable to prove causality; and none of the clinical trials directly compared the impact of more frequent or less frequent ESA dosing strategies on patient care and outcomes. Progress over the past several decades has been substantial; however, unmet needs remain and there is room for improvement in efficiencies of care. Many patients fail to meet Hb targets, and nephrology professionals' time is consumed with preparing, administering, and monitoring therapy. Direct interaction between patients and care providers has been lost as attention has shifted to 'cost-effective' (not necessarily patient-centered) ways to deliver care. Use of ESAs at longer dosage intervals represents one opportunity to improve efficiency of care. Newer ESAs have been developed for less frequent dosing. Once-monthly dosing decreases time spent administering/monitoring therapy and allows nephrology professionals to provide comprehensive renal care, wherein the patient rather than task-oriented processes becomes the primary focus. A fragmented, uncoordinated care-delivery model heightens the urgency to systematically address issues related to delivery of care and improve efficiencies in anemia management as part of the patient-centered approach. ESAs designed for administration

  10. Does erythropoietin cause hemoglobin variability--is it 'normal'?

    Directory of Open Access Journals (Sweden)

    Ashwani K Gupta

    Full Text Available Hemoglobin variability (Hb-var in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients not requiring treatment with erythropoietin. We systematically studied the differences between the groups that needed ESA therapy and those who did not. White race and male sex were significant predictors of need for erythropoietin therapy. We found peritoneal dialysis patients to exhibit significantly increased Hb-var independent of treatment with exogenous erythropoietin (0.99 gm/dL vs. 1.17 gm/dL, p-value60 years peritoneal dialysis patients was similar to that seen in healthy elders, suggesting similarity with anemia of aging. We conclude that exogenous ESA administration does not explain Hb-var entirely but may enhance it. Intrinsic factors affecting erythropoiesis including age may be the major determinants of Hb-var.

  11. Delayed erythropoiesis in irradiated rats grafted with syngeneic marrow: effects of cytotoxic drugs and iron-deficiency anemia

    International Nuclear Information System (INIS)

    Rodday, P.; Bennett, M.; Vitalle, J.J.

    1976-01-01

    Erythropoiesis in spleens of lethally irradiated Lewis rats grafted with 4-35 x 10 6 syngeneic marrow cells was inhibited or delayed during the test period of 5 days; this was in marked contrast to observations in irradiated mice. The mechanism of this inhibition was the subject of this study. Pretreatment of recipients 9 days prior to irradiation with the cytotoxic drugs cyclophosphamide (CY), busulfan (BUS), or dimethylmyleran (DMM), or the induction of iron deficiency with anemia in recipients reversed this delayed erythropoiesis. However, neither iron-deficiency anemia nor pretreatment with BUS or DMM affected the ability of irradiated recipients to reject 20 to 50 x 10 6 allogeneic marrow cells. The administration of commercial preparations of erythropoietin to hosts stimulated erythropoiesis moderately. However, proliferation of syngeneic marrow cells was not enhanced when infused into lethally irradiated spontaneous hypertensive (SH) inbred-strain rats which have high levels of endogenous erythropoietin. Finally, plasma from irradiated rats treated with phenylhydrazine to produce severe anemia was rich in erythropoietin but failed to stimulate erythropoiesis in the cell transfer system. Two hypotheses are considered

  12. Ferrokinetic study of splenic erythropoiesis: Relationships among clinical diagnosis, myelofibrosis, splenomegaly, and extramedullary erythropoiesis

    International Nuclear Information System (INIS)

    Beguin, Y.; Fillet, G.; Bury, J.; Fairon, Y.

    1989-01-01

    Splenic erythropoiesis was demonstrated by surface counting of 59 Fe in 129 of 1,350 ferrokinetic studies performed over a 15 year period. These 129 studies were carried out in 108 patients, including 40 with chronic myelogenous leukemia (CML), 24 with agnogenic myeloid metaplasia (AMM), 18 with polycythemia vera (PV), six with a myelodysplastic syndrome, five with acute leukemia, three with prostate or breast carcinoma, two each with aplastic anemia or Hodgkin's disease, and one each with idiopathic thrombocythemia, multiple myeloma, chronic renal failure, or treated hypopituitarism. Splenomegaly was present in 83% of the studies and hepatomegaly in 72%. Grade II-III myelofibrosis was demonstrated in 62% of the cases. Hepatic erythropoiesis was present in 77% of the studies (only 38% in PV), and marrow erythropoiesis was undetectable in 33%. Total erythropoiesis was about twice normal (range 0.2 to 8 times normal) but was ineffective to varying degrees in 86% of the studies. Relationships between organomegaly, myelofibrosis, and extramedullary erythropoiesis, as well as differences among clinical disorders, are discussed. Differences observed between CML in chronic or blastic phase suggested that the erythroid cell line was involved in the proliferative process. It is concluded that splenic erythropoiesis (1) is encountered in a variety of clinical conditions; (2) is not necessarily associated with splenomegaly or myelofibrosis, even in the myeloproliferative disorders; (3) is part of a predominantly extramedullary (in the liver as well as in the spleen), expanded, and largely inefficient total erythropoiesis; and (4) can be evaluated in a semiquantitative manner by surface counting

  13. Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.

    Science.gov (United States)

    Parekh, Chintan; Sahaghian, Arineh; Kim, William; Scholes, Jessica; Ge, Shundi; Zhu, Yuhua; Asgharzadeh, Shahab; Hollis, Roger; Kohn, Donald; Ji, Lingyun; Malvar, Jemily; Wang, Xiaoyan; Crooks, Gay

    2012-04-01

    The cytokine thrombopoietin (Tpo) plays a critical role in hematopoiesis by binding to the extracellular domain and inducing homodimerization of the intracellular signaling domain of its receptor, c-Mpl. Mpl homodimerization can also be accomplished by binding of a synthetic ligand to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. Unexpectedly, in contrast to Tpo stimulation, robust erythropoiesis is induced after dimerization of F36VMpl in human CD34+ progenitor cells. The goal of this study was to define the hematopoietic progenitor stages at which dimerization of intracellular Mpl induces erythropoiesis and the downstream molecular events that mediate this unanticipated effect. Dimerization (in the absence of erythropoietin and other cytokines) in human common myeloid progenitors and megakaryocytic erythroid progenitors caused a significant increase in CD34+ cells (p Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis through molecular mechanisms that are not shared by Tpo stimulation of endogenous Mpl. Copyright © 2012 AlphaMed Press.

  14. Erythropoiesis in the aged mouse. I. Response to stimulation in vivo

    International Nuclear Information System (INIS)

    Udupa, K.B.; Lipschitz, D.A.

    1984-01-01

    Changes in erythropoiesis with age were studied by examining the hematocrit increase in response to hypoxia in aged mice and by assessing the change in erythropoiesis following the injection of erythropoietin in young and old polycythemic mice. The increase in hematocrit after exposure to hypoxia was more variable and generally lower in old mice than in young mice. When erythropoietin was injected into polycythemic animals, the increase in differentiated erythroid cells and 59 Fe incorporation into erythroid marrow and peripheral blood cells was significantly lower in old mice than in young mice. In contrast to differentiated erythroid cells, there was less evidence of a reduced response to simulation of the more primitive erythroid progenitor cells of aged animals. The early undifferentiated erythroid progenitor, burst-forming units, did not decrease when either young or aged mice were made polycythemic, and no change following erythropoietin injection was noted. Polycythemia suppressed the late-differentiated erythroid progenitor, erythroid colony-forming units, to a greater extent in aged animals, but when erythropoietin was injected, the percent increase over the subsequent 24 hours was identical to that in young mice. These observations indicate a reduced erythropoietic capacity with age, the abnormality being most obvious in the more mature erythroid precursors

  15. Thrombopoietin has a differentiative effect on late-stage human erythropoiesis.

    Science.gov (United States)

    Liu, W; Wang, M; Tang, D C; Ding, I; Rodgers, G P

    1999-05-01

    To further explore the mechanism of the effect of thrombopoietin (TPO) on erythropoiesis, we used a two-phase culture system to investigate the effect of TPO on late-stage human erythroid lineage differentiation. In serum-free suspension and semisolid cultures of human peripheral blood derived erythroid progenitors, TPO alone did not produce benzidine-positive cells. However, in serum-containing culture, TPO alone stimulated erythroid cell proliferation and differentiation, demonstrated by erythroid colony formation, production of benzidine-positive cells and haemoglobin (Hb) synthesis. Monoclonal anti-human erythropoietin antibody and anti-human erythropoietin receptor antibody completely abrogated the erythroid differentiative ability of TPO in the serum-containing systems. This implied that binding of EPO and EPO-R was essential for erythropoiesis and the resultant signal transduction may be augmented by the signals emanating from TPO-c-Mpl interaction. Experiment of withdrawal of TPO further demonstrated the involvement of TPO in late-stage erythropoiesis. RT-PCR results showed that there was EPO-R but not c-Mpl expression on developing erythroblasts induced by TPO in serum-containing system. Our results establish that TPO affects not only the proliferation of erythroid progenitors but also the differentiation of erythroid progenitors to mature erythroid cells.

  16. Are erythropoiesis-stimulating agents beneficial for anemia in chronic heart failure patients?

    Directory of Open Access Journals (Sweden)

    Diego Araneda

    2016-12-01

    Full Text Available Resumen La anemia es común en la insuficiencia cardiaca, y se asocia a una mayor morbimortalidad. Sin embargo, no está claro si corregirla con agentes estimulantes de la eritropoyesis se traduce en un beneficio clínico. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos 11 revisiones sistemáticas que en conjunto incluyen 17 estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de agentes estimulantes de la eritropoyesis en pacientes con insuficiencia cardiaca y anemia no disminuye la mortalidad, y que no está claro si disminuye las hospitalizaciones o si mejora la capacidad funcional porque la certeza de la evidencia es muy baja. Probablemente aumenta el riesgo de eventos tromboembólicos totales.

  17. Comparative efficacy and safety in ESA biosimilars vs. originators in adults with chronic kidney disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Amato, Laura; Addis, Antonio; Saulle, Rosella; Trotta, Francesco; Mitrova, Zuzana; Davoli, Marina

    2018-06-01

    Several Erythropoiesis-stimulating agents (ESAs) are available to treat anemia in patients with chronic kidney disease (CKD). Questions about the comparability of such therapeutic options are not purely a regulatory or economical matter. Appropriate use of originator or biosimilar in these patients need to be supported by clinical data. Regarding the prevention of blood transfusion, reduction of fatigue, breathlessness and mortality or cardiovascular events, a summary of the comparative efficacy and safety data of these drugs is lacking. We performed a systematic literature search of CENTRAL, PubMed, and Embase through November 11, 2015. Our inclusion criteria encompassed randomized, controlled clinical trials that evaluated the comparative effectiveness of different ESAs originators and/or biosimilar. The considered participants were adults aged 18 years or older with anemia due to CKD. The overall quality of evidence was assessed using the GRADE system. We identified 30 eligible studies including 7843 patients with CKD, and 21/30 studies included patients using hemodialysis or peritoneal dialysis. Compared with ESA biosimilars, epoetin α did not statistically differ for any of the ten measured outcomes. The quality of evidence varied from low to very low. In the comparison between epoetin α vs. darbepoetin α, no differences were observed for all outcomes, but blood transfusions showed favorable results for darbepoetin α: RR 2.18 (1.31-3.62). The quality of evidence varied from low to very low. No differences were observed between epoetin β and methoxy polyethylene glycol-epoetin β, and between darbepoetin α and methoxy polyethylene glycol-epoetin β, the quality of evidence varied from moderate to very low. Data from 31 included studies allowed to pool data in meta-analysis related to four different comparisons and eleven outcome measures. Nevertheless, only one result was statistically significant in favor of darbepoetin α in the comparison with epoetin

  18. Effects of radiation on erythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Harriss, E B

    1971-04-01

    Since the pioneer work of Heineke (1903; 1905) many workers have studied the effect of radiation on haemopoiesis. Their work has been reviewed by Bloom (1948), by Jacobson (1954) and more recently by Bond et al. (1965). The subject continues to stimulate much interest but is now more concerned with the effects of radiation on the multipotential stem cell pool than on radiation damage to the erythropoietic cells themselves. Death from haemopoietic failure following an LD{sub 50/30} dose of radiation is probably not attributable to failure of erythropoiesis; while damage to the erythropoietic system certainly plays a part in the syndrome, it is not a major factor contributing to the death of the animal. Although the severity and time course of the response vary with the species studied, the general effects of radiation on erythropoiesis are similar in all mammalian bone marrow studied to date. Likewise, though the severity of the reaction varies somewhat with the energy of the radiation and has been used to compare the relative biological effectiveness of different types of radiation (Sinclair et al., 1962; Sztanyik, 1967), the response is different only in degree and not in its fundamental pattern. The initial syndrome of depression and recovery will therefore be described largely by reference to work performed on the response of the rat to single acute exposures of either whole-body or partial-body irradiation with conventional X-rays.

  19. Triumph and tragedy: anemia management in chronic kidney disease.

    Science.gov (United States)

    Novak, James E; Szczech, Lynda A

    2008-11-01

    Recent trial data have resulted in a reevaluation of the management of anemia in chronic kidney disease, including the use of erythropoiesis-stimulating agents, intravenous iron, and novel pharmaceuticals. In this review, we evaluate the latest research on anemia management in chronic kidney disease. Clinical trials of erythropoiesis-stimulating agents indicate that targeting the complete correction of anemia in patients with chronic kidney disease results in a greater risk of morbidity and mortality despite improved hemoglobin and quality of life. Conversely, intravenous iron has been found effective and relatively well tolerated in treating anemia in chronic kidney disease, even in patients with elevated ferritin. New agents to manage anemia, including long-acting erythropoietin derivatives, are also in active development. Erythropoiesis-stimulating agents should be used to target hemoglobin 11-12 g/dl in patients with chronic kidney disease. Intravenous iron may be beneficial for patients with hemoglobin less than 11 g/dl and transferrin saturation less than 25% despite elevated ferritin (500-1200 ng/ml). An upcoming placebo-controlled trial of darbepoetin should help to define the role of erythropoiesis-stimulating agents in chronic kidney disease.

  20. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  1. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2011-01-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  2. Abscopal suppression of bone marrow erythropoiesis

    International Nuclear Information System (INIS)

    Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

    1978-01-01

    Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

  3. Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.

    Science.gov (United States)

    Komrokji, Rami; Swern, Arlene S; Grinblatt, David; Lyons, Roger M; Tobiasson, Magnus; Silverman, Lewis R; Sayar, Hamid; Vij, Ravi; Fliss, Albert; Tu, Nora; Sugrue, Mary M

    2018-02-01

    After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS. We searched English-language articles for prospective phase II and III azacitidine clinical trials and patient registries published between 2000 and 2015, and Embase abstracts from 2015 conferences. Patient-level data from identified relevant studies were provided by investigators. Meta-analyses followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Efficacy endpoints were RBC transfusion independence (TI) and Clinical Benefit (RBC-TI, erythroid response, and complete or partial remission, per International Working Group 2006 criteria for MDS). Data for 233 patients from 6 clinical studies and 1 registry study met criteria for inclusion in analyses. Overall, 90.3% of patients had non-del(5q) LR-MDS. Pooled estimates from random-effects models of RBC-TI and Clinical Benefit were 38.9% and 81.1%, respectively; for the ESA-refractory subgroup, they were 40.5% and 77.3%; and for patients with isolated anemia, they were 41.9% and 82.5%. In multivariate analyses, planned use of ≥6 azacitidine treatment cycles was significantly predictive of response. Azacitidine effects in these patients, most with non-del(5q) LR-MDS, were promising and generally similar to those reported for lenalidomide in similar patients. The choice of initial therapy is important because most patients eventually stop responding to front-line therapy and alternatives are limited. Lower-risk myelodysplastic syndromes (LR-MDS) are primarily characterized by

  4. Epoetin beta for the treatment of chemotherapy-induced anemia: an update

    Directory of Open Access Journals (Sweden)

    Galli L

    2015-03-01

    Full Text Available Luca Galli,1 Clara Ricci,2 Colin Gerard Egan2 1Oncology Unit 2, University Hospital of Pisa, Pisa, Italy; 2Primula Multimedia SRL, Pisa, Italy Abstract: Epoetin beta belongs to the class of erythropoiesis-stimulating agents (ESAs that are currently available to treat anemic patients receiving chemotherapy. Chemotherapy-induced anemia affects a high percentage of cancer patients and, due to its negative effects on disease outcome and the patient’s quality of life, should be treated when first diagnosed. Initial trials with ESAs have shown efficacy in improving quality of life and reducing the need for blood transfusions in patients with chemotherapy-induced anemia. However, recent meta-analyses have provided conflicting data on the impact of ESAs on survival and tumor progression. Here we provide an overview of these recent data and review the role of epoetin beta in the treatment of chemotherapy-induced anemia over the past 20 years. Keywords: epoetin beta, erythropoietin, chemotherapy, cancer, anemia, treatment

  5. Hypoxia Induced Factor in Chronic Kidney Disease: Friend or Foe?

    Science.gov (United States)

    Li, Weiying; Zhao, Yuliang; Fu, Ping

    2017-01-01

    Many studies have shown evidence that erythropoiesis-stimulating agents (ESAs), as a classic treatment for chronic kidney disease (CKD)-related anemia, have several disadvantages and may trigger various adverse events with long-term use. The hypoxia-induced factor (HIF) pathway has been intensively investigated in kidney disease, especially in CKD, as research has shown that HIF-mediated erythropoiesis might work as a potential therapeutic strategy for managing CKD-related anemia. Development of prolyl hydroxylase domain inhibitors (PHIs), as an effective HIF activator, is a valuable step toward finding a replacement for ESAs, which showed an effective erythropoiesis through a comprehensive and physiological approach by promoting erythropoietin production, increasing iron bioavailability and improving chronic inflammatory status. Heretofore no adverse events or obvious off-target effects have been reported in clinical trials of PHIs. Nevertheless, a cautious inspection with extended follow-up period is warranted to validate the safety of prolonged HIF elevation, especially considering its ambiguous role in fibrogenesis and inflammation responses and possible risks in accelerating vascular calcification and tumorigenesis. A weighed dosing strategy might be the key to circumvent the unexpected side-effect brought by pleotropic effects of HIF elevation and achieve a selective augmentation of HIF-mediated signaling pathway. New studies with longer follow-up period and adequate analysis about the risks for proinflammation, vascular calcification and tumorigenesis are needed to ensure the drugs are safe for long-term use before being widely accepted in daily clinical practice.

  6. Anemia management among hemodyalisis patients at the University Hospital in Puerto Rico.

    Science.gov (United States)

    Ocasio, Heana E; Diaz, Hector; Cangiano, José L; Báez, Rafael; Suárez, Erick

    2014-01-01

    End-stage renal disease is frequently complicated with anemia. Iron deficiency anemia occurs in most hemodialysis patients secondary to increased iron demand driven by the accelerated erythropoiesis that occurs when stimulating agents are administered as treatment of the anemia. The purpose of this study was to determine the prevalence of anemia and iron stores in patients undergoing hemodialysis at our unit; identify their treatment and effectiveness. Medical records of fifty-three patients undergoing ambulatory hemodialysis were evaluated for three months. Patient's hemoglobin, ferritin, iron, total iron binding capacity and percent transferrin saturation were recorded. 91% patients had arterial hypertension and 62% were diabetic. The prevalence of anemia was 34%, 57% and 47% during the three-month period respectively. Only 21% of the population had transferrin saturation less than 20% and none had ferritin below 200 ng/ml. Throughout the study, the majority of patients were managed with combination of iron and erythropoietin stimulating agents (ESAs). The prevalence of anemia remained elevated despite treatment with iron and ESAs. However, 56% of anemic patients throughout the three months showed an increase in hemoglobin levels by the end of the observation period. 53% of patients were treated with iron alone or with ESAs for the three consecutive month periods and only two had transferrin saturation less than 20%. In our population, ESAs low responsiveness is not related to iron deficiency but to the morbidity of their disease.

  7. β-Thalassemia and Polycythemia vera: targeting chronic stress erythropoiesis.

    Science.gov (United States)

    Crielaard, Bart J; Rivella, Stefano

    2014-06-01

    β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective erythrocytes and anemia, while patients with Polycythemia vera present with high hemoglobin levels because of excessive red blood cell synthesis - both pathologies may characterized by lasting high erythropoietic activity, i.e. chronic stress erythropoiesis. In both diseases, therapeutic strategies targeting chronic stress erythropoiesis may improve the address phenotype and prevent secondary pathology, such as iron overload. The current review will address the basic concepts of these strategies to reduce chronic stress erythropoiesis, which may have significant clinical implications in the near future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Altered erythropoiesis and iron metabolism in carriers of thalassemia

    Science.gov (United States)

    Guimarães, Jacqueline S.; Cominal, Juçara G.; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z.; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

    2014-01-01

    The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis and dysfunctional iron metabolism have not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changings in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferrin and (hepcidin/ferritin)/sTfR are respectively increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis. PMID:25307880

  9. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  10. Study of erythropoiesis with 59Fe and erythrocyte survival with 51Cr in aplastic anemia

    International Nuclear Information System (INIS)

    Avramova, D.; Karakostov, K.; Dimtrov, L.; Osmanliev, P.

    1979-01-01

    A study of erythropoiesis with 59 Fe and erythrocyte survival with 51 Cr was carried out in 25 patients with aplastic anemia and in a control group of 23 healthy persons. Bone marrow aplasia was uniform in all patients but differences in erythropoiesis were established. According to the state of erythropoiesis, the patients were divided into two groups: 1) patients with severe damage of erythropoiesis and 2) patients with preserved erythropoiesis. Erythrocyte survival in both groups was shortened. The data obtained correlate with the anemic syndrome and help to explain its pathogenesis. It is suggested that the investigation of erythropoiesis with 59 Fe and 51 Cr is of prognostic value. (author)

  11. Treatment and management of myelofibrosis in the era of JAK inhibitors.

    Science.gov (United States)

    Keohane, Clodagh; Radia, Deepti H; Harrison, Claire N

    2013-01-01

    Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.

  12. Coordinate expression of heme and globin is essential for effective erythropoiesis.

    Science.gov (United States)

    Doty, Raymond T; Phelps, Susan R; Shadle, Christina; Sanchez-Bonilla, Marilyn; Keel, Siobán B; Abkowitz, Janis L

    2015-12-01

    Erythropoiesis requires rapid and extensive hemoglobin production. Heme activates globin transcription and translation; therefore, heme synthesis must precede globin synthesis. As free heme is a potent inducer of oxidative damage, its levels within cellular compartments require stringent regulation. Mice lacking the heme exporter FLVCR1 have a severe macrocytic anemia; however, the mechanisms that underlie erythropoiesis dysfunction in these animals are unclear. Here, we determined that erythropoiesis failure occurs in these animals at the CFU-E/proerythroblast stage, a point at which the transferrin receptor (CD71) is upregulated, iron is imported, and heme is synthesized--before ample globin is produced. From the CFU-E/proerythroblast (CD71(+) Ter119(-) cells) stage onward, erythroid progenitors exhibited excess heme content, increased cytoplasmic ROS, and increased apoptosis. Reducing heme synthesis in FLVCR1-defient animals via genetic and biochemical approaches improved the anemia, implying that heme excess causes, and is not just associated with, the erythroid marrow failure. Expression of the cell surface FLVCR1 isoform, but not the mitochondrial FLVCR1 isoform, restored normal rbc production, demonstrating that cellular heme export is essential. Together, these studies provide insight into how heme is regulated to allow effective erythropoiesis, show that erythropoiesis fails when heme is excessive, and emphasize the importance of evaluating Ter119(-) erythroid cells when studying erythroid marrow failure in murine models.

  13. Blood doping: risks to athletes' health and strategies for detection.

    Science.gov (United States)

    Oliveira, Carolina Dizioli Rodrigues de; Bairros, André Valle de; Yonamine, Mauricio

    2014-07-01

    Blood doping has been defined as the misuse of substances or certain techniques to optimize oxygen delivery to muscles with the aim to increase performance in sports activities. It includes blood transfusion, administration of erythropoiesis-stimulating agents or blood substitutes, and gene manipulations. The main reasons for the widespread use of blood doping include: its availability for athletes (erythropoiesis-stimulating agents and blood transfusions), its efficiency in improving performance, and its difficult detection. This article reviews and discusses the blood doping substances and methods used for in sports, the adverse effects related to this practice, and current strategies for its detection.

  14. An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Besarab Anatole

    2012-08-01

    Full Text Available Abstract Background Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. Methods Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1 how the peginesatide starting dose was determined (using a single epoetin alfa–to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table and on (2 whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline. Results A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2–13 to 54% (Weeks 18–25. Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. Conclusions The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once

  15. Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

    Science.gov (United States)

    Krieger, N S; Stappenbeck, T S; Stern, P H

    1987-01-01

    The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 microM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations below 0.1 mM did not affect calvarial cyclic AMP. 0.5 microM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones. 3 nM calcitonin inhibited milrinone-stimulated resorption and there was no escape from this inhibition. Structural homology between milrinone and thyroxine has been reported. We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition. PMID:3027124

  16. Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

    OpenAIRE

    Krieger, N S; Stappenbeck, T S; Stern, P H

    1987-01-01

    The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 microM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations bel...

  17. Intensity of erythropoiesis in different erythropoietic regions following bone marrow transplantation

    International Nuclear Information System (INIS)

    Hola, J.; Vacha, J.; Lukas, P.

    1982-01-01

    By applying 59 Fe-citrate to irradiated mice it was found that irradiation suppresses iron incorporation especially in tubular bones. Following the transfusion of bone marrow cells there was a significant increase in 59 Fe incorporation in all bone groups, i.e., an increase in erythropoiesis. The graft with erythropoietic potency proliferated especially in places where there was a high intensity of erythropoiesis already before irradiation. (M.D.)

  18. Artificial intelligence for optimal anemia management in end-stage renal disease.

    Science.gov (United States)

    Brier, Michael E; Gaweda, Adam E

    2016-08-01

    Computational intelligence for the prediction of hemoglobin to guide the selection of erythropoiesis-stimulating agent dose results in improved anemia management. The models used for the prediction result from the use of individual patient data and help to increase the number of hemoglobin observations within the target range. The benefits of using these modeling techniques appear to be a decrease in erythropoiesis-stimulating agent use and a decrease in the number of transfusions. This study confirms the results of previous smaller studies and suggests that additional beneficial results may be achieved. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Bubble Jet agent release cartridge for chemical single cell stimulation.

    Science.gov (United States)

    Wangler, N; Welsche, M; Blazek, M; Blessing, M; Vervliet-Scheebaum, M; Reski, R; Müller, C; Reinecke, H; Steigert, J; Roth, G; Zengerle, R; Paust, N

    2013-02-01

    We present a new method for the distinct specific chemical stimulation of single cells and small cell clusters within their natural environment. By single-drop release of chemical agents with droplets in size of typical cell diameters (d agent release cartridge with integrated fluidic structures and integrated agent reservoirs are shown, tested, and compared in this publication. The single channel setup features a fluidic structure fabricated by anisotropic etching of silicon. To allow for simultaneous release of different agents even though maintaining the same device size, the second type comprises a double channel fluidic structure, fabricated by photolithographic patterning of TMMF. Dispensed droplet volumes are V = 15 pl and V = 10 pl for the silicon and the TMMF based setups, respectively. Utilizing the agent release cartridges, the application in biological assays was demonstrated by hormone-stimulated premature bud formation in Physcomitrella patens and the individual staining of one single L 929 cell within a confluent grown cell culture.

  20. Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

    Science.gov (United States)

    Taupin, Philippe

    2009-05-01

    The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

  1. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

    Directory of Open Access Journals (Sweden)

    Lina M. Ruiz

    2015-01-01

    Full Text Available Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2∙- production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.

  2. Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS.

    Science.gov (United States)

    Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P

    2018-04-01

    Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

  3. Anaemia management in cardio renal disease.

    Science.gov (United States)

    Silverberg, Donald S; Wexler, Dov; Iaina, Adrian; Schwartz, Doron

    2010-05-01

    Anaemia is common in congestive heart failure (CHF) and is associated with increased mortality, morbidity and progressive renal failure. The common causes of the anaemia are the associated renal failure and excessive cytokine production, both of which can cause depression of the erythropoietin (EPO) production in the kidney and depression of EPO response in bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. Attempts to control this anaemia will have to consider the use of both erythropoiesis stimulating agents (ESA) as well as oral and, probably more importantly, intravenous (IV) iron. Studies of anaemia in CHF with ESA and oral or IV iron and even with IV iron alone have shown a positive effect on hospitalisation, fatigue and shortness of breath, cardiac and renal function, quality-of-life, exercise capacity and reduced beta natriuretic peptide and have not demonstrated an increase in cardiovascular damage related to therapy. Although some studies and meta-analyses have revealed improvement in these parameters others have not. Adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are needed and are currently being carried out.

  4. Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis.

    Science.gov (United States)

    Naci, Huseyin; de Lissovoy, Gregory; Hollenbeak, Christopher; Custer, Brian; Hofmann, Axel; McClellan, William; Gitlin, Matthew

    2012-01-01

    To determine whether Medicare's decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time. The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses. Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses. This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature. This study indicates that Medicare's coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.

  5. Reticulocyte Hemoglobin Content Helps Avoid Iron Overload in Hemodialysis Patients: A Retrospective Observational Study.

    Science.gov (United States)

    Capone, Domenico; Cataldi, Mauro; Vinciguerra, Mauro; Mosca, Teresa; Barretta, Salvatore; Ragosta, Annalisa; Sorrentino, Aniello; Vecchione, Alessandra; Barretta, Luca; Tarantino, Giovanni

    2017-01-01

    Anemia in patients suffering from end-stage renal failure is currently treated with Erythropoiesis-Stimulating Agents (ESA). This treatment needs sufficient iron supplementation to avoid an inadequate dosage of ESA. Nowadays modern analytical instruments allow to accurately calculate the content of Hemoglobin (Hb) in reticulocytes (CHr), that can be used as a guide for prescribing patients with the appropriate amount of iron. Patients, undergoing hemodialysis, were retrospectively selected from the database and were divided in two groups: group A received intravenous (IV) iron and subcutaneously ESA, and their dosages were adjusted on the basis of the following parameters: Hb, Mean corpuscular haemoglobin (MCH), CHr with consequent MCH/CHr ratio and reticulocyte count determined by the ADVIA 120 Hematology System of Siemens; group B patients were administered IV iron and ESA monitoring iron storage, Hb and ferritin. The aforementioned parameters and the administered amount of iron and ESA were monitored at baseline, four and eight months from the begining of the study. For ESA supplementation, no difference was observed between the groups at the various observed times. Despite similar Hb levels, the patients of group A needed significant lower doses of IV iron (-57.8%) avoiding risks of organ toxicity and obtaining consequent cost saving of nearly 1 €/patient/month. The use of CHr and its related parameters allows the avoidance of overdosage of IV iron, which can potentially damage organs, and the reduction of health care direct and indirect costs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo.

    Science.gov (United States)

    Ohls, Robin K; Kamath-Rayne, Beena D; Christensen, Robert D; Wiedmeier, Susan E; Rosenberg, Adam; Fuller, Janell; Lacy, Conra Backstrom; Roohi, Mahshid; Lambert, Diane K; Burnett, Jill J; Pruckler, Barbara; Peceny, Hannah; Cannon, Daniel C; Lowe, Jean R

    2014-06-01

    We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs. We performed a randomized, masked, multicenter study comparing Darbe (10 μg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/week) given through 35 weeks' postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months' corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed. Of the original 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 ± 7.3; mean ± SD) and Epo recipients (97.9 ± 14.3) compared with placebo recipients (88.7 ± 13.5; P = .01 vs ESA recipients) as was object permanence (P = .05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P < .001). No differences among groups were found in visual or hearing impairment. Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants. Copyright © 2014 by the American Academy of Pediatrics.

  7. Erythroblastic Islands: Specialized Mircoenvironmental Niches forErythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Chasis, Joel Anne

    2006-01-06

    This review focuses on current understanding of molecular mechanisms operating within erythroblastic islands including cell-cell adhesion, regulatory feedback, and central macrophage function. RECENT FINDINGS: Erythroblasts express a variety of adhesion molecules and recently two interactions have been identified that appear to be critical for island integrity. Erythroblast macrophage protein, expressed on erythroblasts and macrophages, mediates cell-cell attachments via homophilic binding. Erythroblast intercellular adhesion molecule-4 links erythroblasts to macrophages through interaction with macrophage alphav integrin. In intercellular adhesion molecule-4 knockout mice, erythroblastic islands are markedly reduced, whereas the erythroblast macrophage protein null phenotype is severely anemic and embryonic lethal. Retinoblastoma tumor suppressor (Rb) protein stimulates macrophage differentiation by counteracting inhibition of Id2 on PU.1, a transcription factor that is a crucial regulator of macrophage differentiation. Rb-deficient macrophages do not bind Rb null erythroblasts and the Rb null phenotype is anemic and embryonic lethal. Lastly, extruded nuclei rapidly expose phosphatidylserine on their surface, providing a recognition signal similar to apoptotic cells. SUMMARY: Although understanding of molecular mechanisms operating within islands is at an early stage, tantalizing evidence suggests that erythroblastic islands are specialized niches where intercellular interactions in concert with cytokines play critical roles in regulating erythropoiesis.

  8. Heme transport and erythropoiesis

    Science.gov (United States)

    Yuan, Xiaojing; Fleming, Mark D.; Hamza, Iqbal

    2013-01-01

    In humans, systemic heme homeostasis is achieved via coordinated regulation of heme synthesis, transport and degradation. Although the heme biosynthesis and degradation pathways have been well characterized, the pathways for heme trafficking and incorporation into hemoproteins remains poorly understood. In the past few years, researchers have exploited genetic, cellular and biochemical tools, to identify heme transporters and, in the process, reveal unexpected functions for this elusive group of proteins. However, given the complexity of heme trafficking pathways, current knowledge of heme transporters is fragmented and sometimes contradictory. This review seeks to focus on recent studies on heme transporters with specific emphasis on their functions during erythropoiesis. PMID:23415705

  9. Decreased "ineffective erythropoiesis" preserves polycythemia in mice under long-term hypoxia.

    Science.gov (United States)

    Harada, Tomonori; Tsuboi, Isao; Hirabayashi, Yukio; Kosaku, Kazuhiro; Naito, Michiko; Hara, Hiroyuki; Inoue, Tohru; Aizawa, Shin

    2015-05-01

    Hypoxia induces innumerable changes in humans and other animals, including an increase in peripheral red blood cells (polycythemia) caused by the activation of erythropoiesis mediated by increased erythropoietin (EPO) production. However, the elevation of EPO is limited and levels return to normal ranges under normoxia within 5-7 days of exposure to hypoxia, whereas polycythemia continues for as long as hypoxia persists. We investigated erythropoiesis in bone marrow and spleens from mouse models of long-term normobaric hypoxia (10 % O2) to clarify the mechanism of prolonged polycythemia in chronic hypoxia. The numbers of erythroid colony-forming units (CFU-E) in the spleen remarkably increased along with elevated serum EPO levels indicating the activation of erythropoiesis during the first 7 days of hypoxia. After 14 days of hypoxia, the numbers of CFU-E returned to normoxic levels, whereas polycythemia persisted for >140 days. Flow cytometry revealed a prolonged increase in the numbers of TER119-positive cells (erythroid cells derived from pro-erythroblasts through mature erythrocyte stages), especially the TER119 (high) CD71 (high) population, in bone marrow. The numbers of annexin-V-positive cells among the TER119-positive cells particularly declined under chronic hypoxia, suggesting that the numbers of apoptotic cells decrease during erythroid cell maturation. Furthermore, RT-PCR analysis showed that the RNA expression of BMP-4 and stem cell factor that reduces apoptotic changes during erythroid cell proliferation and maturation was increased in bone marrow under hypoxia. These findings indicated that decreased apoptosis of erythroid cells during erythropoiesis contributes to polycythemia in mice during chronic exposure to long-term hypoxia.

  10. Comparison of methodologies to define hemodialysis patients hyporesponsive to epoetin and impact on counts and characteristics

    Directory of Open Access Journals (Sweden)

    Gilbertson David T

    2013-02-01

    Full Text Available Abstract Background Some hemodialysis patients require large doses of erythropoiesis-stimulating agents (ESAs to manage anemia. These patients, termed “ESA hyporesponsive,” have been characterized using various definitions. We applied three definitions of hyporesponsiveness to a large, national cohort of hemodialysis patients to assess the impact of definition on counts and on characteristics associated with hyporesponsiveness. Methods We studied point-prevalent hemodialysis patients on May 1, 2008, with Medicare as primary payer, who survived through December 31, 2008. Included patients received recombinant human erythropoietin (EPO in each month, August-December. Hyporesponsiveness definitions were: above the ninetieth percentile of total monthly EPO dose; above the ninetieth percentile of total monthly EPO dose divided by weight in kg; above the ninetieth percentile of total monthly EPO dose divided by hemoglobin level. Hyporesponsiveness was further classified as chronic, acute, or other. Comorbid conditions were assessed before and concurrent with the hyporesponsive period. Results Women, African Americans, and patients aged Conclusions As associations were similar between patient characteristics and three methods of characterizing EPO hyporesponsiveness, the simplest definition using EPO dose can be used.

  11. β-Thalassemia and Polycythemia vera : Targeting chronic stress erythropoiesis

    NARCIS (Netherlands)

    Crielaard, Bart J; Rivella, Stefano

    β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective

  12. The distribution of erythropoiesis over the various anatomical regions of the erythropoietic system in some inbred strains of mice

    Energy Technology Data Exchange (ETDEWEB)

    Vacha, J.; Hola, J.; Dungel, J.; Znojil, V.

    1982-10-01

    The extraction of /sup 59/Fe bound to the heme in the erythropoietic organs by means of acid ethylacetate was used to establish the proportion of erythropoiesis for which individual bones and the spleens of some inbred mouse strains are responsible. The proportion of splenic erythropoiesis differs from strain to strain, being in the range 9-42% of total erythropoiesis. In the strain BALB/c erythropoiesis is shifted in comparison with C57B1/10 strain towards the spine and away from the bones of the skull, the long bones of the limbs and the pelvis. Calculations of the erythroid cellularity and/or the intensity of erythropoiesis of the total bone marrow on the basis of a single bone should take into account both these interstrain differences in the participation of different regions and the possibility of various proportions of red and white blood cells and cells containing non-heme iron existing in different regions (bones).

  13. Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of novel biomarkers.

    Directory of Open Access Journals (Sweden)

    Britt Christensen

    Full Text Available Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA exposure (Darbepoietin-α and/or aerobic training.Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9, Sedentary-ESA (n = 9, Training-placebo (n = 10, or Training-ESA (n = 8. They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α, week 10 (reduced dose Darbepoietin-α, and after a 3-week washout period.Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis. The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.ClinicalTrials.gov NCT01320449.

  14. Individualized anemia management reduces hemoglobin variability in hemodialysis patients.

    Science.gov (United States)

    Gaweda, Adam E; Aronoff, George R; Jacobs, Alfred A; Rai, Shesh N; Brier, Michael E

    2014-01-01

    One-size-fits-all protocol-based approaches to anemia management with erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of hemoglobin variability. In this single-center, double-blind, randomized controlled trial, we tested the hypothesis that individualized dosing of ESA improves hemoglobin variability over a standard population-based approach. We enrolled 62 hemodialysis patients and followed them over a 12-month period. Patients were randomly assigned to receive ESA doses guided by the Smart Anemia Manager algorithm (treatment) or by a standard protocol (control). Dose recommendations, performed on a monthly basis, were validated by an expert physician anemia manager. The primary outcome was the percentage of hemoglobin concentrations between 10 and 12 g/dl over the follow-up period. A total of 258 of 356 (72.5%) hemoglobin concentrations were between 10 and 12 g/dl in the treatment group, compared with 208 of 336 (61.9%) in the control group; 42 (11.8%) hemoglobin concentrations were hemoglobin concentrations were >12 g/dl in the treatment group compared with 46 (13.4%) in the control group. The median ESA dosage per patient was 2000 IU/wk in both groups. Five participants received 6 transfusions (21 U) in the treatment group, compared with 8 participants and 13 transfusions (31 U) in the control group. These results suggest that individualized ESA dosing decreases total hemoglobin variability compared with a population protocol-based approach. As hemoglobin levels are declining in hemodialysis patients, decreasing hemoglobin variability may help reduce the risk of transfusions in this population.

  15. Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.

    Science.gov (United States)

    Ohls, Robin K; Cannon, Daniel C; Phillips, John; Caprihan, Arvind; Patel, Shrena; Winter, Sarah; Steffen, Michael; Yeo, Ronald A; Campbell, Richard; Wiedmeier, Susan; Baker, Shawna; Gonzales, Sean; Lowe, Jean

    2016-03-01

    We previously reported improved neurodevelopmental outcomes at 2 years among infants treated with the erythropoiesis-stimulating agents (ESAs) darbepoetin alfa (darbepoetin) or erythropoietin. Here we characterize 4-year outcomes. Former preterm infants randomly assigned to receive darbepoetin (10 μg/kg, once per week), erythropoietin (400 U/kg, 3 times/week), or placebo through 35 weeks' postconceptual age were evaluated at 3.5 to 4 years of age. For comparison, healthy children formerly delivered full term (term controls [TCs]) were also recruited. All participants were assessed by using measures of full-scale IQ (FSIQ) and general language from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, and an overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory. Rates of neurodevelopmental impairment were compared across groups. Multivariate analysis of variance compared children randomly assigned to ESAs (n = 39), placebo (n =14), and TCs (n = 24). FSIQ and performance IQ were significantly higher in the ESA group than in the placebo group (FSIQ: 91.1 ± 17.5 vs 79.2 ± 18.5, P = .036; performance IQ: 93.0 ± 17.0 vs 79.5 ± 19.5, P = .018). Follow-up analyses revealed that the children receiving ESAs performed better than those who received placebo on executive function tasks. The ESA group's performance was below that of TCs, but the results did not reach significance on executive function. The incidence of neurodevelopmental impairment was greater in the placebo group than in the ESA group. ESA-treated infants had better cognitive outcomes and less developmental impairment at 3.5 to 4 years of age compared with placebo-treated infants. ESAs show promise in improving long-term cognitive outcomes of infants born prematurely. Copyright © 2016 by the American Academy of Pediatrics.

  16. Treatment and management of myelofibrosis in the era of JAK inhibitors

    Directory of Open Access Journals (Sweden)

    Keohane C

    2013-08-01

    Full Text Available Clodagh Keohane, Deepti H Radia, Claire N HarrisonDepartment of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UKAbstract: Myelofibrosis (MF can present as a primary disorder or evolve from polycythemia vera (PV or essential thrombocythemia (ET to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT, the use of cytoreductive agents (ie, hydroxyurea, splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs, androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.Keywords: myelofibrosis, ruxolitinib, JAK inhibitor

  17. Selectivity of beta-adrenergic stimulating and blocking agents.

    Science.gov (United States)

    Löfdahl, C G; Svedmyr, N

    1984-01-01

    Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

  18. [MAXIMUM SINGLE DOSE OF COLLOIDAL SILVER NEGATIVELY AFFECTS ERYTHROPOIESIS IN VITRO].

    Science.gov (United States)

    Tishevskayal, N V; Zakharovl, Y M; Bolotovl, A A; Arkhipenko, Yu V; Sazontova, T G

    2015-01-01

    Erythroblastic islets (EI) of rat bone marrow were cultured for 24 h in the presence of silver nanoparticles (1.07 · 10(-4) mg/ml; 1.07 · 10(-3) mg/ml; and 1.07 · 10(-2) mg/mL). The colloidal silver at 1.07 · 10(-3) mg/ml concentration inhibited the formation of new Elby disrupting contacts of bone marrow macrophages with CFU-E (erythropoiesis de novo) by 65.3% (p Colloidal silver nanoparticles suppressed the reconstruction of erythropoiesis and inhibited the formation of new EI by disrupting contacts of CFU-E and central macrophages with matured erythroidal "crown" (erythropoiesis de repeto). The colloidal silver concentration of 1.07 · 10(-3) mg/ml in the culture medium also reduced the number of self-reconstructing EI by 67.5% (p colloidal silver reduced this value by 93.7% (p Silver nanoparticles retarded maturation of erythroid cells at the stage of oxiphylic normoblast denucleation: 1.07 · 10(-3) mg/ml colloidal silver increased the number of mature El by 53% (p colloidal silver in concentration equivalent to the maximum single dose is related to the effect of silver nanoparticles rather than glycerol present in the colloidal suspension.

  19. MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver

    DEFF Research Database (Denmark)

    Bonnesen, Barbara; Ørskov, Cathrine; Rasmussen, Susanne

    2005-01-01

    for MEKK1 in definitive mouse erythropoiesis. Although Mekk1(DeltaKD) mice are alive and fertile on a 129 x C57/BL6 background, the frequency of Mekk1(DeltaKD) embryos that develop past embryonic day (E) 14.5 is dramatically reduced when backcrossed into the C57/BL6 background. At E13.5, Mekk1(Delta......KD) embryos have normal morphology but are anemic due to failure of definitive erythropoiesis. When Mekk1(DeltaKD) fetal liver cells were transferred to lethally irradiated wild-type hosts, mature red blood cells were generated from the mutant cells, suggesting that MEKK1 functions in a non......-cell-autonomous manner. Based on immunohistochemical and hemoglobin chain transcription analysis, we propose that the failure of definitive erythropoiesis is due to a deficiency in enucleation activity caused by insufficient macrophage-mediated nuclear DNA destruction....

  20. Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

    Science.gov (United States)

    Jones, Emma; Pasricha, Sant-Rayn; Allen, Angela; Evans, Patricia; Fisher, Chris A.; Wray, Katherine; Premawardhena, Anuja; Bandara, Dyananda; Perera, Ashok; Webster, Craig; Sturges, Pamela; Olivieri, Nancy F.; St. Pierre, Timothy; Armitage, Andrew E.; Porter, John B.; Weatherall, David J.

    2015-01-01

    Hemoglobin E (HbE) β-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE β-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE β-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, β-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE β-thalassemia and indicates that the epidemiology of β-thalassemia trait requires consideration when planning public health iron interventions. PMID:25519750

  1. Bench to Bedside: Future Therapies For Treatment Of Anemia In Patients With Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    KM Murali

    2017-10-01

    Full Text Available The link between chronic kidney disease (CKD and anemia has been known for over 180 years ever since it was highlighted by the legendary Richard Bright. The key etiological factors responsible for anemia due to renal disease were identified in the 1950s as relative deficiency of erythropoietin and reduced red cell survival as well as abnormalities in iron metabolism. This knowledge was not translated to therapeutics for the next three decades and red cell transfusions were the main-stay of treatment of renal anemia till recombinant human erythropoietin (rHuEPO was introduced in the 1980s. Recurrent transfusions, in addition to causing HLA sensitization, frequently resulted in iron overload with subsequent parenchymal iron deposition and organ dysfunction - a well-known scenario in the pre-erythropoetin era and use of iron chelation therapy was a feasible therapeutic option in long-term dialysis patients. This situation changed dramatically with the widespread clinical use of erythropoiesis stimulating agents (ESA, and polar opposite to the iron overload problems, most patient on erythropoietin therapy required oral or parenteral iron supplements to replenish iron stores for optimal erythropoiesis. Over the last three decades developments in molecular engineering lead to the modification of the original rHuEPO to longer acting analogues such as darbepoetin (Aranesp ® and methoxy polyethylene glycol-epoetin beta (Mircera ® and a raft of EPO biosimilars. In India, where the cost of medications constrains the universal access to ESA therapy, biosimilar erythropoetins offer a relative advantage in that they cost less than half the price of the premium brands. Nevertheless, the progress in clinically prescribed ESA therapy since the discovery of rHuEPO has resulted from modest modification of existing knowledge rather than a revolutionary break from convention. Over the last few years newer molecules capable of revolutionizing the therapy of renal

  2. Ginger Stimulates Hematopoiesis via Bmp Pathway in Zebrafish

    Science.gov (United States)

    Ferri-Lagneau, Karine F.; Moshal, Karni S.; Grimes, Matthew; Zahora, Braden; Lv, Lishuang; Sang, Shengmin; Leung, TinChung

    2012-01-01

    Background Anemia is a hematologic disorder with decreased number of erythrocytes. Erythropoiesis, the process by which red blood cells differentiate, are conserved in humans, mice and zebrafish. The only known agents available to treat pathological anemia are erythropoietin and its biologic derivatives. However, erythropoietin therapy elicits unwanted side-effects, high cost and intravenous or subcutaneous injection, warranting the development of a more cost effective and non-peptide alternative. Ginger (Zingiber officinale) has been widely used in traditional medicine; however, to date there is no scientific research documenting the potential of ginger to stimulate hematopoiesis. Methodology/Principal Findings Here, we utilized gata1:dsRed transgenic zebrafish embryos to investigate the effect of ginger extract on hematopoiesis in vivo and we identified its bioactive component, 10-gingerol. We confirmed that ginger and 10-gingerol promote the expression of gata1 in erythroid cells and increase the expression of hematopoietic progenitor markers cmyb and scl. We also demonstrated that ginger and 10-gingerol can promote the hematopoietic recovery from acute hemolytic anemia in zebrafish, by quantifying the number of circulating erythroid cells in the dorsal aorta using video microscopy. We found that ginger and 10-gingerol treatment during gastrulation results in an increase of bmp2b and bmp7a expression, and their downstream effectors, gata2 and eve1. At later stages ginger and 10-gingerol can induce bmp2b/7a, cmyb, scl and lmo2 expression in the caudal hematopoietic tissue area. We further confirmed that Bmp/Smad pathway mediates this hematopoiesis promoting effect of ginger by using the Bmp-activated Bmp type I receptor kinase inhibitors dorsomorphin, LND193189 and DMH1. Conclusions/Significance Our study provides a strong foundation to further evaluate the molecular mechanism of ginger and its bioactive components during hematopoiesis and to investigate their

  3. SPICE for ESA Planetary Missions

    Science.gov (United States)

    Costa, M.

    2018-04-01

    The ESA SPICE Service leads the SPICE operations for ESA missions and is responsible for the generation of the SPICE Kernel Dataset for ESA missions. This contribution will describe the status of these datasets and outline the future developments.

  4. Living high-training low: effect on erythropoiesis and maximal aerobic performance in elite Nordic skiers

    DEFF Research Database (Denmark)

    Robach, P.; Schmitt, L.; Brugniaux, J.V.

    2006-01-01

    The "living high-training low" model (Hi-Lo) may improve aerobic performance in athletes, and the main mechanism of this improvement is thought to be augmented erythropoiesis. A positive effect of Hi-Lo has been demonstrated previously by using altitudes of 2,000-3,000 m. Since the rate...... of erythropoiesis is altitude-dependent, we tested whether a higher altitude (3,500 m) during Hi-Lo increases erythropoiesis and maximal aerobic performance. Nordic skiers trained for 18 days at 1,200 m, while sleeping at 1,200 m in ambient air (control group, n = 5) or in hypoxic rooms (Hi-Lo, n = 6; 3 x 6 days......(2max)), respectively. Erythropoietin and soluble transferrin receptor responses were higher during Hi-Lo, whereas reticulocytes did not change. In POST (vs. before): hematological parameters were similar to basal levels, as well as red blood cell volume, being 2.68 +/- 0.83 l (vs. 2.64+/-0.54 l...

  5. Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response

    Directory of Open Access Journals (Sweden)

    Vrushali A. Pathak

    2016-01-01

    Full Text Available Anemia is the primary clinical manifestation of malarial infections and is responsible for the substantial rate of morbidity. The pathophysiology discussed till now catalogued several causes for malarial anemia among which ineffective erythropoiesis being remarkable one occurs silently in the bone marrow. A systematic literature search was performed and summarized information on erythropoietic response upon malaria infection and the factors responsible for the same. This review summarizes the clinical and experimental studies on patients, mouse models, and in vitro cell cultures reporting erythropoietic changes upon malaria infection as well as factors accountable for the same. Inadequate erythropoietic response during malaria infection may be the collective effect of various mediators generated by host immune response as well as parasite metabolites. The interplay between various modulators causing the pathophysiology needs to be explored further. Globin gene expression profiling upon malaria infection should also be looked into as abnormal production of globin chains could be a possible contributor to ineffective erythropoiesis.

  6. Methoxy polyethylene glycol-epoetin beta for the treatment of anemia associated with chronic renal failure.

    Science.gov (United States)

    Schmid, Holger

    2016-01-01

    Since more than two decades erythropoiesis-stimulating agents are the main pillar for treatment of anemia associated with chronic kidney disease. Methoxy polyethylene glycol-epoetin beta (MPG-EPO), also called continuous erythropoietin receptor activator, is the longest acting erythropoiesis-stimulating agent currently available. MPG-EPO is characterized by an elimination half-life of approximately 137 h and offers extended dosing intervals up to 4 weeks. Numerous phase I/II studies and a comprehensive clinical phase III program demonstrated the feasibility of MPG-EPO therapy for anemia correction and maintenance of stable hemoglobin levels in adult chronic kidney disease patients. Due to patent disputes MPG-EPO was only available outside the US market so far. In view of a prevailing US market introduction, this review focuses on efficacy and safety data from pivotal trials, summarizes recent clinical research and finally tries to substantiate potential benefits associated with the use of this anti-anemic drug.

  7. CERN and ESA: fundamentally contrasting organisations?

    International Nuclear Information System (INIS)

    Bowell, Valerie

    1988-01-01

    The paper concerns the European Organisation for Nuclear Research (CERN) and the European Space Agency (ESA), and questions whether the United Kingdom (U.K.) will continue as a full member of these two organisations. A description is given of the establishment of these institutions, their collaboration and their activities. The effect of the U.K.'s financial difficulties on both CERN and ESA programmes is discussed. Figures are given on the actual cost to the U.K. of CERN and ESA, and also the CERN and ESA subscriptions as a percentage of total spending on particle physics and astronomy, for the period 1980-8. The U.K. committment to the ESA and CERN programmes are both described. (U.K.)

  8. ESA Earth Observation Ground Segment Evolution Strategy

    Science.gov (United States)

    Benveniste, J.; Albani, M.; Laur, H.

    2016-12-01

    One of the key elements driving the evolution of EO Ground Segments, in particular in Europe, has been to enable the creation of added value from EO data and products. This requires the ability to constantly adapt and improve the service to a user base expanding far beyond the `traditional' EO user community of remote sensing specialists. Citizen scientists, the general public, media and educational actors form another user group that is expected to grow. Technological advances, Open Data policies, including those implemented by ESA and the EU, as well as an increasing number of satellites in operations (e.g. Copernicus Sentinels) have led to an enormous increase in available data volumes. At the same time, even with modern network and data handling services, fewer users can afford to bulk-download and consider all potentially relevant data and associated knowledge. The "EO Innovation Europe" concept is being implemented in Europe in coordination between the European Commission, ESA and other European Space Agencies, and industry. This concept is encapsulated in the main ideas of "Bringing the User to the Data" and "Connecting the Users" to complement the traditional one-to-one "data delivery" approach of the past. Both ideas are aiming to better "empower the users" and to create a "sustainable system of interconnected EO Exploitation Platforms", with the objective to enable large scale exploitation of European EO data assets for stimulating innovation and to maximize their impact. These interoperable/interconnected platforms are virtual environments in which the users - individually or collaboratively - have access to the required data sources and processing tools, as opposed to downloading and handling the data `at home'. EO-Innovation Europe has been structured around three elements: an enabling element (acting as a back office), a stimulating element and an outreach element (acting as a front office). Within the enabling element, a "mutualisation" of efforts

  9. Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice

    Directory of Open Access Journals (Sweden)

    Susann Rahmig

    2016-10-01

    Full Text Available Human erythro-megakaryopoiesis does not occur in humanized mouse models, preventing the in vivo analysis of human hematopoietic stem cell (HSC differentiation into these lineages in a surrogate host. Here we show that stably engrafted KIT-deficient NOD/SCID Il2rg−/− KitW41/W41 (NSGW41 mice support much improved human erythropoiesis and platelet formation compared with irradiated NSG recipients. Considerable numbers of human erythroblasts and mature thrombocytes are present in the bone marrow and blood, respectively. Morphology, composition, and enucleation capacity of de novo generated human erythroblasts in NSGW41 mice are comparable with those in human bone marrow. Overexpression of human erythropoietin showed no further improvement in human erythrocyte output, but depletion of macrophages led to the appearance of human erythrocytes in the blood. Human erythropoiesis up to normoblasts and platelet formation is fully supported in NSGW41 mice, allowing the analysis of human HSC differentiation into these lineages, the exploration of certain pathophysiologies, and the evaluation of gene therapeutic approaches.

  10. Erythropoiesis in the aged mouse. II. Response to stimulation in vitro

    International Nuclear Information System (INIS)

    Udupa, K.B.; Lipschitz, D.A.

    1984-01-01

    In this study, in vitro evidence is presented that erythropoietic precursors in aged mice respond less to stimulation by erythropoietin than do precursors in young mice. The effect of age on proliferation of differentiated erythroid cells from the marrow of young and old mice was examined in liquid culture to which increasing concentrations of erythropoietin were added. Cellular proliferation was measured indirectly by 59 Fe incorporation into heme and directly as tritiated thymidine incorporation into DNA. The number of normoblasts remaining in culture with and without the addition of erythropoietin was also measured. In each case, cellular proliferation was significantly lower in marrow in old than in young mice. In contrast, CFU-E colonies cultured with increasing doses of erythropoietin were similar in young and old animals. These findings indicate that aging causes a reduction in the proliferative response of differentiated erythroid cells. Failure of these cells to respond to stimulation is the likely mechanism for the reduced erythropoietic proliferative capacity found in aged animals

  11. Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation.

    Science.gov (United States)

    Chennupati, Vijaykumar; Veiga, Diogo Ft; Maslowski, Kendle M; Andina, Nicola; Tardivel, Aubry; Yu, Eric Chi-Wang; Stilinovic, Martina; Simillion, Cedric; Duchosal, Michel A; Quadroni, Manfredo; Roberts, Irene; Sankaran, Vijay G; MacDonald, H Robson; Fasel, Nicolas; Angelillo-Scherrer, Anne; Schneider, Pascal; Hoang, Trang; Allam, Ramanjaneyulu

    2018-04-02

    Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor 1 (RNH1) is a ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases. Here, we report that RNH1 binds to ribosomes and regulates erythropoiesis by controlling translation of the erythroid transcription factor GATA1. Rnh1-deficient mice die between embryonic days E8.5 and E10 due to impaired production of mature erythroid cells from progenitor cells. In Rnh1-deficient embryos, mRNA levels of Gata1 are normal, but GATA1 protein levels are decreased. At the molecular level, we found that RNH1 binds to the 40S subunit of ribosomes and facilitates polysome formation on Gata1 mRNA to confer transcript-specific translation. Further, RNH1 knockdown in human CD34+ progenitor cells decreased erythroid differentiation without affecting myelopoiesis. Our results reveal an unsuspected role for RNH1 in the control of GATA1 mRNA translation and erythropoiesis.

  12. Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial.

    Science.gov (United States)

    Forni, Valentina; Bianchi, Giorgia; Ogna, Adam; Salvadé, Igor; Vuistiner, Philippe; Burnier, Michel; Gabutti, Luca

    2013-07-22

    In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients. The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference. No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa. The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy

  13. Friend of GATA (FOG) interacts with the nucleosome remodeling and deacetylase complex (NuRD) to support primitive erythropoiesis in Xenopus laevis.

    Science.gov (United States)

    Mimoto, Mizuho S; Christian, Jan L

    2012-01-01

    Friend of GATA (FOG) plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC) development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD), but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.

  14. 29 CFR 42.9 - Farm Labor Specialist (ESA).

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Farm Labor Specialist (ESA). 42.9 Section 42.9 Labor Office of the Secretary of Labor COORDINATED ENFORCEMENT § 42.9 Farm Labor Specialist (ESA). (a) The Assistant Secretary for ESA shall designate ESA Compliance Officers as Farm Labor Specialists (Specialists...

  15. From the Cradle to the Grave: The Role of Macrophages in erythropoiesis and erythrophagocytosis

    NARCIS (Netherlands)

    Klei, Thomas R. L.; Meinderts, Sanne M.; van den Berg, Timo K.; van Bruggen, Robin

    2017-01-01

    Erythropoiesis is a highly regulated process where sequential events ensure the proper differentiation of hematopoietic stem cells into, ultimately, red blood cells (RBCs). Macrophages in the bone marrow play an important role in hematopoiesis by providing signals that induce differentiation and

  16. Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients.

    Science.gov (United States)

    Locatelli, Francesco; Villa, Giuseppe; Messa, Piergiorgio; Filippini, Armando; Cannella, Giuseppe; De Ferrari, Giacomo; Naso, Agostino; Rossi, Egidio; Formica, Marco; Lombardi, Luigi; Rotolo, Ugo; Conte, Feruccio

    2008-01-01

    Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (phemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.

  17. Friend of GATA (FOG interacts with the nucleosome remodeling and deacetylase complex (NuRD to support primitive erythropoiesis in Xenopus laevis.

    Directory of Open Access Journals (Sweden)

    Mizuho S Mimoto

    Full Text Available Friend of GATA (FOG plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD, but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.

  18. Association Between Changes in CMS Reimbursement Policy and Drug Labels for Erythrocyte-Stimulating Agents With Outcomes for Older Patients Undergoing Hemodialysis Covered by Fee-for-Service Medicare.

    Science.gov (United States)

    Wang, Cunlin; Kane, Robert; Levenson, Mark; Kelman, Jeffrey; Wernecke, Michael; Lee, Joo-Yeon; Kozlowski, Steven; Dekmezian, Carmen; Zhang, Zhiwei; Thompson, Aliza; Smith, Kimberly; Wu, Yu-Te; Wei, Yuqin; Chillarige, Yoganand; Ryan, Qin; Worrall, Chris; MaCurdy, Thomas E; Graham, David J

    2016-12-01

    In 2011, the US Centers for Medicare & Medicaid Services (CMS) changed its reimbursement policy for hemodialysis to a bundled comprehensive payment system that included the cost of erythrocyte-stimulating agents (ESAs). Also in 2011, the US Food and Drug Administration revised the drug label for ESAs, recommending more conservative dosing in patients with chronic kidney disease. In response to concerns that these measures could have adverse effects on patient care and outcomes, the CMS and the FDA initiated a collaboration to assess the effect. To assess the effects of the changes in reimbursement policy and the ESA drug label on patients who underwent incident hemodialysis. For this retrospective cohort study, patients 66 years or older who had undergone incident hemodialysis, and were enrolled in Medicare parts A, B, or D for at least 12 months prior to hemodialysis initiation between January 1, 2008, and December 31, 2013, were recruited from hemodialysis centers across the United States. Patients were divided into 2 cohorts based on their date of hemodialysis initiation and followed: January 1, 2008, to December 31, 2009, for the prepolicy cohort and July 1, 2011, to June 30, 2013, for the postpolicy cohort, with the exclusion of January 1, 2010, to June 30, 2011, as a transition period. Changes in CMS reimbursement policy for dialysis and the FDA label for ESAs. Major adverse cardiovascular events (MACEs), including acute myocardial infarction (AMI), stroke, and all-cause mortality; hospitalized congestive heart failure (H-CHF); venous thromboembolism; and red blood cell transfusions. Secondary outcomes included evaluating effects on black and other patient subgroups. Baseline characteristics of the 69 718 incident hemodialysis patients were similar between cohorts. Compared with the prepolicy period, the risk of MACE, death, H-CHF, and venous thromboembolism were similar in the postpolicy period, and the risk of stroke decreased (hazard ratio [HR], 0.77; 95

  19. Sox6 directly silences epsilon globin expression in definitive erythropoiesis.

    Directory of Open Access Journals (Sweden)

    2006-02-01

    Full Text Available Sox6 is a member of the Sox transcription factor family that is defined by the conserved high mobility group (HMG DNA binding domain, first described in the testis determining gene, Sry. Previous studies have suggested that Sox6 plays a role in the development of the central nervous system, cartilage, and muscle. In the Sox6-deficient mouse, p100H, epsilony globin is persistently expressed, and increased numbers of nucleated red cells are present in the fetal circulation. Transfection assays in GM979 (erythroleukemic cells define a 36-base pair region of the epsilony proximal promoter that is critical for Sox6 mediated repression. Electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP assays demonstrate that Sox6 acts as a repressor by directly binding to the epsilony promoter. The normal expression of Sox6 in wild-type fetal liver and the ectopic expression of epsilony in p100H homozygous fetal liver demonstrate that Sox6 functions in definitive erythropoiesis. The present study shows that Sox6 is required for silencing of epsilony globin in definitive erythropoiesis and suggests a role for Sox6 in erythroid cell maturation. Thus, Sox6 regulation of epsilony globin might provide a novel therapeutical target in the treatment of hemoglobinopathies such as sickle cell anemia and thalassemia.

  20. Safety and efficacy of the CD95-ligand inhibitor asunercept in transfusion-dependent patients with low and intermediate risk MDS.

    Science.gov (United States)

    Boch, Tobias; Luft, Thomas; Metzgeroth, Georgia; Mossner, Maximilian; Jann, Johann-Christoph; Nowak, Daniel; Meir, Franziska La; Schumann, Christiane; Klemmer, Jennifer; Brendel, Susanne; Fricke, Harald; Kunz, Claudia; Weiß, Christel; Hofmann, Wolf-Karsten; Nolte, Florian

    2018-05-01

    In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs). Copyright © 2018. Published by Elsevier Ltd.

  1. Biomarkers of Hypochromia: The Contemporary Assessment of Iron Status and Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Eloísa Urrechaga

    2013-01-01

    Full Text Available Iron status is the result of the balance between the rate of erythropoiesis and the amount of the iron stores. Direct consequence of an imbalance between the erythroid marrow iron requirements and the actual supply is a reduction of red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. The diagnosis of iron deficiency is particularly challenging in patients with acute or chronic inflammatory conditions because most of the biochemical markers for iron metabolism (serum ferritin and transferrin are affected by acute phase reaction. For these reasons, interest has been generated in the use of erythrocyte and reticulocyte parameters, available on the modern hematology analyzers. Reported during blood analysis routinely performed on the instrument, these parameters can assist in early detection of clinical conditions (iron deficiency, absolute, or functional; ineffective erythropoiesis, including iron restricted or thalassemia, without additional cost. Technological progress has meant that in recent years modern analyzers report new parameters that provide further information from the traditional count. Nevertheless these new parameters are exclusive of each manufacturer, and they are patented. This is an update of these new laboratory test biomarkers of hypochromia reported by different manufactures, their meaning, and clinical utility on daily practice.

  2. Garlic accelerates red blood cell turnover and splenic erythropoietic gene expression in mice: evidence for erythropoietin-independent erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Bünyamin Akgül

    2010-12-01

    Full Text Available Garlic (Allium sativum has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic

  3. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  4. ESRD POST-HOSPITALIZATION ANEMIA AND ESA UTILIZATION

    Directory of Open Access Journals (Sweden)

    Alex Yang

    2012-06-01

    The majority of hospitalizations (∼2/3 had considerable post-hosp Hb drops (mean >1g/dL, with >50% permanently reduced. ∼1.5 months were needed to recover Hb, with elevated ESA doses for >2 months. ESA dose was permanently elevated in 27% of hospitalizations that recovered Hb. Strategies to address post-hosp anemia may mitigate the protracted recovery time and increased ESA use. fx1

  5. Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis

    NARCIS (Netherlands)

    von Lindern, M.; Deiner, E. M.; Dolznig, H.; Parren-van Amelsvoort, M.; Hayman, M. J.; Mullner, E. W.; Beug, H.

    2001-01-01

    Primary erythroid progenitors can be expanded by the synergistic action of erythropoietin (Epo), stem cell factor (SCF) and glucocorticoids. While Epo is required for erythropoiesis in general, glucocorticoids and SCF mainly contribute to stress erythropoiesis in hypoxic mice. This ability of normal

  6. ESA Atmospheric Toolbox

    Science.gov (United States)

    Niemeijer, Sander

    2017-04-01

    The ESA Atmospheric Toolbox (BEAT) is one of the ESA Sentinel Toolboxes. It consists of a set of software components to read, analyze, and visualize a wide range of atmospheric data products. In addition to the upcoming Sentinel-5P mission it supports a wide range of other atmospheric data products, including those of previous ESA missions, ESA Third Party missions, Copernicus Atmosphere Monitoring Service (CAMS), ground based data, etc. The toolbox consists of three main components that are called CODA, HARP and VISAN. CODA provides interfaces for direct reading of data from earth observation data files. These interfaces consist of command line applications, libraries, direct interfaces to scientific applications (IDL and MATLAB), and direct interfaces to programming languages (C, Fortran, Python, and Java). CODA provides a single interface to access data in a wide variety of data formats, including ASCII, binary, XML, netCDF, HDF4, HDF5, CDF, GRIB, RINEX, and SP3. HARP is a toolkit for reading, processing and inter-comparing satellite remote sensing data, model data, in-situ data, and ground based remote sensing data. The main goal of HARP is to assist in the inter-comparison of datasets. By appropriately chaining calls to HARP command line tools one can pre-process datasets such that two datasets that need to be compared end up having the same temporal/spatial grid, same data format/structure, and same physical unit. The toolkit comes with its own data format conventions, the HARP format, which is based on netcdf/HDF. Ingestion routines (based on CODA) allow conversion from a wide variety of atmospheric data products to this common format. In addition, the toolbox provides a wide range of operations to perform conversions on the data such as unit conversions, quantity conversions (e.g. number density to volume mixing ratios), regridding, vertical smoothing using averaging kernels, collocation of two datasets, etc. VISAN is a cross-platform visualization and

  7. PLEIOTROPIC EFFECTS OF PARATHYROIDECTOMY AND AGONIST CALCIUM-SENSITIVE RECEPTOR, CINACALCET

    Directory of Open Access Journals (Sweden)

    L. V. Egshatyan

    2013-01-01

    Full Text Available Aim. To evaluate the effect of parathyroidectomy and cinacalcet on anemia, lipid profile and blood pressure (BP in uremic hyperparathyroidism.Material and methods. Uremic patients (n=39 treated with hemodialysis and having secondary hyperparathyroidism were included into the study. Radical parathyroidectomy was performed in 21 patients, 18 patients were treated with cinacalcet. BP measurement, determination of blood levels of albumin, total calcium, phosphorus, total cholesterol (TC, low (LDL and high density lipoproteins, triglycerides, intact parathyroid hormone, and hemoglobin were performed in all patients initially and during treatment. Doses of antihypertensive and erythropoiesis-stimulating agents were also assessed.Results. Calcium-phosphorus metabolism indices improved after 6 months of cinacalcet therapy and parathyroidectomy (p<0.05. BP reduction not requiring antihypertensive drugs dose adjustment was found in patients treated with cinacalcet. Significant BP reduction (p<0.05 was observed after parathyroidectomy and it required antihypertensive drugs cancellation or dose lowering. Cinacalcet therapy and parathyroidectomy led to increase in hemoglobin level by 2.02% (p=0.143 and 7.6% (p=0.029, respectively, as well as reduction in weekly dose of erythropoiesis-stimulating drugs by 2.7% (p=0.875 and 8.9% (p=0.751, respectively. Significant (p<0.05 decrease in LDL (5.6%, and triglycerides (23.7% levels was found in patients treated with cinacalcet. Reduction (p<0.05 in total cholesterol (1.4% and LDL (4.3% levels was observed after parathyroidectomy.Conclusion. The pleiotropic effects (reduction in BP and atherogenic lipids levels, as well as decrease in anemia resistant to the action of erythropoiesis-stimulating agents were found after parathyroidectomy and cinacalcet therapy additionally to calcium-phosphorus metabolism improvement.

  8. The anaemia control model: Does it help nephrologists in therapeutic decision-making in the management of anaemia?

    Science.gov (United States)

    Bucalo, María Laura; Barbieri, Carlo; Roca, Susana; Ion Titapiccolo, Jasmine; Ros Romero, Maria Soledad; Ramos, Rosa; Albaladejo, Mercedes; Manzano, Diana; Mari, Flavio; Molina, Manuel

    2018-06-03

    Anaemia is common in haemodialysis patients and treating it with erythropoiesis-stimulating agents (ESAs) is complex due to many factors. To assess the usefulness of the Anaemia Control Model (ACM) in the treatment of anaemia in haemodialysis. ACM is a software that predicts the optimal dose of darbepoetin and iron sucrose to achieve target haemoglobin (Hb) and ferritin levels, and makes prescription suggestions. Study conducted in dialysis clinics lasting 18months with two intervention phases (IPs) with ACM (IP1, n:213; IP2, n:218) separated by a control phase (CP, n:219). The primary outcome was the percentage of Hb in range and the median dose of ESAs, and the secondary outcomes were transfusion, hospitalisation and cardiovascular events. Clinical and patient analyses were performed. Hb variability was assessed by the standard deviation (SD) of the Hb. We also analysed the patients with most of the suggestions confirmed (ACM compliant group). ACM increased the percentage of Hb in range: 80.9% in IP2, compared with 72.7% in the CP and reduced the intake of darbepoetin (IP1: 20 [70]; CP 30 [80] μg P=0.032) with less Hb fluctuation (0.91±0.49 in the CP to 0.82±0.37g/dl in IP2, P<0.05), improving in the ACM compliant group. The secondary outcomes decreased with the use of ACM. ACM helps to obtain better anaemia results in haemodialysis patients, minimising the risks of treatment with ESAs and reducing costs. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  9. The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

    Science.gov (United States)

    Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

    2014-04-01

    Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

  10. Elements of ESA's policy on space and security

    Science.gov (United States)

    Giannopapa, Christina; Adriaensen, Maarten; Antoni, Ntorina; Schrogl, Kai-Uwe

    2018-06-01

    In the past decade Europe has been facing rising security threats, ranging from climate change, migrations, nearby conflicts and crises, to terrorism. The demand to tackle these critical challenges is increasing in Member States. Space is already contributing, and could further contribute with already existing systems and future ones. The increasing need for security in Europe and for safety and security of Europe's space activities has led to a growing number of activities in ESA in various domains. It has also driven new and strengthened partnerships with security stakeholders in Europe. At the European level, ESA is collaborating closely with the main European institutions dealing with space security. In addition, as an organisation ESA has evolved to conduct security-related projects and programmes and to address the threats to its own activities, thereby securing the investments of the Member States. Over the past years the Agency has set up a comprehensive regulatory framework in order to be able to cope with security related requirements. Over the past years, ESA has increased its exchanges with its Member States. The paper presents main elements of the ESA's policy on space and security. It introduces the current European context for space and security, the European goals in this domain and the specific objectives to which the Agency intends to contribute. Space and security in the ESA context is set out under two components: a) security from space and b) security in space, including the security of ESA's own activities (corporate security and the security of ESA's space missions). Subsequently, ESA's activities are elaborated around these two pillars, composed of different activities conducted in the most appropriate frameworks and in coordination with the relevant stakeholders and shareholders.

  11. Bringing the science of proteins into the realm of organic chemistry: total chemical synthesis of SEP (synthetic erythropoiesis protein).

    Science.gov (United States)

    Kent, Stephen B H

    2013-11-11

    Erythropoietin, commonly known as EPO, is a glycoprotein hormone that stimulates the production of red blood cells. Recombinant EPO has been described as "arguably the most successful drug spawned by the revolution in recombinant DNA technology". Recently, the EPO glycoprotein molecule has re-emerged as a major target of synthetic organic chemistry. In this article I will give an account of an important body of earlier work on the chemical synthesis of a designed EPO analogue that had full biological activity and improved pharmacokinetic properties. The design and synthesis of this "synthetic erythropoiesis protein" was ahead of its time, but has gained new relevance in recent months. Here I will document the story of one of the major accomplishments of synthetic chemistry in a more complete way than is possible in the primary literature, and put the work in its contemporaneous context. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Ulysses - An ESA/NASA cooperative programme

    Science.gov (United States)

    Meeks, W.; Eaton, D.

    1990-01-01

    Cooperation between ESA and NASA is discussed, noting that the Memorandum of Understanding lays the framework for this relationship, defining the responsibilities of ESA and NASA and providing for appointment of leadership and managers for the project. Members of NASA's Jet Propulsion Laboratory and ESA's ESTEC staff have been appointed to leadership positions within the project and ultimate control of the project rests with the Joint Working Group consisting of two project managers and two project scientists, equally representing both organizations. Coordination of time scales and overall mission design is discussed, including launch cooperation, public relations, and funding of scientific investigations such as Ulysses. Practical difficulties of managing an international project are discussed such as differing documentation requirements and communication techniques, and assurance of equality on projects.

  13. Studies on the effects of copper purpurin 18 on erythropoiesis

    International Nuclear Information System (INIS)

    Xang Yingsong; Yang Rujun; Meng Xiangshun; Gao Jianguo; Li Bailong

    1999-01-01

    Attempts were afforded to search for new antiaplastic anemia draws from tetrapyrroles. Observation of the effects of copper purpurin 18, a representative one of the metal tetrapyrroles was synthesized by ours, on erythropoiesis in Kungming mice lethally irradiated. It was shown that copper purpurin 18 preferably increased stem cells (CFU-S) into erythroidprogenitor cells (CFU-E), and increase WBC and nucleated cells of bone marrow significantly in the phase of recover. It suggested that there may be good prospect in developing new drugs for treatment of aplastic anemia with copper purpurin 18, and it was worth to further investigations

  14. ESA innovation rescues Ultraviolet Observatory

    Science.gov (United States)

    1995-10-01

    Astrophysicist Freeman J. Dyson from the Institute for Advanced Studies in Princeton characterizes IUE as "A little half-meter mirror sitting in the sky, unnoticed by the public, pouring out results". By use of the IUE satellite, astronomers obtain access to the ultraviolet radiation of celestial bodies in unique ways not available by any other means, neither from the ground nor by any other spacecraft currently in orbit. IUE serves a wide community of astronomers all over Europe, the United States and many other parts of the world. It allows the acquisition of critical data for fundamental studies of comets and their evaporation when they approach the Sun, of the mechanisms driving the stellar winds which make many stars lose a significant fraction of their mass (before they die slowly as White Dwarfs or in sudden Supernova explosions), as well as in the search to understand the ways in which black holes possibly power the violent nuclei of Active galaxies. One year ago the project was threatened with termination and serious concern was expressed by astronomers about the potential loss of IUE's capabilities, as a result of NASA not continuing to operate the spacecraft. Under the leadership of ESA, the three Agencies involved in the operations of IUE (ESA, NASA and the United Kingdom's Particle Physics and Astronomy Research Council, PPARC), reviewed the operations agreements of the Project. A minor investment allowing the implementation of modern management and engineering techniques as well as a complete revision of the communication infrastructure of the project and continuous improvements in efficiency in the ESA management, also taking advantage of today's technologies, both in computing and communications, have made it possible to continue IUE operations within the financial means available, with ESA taking up most of NASA's share in the operations. According to Dr. Willem Wamsteker, ESA's Dutch IUE Project Scientist, "it was a extremely interesting

  15. Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials.

    Science.gov (United States)

    Locatelli, Francesco; Choukroun, Gabriel; Truman, Matt; Wiggenhauser, Alfons; Fliser, Danilo

    2016-04-01

    Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups. Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (Basel, Switzerland.

  16. The ESA Scientific Exploitation of Operational Missions element

    Science.gov (United States)

    Desnos, Yves-Louis; Regner, Peter; Zehner, Claus; Engdahl, Marcus; Benveniste, Jerome; Delwart, Steven; Gascon, Ferran; Mathieu, Pierre-Philippe; Bojkov, Bojan; Koetz, Benjamin; Arino, Olivier; Donlon, Craig; Davidson, Malcolm; Goryl, Philippe; Foumelis, Michael

    2014-05-01

    The objectives of the ESA Scientific Exploitation of Operational Missions (SEOM) programme element are • to federate, support and expand the research community • to strengthen the leadership of European EO research community • to enable the science community to address new scientific research As a preparation for the SEOM element a series of international science users consultation has been organized by ESA in 2012 and 2013 In particular the ESA Living Planet Symposium was successfully organized in Edinburgh September 2013 and involving 1700 participants from 60 countries. The science users recommendations have been gathered and form the basis for the 2014 SEOM work plan approved by ESA member states. The SEOM element is organized along the following action lines: 1. Developing open-source, multi-mission, scientific toolboxes : the new toolboxes for Sentinel 1/2/3 and 5P will be introduced 2. Research and development studies: the first SEOM studies are being launched such as the INSARAP studies for Sentinel 1 interferometry in orbit demonstration , the IAS study to generate an improved spectroscopic database of the trace gas species CH4, H2O, and CO in the 2.3 μm region and SO2 in the UV region for Sentinel 5 P. In addition larger Sentinels for science call will be tendered in 2014 covering grouped studies for Sentinel 1 Land , Sentinel 1 Ocean , Sentinel 2 Land, Sentinel 3 SAR Altimetry ,Sentinel 3 Ocean color, Sentinel 3 Land and Sentinels Synergy . 3. Science users consultation : the Sentinel 2 for Science workshop is planned from 20 to 22 may 2014 at ESRIN to prepare for scientific exploitation of the Sentinel-2 mission (http://seom.esa.int/S2forScience2014 ) . In addition the FRINGE workshop focusing on scientific explotation of Sentinel1 using SAR interferometry is planned to be held at ESA ESRIN in Q2 2015 4. Training the next generation of European EO scientists on the scientific exploitation of Sentinels data: the Advanced Training course Land

  17. Oral Zinc Supplementation Reduces the Erythropoietin Responsiveness Index in Patients on Hemodialysis

    Directory of Open Access Journals (Sweden)

    Hiroki Kobayashi

    2015-05-01

    Full Text Available Background: In hemodialysis (HD patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI. Methods: Patients on HD with low serum zinc levels (<65 μg/dL were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc (n = 35 and the control group (no supplementation (n = 35 for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units/dry weight (kg/hemoglobin (g/dL. Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

  18. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients

    Science.gov (United States)

    Caceres, Gisela; McGraw, Kathy; Yip, Bon Ham; Pellagatti, Andrea; Johnson, Joseph; Zhang, Ling; Liu, Kenian; Zhang, Lan Min; Fulp, William J.; Lee, Ji-Hyun; Al Ali, Najla H.; Basiorka, Ashley; Smith, Larry J.; Daugherty, F. Joseph; Littleton, Neil; Wells, Richard A.; Sokol, Lubomir; Wei, Sheng; Komrokji, Rami S.; Boultwood, Jacqueline; List, Alan F.

    2013-01-01

    Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS. PMID:24043769

  19. Effect of hepatitis C virus infection on erythropoiesis in patients on hemodialysis

    Directory of Open Access Journals (Sweden)

    Saifan C

    2013-06-01

    Full Text Available Chadi Saifan, Elie El-Charabaty, Morton Kleiner, Suzanne El-SayeghDepartment of Medicine, Division of Nephrology, Staten Island University Hospital, Staten Island, NY, USABackground: Erythropoietin is a hormone that regulates erythropoiesis and is mainly produced by the kidneys. Several animal studies as well as a few case reports and case series have demonstrated that regenerating hepatic tissue can produce more erythropoietin than normal hepatic tissue. The purpose of the study was to examine the difference in hemoglobin and hematocrit levels as well as epoetin dosage in patients on hemodialysis with and without hepatitis C (HCV.Methods: A retrospective chart review was performed. Seventy-six patients were included in the study (19 with HCV and 57 without HCV at a ratio of 1:3. Exclusion criteria were a history of gastrointestinal bleeding or blood transfusion over the previous six months, polycystic kidney disease, and pregnancy. Variables examined included gender, age, duration of hemodialysis, hemoglobin, hematocrit, epoetin dose, aspartate transaminase, and ferritin levels over a three-month period.Results: The patients were divided into two groups. The first consisted of patients with HCV on hemodialysis and the second of patients on hemodialysis without HCV. Mean hemoglobin was 12.6 ± 1.2 g/dL for the HCV-positive group and 11.9 ± 1.1 g/dL for the HCV-negative group. The difference was statistically significant (P = 0.03. Mean hematocrit was higher in the HCV-positive group, but was not significantly different at 39.08% ± 4.06% versus 37.43% ± 3.4% in the HCV-negative group (t-test, P = 0.11. Further, the HCV-positive group required less epoetin, but this was not significantly different from that required in the HCV-negative group at 6258 ± 5208 IU versus 7596 ± 7056 IU, respectively (t-test, P = 0.38.Conclusion: In our study, patients with HCV infection were found to have higher hemoglobin and hematocrit levels and lower epoetin

  20. Medication-use evaluation with a Web application.

    Science.gov (United States)

    Burk, Muriel; Moore, Von; Glassman, Peter; Good, Chester B; Emmendorfer, Thomas; Leadholm, Thomas C; Cunningham, Francesca

    2013-12-15

    A Web-based application for coordinating medication-use evaluation (MUE) initiatives within the Veterans Affairs (VA) health care system is described. The MUE Tracker (MUET) software program was created to improve VA's ability to conduct national medication-related interventions throughout its network of 147 medical centers. MUET initiatives are centrally coordinated by the VA Center for Medication Safety (VAMedSAFE), which monitors the agency's integrated databases for indications of suboptimal prescribing or drug therapy monitoring and adverse treatment outcomes. When a pharmacovigilance signal is detected, VAMedSAFE identifies "trigger groups" of at-risk veterans and uploads patient lists to the secure MUET application, where locally designated personnel (typically pharmacists) can access and use the data to target risk-reduction efforts. Local data on patient-specific interventions are stored in a centralized database and regularly updated to enable tracking and reporting for surveillance and quality-improvement purposes; aggregated data can be further analyzed for provider education and benchmarking. In a three-year pilot project, the MUET program was found effective in promoting improved prescribing of erythropoiesis-stimulating agents (ESAs) and enhanced laboratory monitoring of ESA-treated patients in all specified trigger groups. The MUET initiative has since been expanded to target other high-risk drugs, and efforts are underway to refine the tool for broader utility. The MUET application has enabled the increased standardization of medication safety initiatives across the VA system and may serve as a useful model for the development of pharmacovigilance tools by other large integrated health care systems.

  1. Blood doping at the Olympic Games.

    Science.gov (United States)

    Fitch, Kenneth D

    2017-11-01

    The objective of this paper was to review our knowledge of athletes who have, are believed to have or have attempted to engage in blood doping to enhance their performance at an Olympic Games. The paper focused on the Games from Munich 1972 to London 2012 and the author had a medical role at each of the Olympics that is discussed. The study revealed that Olympic athletes have benefitted from manipulating their blood by re-infusion of autologous or infusion of homologous blood and by administering erythropoiesis stimulating agents, notably the three generations of erythropoietins. Fifty seven athletes have been sanctioned with 12 athletes forfeiting 17 Olympic medals including 12 gold medals because of blood doping. Until 1986, the infusion of blood was not prohibited in sport but considered unethical. Erythropoietin was prohibited by the International Olympic Committee's Medical Commission in 1990. There has been a change as to how Olympic athletes have enhanced performance by blood doping, commencing with blood infusion and later administering erythropoiesis stimulating agents and significant advances have occurred in detecting such misuse. Currently, the hematological component of World Anti-Doping Agency's athlete biological passport is an important but not infallible mechanism to identify athletes who cheat by blood doping.

  2. Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

    Directory of Open Access Journals (Sweden)

    William P Lafuse

    Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

  3. NASA and ESA Collaboration on Hexavalent Chrome Free Coatings

    Science.gov (United States)

    Greene, Brian

    2017-01-01

    Presentation on the NASA and ESA Collaboration on Hexavalent Chrome Free Coatings project. Project is in response to a Memorandum of Understanding between NASA and ESA Concerning Cooperation in the Field of Space Transportation - signed September 11, 2009. The National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) have expressed mutual interest in pursuing cooperation in the areas of evaluating hexavalent chrome-free coatings, environmentally-preferable coatings for maintenance of launch facilities and ground support equipment, citric acid as an alternative to nitric acid for passivation of stainless steel alloys.

  4. Implementation of an ESA delta-DOR capability

    Science.gov (United States)

    James, Nick; Abello, Ricard; Lanucara, Marco; Mercolino, Mattia; Maddè, Roberto

    2009-06-01

    This paper describes the implementation of delta-DOR (delta-differential one-way ranging) receivers within the ESA Deep Space ground station network. Delta-DOR provides very accurate plane-of-sky measurements of spacecraft position which complement existing line-of-sight ranging and Doppler measurements. We discuss how this technique has been adapted and implemented at the two ESA deep-space ground stations using existing equipment and infrastructure. These new capabilities were added by writing new software modules for the standard ESA digital receiver (the intermediate frequency modem system—IFMS). With these upgrades the receiver has the ability to record accurately timetagged signals from up to eight IF sub-channels. These sub-channels can have bandwidths of 50 kHz-2 MHz with a sample quantization of 1-16 bits per component. The IF samples are stored locally for subsequent retrieval over a WAN by the correlator facility at ESOC.

  5. Practical Approaches to the Use of Lenalidomide in Multiple Myeloma: A Canadian Consensus

    Directory of Open Access Journals (Sweden)

    Donna Reece

    2012-01-01

    Full Text Available In Canada, lenalidomide combined with dexamethasone (Len/Dex is approved for use in relapsed or refractory multiple myeloma (RRMM. Our expert panel sought to provide an up-to-date practical guide on the use of lenalidomide in the managing RRMM within the Canadian clinical setting, including management of common adverse events (AEs. The panel concluded that safe, effective administration of Len/Dex treatment involves the following steps: (1 lenalidomide dose adjustment based on creatinine clearance and the extent of neutropenia or thrombocytopenia, (2 dexamethasone administered at 20–40 mg/week, and (3 continuation of treatment until disease progression or until toxicity persists despite dose reduction. Based on available evidence, the following precautions should reduce the risk of common Len/Dex AEs: (1 all patients treated with Len/Dex should receive thromboprophylaxis, (2 erythropoiesis-stimulating agents (ESAs should be used cautiously, and (3 females of child-bearing potential and males in contact with such females must use multiple contraception methods. Finally, while Len/Dex can be administered irrespective of prior therapy and in all prognostic subsets, patients with chromosomal deletion 17(p13 have less favorable outcomes with all treatments, including Len/Dex. New directions for the use of lenalidomide in RRMM are also considered.

  6. ESA is now a major player in global space science

    Science.gov (United States)

    1997-07-01

    * Results from the star-fixing satellite Hipparcos, released this summer to the world's astronomers, give the positions and motions of 118,000 stars a hundred times more accurately than ever before. * Every day the Infrared Space Observatory, ISO, examines 45 cosmic objects on average at many different wavelengths never observable before, giving fresh insights into cosmic history and chemistry. * Invaluable new knowledge of the Sun comes from SOHO, the Solar and Heliospheric Observatory, which is the first spacecraft able to observe the Sun's deep interior as well as its stormy surface and atmosphere. Besides these missions making present headlines, several other spacecraft are helping to fulfil ESA's scientific objectives. * 2 - * The launch in October 1997 of ESA's probe Huygens, aboard the Cassini spacecraft bound for Saturn, foreshadows a breakthrough in planetary science in 2004. That is when Huygens will carry its scientific instruments into the unique and puzzling atmosphere of Saturn's moon Titan. * Ulysses, also built in Europe, is exploring hitherto unknown regions of space, after making the first-ever visit to the Sun's polar regions in 1994-95. It will return to the Sun in 2000-2001, to observe the effects of the climax of solar activity due at that time. * The Cluster 2 mission, announced in April 1997 and to be launched in 2000, will explore the Earth's space environment far more throughly than ever before. ESA's decision to replace the four Cluster satellites lost in a launch accident in 1996 ensures that Europe will continue as the leader in solar-terrestrial research in space. * An example of the three unique 58-mirror X-ray telescopes for the XMM mission was unveiled for the press in May 1997. When it goes into orbit in 1999 XMM will make, in seconds, observations of cosmic objects that took hours with previous X-ray astronomy missions. * The Hubble Space Telescope, in which ESA is a partner, continues to deliver the sharpest pictures of the

  7. Investigation of high-energy sources in optical light by ESA Gaia

    Czech Academy of Sciences Publication Activity Database

    Hudec, R.; Šimon, Vojtěch; Hudec, L.; Hudcová, Věra

    2010-01-01

    Roč. 81, č. 1 (2010), s. 476-481 ISSN 0037-8720. [Multifrequency behaviour of high energy cosmic sources. Vulcano, 25.05.2009-30.05. 2009] R&D Projects: GA ČR GA205/08/1207 Grant - others:ESA(XE) ESA- PECS project No. 98058; GA ČR(CZ) GA102/09/0997; GA MŠk(CZ) ME09027; ESA(XE) ESA- PECS project No. 98023 Institutional research plan: CEZ:AV0Z10030501 Keywords : high-energy sources * cataclysmic variables * low-dispersion spectra Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  8. ESA's tools for internal charging

    International Nuclear Information System (INIS)

    Soerensen, J.; Rodgers, D.J.; Ryden, K.A.; Latham, P.M.; Wrenn, G.L.; Levy, L.; Panabiere, G.

    1999-01-01

    Electrostatic discharges, caused by bulk charging of spacecraft insulating materials, are a major cause of satellite anomalies. This is a presentation of ESA's tools to assess whether a given structure is liable to experience electrostatic discharges. (authors)

  9. ESA-NASA collaboration in support of CryoSat-2

    Science.gov (United States)

    Casal, T. G.; Davidson, M.; Schuettemeyer, D.; Perrera, A.; Armitage, T.; Bianchi, R.; Parrinello, T.; Fornari, M.; Skourup, H.

    2012-12-01

    In the framework of its Earth Observation Programmes the European Space Agency (ESA) carries out groundbased and airborne campaigns to support geophysical algorithm development, calibration/validation, simulation of future spaceborne earth observation missions, and applications development related to land, oceans and atmosphere. ESA has been conducting airborne and ground measurements campaigns since 1981 by deploying a broad range of active and passive instrumentation in both the optical and microwave regions of the electromagnetic spectrum such as lidars, limb/nadir sounding interferometers/spectrometers, high-resolution spectral imagers, advanced synthetic aperture radars, altimeters and radiometers. These campaigns take place inside and outside Europe in collaboration with national research organisations in the ESA member states as well as with international organisations harmonising European campaign activities. For the different activities a rich variety of datasets has been recorded, are archived and users can access campaign data through the EOPI web portal [http://eopi.esa.int]. CryoSat-2, ESA's third Earth Explorer, is Europe's first mission dedicated to monitoring Earth's ice fields. The satellite carries a sophisticated radar altimeter that can measure the thickness of sea ice down to centimetres and also monitor changes in ice sheets, particularly around the edges where icebergs are calved from the vast ice sheets that cover Greenland and Antarctica. On order to gather data to help ensure the accuracy of ESA's ice mission, in yet another remarkable collaborative effort, ESA and NASA met up over the Arctic Ocean in April 2012 to perform some carefully coordinated flights directly under CryoSat orbiting above. The aim of this large-scale campaign was to record sea-ice thickness and conditions of the ice exactly along the line traced by ESA's CryoSat satellite orbiting high above. A range of sensors installed on the different aircraft was used to gather

  10. Resolving the Framework Position of Organic Structure-Directing Agents in Hierarchical Zeolites via Polarized Stimulated Raman Scattering.

    Science.gov (United States)

    Fleury, Guillaume; Steele, Julian A; Gerber, Iann C; Jolibois, F; Puech, P; Muraoka, Koki; Keoh, Sye Hoe; Chaikittisilp, Watcharop; Okubo, Tatsuya; Roeffaers, Maarten B J

    2018-04-05

    The direct synthesis of hierarchically intergrown silicalite-1 can be achieved using a specific diquaternary ammonium agent. However, the location of these molecules in the zeolite framework, which is critical to understand the formation of the material, remains unclear. Where traditional characterization tools have previously failed, herein we use polarized stimulated Raman scattering (SRS) microscopy to resolve molecular organization inside few-micron-sized crystals. Through a combination of experiment and first-principles calculations, our investigation reveals the preferential location of the templating agent inside the linear pores of the MFI framework. Besides illustrating the attractiveness of SRS microscopy in the field of material science to study and spatially resolve local molecular distribution as well as orientation, these results can be exploited in the design of new templating agents for the preparation of hierarchical zeolites.

  11. Photometry and Low Dispersion Spectroscopy with ESA Gaia

    Czech Academy of Sciences Publication Activity Database

    Hudec, R.; Šimon, Vojtěch; Hudec, L.

    2010-01-01

    Roč. 2010, - (2010), 781421/1-781421/7 ISSN 1687-7969 R&D Projects: GA ČR GA205/08/1207 Grant - others:GA AV ČR(CZ) GA102/09/0997; GA MŠk(CZ) ME09027; ESA(XE) ESA- PECS project No. Institutional research plan: CEZ:AV0Z10030501 Keywords : high-energy sources * cataclysmic variables * low-dispersion spectra Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  12. The ESA's Space Trajectory Analysis software suite

    Science.gov (United States)

    Ortega, Guillermo

    The European Space Agency (ESA) initiated in 2005 an internal activity to develop an open source software suite involving university science departments and research institutions all over the world. This project is called the "Space Trajectory Analysis" or STA. This article describes the birth of STA and its present configuration. One of the STA aims is to promote the exchange of technical ideas, and raise knowledge and competence in the areas of applied mathematics, space engineering, and informatics at University level. Conceived as a research and education tool to support the analysis phase of a space mission, STA is able to visualize a wide range of space trajectories. These include among others ascent, re-entry, descent and landing trajectories, orbits around planets and moons, interplanetary trajectories, rendezvous trajectories, etc. The article explains that STA project is an original idea of the Technical Directorate of ESA. It was born in August 2005 to provide a framework in astrodynamics research at University level. As research and education software applicable to Academia, a number of Universities support this development by joining ESA in leading the development. ESA and Universities partnership are expressed in the STA Steering Board. Together with ESA, each University has a chair in the board whose tasks are develop, control, promote, maintain, and expand the software suite. The article describes that STA provides calculations in the fields of spacecraft tracking, attitude analysis, coverage and visibility analysis, orbit determination, position and velocity of solar system bodies, etc. STA implements the concept of "space scenario" composed of Solar system bodies, spacecraft, ground stations, pads, etc. It is able to propagate the orbit of a spacecraft where orbital propagators are included. STA is able to compute communication links between objects of a scenario (coverage, line of sight), and to represent the trajectory computations and

  13. Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial
.

    Science.gov (United States)

    Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Wyck, David Van; Meier, Yvonne; Larroque, Sylvain; Perrin, Amandine; Roger, Simon D

    2017-12-01

    To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as ≥ 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on ≥ 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders, < 30% responded at any subsequent time point. Earlier consideration of alternative therapy could improve anemia management in this population.
.

  14. Neuroprotective properties of a novel, non-haematopoietic agonist of the erythropoietin receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Kiryushko, Dar'Ya; Sonn, Katrin

    2010-01-01

    they are involved in tissue protection. However, the use of erythropoietin as a neuroprotective agent may be hampered by its erythropoietic activity. Therefore, developing non-haematopoietic erythropoietin mimetics is important. Based on the crystal structure of the complex of erythropoietin and its receptor, we...... attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin...

  15. Space strategy and governance of ESA small member states

    Science.gov (United States)

    Sagath, Daniel; Papadimitriou, Angeliki; Adriaensen, Maarten; Giannopapa, Christina

    2018-01-01

    The European Space Agency (ESA) has twenty-two Member States with a variety of governance structures and strategic priorities regarding their space activities. The objective of this paper is to provide an up-to date overview and a holistic assessment of the national space governance structures and strategic priorities of the eleven smaller Member States (based on annual ESA contributions). A link is made between the governance structure and the main strategic objectives. The specific needs and interests of small and new Member States in the frame of European Space Integration are addressed. The first part of the paper focuses on the national space governance structures in the eleven smaller ESA Member States. The governance models of these Member States are identified including the responsible ministries and the entities entrusted with the implementation of space strategy/policy and programmes of the country. The second part of this paper focuses on the content and analysis of the national space strategies and indicates the main priorities and trends in the eleven smaller ESA Member States. The priorities are categorised with regards to technology domains, the role of space in the areas of sustainability and the motivators for space investments. In a third and final part, attention is given to the specific needs and interests of the smaller Member States in the frame of European space integration. ESA instruments are tailored to facilitate the needs and interests of the eleven smaller and/or new Member States.

  16. A population approach to disease management: hepatitis C direct-acting antiviral use in a large health care system.

    Science.gov (United States)

    Belperio, Pamela S; Backus, Lisa I; Ross, David; Neuhauser, Melinda M; Mole, Larry A

    2014-06-01

    The introduction of the first direct-acting antiviral agents (DAAs) for the treatment of hepatitis C virus (HCV), telaprevir and boceprevir, marked a unique event in which 2 disease-changing therapies received FDA approval at the same time. Comparative safety and effectiveness data in real-world populations upon which to make formulary decisions did not exist. To describe the implementation, measurement, and outcomes of an enduring population-based approach of surveillance of medication management for HCV. The foundation of the population approach to HCV medication management used by the Department of Veterans Affairs (VA) relied upon a basic framework of (a) providing data for effective regional and local management, (b) education and training, (c) real-time oversight and feedback from a higher organization level, and (d) prompt outcome sharing. These population-based processes spanned across the continuum of the direct-acting antiviral oversight process. We used the VA's HCV Clinical Case Registry-which includes pharmacy, laboratory, and diagnosis information for all HCV-infected veterans from all VA facilities-to assess DAA treatment eligibility, DAA uptake and timing, appropriate use of DAAs including HCV RNA monitoring and medication possession ratios (MPR), nonconcordance with guidance for adjunct erythropoiesis-stimulating agent (ESA) and granulocyte colony-stimulating factor (GCSF) use, hematologic adverse effects, discontinuation rates, and early and sustained virologic responses. Training impact was assessed via survey and change in pharmacist scope of practice. One year after FDA approval, DAAs had been prescribed at 120 of 130 VA facilities. Over 680 VA providers participated in live educational training programs including 380 pharmacists, and pharmacists with a scope of practice for HCV increased from 59 to 110 pharmacists (86%). HCV RNA futility testing improved such that only 1%-3% of veterans did not have appropriate testing compared with 15%-17% 6

  17. NASA and ESA Partnership on the Multi-Purpose Crew Vehicle Service Module

    Science.gov (United States)

    Schubert, Kathleen E.; Grantier, Julie A.

    2012-01-01

    (1) ESA decided in its Council Meeting in March 2011 to partially offset the European ISS obligations after 2015 with different means than ATVs; (2) The envisioned approach is based on a barter element(s) that would generate cost avoidance on the NASA side; (3) NASA and ESA considered a number of Barter options, NASA concluded that the provision by ESA of the Service Module for the NASA Multi-Purpose Crew Vehicle (MPCV) was the barter with the most interest;. (4) A joint ESA - NASA working group was established in May 2011 to assess the feasibility of Europe developing this Module based on ATV heritage; (5)The working group was supported by European and US industry namely Astrium, TAS-I and Lockheed-Martin; and (6) The project is currently in phase B1 with the objective to prepare a technical and programmatic proposal for an ESA MPCV-SM development. This proposal will be one element of the package that ESA plans submit to go forward for approval by European Ministers in November 2012.

  18. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial.

    Science.gov (United States)

    Swain, Sandra M; Tang, Gong; Geyer, Charles E; Rastogi, Priya; Atkins, James N; Donnellan, Paul P; Fehrenbacher, Louis; Azar, Catherine A; Robidoux, André; Polikoff, Jonathan A; Brufsky, Adam M; Biggs, David D; Levine, Edward A; Zapas, John L; Provencher, Louise; Northfelt, Donald W; Paik, Soonmyung; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

    2013-09-10

    Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

  19. Oxygen Status Parameters as Markers of Renal Dysfunction in Neonatal Infants with Critical Status

    Directory of Open Access Journals (Sweden)

    Ye. V. Parshin

    2010-01-01

    Full Text Available Objective: to study whether the use of donor blood components can be reduced in patients with baseline anemia during endo-prosthetic replacement of the hip joint. Subjects and methods. The trial was carried out in 262 patients, including 233 patients who had normal preoperative hemoglobin levels and 29 were found to have anemia that was perioperatively corrected using erythropoiesis stimulants (Eprex® (Silag AG, Switzerland. The patients with normal hemoglobin levels were operated on under normotensive spinal anesthesia (SA (n=129 and spinal anesthesia with moderate controlled intraoperative hypotension during infusion of microdoses of adrenaline (n=104. All the patients with baseline anemia were operated on under SA with moderate controlled intraoperative hypotension. Results. Preoperative hemopoiesis stimulation in patients with anemia caused a significant increase in hemoglobin and red blood cells in the preoperative period. The volume of intraoperative, drainage, and total blood losses under SA in patients with intraoperative moderate hypotension was significantly lower than that in those with normotensive SA. Throughout the hospitalization, hemotransfusions during erythropoiesis stimulation were needed in 17% of the patients with baseline anemia, in 7% of those with normal preoperative hemoglobin levels, operated on under SA with moderate intraoperative hypotension, and in 40% of those operated on under normotensive SA. Conclusion. The use of erythropoiesis stimulants during preoperative preparation of patients with baseline anemia makes it possible to substantially elevate hemoglobin before surgery and to avoid its considerable postoperative decrease. That of SA with moderate controlled hypotension during endoprosthetic replacement of the hip joint results in the volume of perioperative blood loss, which permits avoidance of packed donor red blood cells in the majority of patients with preoperative anemia during its correction with

  20. ESA Science Archives, VO tools and remote Scientific Data reduction in Grid Architectures

    Science.gov (United States)

    Arviset, C.; Barbarisi, I.; de La Calle, I.; Fajersztejn, N.; Freschi, M.; Gabriel, C.; Gomez, P.; Guainazzi, M.; Ibarra, A.; Laruelo, A.; Leon, I.; Micol, A.; Parrilla, E.; Ortiz, I.; Osuna, P.; Salgado, J.; Stebe, A.; Tapiador, D.

    2008-08-01

    This paper presents the latest functionalities of the ESA Science Archives located at ESAC, Spain, in particular, the following archives : the ISO Data Archive (IDA {http://iso.esac.esa.int/ida}), the XMM-Newton Science Archive (XSA {http://xmm.esac.esa.int/xsa}), the Integral SOC Science Data Archive (ISDA {http://integral.esac.esa.int/isda}) and the Planetary Science Archive (PSA {http://www.rssd.esa.int/psa}), both the classical and the map-based Mars Express interfaces. Furthermore, the ESA VOSpec {http://esavo.esac.esa.int/vospecapp} spectra analysis tool is described, which allows to access and display spectral information from VO resources (both real observational and theoretical spectra), including access to Lines database and recent analysis functionalities. In addition, we detail the first implementation of RISA (Remote Interface for Science Analysis), a web service providing remote users the ability to create fully configurable XMM-Newton data analysis workflows, and to deploy and run them on the ESAC Grid. RISA makes fully use of the inter-operability provided by the SIAP (Simple Image Access Protocol) services as data input, and at the same time its VO-compatible output can directly be used by general VO-tools.

  1. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia.

    Science.gov (United States)

    Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Nolen, Jacqueline G; Roger, Simon D

    2014-11-01

    The optimal iron therapy regimen in patients with non-dialysis-dependent chronic kidney disease (CKD) is unknown. Ferinject® assessment in patients with Iron deficiency anaemia and Non-Dialysis-dependent Chronic Kidney Disease (FIND-CKD) was a 56-week, open-label, multicentre, prospective and randomized study of 626 patients with non-dialysis-dependent CKD, anaemia and iron deficiency not receiving erythropoiesis-stimulating agents (ESAs). Patients were randomized (1:1:2) to intravenous (IV) ferric carboxymaltose (FCM), targeting a higher (400-600 µg/L) or lower (100-200 µg/L) ferritin or oral iron therapy. The primary end point was time to initiation of other anaemia management (ESA, other iron therapy or blood transfusion) or haemoglobin (Hb) trigger of two consecutive values <10 g/dL during Weeks 8-52. The primary end point occurred in 36 patients (23.5%), 49 patients (32.2%) and 98 patients (31.8%) in the high-ferritin FCM, low-ferritin FCM and oral iron groups, respectively [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.44-0.95; P = 0.026 for high-ferritin FCM versus oral iron]. The increase in Hb was greater with high-ferritin FCM versus oral iron (P = 0.014) and a greater proportion of patients achieved an Hb increase ≥1 g/dL with high-ferritin FCM versus oral iron (HR: 2.04; 95% CI: 1.52-2.72; P < 0.001). Rates of adverse events and serious adverse events were similar in all groups. Compared with oral iron, IV FCM targeting a ferritin of 400-600 µg/L quickly reached and maintained Hb level, and delayed and/or reduced the need for other anaemia management including ESAs. Within the limitations of this trial, no renal toxicity was observed, with no difference in cardiovascular or infectious events. NCT00994318. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

  2. Evolution of ESA's SSA Conjunction Prediction Service

    Science.gov (United States)

    Escobar, D.; Sancho, A. Tirado, J.; Agueda, A.; Martin, L.; Luque, F.; Fletcher, E.; Navarro, V.

    2013-08-01

    This paper presents the recent evolution of ESA's SSA Conjunction Prediction Service (CPS) as a result of an on-going activity in the Space Surveillance and Tracking (SST) Segment of ESA's Space Situational Awareness (SSA) Programme. The CPS is one of a number of precursor services being developed as part of the SST segment. It has been implemented as a service to provide external users with web-based access to conjunction information and designed with a service-oriented architecture. The paper encompasses the following topics: service functionality enhancements, integration with a live objects catalogue, all vs. all analyses supporting an operational concept based on low and high fidelity screenings, and finally conjunction detection and probability algorithms.

  3. New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

    Science.gov (United States)

    2015-11-01

    Award Number: W81XWH-12-1-0449 TITLE: New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis...COVERED 1Sep2012 - 31Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER New Drugs for Anemia Treatment Based on a New Understanding of the...cell formation in "Nan" (neonatal anemia ) mice, raising the level of red cells to almost normal. It also causes an increase in the numbers of splenic

  4. Primitive and definitive erythropoiesis in mammals

    Directory of Open Access Journals (Sweden)

    James ePalis

    2014-01-01

    Full Text Available Red blood cells (RBCs, which constitute the most abundant cell type in the body, come in two distinct flavors- primitive and definitive. Definitive RBCs in mammals circulate as smaller, anucleate cells during fetal and postnatal life, while primitive RBCs circulate transiently in the early embryo as large, nucleated cells before ultimately enucleating. Both cell types are formed from lineage-committed progenitors that generate a series of morphologically identifiable precursors that enucleate to form mature RBCs. While definitive erythroid precursors mature extravascularly in the fetal liver and postnatal marrow in association with macrophage cells, primitive erythroid precursors mature as a semi-synchronous cohort in the embryonic bloodstream. While the cytoskeletal network is critical for the maintenance of cell shape and the deformability of definitive RBCs, little is known about the components and function of the cytoskeleton in primitive erythroblasts. Erythropoietin (EPO is a critical regulator of late-stage definitive, but not primitive, erythroid progenitor survival. However, recent studies indicate that EPO regulates multiple aspects of terminal maturation of primitive murine and human erythroid precursors, including cell survival, proliferation, and the rate of terminal maturation. Primitive and definitive erythropoiesis share central transcriptional regulators, including Gata1 and Klf1, but are also characterized by the differential expression and function of other regulators, including myb, Sox6, and Bcl11A. Flow cytometry-based methodologies, developed to purify murine and human stage-specific erythroid precursors, have enabled comparative global gene expression studies and are providing new insights into the biology of erythroid maturation.

  5. HST's 10th anniversary, ESA and Hubble : changing our vision

    Science.gov (United States)

    2000-04-01

    With the astronauts who took part in the most recent Servicing Mission (SM3A) in attendance, ESA is taking the opportunity to give a - first - complete overview of Europe's major contribution to the HST mission. It will also review the first ten years of operations and the outstanding results that have "changed our vision" of the cosmos. A new fully European outreach initiative - the "European Space Agency Hubble Information Centre" - will be presented and officially launched; it has been set up by ESA to provide information on Hubble from a European perspective. A public conference will take place in the afternoon to celebrate Hubble's achievements midway through its life. Ten years of outstanding performance Launched on 24 April 1990, Hubble is now midway through its operating life and it is considered one of the most successful space science missions ever. So far more than 10,000 scientific papers based on Hubble results have been published and European scientists have contributed to more than 25% of these. Not only has Hubble produced a rich harvest of scientific results, it has impressed the man in the street with its beautiful images of the sky. Thousands of headlines all over the world have given direct proof of the public's great interest in the mission - 'The deepest images ever', 'The sharpest view of the Universe', 'Measurements of the earliest galaxies' and many others, all reflecting Hubble's performance as a top-class observatory. The Servicing Missions that keep the observatory and its instruments in prime condition are one of the innovative ideas behind Hubble. Astronauts have serviced Hubble three times, and ESA astronauts have taken part in two of these missions. Claude Nicollier (CH) worked with American colleagues on the First Servicing Mission, when Hubble's initial optical problems were repaired. On the latest, Servicing Mission 3A, both Claude Nicollier and Jean-François Clervoy (F) were members of the crew. Over the next 10 years European

  6. ESA GlobSnow Snow Water Equivalent (SWE)

    Data.gov (United States)

    National Aeronautics and Space Administration — The European Space Agency (ESA) Global Snow Monitoring for Climate Research (GlobSnow) snow water equivalent (SWE) v2.0 data record contains snow information derived...

  7. Soluble transferrin receptor as a marker of erythropoiesis in patients undergoing high-flux hemodialysis

    Directory of Open Access Journals (Sweden)

    Pei Yin

    2017-11-01

    Full Text Available Anemia is a common complication in chronic kidney disease (CKD patients receiving hemodialysis. The effect of high-flux dialysis (HFD on anemia remains unclear. This prospective study aimed to evaluate the effect of HFD on anemia, and the potential of soluble transferrin receptor (sTfR as a marker of iron status and erythropoiesis in CKD patients on hemodialysis. Forty patients, who switched from conventional low-flux dialysis to HFD for 12 months, were enrolled in this study. The levels of sTfR, hemoglobin (Hb, iron, and nutritional markers, as well as the dose of recombinant human erythropoietin (rhEPO and use of chalybeate were determined at 0, 2, 6, and 12 months after starting HFD. HFD significantly increased the hemoglobin level and reduced sTfR level in CKD patients (p < 0.05. In addition, significant decreasing linear trends were observed for rhEPO dosage and chalybeate use (p < 0.05. The level of sTfR was positively correlated with the percentage of reticulocytes (RET%, rhEPO dose, and chalybeate use, while it was negatively correlated with Hb levels and total iron-binding capacity results (all p < 0.05. A univariate generalized estimating equation (GEE model showed that the Hb level, RET%, rhEPO dose, and chalybeate use were the variables associated with sTfR levels. A multivariate GEE model showed that the time points when hemodialysis was performed were the variables associated significantly with sTfR levels. Overall, our findings suggest that HFD can effectively improve renal anemia in hemodialysis patients, and sTfR could be used as a marker of erythropoiesis in HFD patients.

  8. Swarm: ESA's Magnetic Field Mission

    Science.gov (United States)

    Plank, G.; Floberghagen, R.; Menard, Y.; Haagmans, R.

    2013-12-01

    Swarm is the fifth Earth Explorer mission in ESA's Living Planet Programme, and is scheduled for launch in fall 2013. The objective of the Swarm mission is to provide the best-ever survey of the geomagnetic field and its temporal evolution using a constellation of three identical satellites. The mission shall deliver data that allow access to new insights into the Earth system by improved scientific understanding of the Earth's interior and near-Earth electromagnetic environment. After launch and triple satellite release at an initial altitude of about 490 km, a pair of the satellites will fly side-by-side with slowly decaying altitude, while the third satellite will be lifted to 530 km to complete the Swarm constellation. High-precision and high-resolution measurements of the strength, direction and variation of the magnetic field, complemented by precise navigation, accelerometer and electric field measurements, will provide the observations required to separate and model various sources of the geomagnetic field and near-Earth current systems. The mission science goals are to provide a unique view into Earth's core dynamics, mantle conductivity, crustal magnetisation, ionospheric and magnetospheric current systems and upper atmosphere dynamics - ranging from understanding the geodynamo to contributing to space weather. The scientific objectives and results from recent scientific studies will be presented. In addition the current status of the project, which is presently in the final stage of the development phase, will be addressed. A consortium of European scientific institutes is developing a distributed processing system to produce geophysical (Level 2) data products for the Swarm user community. The setup of the Swarm ground segment and the contents of the data products will be addressed. In case the Swarm satellites are already in orbit, a summary of the on-going mission operations activities will be given. More information on Swarm can be found at www.esa.int/esaLP/LPswarm.html.

  9. RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

    Science.gov (United States)

    Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

    2017-01-01

    According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

  10. ESA's X-ray space observatory XMM takes first pictures

    Science.gov (United States)

    2000-02-01

    Under the aegis of Prof. Roger Bonnet, ESA Director of Science, the mission's Principal Investigators will be presenting these spectacular first images at a press conference to be held on 9 February at the ESA Vilspa facility at Villafranca/Madrid in Spain, where the XMM Science Operations Centre is located. The event will also be the occasion for several major announcements concerning the XMM mission. In particular Professor Bonnet will launch the third XMM competition "Stargazing" - previously announced in September 1999. This will address European youngsters, 16 to 18 years old, who will be offered the unique opportunity of winning observing time using the X-ray telescope. Commissioning phase starts After a successful launch from Kourou on Ariane 504 on 10 December 1999, XMM was brought to its final operational orbit in the following week. The telescope doors on the X-ray Mirror Modules and on the Optical Monitor telescope were opened on 17/18 December. The Radiation Monitor was activated on 19 December and the spacecraft was put into a quiet mode over the Christmas and New Year period. The mission's scientific data is being received, processed and dispatched to astronomers by the XMM Science Operations Centre in Villafranca. Operations with the spacecraft restarted there on 4 January when, as part of the commissioning phase, all the science payloads were switched on one after the other for initial verifications. By the week of 17 January functional tests had begun on the Optical Monitor, the EPIC pn, the two EPIC MOS and the two RGS instruments. The internal doors of the EPIC cameras were opened whilst keeping the camera filter wheels closed. Astounding first images After a series of engineering exposures, all three EPIC cameras were used in turn, between 19-24 January, to take several views of two different extragalactic regions of the Universe. These views, featuring a variety of extended and X-ray point sources, were chosen to demonstrate the full

  11. Second space Christmas for ESA: Huygens to begin its final journey to Titan/ Media activities.

    Science.gov (United States)

    2004-12-01

    At 1.25 billion km from Earth, after a 7-year journey through the Solar system, ESA’s Huygens probe is about to separate from the Cassini orbiter to enter a ballistic trajectory toward Titan, the largest and most mysterious moon of Saturn, in order to dive into its atmosphere on 14 January. This will be the first man-made object to explore in-situ this unique environment, whose chemistry is assumed to be very similar to that of the early Earth just before life began, 3.8 billion years ago. The Cassini-Huygens pair, a joint mission conducted by NASA, ESA and the Italian space agency (ASI), was launched into space on 15 October 1997. With the help of several gravity assist manoeuvres during flybys of Venus, Earth and Jupiter, it took almost 7 years for the spacecraft to reach Saturn. The Cassini orbiter, carrying Huygens on its flank, entered an orbit around Saturn on 1 July 2004, and began to investigate the ringed planet and its moons for a mission that will last at least four years. The first distant flyby of Titan took place on 2-3 July 2004. It provided data on Titan's atmosphere which were confirmed by the data obtained during the first close flyby on 26 October 2004 at an altitude of 1174 km. These data were used to validate the entry conditions of the Huygens probe. A second close flyby of Titan by Cassini-Huygens at an altitude of 1200 km is scheduled on 13 December and will provide additional data to further validate the entry conditions of the Huygens probe. On 17 December the orbiter will be placed on a controlled collision course with Titan in order to release Huygens on the proper trajectory, and on 21 December (some dates and times are subject to minor adjustment for operational reasons, except the entry time on 14 January which is know to within an accuracy of under 2 minutes) all systems will be set up for separation and the Huygens timers will be set to wake the probe a few hours before its arrival at Titan. The Huygens probe is due to separate on

  12. Data in support of transcriptional regulation and function of Fas-antisense long noncoding RNA during human erythropoiesis

    Directory of Open Access Journals (Sweden)

    Olga Villamizar

    2016-06-01

    Full Text Available This paper describes data related to a research article titled, “Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death” [1]. Long noncoding RNAs (lncRNAs are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis. Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf described in the research article. Also included are 5′ untranslated sequences (UTR for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34+ cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34+ cells transduced using mock conditions or with lentivirus particles encoding for Saf.

  13. Radioactive effect of ribomunyl

    International Nuclear Information System (INIS)

    Vavrova, J.

    1994-01-01

    Ribomunyl is an immunomodulation agent used in prevention of chronic respiratory disease in man. A single s.c. and i.p. Ribomunyl administration in the dose of 50 and 125 g/mouse, resp., resulted for the non-irradiated animals in stimulation of the 125 IUdR incorporation into the spleen and the marrow. On the other hand there occurred erythropoiesis suppression in the marrow, measured by the 59 Fe incorporation. In sublethally irradiated mice Ribomunyl stimulates a faster regeneration of the 125 IUdR incorporation into the spleen. In the irradiated mice we proved a radioprotective effect of Ribomunyl in case of single i.p. and s.c. administration 24 hr before irradiation. The value of the dose reduction factor (DRF) equals to 1.2. (author)

  14. Stimulating household flood risk mitigation investments through insurance and subsidies: an Agent-Based Modelling approach

    Science.gov (United States)

    Haer, Toon; Botzen, Wouter; de Moel, Hans; Aerts, Jeroen

    2015-04-01

    In the period 1998-2009, floods triggered roughly 52 billion euro in insured economic losses making floods the most costly natural hazard in Europe. Climate change and socio/economic trends are expected to further aggrevate floods losses in many regions. Research shows that flood risk can be significantly reduced if households install protective measures, and that the implementation of such measures can be stimulated through flood insurance schemes and subsidies. However, the effectiveness of such incentives to stimulate implementation of loss-reducing measures greatly depends on the decision process of individuals and is hardly studied. In our study, we developed an Agent-Based Model that integrates flood damage models, insurance mechanisms, subsidies, and household behaviour models to assess the effectiveness of different economic tools on stimulating households to invest in loss-reducing measures. Since the effectiveness depends on the decision making process of individuals, the study compares different household decision models ranging from standard economic models, to economic models for decision making under risk, to more complex decision models integrating economic models and risk perceptions, opinion dynamics, and the influence of flood experience. The results show the effectiveness of incentives to stimulate investment in loss-reducing measures for different household behavior types, while assuming climate change scenarios. It shows how complex decision models can better reproduce observed real-world behaviour compared to traditional economic models. Furthermore, since flood events are included in the simulations, the results provide an analysis of the dynamics in insured and uninsured losses for households, the costs of reducing risk by implementing loss-reducing measures, the capacity of the insurance market, and the cost of government subsidies under different scenarios. The model has been applied to the City of Rotterdam in The Netherlands.

  15. Space transportation systems within ESA programmes: Current status and perspectives

    Science.gov (United States)

    Delahais, Maurice

    1993-03-01

    An overview of the space transportation aspects of the ESA (European Space Agency) programs as they result from history, present status, and decisions taken at the ministerial level conference in Granada, Spain is presented. The new factors taken into consideration for the long term plan proposed in Munich, Germany, the three strategic options for the reorientation of the ESA long term plan, and the essential elements of space transportation in the Granada long term plan in three areas of space activities, scientific, and commercial launches with expendable launch vehicles, manned flight and in-orbit infrastructure, and future transportation systems are outlined. The new ESA long term plan, in the field of space transportation systems, constitutes a reorientation of the initial program contemplated in previous councils at ministerial level. It aims at balancing the new economic situation with the new avenues of cooperation, and the outcome will be a new implementation of the space transportation systems policy.

  16. ESA's tools for internal charging; Outils developpes par l'ESA pour evaluer les repartitions de charges electrostatiques

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, J. [ESA/ESTEC (Netherlands); Rodgers, D.J.; Ryden, K.A.; Latham, P.M. [DERA, Farnborough (United Kingdom); Wrenn, G.L. [T.S. Space Systems (United Kingdom); Levy, L.; Panabiere, G. [Office National d' Etudes et de Recherches Aerospatiales (ONERA/DESP), 31 - Toulouse (France)

    1999-07-01

    Electrostatic discharges, caused by bulk charging of spacecraft insulating materials, are a major cause of satellite anomalies. This is a presentation of ESA's tools to assess whether a given structure is liable to experience electrostatic discharges. (authors)

  17. Role of androgen-mediated enhancement of erythropoiesis in the increased body iron stores of patients with polycystic ovary syndrome.

    Science.gov (United States)

    Escobar-Morreale, Héctor F; Luque-Ramírez, Manuel

    2011-04-01

    To determine whether androgen excess contributes to the increased body iron stores of polycystic ovary syndrome (PCOS) by stimulating erythropoietic activity, by measuring serum soluble transferrin receptor (sTfR) concentrations and its ratio to ferritin levels in patients with PCOS, as surrogate markers of erythropoietic activity and of the appropriateness of cellular iron demands for the total body iron contents, respectively. Case-control study. Academic hospital. One hundred-four patients with PCOS and 100 controls without androgen excess. Blood sampling and oral glucose tolerance test. Serum sTfR and ferritin concentrations, as well as indexes of androgen excess, inflammation, obesity, and insulin and glucose metabolism. Serum ferritin levels increased in women presenting with PCOS, obesity, and/or abnormal glucose tolerance, but these disorders did not influence sTfR concentrations. The sTfR/ferritin ratio decreased with obesity and abnormal glucose tolerance, and its logarithm correlated inversely with body mass index, free T, and C-reactive protein levels and directly with the insulin sensitivity and disposition indexes. A stepwise multiple regression analysis indicated that the changes in the insulin sensitivity index explained 7% of the variability of the logarithm of sTfR/ferritin ratio. Increased serum ferritin levels in patients with PCOS are associated with a reduction in insulin sensitivity but do not result from a putative enhancement of erythropoiesis by androgen excess. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Software Dependability and Safety Evaluations ESA's Initiative

    Science.gov (United States)

    Hernek, M.

    ESA has allocated funds for an initiative to evaluate Dependability and Safety methods of Software. The objectives of this initiative are; · More extensive validation of Safety and Dependability techniques for Software · Provide valuable results to improve the quality of the Software thus promoting the application of Dependability and Safety methods and techniques. ESA space systems are being developed according to defined PA requirement specifications. These requirements may be implemented through various design concepts, e.g. redundancy, diversity etc. varying from project to project. Analysis methods (FMECA. FTA, HA, etc) are frequently used during requirements analysis and design activities to assure the correct implementation of system PA requirements. The criticality level of failures, functions and systems is determined and by doing that the critical sub-systems are identified, on which dependability and safety techniques are to be applied during development. Proper performance of the software development requires the development of a technical specification for the products at the beginning of the life cycle. Such technical specification comprises both functional and non-functional requirements. These non-functional requirements address characteristics of the product such as quality, dependability, safety and maintainability. Software in space systems is more and more used in critical functions. Also the trend towards more frequent use of COTS and reusable components pose new difficulties in terms of assuring reliable and safe systems. Because of this, its dependability and safety must be carefully analysed. ESA identified and documented techniques, methods and procedures to ensure that software dependability and safety requirements are specified and taken into account during the design and development of a software system and to verify/validate that the implemented software systems comply with these requirements [R1].

  19. Software Agents Applications Using Real-Time CORBA

    Science.gov (United States)

    Fowell, S.; Ward, R.; Nielsen, M.

    This paper describes current projects being performed by SciSys in the area of the use of software agents, built using CORBA middleware, to improve operations within autonomous satellite/ground systems. These concepts have been developed and demonstrated in a series of experiments variously funded by ESA's Technology Flight Opportunity Initiative (TFO) and Leading Edge Technology for SMEs (LET-SME), and the British National Space Centre's (BNSC) National Technology Programme. Some of this earlier work has already been reported in [1]. This paper will address the trends, issues and solutions associated with this software agent architecture concept, together with its implementation using CORBA within an on-board environment, that is to say taking account of its real- time and resource constrained nature.

  20. ATLID, ESA Atmospheric LIDAR Developement Status

    Directory of Open Access Journals (Sweden)

    do Carmo João Pereira

    2016-01-01

    Full Text Available The ATmospheric LIDAR ATLID[1] is part of the payload of the Earth Cloud and Aerosol Explorer[2] (EarthCARE satellite mission, the sixth Earth Explorer Mission of the European Space Agency (ESA Living Planet Programme. EarthCARE is a joint collaborative satellite mission conducted between ESA and the National Space Development Agency of Japan (JAXA that delivers the Cloud Profiling Radar (CPR instrument. The payload consists of four instruments on the same platform with the common goal to provide a picture of the 3D-dimensional spatial and the temporal structure of the radiative flux field at the top of atmosphere, within the atmosphere and at the Earth’s surface. This paper is presenting an updated status of the development of the ATLID instrument and its subsystem design. The instrument has recently completed its detailed design, and most of its subsystems are already under manufacturing of their Flight Model (FM parts and running specific qualification activities. Clouds and aerosols are currently one of the biggest uncertainties in our understanding of the atmospheric conditions that drive the climate system. A better modelling of the relationship between clouds, aerosols and radiation is therefore amongst the highest priorities in climate research and weather prediction.

  1. Sharing ESA's knowledge and experience - the Erasmus Experiment Archive

    Science.gov (United States)

    Isakeit, Dieter; Sabbatini, Massimo; Carey, William

    2004-11-01

    The Erasmus Experiment Archive is an electronic database, that collects all experiments performed to date in the faciliteis that fall under the responsibility of the ESA (human spaceflight, microgravity, exploration).

  2. Osteoclasts Are Required for Hematopoietic Stem and Progenitor Cell Mobilization but Not for Stress Erythropoiesis in Plasmodium chabaudi adami Murine Malaria

    Directory of Open Access Journals (Sweden)

    Hugo Roméro

    2016-01-01

    Full Text Available The anemia and inflammation concurrent with blood stage malaria trigger stress haematopoiesis and erythropoiesis. The activity of osteoclasts seems required for the mobilization of hematopoietic stem and progenitor cells (HSPC from the bone marrow to the periphery. Knowing that BALB/c mice with acute Plasmodium chabaudi adami malaria have profound alterations in bone remodelling cells, we evaluated the extent to which osteoclasts influence their hematopoietic response to infection. For this, mice were treated with osteoclast inhibiting hormone calcitonin prior to parasite inoculation, and infection as well as hematological parameters was studied. In agreement with osteoclast-dependent HSPC mobilization, administration of calcitonin led to milder splenomegaly, reduced numbers of HSPC in the spleen, and their retention in the bone marrow. Although C-terminal telopeptide (CTX levels, indicative of bone resorption, were lower in calcitonin-treated infected mice, they remained comparable in naive and control infected mice. Calcitonin-treated infected mice conveniently responded to anemia but generated less numbers of splenic macrophages and suffered from exacerbated infection; interestingly, calcitonin also decreased the number of macrophages generated in vitro. Globally, our results indicate that although osteoclast-dependent HSC mobilization from bone marrow to spleen is triggered in murine blood stage malaria, this activity is not essential for stress erythropoiesis.

  3. The DTU-ESA Millimeter-Wave Validation Standard Antenna – Manufacturing and Testing

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Pivnenko, Sergey; Breinbjerg, Olav

    2015-01-01

    A new precision tool for antenna test range qualification and inter-comparisons at mm-waves – the mm-VAST antenna – is under development at the Technical University of Denmark (DTU) in collaboration with TICRA under a European Space Agency (ESA) contract. The DTU-ESA mm-VAST antenna will facilita...... mechanical design, fabrication and assembling procedures. The performance verification test plan as well as first measurement results are also discussed....

  4. ESA personal communications and digital audio broadcasting systems based on non-geostationary satellites

    Science.gov (United States)

    Logalbo, P.; Benedicto, J.; Viola, R.

    1993-01-01

    Personal Communications and Digital Audio Broadcasting are two new services that the European Space Agency (ESA) is investigating for future European and Global Mobile Satellite systems. ESA is active in promoting these services in their various mission options including non-geostationary and geostationary satellite systems. A Medium Altitude Global Satellite System (MAGSS) for global personal communications at L and S-band, and a Multiregional Highly inclined Elliptical Orbit (M-HEO) system for multiregional digital audio broadcasting at L-band are described. Both systems are being investigated by ESA in the context of future programs, such as Archimedes, which are intended to demonstrate the new services and to develop the technology for future non-geostationary mobile communication and broadcasting satellites.

  5. ESA and CERN link on data and communication

    CERN Multimedia

    1998-01-01

    ESA and CERN have agreed to set up working groups to learn from each others experiences in areas such as handling and networking large amounts of data generated by large-scale experiments and in communicating the results of their experiments to the public (2 paragraphs).

  6. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull 2007; 6(6.000: 491-500

  7. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull. 2007; 6(6: 491-500

  8. ESA presents INTEGRAL, its space observatory for Gamma-ray astronomy

    Science.gov (United States)

    1998-09-01

    A unique opportunity for journalists and cameramen to view INTEGRAL will be provided at ESA/ESTEC, Noordwijk, the Netherlands on Tuesday 22 September. On show will be the full-size structural thermal model which is now beeing examined in ESA's test centre. Following introductions to the project, the INTEGRAL spacecraft can be seen, filmed and photographed in its special clean room environment.. Media representatives wishing to participate in the visit to ESA's test centre and the presentation of INTEGRAL are kindly requested to return by fax the attached registration form to ESA Public relations, Tel. +33 (0) 1.53.69.71.55 - Fax. +33 (0) 1.53.69.76.90. For details please see the attached programme Gamma-ray astronomy - why ? Gamma-rays cannot be detected from the ground since the earth's atmosphere shields us from high energetic radiation. Only space technology has made gamma-astronomy possible. To avoid background radiation effects INTEGRAL will spend most of its time in the orbit outside earth's radiation belts above an altitude of 40'000 km. Gamma-rays are the highest energy form of electromagnetic radiation. Therefore gamma-ray astronomy explores the most energetic phenomena occurring in nature and addresses some of the most fundamental problems in physics. We know for instance that most of the chemical elements in our bodies come from long-dead stars. But how were these elements formed? INTEGRAL will register gamma-ray evidence of element-making. Gamma-rays also appear when matter squirms in the intense gravity of collapsed stars or black holes. One of the most important scientific objectives of INTEGRAL is to study such compact objects as neutron stars or black holes. Besides stellar black holes there may exist much bigger specimens of these extremely dense objects. Most astronomers believe that in the heart of our Milky Way as in the centre of other galaxies there may lurk giant black holes. INTEGRAL will have to find evidence of these exotic objects. Even

  9. Use of Data Denial Experiments to Evaluate ESA Forecast Sensitivity Patterns

    Energy Technology Data Exchange (ETDEWEB)

    Zack, J; Natenberg, E J; Knowe, G V; Manobianco, J; Waight, K; Hanley, D; Kamath, C

    2011-09-13

    The overall goal of this multi-phased research project known as WindSENSE is to develop an observation system deployment strategy that would improve wind power generation forecasts. The objective of the deployment strategy is to produce the maximum benefit for 1- to 6-hour ahead forecasts of wind speed at hub-height ({approx}80 m). In this phase of the project the focus is on the Mid-Columbia Basin region which encompasses the Bonneville Power Administration (BPA) wind generation area shown in Figure 1 that includes Klondike, Stateline, and Hopkins Ridge wind plants. The Ensemble Sensitivity Analysis (ESA) approach uses data generated by a set (ensemble) of perturbed numerical weather prediction (NWP) simulations for a sample time period to statistically diagnose the sensitivity of a specified forecast variable (metric) for a target location to parameters at other locations and prior times referred to as the initial condition (IC) or state variables. The ESA approach was tested on the large-scale atmospheric prediction problem by Ancell and Hakim 2007 and Torn and Hakim 2008. ESA was adapted and applied at the mesoscale by Zack et al. (2010a, b, and c) to the Tehachapi Pass, CA (warm and cools seasons) and Mid-Colombia Basin (warm season only) wind generation regions. In order to apply the ESA approach at the resolution needed at the mesoscale, Zack et al. (2010a, b, and c) developed the Multiple Observation Optimization Algorithm (MOOA). MOOA uses a multivariate regression on a few select IC parameters at one location to determine the incremental improvement of measuring multiple variables (representative of the IC parameters) at various locations. MOOA also determines how much information from each IC parameter contributes to the change in the metric variable at the target location. The Zack et al. studies (2010a, b, and c), demonstrated that forecast sensitivity can be characterized by well-defined, localized patterns for a number of IC variables such as 80-m

  10. IMPROVING THE SKILL AND THE INTEREST OF WRITING ADVERTISEMENTS AND POSTERS THROUGH ESA SEQUENCE

    Directory of Open Access Journals (Sweden)

    Fatma Yuniarti

    2016-04-01

    Full Text Available The action reserach aims at improving the students’ writing skill especially to write advertsements and posters. Both are the short functional texts to be learned at the first semester of the ninth grade. According to the data on pre cycle, the students of class IXA Junior High School Swadhipa Natar, South Lampung got difficulties in writing advertisements and posters. A treatment was necessary to help the students overcome their problem. To consider the related literature, the writer decided to implement ESA sequence in the class. The elements of teaching in ESA Sequence are Engage (to arouse the students’ interests, Study (learn the language focus, and Activate (use the language freely and communicatively.The data were taken from the test of the linguistic competence mastery, the students writing, and the questionnaire. The result shows ESA Sequence can improve the students’ ability in writing advertisements and posters.Key words : ESA (Engange Study Activate, advertisement, poster.

  11. Cryosphere campaigns in support of ESA's Earth Explorers Missions

    Science.gov (United States)

    Casal, Tânia; Davidson, Malcolm; Plank, Gernot; Floberghagen, Rune; Parrinello, Tommaso; Mecklenburg, Susanne; Drusch, Matthias; Fernandez, Diego

    2014-05-01

    In the framework of its Earth Observation Programmes the European Space Agency (ESA) carries out ground based and airborne campaigns to support geophysical algorithm development, calibration/validation, simulation of future spaceborne Earth observation missions, and applications development related to land, oceans, atmosphere and solid Earth. ESA has conducted over 110 airborne and ground measurements campaigns since 1981 and this presentation will describe three campaigns in Antarctica and the Arctic. They were undertaken during the calibration/validation phase of Earth Explorer (EE) missions, such as SMOS (Soil Moisture and Ocean Salinity), GOCE (Gravity field and steady-state Ocean Circulation Explorer) and CryoSat-2. In support of SMOS and GOCE, the DOMECair airborne campaign took place in Antarctica, in the Dome C region in the middle of January 2013. The two main objectives were a) to quantify and document the spatial variability in the DOME C area (SMOS) and b) to fill a gap in the high-quality gravity anomaly maps in Antarctica where airborne gravity measurements are sparse (GOCE). Results from the campaign for the SMOS component, showed that the DOME C area is not as spatially homogenous as previously assumed, therefore comparisons of different missions (e.g. SMOS and NASA's Aquarius) with different footprints must be done with care, highlighting once again the importance of field work to test given assumptions. One extremely surprising outcome of this campaign was the pattern similarity between the gravity measurements and brightness temperature fields. To date, there has never been an indication that L-Band brightness temperatures could be correlated to gravity, but preliminary analysis showed coincident high brightness temperature with high gravity values, suggesting that topography may influence microwave emissions. Also in support of SMOS, the SMOSice airborne campaign has been planned in the Arctic. It was motived by a previous ESA SMOSice study that

  12. The ESA Space Weather Applications Pilot Project

    Science.gov (United States)

    Glover, A.; Hilgers, A.; Daly, E.

    Following the completion in 2001 of two parallel studies to consider the feasibility of a European Space Weather Programme ESA embarked upon a space weather pilot study with the goal of prototyping European space weather services and assessing the overall market for such within Europe This pilot project centred on a number of targeted service development activities supported by a common infrastructure and making use of only existing space weather assets Each service activity included clear participation from at least one identified service user who was requested to provide initial requirements and regular feedback during the operational phase of the service These service activities are now reaching the end of their 2-year development and testing phase and are now accessible each with an element of the service in the public domain see http www esa-spaceweathet net swenet An additional crucial element of the study was the inclusion of a comprehensive and independent analysis of the benefits both economic and strategic of embarking on a programme which would include the deployment of an infrastructure with space-based elements The results of this study will be reported together with their implication for future coordinated European activities in this field

  13. ESA technology flies on Italian mini-satellite launched from Russia

    Science.gov (United States)

    2000-07-01

    Owned by the Italian space agency (ASI) and developed by Carlo Gavazzi with contributions from many other Italian companies, MITA has two tasks to perform: in a circular orbit at 450 km altitude, the mini satellite will carry a cosmic particle detector, while its platform will be tested for the first time as a vehicle for future scientific missions. MITA also carries the MTS-AOMS payload (MicroTechSensor for Attitude and Orbit Measurement System), developed by Astrium in the framework of ESA's Technology Flight Opportunity trial programme. With the Technology Flight Opportunity scheme, funded by its General Studies Programme, ESA intends to provide access to space for European industry's technology products needing in-orbit demonstration to enhance their competitiveness on the space market. This new form of support to the European space industry ties in with ESA's strategy for fostering the competitiveness of European-made technology for eventual commercialisation. In-orbit demonstration is essential if new technologies are to compete on level terms on non-European markets. It thus consolidates strategic investments made by the space industry. The MTS-AOMS is a highly integrated sensor for autonomous attitude and orbit control systems. It combines three functions in one unit: Earth sensing, star sensing and magnetic field sensing. The equipment incorporates an active pixel array sensor and a 2-D fluxgate magnetometer. The aims of the flight are to verify in situ the payload's inherent functions and performance, which cannot be done on the ground, and to assess the behaviour of this type of technology when exposed to the space environment. The Technology Flight Opportunity rule is that ESA funds the launch and integration costs, industry the development and operating costs. According to present planning, two further in-orbit demonstrations funded by this scheme will be carried out between now and January 2001.

  14. ESA's satellite communications programme

    Science.gov (United States)

    Bartholome, P.

    1985-02-01

    The developmental history, current status, and future plans of the ESA satellite-communications programs are discussed in a general survey and illustrated with network diagrams and maps. Consideration is given to the parallel development of national and European direct-broadcast systems and telecommunications networks, the position of the European space and electronics industries in the growing world market, the impact of technological improvements (both in satellite systems and in ground-based networks), and the technological and commercial advantages of integrated space-terrestrial networks. The needs for a European definition of the precise national and international roles of satellite communications, for maximum speed in implementing such decisions (before the technology becomes obsolete), and for increased cooperation and standardization to assure European equipment manufacturers a reasonable share of the market are stressed.

  15. The ESA Scientific Exploitation of Operational Missions element, first results

    Science.gov (United States)

    Desnos, Yves-Louis; Regner, Peter; Delwart, Steven; Benveniste, Jerome; Engdahl, Marcus; Mathieu, Pierre-Philippe; Gascon, Ferran; Donlon, Craig; Davidson, Malcolm; Pinnock, Simon; Foumelis, Michael; Ramoino, Fabrizio

    2016-04-01

    SEOM is a program element within the fourth period (2013-2017) of ESA's Earth Observation Envelope Programme (http://seom.esa.int/). The prime objective is to federate, support and expand the international research community that the ERS, ENVISAT and the Envelope programmes have built up over the last 25 years. It aims to further strengthen the leadership of the European Earth Observation research community by enabling them to extensively exploit future European operational EO missions. SEOM will enable the science community to address new scientific research that are opened by free and open access to data from operational EO missions. Based on community-wide recommendations for actions on key research issues, gathered through a series of international thematic workshops and scientific user consultation meetings, a work plan is established and is approved every year by ESA Members States. During 2015 SEOM, Science users consultation workshops have been organized for Sentinel1/3/5P ( Fringe, S3 Symposium and Atmospheric science respectively) , new R&D studies for scientific exploitation of the Sentinels have been launched ( S3 for Science SAR Altimetry and Ocean Color , S2 for Science,) , open-source multi-mission scientific toolboxes have been launched (in particular the SNAP/S1-2-3 Toolbox). In addition two advanced international training courses have been organized in Europe to exploit the new S1-A and S2-A data for Land and Ocean remote sensing (over 120 participants from 25 countries) as well as activities for promoting the first scientific results ( e.g. Chili Earthquake) . In addition the First EO Open Science 2.0 was organised at ESA in October 2015 with 225 participants from 31 countries bringing together young EO scientists and data scientists. During the conference precursor activities in EO Open Science and Innovation were presented, while developing a Roadmap preparing for future ESA scientific exploitation activities. Within the conference, the first

  16. Taking CERN and ESA technology to the World’s largest industry fair

    CERN Multimedia

    2014-01-01

    Signed just two weeks ago, the new CERN-ESA agreement is already bearing fruit. This week, our two organisations went to the World’s leading industrial fair, the Hannover Messe, with a joint stand showcasing technologies derived from particle physics and space research.   The notion that space brought us Teflon is something of a cliché, and of dubious veracity, while the World Wide Web is the technology most closely, and in this case correctly, identified with CERN. But technology transfer from ESA and CERN goes well beyond clichés: much of the technology we take for granted today can be traced back to basic research in the highly demanding research fields our organizations deal in. This is a message that both CERN and ESA strive to communicate, and the Hannover Messe gave us that opportunity. But going to Hannover was about more than showcasing past success: it was first and foremost about laying the groundwork for future success. Much of the technology deve...

  17. Spaceborne measurement of Greenland ice sheet changes: the ESA Greenland CCI project

    DEFF Research Database (Denmark)

    Forsberg, René; Sørensen, Louise Sandberg; Meister, Rakia

    The ESA “Greenland_ice_sheet_cci” project is currently making past and present space measurements of Greenland ice sheet changes available for use by scientists, stakeholders and the general public. The data are part of a large set of ECV’s (Essential Climate Variables) made available by the ESA...... Climate Initiative, as a contribution to the global Climate Observing System. The ECV data produced for the Greenlandice sheet include detailed grids of elevation changes and ice flow velocities, as well as line data of grounding lines and calving front locations for major outlet glaciers. The “ice_sheets......_cci” goal is to generate a consistent, validated, long-term and timely set of ECV’s, a.o. to improve the impact of satellite data on climate research and coupled ice sheet/climate models. Special focus is on use of data from ESA missions such as ERS, Envisat and the new Sentinel missions, but in the 2nd...

  18. The ESA Scientific Exploitation of Operational Missions element

    Science.gov (United States)

    Desnos, Yves-Louis; Regner, Peter; Delwart, Steven; Benveniste, Jerome; Engdahl, Marcus; Zehner, Claus; Mathieu, Pierre-Philippe; Bojkov, Bojan; Gascon, Ferran; Donlon, Craig; Davidson, Malcolm; Goryl, Philippe; Pinnock, Simon

    2015-04-01

    SEOM is a program element within the fourth period (2013-2017) of ESA's Earth Observation Envelope Programme (http://seom.esa.int/). The prime objective is to federate, support and expand the international research community that the ERS,ENVISAT and the Envelope programmes have built up over the last 25 years. It aims to further strengthen the leadership of the European Earth Observation research community by enabling them to extensively exploit future European operational EO missions. SEOM will enable the science community to address new scientific research that are opened by free and open access to data from operational EO missions. Based on community-wide recommendations for actions on key research issues, gathered through a series of international thematic workshops and scientific user consultation meetings, a work plan has been established and is approved every year by ESA Members States. The 2015 SEOM work plan is covering the organisation of three Science users consultation workshops for Sentinel1/3/5P , the launch of new R&D studies for scientific exploitation of the Sentinels, the development of open-source multi-mission scientific toolboxes, the organisation of advanced international training courses, summer schools and educational materials, as well as activities for promoting the scientific use of EO data. The first SEOM projects have been tendered since 2013 including the development of Sentinel toolboxes, advanced INSAR algorithms for Sentinel-1 TOPS data exploitation, Improved Atmospheric Spectroscopic data-base (IAS), as well as grouped studies for Sentinel-1, -2, and -3 land and ocean applications and studies for exploiting the synergy between the Sentinels. The status and first results from these SEOM projects will be presented and an outlook for upcoming SEOM studies will be given.

  19. Operational support to collision avoidance activities by ESA's space debris office

    Science.gov (United States)

    Braun, V.; Flohrer, T.; Krag, H.; Merz, K.; Lemmens, S.; Bastida Virgili, B.; Funke, Q.

    2016-09-01

    The European Space Agency's (ESA) Space Debris Office provides a service to support operational collision avoidance activities. This support currently covers ESA's missions Cryosat-2, Sentinel-1A and -2A, the constellation of Swarm-A/B/C in low-Earth orbit (LEO), as well as missions of third-party customers. In this work, we describe the current collision avoidance process for ESA and third-party missions in LEO. We give an overview on the upgrades developed and implemented since the advent of conjunction summary messages (CSM)/conjunction data messages (CDM), addressing conjunction event detection, collision risk assessment, orbit determination, orbit and covariance propagation, process control, and data handling. We pay special attention to the effect of warning thresholds on the risk reduction and manoeuvre rates, as they are established through risk mitigation and analysis tools, such as ESA's Debris Risk Assessment and Mitigation Analysis (DRAMA) software suite. To handle the large number of CDMs and the associated risk analyses, a database-centric approach has been developed. All CDMs and risk analysis results are stored in a database. In this way, a temporary local "mini-catalogue" of objects close to our target spacecraft is obtained, which can be used, e.g., for manoeuvre screening and to update the risk analysis whenever a new ephemeris becomes available from the flight dynamics team. The database is also used as the backbone for a Web-based tool, which consists of the visualization component and a collaboration tool that facilitates the status monitoring and task allocation within the support team as well as communication with the control team. The visualization component further supports the information sharing by displaying target and chaser motion over time along with the involved uncertainties. The Web-based solution optimally meets the needs for a concise and easy-to-use way to obtain a situation picture in a very short time, and the support for

  20. Solar Flare Prediction Science-to-Operations: the ESA/SSA SWE A-EFFort Service

    Science.gov (United States)

    Georgoulis, Manolis K.; Tziotziou, Konstantinos; Themelis, Konstantinos; Magiati, Margarita; Angelopoulou, Georgia

    2016-07-01

    We attempt a synoptical overview of the scientific origins of the Athens Effective Solar Flare Forecasting (A-EFFort) utility and the actions taken toward transitioning it into a pre-operational service of ESA's Space Situational Awareness (SSA) Programme. The preferred method for solar flare prediction, as well as key efforts to make it function in a fully automated environment by coupling calculations with near-realtime data-downloading protocols (from the Solar Dynamics Observatory [SDO] mission), pattern recognition (solar active-region identification) and optimization (magnetic connectivity by simulated annealing) will be highlighted. In addition, the entire validation process of the service will be described, with its results presented. We will conclude by stressing the need for across-the-board efforts and synergistic work in order to bring science of potentially limited/restricted interest into realizing a much broader impact and serving the best public interests. The above presentation was partially supported by the ESA/SSA SWE A-EFFort project, ESA Contract No. 4000111994/14/D/MRP. Special thanks go to the ESA Project Officers R. Keil, A. Glover, and J.-P. Luntama (ESOC), M. Bobra and C. Balmer of the SDO/HMI team at Stanford University, and M. Zoulias at the RCAAM of the Academy of Athens for valuable technical help.

  1. Clinical, analytical and bioimpedance characteristics of persistently overhydrated haemodialysis patients.

    Science.gov (United States)

    Castellano, Sandra; Palomares, Inés; Molina, Manuel; Pérez-García, Rafael; Aljama, Pedro; Ramos, Rosa; Merello, J Ignacio

    2014-11-17

    Fluid overload is an important and modifiable cardiovascular risk factor for haemodialysis patients. So far, the diagnosis was based on clinical methods alone. Nowadays, we have new tools to assess more objectively the hydration status of the patients on haemodialysis, as BCM (Body Composition Monitor). A Relative Overhydration (AvROH) higher than 15% (it means, Absolute Overhydration or AWOH higher than 2.5 Litres) is associated to greater risk in haemodialysis. However, there is a group of maintained hyperhydrated patients. The aim of the present study is to identify the characteristics of patients with maintained hyperhydrated status (AvROH higher than 15% or AWOH higher than 2.5 liters). The secondary aim is to show the hemodynamic and analytical changes that are related to the reduction in hyperhydration status. Longitudinal cohort study during six months in 2959 patients in haemodialysis (HD) that are grouped according to their hydration status by BCM. And we compare their clinical, analytical and bioimpedance spectroscopy parameters. The change in overhydration status is followed by a decrease in blood pressure and the need for hypotensive drugs (AHT) and erythropoiesis stimulating agents (ESA). The target hydration status is not reached by two subgroups of patients. First, in diabetic patients with a high comorbidity index and high number of hypotensive drugs (AHT) but a great positive sodium gradient during dialysis sessions; and, younger non-diabetic patients with longer time on hemodialysis and positive sodium gradient, lower fat tissue index (FTI) but similar lean tissue index (LTI) and albumin than those with a reduction in hyperhydration status. Those patients with a reduction in hyperhydration status, also show a better control in blood pressure and anemia with less number of AHT and ESA. The maintained hyperhydrated patients, diabetic patients with many comorbidities and young men patients with longer time on hemodialysis and non-adherence treatment

  2. Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study.

    Science.gov (United States)

    Mafodda, Antonino; Giuffrida, D; Prestifilippo, A; Azzarello, D; Giannicola, R; Mare, M; Maisano, R

    2017-09-01

    Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL). The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL. There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated. In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides

  3. Anemia prevalence and treatment practice in patients with non-myeloid tumors receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Merlini L

    2013-08-01

    .2%; 196 patients (14% were deemed anemic based on Hb ≤10 g/dL, 131 (9% on ongoing anemia treatment, and 121 (9% on physician diagnosis/anemia symptom. Overall, 1153 patients (82% had Hb data; mean (standard deviation [SD] Hb levels were 11.7 (1.7 g/dL. In total, 456 patients (32% had anemia symptoms: fatigue (n = 392; 28%, depression (n = 122; 9%, and dyspnea (n = 107; 8% were most common. Fifty-one patients (4% had had their current chemotherapy cycle delayed due to anemia. On visit day, or ≤ 28 days prior, 91 (6%, 188 (13%, and 81 patients (6% had evidence of whole blood/red blood cell transfusion, erythropoiesis-stimulating agent use, or iron use, respectively. Conclusion: On the prespecified study day, one-third of patients with non-myeloid tumors undergoing chemotherapy were found to be anemic and 13% had evidence of erythropoiesis-stimulating agent use then or in the 28 days prior. Keywords: erythropoiesis-stimulating agent, hemoglobin, iron, management, transfusion 

  4. CERN, ESA and ESO Launch "Physics On Stage"

    Science.gov (United States)

    2000-03-01

    Physics is everywhere . The laws of physics govern the Universe, the Sun, the Earth and even our own lives. In today's rapidly developing society, we are becoming increasingly dependent on high technology - computers, transport, and communication are just some of the key areas that are the result of discoveries by scientists working in physics. But how much do the citizens of Europe really know about physics? Here is a unique opportunity to learn more about this elusive subject! [Go to Physics On Stage Website] Beginning in February 2000, three major European research organisations are organising a unique Europe-wide programme to raise the public awareness of physics and related sciences. "Physics on Stage" is launched by the European Laboratory for Particle Physics (CERN) , the European Space Agency (ESA) and the European Southern Observatory (ESO) , with support from the European Union. Other partners are the European Physical Society (EPS) and the European Association for Astronomy Education (EAAE). This exciting programme is part of the European Week for Science and Technology and will culminate in a Science Festival during November 6-11, 2000, on the CERN premises at the French-Swiss border near Geneva. Why "Physics on Stage"? The primary goal of "Physics on Stage" is to counteract the current decline in interest and knowledge about physics among Europe's citizens by means of a series of highly visible promotional activities. It will bring together leading scientists and educators, government bodies and the media, to confront the diminishing attraction of physics to young people and to develop strategies to reverse this trend. The objective in the short term is to infuse excitement and to provide new educational materials. In the longer term, "Physics on Stage" will generate new developments by enabling experts throughout Europe to meet, exchange and innovate. "Physics on Stage" in 22 European Countries "Physics on Stage" has been initiated in 22 European

  5. Identification of Discriminating Metabolic Pathways and Metabolites in Human PBMCs Stimulated by Various Pathogenic Agents

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    2018-02-01

    Full Text Available Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi, lipopolysaccharide, and Mycobacterium tuberculosis in vitro. By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation. At 4 h of incubation, pathogenic agents inhibited expression of genes involved in both the glycolysis and oxidative phosphorylation pathways. In contrast, at 24 h of incubation, particularly glycolysis was enhanced while genes involved in oxidative phosphorylation remained unaltered in the PBMCs. In general, differential gene expression was less pronounced at 4 h compared to 24 h of incubation. KEGG pathway analysis allowed differentiation between effects induced by Candida and bacterial stimuli. Application of genome-scale metabolic model further generated a Candida-specific set of 103 reporter metabolites (e.g., desmosterol that might serve as biomarkers discriminating Candida-stimulated PBMCs from bacteria-stimuated PBMCs. Our analysis also identified a set of 49 metabolites that allowed discrimination between the effects of Borrelia burgdorferi, lipopolysaccharide and Mycobacterium tuberculosis. We conclude that analysis of pathogen-induced effects on PBMCs by a combination of KEGG pathways and genome-scale metabolic model provides deep insight in the metabolic changes coupled to host defense.

  6. SCOS2: ESA's new generation of mission control systems

    Science.gov (United States)

    Kaufeler, J. F.; Head, N. C.

    1993-01-01

    The paper describes the next generation Spacecraft Control System infrastructure (SCOSII) which is being developed at the Operations Centre (ESOC) of the European Space Agency (ESA). The objectives of the new system and selected areas of the proposed hardware and software approach are described.

  7. ESA Press Event: See Mars Express before its departure to the Red Planet

    Science.gov (United States)

    2002-08-01

    There will be ten participants: four ESA astronauts (Pedro Duque, Leopold Eyharts, Paolo Nespoli and Thomas Reiter), four Japanese astronauts from NASDA (Takao Doi, Koichi Wakata, Satoshi Furukawa and Aikihido Hoshide) and two NASA astronauts (Nicole Passonno Stott and Stephanie D. Wilson). The main objective of this training session is to prepare the astronauts for the tasks they will have to perform when the Japanese experiment module (JEM) and ESA's Columbus laboratory are docked with the core of the International Space Station over the years ahead. After completing their training and certification, the astronauts will be assigned to long-duration missions to the ISS. The advanced training at the EAC will focus on the Columbus systems and the Automated Transfer Vehicle (ATV). It will consist of 24 classroom lectures on the Columbus and ATV systems and 4 on payloads, and 2 sessions in the Columbus Trainer. Instructors are being provided by Astrium for the Columbus systems and Alenia Spazio for the ATV, with ESA/EAC staff as mentors for the Columbus payloads. The astronauts are scheduled to visit Astrium in Bremen on 30 August to get acquainted with the flight unit of the Columbus laboratory module currently undergoing integration. This group of astronauts started their advanced training in April 2001 at NASA's Johnson Space Center (JSC), Houston, where they attended a first course on the US segment of the International Space Station. This was followed by training on the JEM system at NASDA's Tsukuba Space Center, Japan, in December 2001 - January 2002 and additional training at the JSC in May 2002. At the beginning of next year the group will be returning to Tsukuba for training on Japanese payloads. Hands-on sessions on Columbus Payload Training Models are scheduled for the second half of 2003, again at ESA's European Astronaut Centre. On Thursday 5 September, between 16:30 and 18:30 hrs, the astronauts and other ESA specialists will be available for interviews

  8. Fly me to the Sun! ESA inaugurates the European Project on the Sun

    Science.gov (United States)

    2000-11-01

    In an initiative mounted by ECSITE (European Collaborative for Science, Industry and Technology Exhibitions) with funding from the European Commission and under the supervision, coordination and co-sponsorship of ESA, five teams of youngsters (16-18 years old) from Belgium, France, Germany, Italy and the Netherlands were selected and coordinated by European science museums from each of their countries (Musée des Sciences et des Techniques - Parentville, B; Cité de l'Espace - Toulouse, F; Deutsches Museum - Munich, D; Fondazione IDIS - Naples, I; Foundation Noordwijk Space Expo - Noordwijk, NL). The teams each focused on a theme related to solar research: "How does the Sun work?" (I), "The Sun as a star" (F), "Solar activity" (NL), "Observing the Sun" (D), "Humans and the Sun" (B), and built exhibition "modules" that they will present at the inauguration, in the context of European Science and Technology Week 2000 (6-10 November), promoted by the European Commission. During the two-day event, a jury of representatives of other European science and technology museums, ESA scientists, a science journalist, and two ESA astronauts (Frank de Winne and Andre Kuipers) will judge the youngsters' exhibition modules on the basis of their scientific correctness, their museological value and the commitment shown by the young "communication experts". The winning team will be officially announced on 9 November. The prize is a weekend at the Space Camp in Redu, Belgium. The objective of the European Project on the Sun is educational. It aims, through the direct and "fresh" involvement of youngsters, to heighten European citizens' awareness of space research in general and the Sun's influence on our daily lives in particular. The role of the European Space Agency as reference point in Europe for solar research has been fundamental to the project. From ESA's perspective, EPOS is part of this autumn's wider communication initiative called the Solar Season, which is highlighting ESA

  9. The ESA Geohazard Exploitation Platform

    Science.gov (United States)

    Bally, Philippe; Laur, Henri; Mathieu, Pierre-Philippe; Pinto, Salvatore

    2015-04-01

    Earthquakes represent one of the world's most significant hazards in terms both of loss of life and damages. In the first decade of the 21st century, earthquakes accounted for 60 percent of fatalities from natural disasters, according to the United Nations International Strategy for Disaster Reduction (UNISDR). To support mitigation activities designed to assess and reduce risks and improve response in emergency situations, satellite EO can be used to provide a broad range of geo-information services. This includes for instance crustal block boundary mapping to better characterize active faults, strain rate mapping to assess how rapidly faults are deforming, soil vulnerability mapping to help estimate how the soil is behaving in reaction to seismic phenomena, geo-information to assess the extent and intensity of the earthquake impact on man-made structures and formulate assumptions on the evolution of the seismic sequence, i.e. where local aftershocks or future main shocks (on nearby faults) are most likely to occur. In May 2012, the European Space Agency and the GEO Secretariat convened the International Forum on Satellite EO for Geohazards now known as the Santorini Conference. The event was the continuation of a series of international workshops such as those organized by the Geohazards Theme of the Integrated Global Observing Strategy Partnership. In Santorini the seismic community has set out a vision of the EO contribution to an operational global seismic risk program, which lead to the Geohazard Supersites and Natural Laboratories (GSNL) initiative. The initial contribution of ESA to suuport the GSNL was the first Supersites Exploitation Platform (SSEP) system in the framework of Grid Processing On Demand (GPOD), now followed by the Geohazard Exploitation Platform (GEP). In this presentation, we will describe the contribution of the GEP for exploiting satellite EO for geohazard risk assessment. It is supporting the GEO Supersites and has been further

  10. Interoperability at ESA Heliophysics Science Archives: IVOA, HAPI and other implementations

    Science.gov (United States)

    Martinez-Garcia, B.; Cook, J. P.; Perez, H.; Fernandez, M.; De Teodoro, P.; Osuna, P.; Arnaud, M.; Arviset, C.

    2017-12-01

    The data of ESA heliophysics science missions are preserved at the ESAC Science Data Centre (ESDC). The ESDC aims for the long term preservation of those data, which includes missions such as Ulysses, Soho, Proba-2, Cluster, Double Star, and in the future, Solar Orbiter. Scientists have access to these data through web services, command line and graphical user interfaces for each of the corresponding science mission archives. The International Virtual Observatory Alliance (IVOA) provides technical standards that allow interoperability among different systems that implement them. By adopting some IVOA standards, the ESA heliophysics archives are able to share their data with those tools and services that are VO-compatible. Implementation of those standards can be found in the existing archives: Ulysses Final Archive (UFA) and Soho Science Archive (SSA). They already make use of VOTable format definition and Simple Application Messaging Protocol (SAMP). For re-engineered or new archives, the implementation of services through Table Access Protocol (TAP) or Universal Worker Service (UWS) will leverage this interoperability. This will be the case for the Proba-2 Science Archive (P2SA) and the Solar Orbiter Archive (SOAR). We present here which IVOA standards were already used by the ESA Heliophysics archives in the past and the work on-going.

  11. ESA's Planetary Science Archive: Preserve and present reliable scientific data sets

    Science.gov (United States)

    Besse, S.; Vallat, C.; Barthelemy, M.; Coia, D.; Costa, M.; De Marchi, G.; Fraga, D.; Grotheer, E.; Heather, D.; Lim, T.; Martinez, S.; Arviset, C.; Barbarisi, I.; Docasal, R.; Macfarlane, A.; Rios, C.; Saiz, J.; Vallejo, F.

    2018-01-01

    The European Space Agency (ESA) Planetary Science Archive (PSA) is undergoing a significant refactoring of all its components to improve the services provided to the scientific community and the public. The PSA supports ESA's missions exploring the Solar System by archiving scientific peer-reviewed observations as well as engineering data sets. This includes the Giotto, SMART-1, Huygens, Venus Express, Mars Express, Rosetta, Exomars 2016, Exomars RSP, BepiColombo, and JUICE missions. The PSA is offering a newly designed graphical user interface which is simultaneously meant to maximize the interaction with scientific observations and also minimise the efforts needed to download these scientific observations. The PSA still offers the same services as before (i.e., FTP, documentation, helpdesk, etc.). In addition, it will support the two formats of the Planetary Data System (i.e., PDS3 and PDS4), as well as providing new ways for searching the data products with specific metadata and geometrical parameters. As well as enhanced services, the PSA will also provide new services to improve the visualisation of data products and scientific content (e.g., spectra, etc.). Together with improved access to the spacecraft engineering data sets, the PSA will provide easier access to scientific data products that will help to maximize the science return of ESA's space missions.

  12. Clinical factors and the decision to transfuse chronic dialysis patients.

    Science.gov (United States)

    Whitman, Cynthia B; Shreay, Sanatan; Gitlin, Matthew; van Oijen, Martijn G H; Spiegel, Brennan M R

    2013-11-01

    Red blood cell transfusion was previously the principle therapy for anemia in CKD but became less prevalent after the introduction of erythropoiesis-stimulating agents. This study used adaptive choice-based conjoint analysis to identify preferences and predictors of transfusion decision-making in CKD. A computerized adaptive choice-based conjoint survey was administered between June and August of 2012 to nephrologists, internists, and hospitalists listed in the American Medical Association Masterfile. The survey quantified the relative importance of 10 patient attributes, including hemoglobin levels, age, occult blood in stool, severity of illness, eligibility for transplant, iron indices, erythropoiesis-stimulating agents, cardiovascular disease, and functional status. Triggers of transfusions in common dialysis scenarios were studied, and based on adaptive choice-based conjoint-derived preferences, relative importance by performing multivariable regression to identify predictors of transfusion preferences was assessed. A total of 350 providers completed the survey (n=305 nephrologists; mean age=46 years; 21% women). Of 10 attributes assessed, absolute hemoglobin level was the most important driver of transfusions, accounting for 29% of decision-making, followed by functional status (16%) and cardiovascular comorbidities (12%); 92% of providers transfused when hemoglobin was 7.5 g/dl, independent of other factors. In multivariable regression, Veterans Administration providers were more likely to transfuse at 8.0 g/dl (odds ratio, 5.9; 95% confidence interval, 1.9 to 18.4). Although transplant eligibility explained only 5% of decision-making, nephrologists were five times more likely to value it as important compared with non-nephrologists (odds ratio, 5.2; 95% confidence interval, 2.4 to 11.1). Adaptive choice-based conjoint analysis was useful in predicting influences on transfusion decisions. Hemoglobin level, functional status, and cardiovascular comorbidities

  13. Anemia prevalence and treatment practice in patients with non-myeloid tumors receiving chemotherapy

    International Nuclear Information System (INIS)

    Merlini, Laura; Cartenì, Giacomo; Iacobelli, Stefano; Stelitano, Caterina; Airoldi, Mario; Balcke, Peter; Keil, Felix; Haslbauer, Ferdinand; Belton, Laura; Pujol, Beatriz

    2013-01-01

    To describe the prevalence and management of anemia in cancer patients. This cross-sectional, observational survey was conducted in Italy and Austria. Centers prespecified one day, during a 4-month enrollment window, to report specific data collected during normal clinical practice for patients with non-myeloid tumors attending for chemotherapy (±radiotherapy) treatment. The primary endpoint was the prevalence of anemia as determined using a prespecified algorithm: hemoglobin (Hb) ≤10 g/dL on/within 3 days prior to visit; ongoing anemia treatment; physician diagnosis of anemia, together with ≥1 anemia symptom. Between November 18, 2010 and March 18, 2011, data for 1412 patients were collected (Italy n = 1130; Austria n = 282). Most patients (n = 1136; 80%) had solid tumors; 809 (57%) had received ≤3 chemotherapy cycles. The prevalence of anemia was 32% (95% confidence interval: 29.4%–34.2%); 196 patients (14%) were deemed anemic based on Hb ≤10 g/dL, 131 (9%) on ongoing anemia treatment, and 121 (9%) on physician diagnosis/anemia symptom. Overall, 1153 patients (82%) had Hb data; mean (standard deviation [SD]) Hb levels were 11.7 (1.7) g/dL. In total, 456 patients (32%) had anemia symptoms: fatigue (n = 392; 28%), depression (n = 122; 9%), and dyspnea (n = 107; 8%) were most common. Fifty-one patients (4%) had had their current chemotherapy cycle delayed due to anemia. On visit day, or ≤28 days prior, 91 (6%), 188 (13%), and 81 patients (6%) had evidence of whole blood/red blood cell transfusion, erythropoiesis-stimulating agent use, or iron use, respectively. On the prespecified study day, one-third of patients with non-myeloid tumors undergoing chemotherapy were found to be anemic and 13% had evidence of erythropoiesis-stimulating agent use then or in the 28 days prior

  14. Luminescence optically stimulated: theory and applications

    International Nuclear Information System (INIS)

    Rivera M, T.; Azorin N, J.

    2002-01-01

    The thermally stimulated luminescence (Tl) has occupied an important place in the Solid state physics (FES) by the flexibility of the phenomena, mainly for its applications in the fields of Radiation Physics (FR) and Medical Physics (MF). The reason of this phenomena lies in the fact of the electrons release by the action of heat. Under that same reason, it can be used the action of another stimulant agent for releasing the trapped electrons in the metastable states (EM), this agent is the light which has the same effect that the heat, giving as result the production of light photons at using light in the visible spectra, of different wavelength that the excitation light. This phenomena is called Luminescence optically stimulated (LOE). The LOE has a great impact in the Solid State Physics (FES), dating and now in the use of the phenomena as a dosimetric method, alternate to the Tl, for its use in the ionizing and non-ionizing radiations fields. (Author)

  15. Oxidative stress modulates heme synthesis and induces peroxiredoxin-2 as a novel cytoprotective response in β-thalassemic erythropoiesis.

    Science.gov (United States)

    De Franceschi, Lucia; Bertoldi, Mariarita; De Falco, Luigia; Santos Franco, Sara; Ronzoni, Luisa; Turrini, Franco; Colancecco, Alessandra; Camaschella, Clara; Cappellini, Maria Domenica; Iolascon, Achille

    2011-11-01

    β-thalassemic syndromes are inherited red cell disorders characterized by severe ineffective erythropoiesis and increased levels of reactive oxygen species whose contribution to β-thalassemic anemia is only partially understood. We studied erythroid precursors from normal and β-thalassemic peripheral CD34(+) cells in two-phase liquid culture by proteomic, reverse transcriptase polymerase chain reaction and immunoblot analyses. We measured intracellular reactive oxygen species, heme levels and the activity of δ-aminolevulinate-synthase-2. We exposed normal cells and K562 cells with silenced peroxiredoxin-2 to H(2)O(2) and generated a recombinant peroxiredoxin-2 for kinetic measurements in the presence of H(2)O(2) or hemin. In β-thalassemia the increased production of reactive oxygen species was associated with down-regulation of heme oxygenase-1 and biliverdin reductase and up-regulation of peroxiredoxin-2. In agreement with these observations in β-thalassemic cells we found decreased heme levels related to significantly reduced activity of the first enzyme of the heme pathway, δ-aminolevulinate synthase-2 without differences in its expression. We demonstrated that the activity of recombinant δ-aminolevulinate synthase-2 is inhibited by both reactive oxygen species and hemin as a protective mechanism in β-thalassemic cells. We then addressed the question of the protective role of peroxiredoxin-2 in erythropoiesis by exposing normal cells to oxidative stress and silencing peroxiredoxin-2 in human erythroleukemia K562 cells. We found that peroxiredoxin-2 expression is up-regulated in response to oxidative stress and required for K562 cells to survive oxidative stress. We then showed that peroxiredoxin-2 binds heme in erythroid precursors with high affinity, suggesting a possible multifunctional cytoprotective role of peroxiredoxin-2 in β-thalassemia. In β-thalassemic erythroid cells the reduction of δ-aminolevulinate synthase-2 activity and the increased

  16. MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

    OpenAIRE

    Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

    2009-01-01

    The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

  17. Preoperative Stimulation of Erythropoiesis in Patients with Anemia

    Directory of Open Access Journals (Sweden)

    V. I. Zagrekov

    2010-01-01

    Full Text Available Objective: to comparatively study different postoperative analgesia modes in patients undergoing reconstructive interventions into the abdominal aorta. Subjects and methods. The impact of analgesia on the course of the early postoperative period was comparatively studied in 98 patients. According to the mode of postoperative analgesia, the patients were divided into 3 groups: 1 35 patients received traditional analgesia with narcotic analgesics (promedol, morphine i.m.; 2 32 patients had prolonged epidural infusion of 0.2% ropivocaine solution with fractional epidural administration of fentanyl 0.1 mg twice daily; 3 31 patients were given a combination of epidural naropine and fentanyl with parenteral ketorolac 90 mg/day and paracetamol 3 g/day. The magnitude of pain syndrome was analyzed using the visual analogue scale. The parameters of central hemodynamics (CHD were estimated applying thoracic tetrapolar rheocardiography. Autonomic homeostatic changes were studied from the cardiac rhythm variability by computer rhythmocardiography. Results. The least magnitude of pain syndrome, the eutonic type of autonomic regulation of the cardiovascular system, and the highest cardiac index values were recorded in Group 3. Conclusion. The use of mul-timodal postoperative analgesia ensures valid analgesia with the stable parameters of CHD and autonomic homeostasis. Key words: analgesia, epidural infusion, visual analogue scale, central hemodynamics, cardiac rhythm variability.

  18. NASA and ESA Collaboration on Hexavalent Chrome Alternatives - Pretreatments with Primers Screening Final Test Report

    Science.gov (United States)

    Rothgeb, Matthew J.; Kessel, Kurt R.

    2015-01-01

    Hexavalent chromium (hex chrome or Cr(VI)) is a widely used element within applied coating systems because of its self-healing and corrosion-resistant properties. The replacement of hex chrome in the processing of aluminum for aviation and aerospace applications remains a goal of great significance. Aluminum is the major manufacturing material of structures and components in the space flight arena. The National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) are engaged in a collaborative effort to test and evaluate alternatives to hexavalent chromium containing corrosion coating systems. NASA and ESA share common risks related to material obsolescence associated with hexavalent chromium used in corrosion-resistant coatings. In the United States, Occupational Safety and Health Administration (OSHA) studies have concluded that hexavalent chromium is carcinogenic and poses significant risk to human health. On May 5, 2011, amendments to the Defense Federal Acquisition Regulation Supplement (DFARS) were issued in the Federal Register. Subpart 223.73 prohibits contracts from requiring hexavalent chromium in deliverables unless certain exceptions apply. Subpart 252.223-7008 provides the contract clause prohibiting contractors and subcontractors from using or delivering hexavalent chromium in a concentration greater than 0.1 percent by weight for all new contracts associated with supplies, maintenance and repair services, and construction materials. ESA faces its own increasingly stringent regulations within European directives such as Registration, Evaluation, Authorization and Restriction of Chemical (REACH) substances and the Restriction of Hazardous Substances Directive (RoHS) which have set a mid-2017 sunset date for hexavalent chromium. NASA and ESA continue to search for an alternative to hexavalent chromium in coatings applications that meet their performance requirements in corrosion protection, cost, operability, and health and

  19. ESA uncovers Geminga's `hot spot'

    Science.gov (United States)

    2004-07-01

    16 July 2004 Astronomers using ESA’s X-ray observatory XMM-Newton have detected a small, bright ‘hot spot’ on the surface of the neutron star called Geminga, 500 light-years away. The hot spot is the size of a football field and is caused by the same mechanism producing Geminga’s X-ray tails. This discovery identifies the missing link between the X-ray and gamma-ray emission from Geminga. hi-res Size hi-res: 1284 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot This figure shows the effects of charged particles accelerated in the magnetosphere of Geminga. Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (in red) hit the star’s magnetic poles like in an ‘own goal’. Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degrees hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. An animated version of the entire sequence can be found at: Click here for animated GIF [low resolution, animated GIF, 5536 KB] Click here for AVI [high resolution, AVI with DIVX compression, 19128 KB] hi-res Size hi-res: 371 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (a) Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of

  20. Interactions of ionic and nonionic contrast agents with thrombolytic agents

    International Nuclear Information System (INIS)

    Fareed, J.; Moncada, R.; Scanlon, P.; Hoppensteadt, D.; Huan, X.; Walenga, J.M.

    1987-01-01

    Both the ionic and nonionic intravascular contrast media have been used before and after the administration of thrombolytic agents to evaluate clot lysis during angioplasty and the treatment of myocardial infarction. In experimental animal models, the authors found that the clot lytic efficacy of streptokinase, streptokinase-plasminogen complex, and tissue plasminogen activator (t-PA) is markedly augmented if these agents are administered within 1 hour after the angiographic producers. Furthermore, contrast agents injected after the administration of t-Pa exhibit a synergistic action. In stimulated models administration of one ionic contrast medium (Angiovist, Berlex, Wayne, NJ) and two nonionic contrast agents (Isovue-370, Squibb Diagnostics, New Brunswick, NJ; Omnipaque-350, Winthrop, NY) 15 minutes before the administration of t-PA resulted in marked enhancement of the lytic activity. Although the mechanism of this interaction is unknown at this time, it should be taken into consideration in the treatment of patients with myocardial infarction, in whom contrast agents are continually used to evaluate the therapeutic lysis. Furthermore, this interaction may be partly related to the therapeutic efficacy and/or hemorrhagic actions observed

  1. Simultaneous detection of xenon and krypton in equine plasma by gas chromatography-tandem mass spectrometry for doping control.

    Science.gov (United States)

    Kwok, Wai Him; Choi, Timmy L S; So, Pui-Kin; Yao, Zhong-Ping; Wan, Terence S M

    2017-02-01

    Xenon can activate the hypoxia-inducible factors (HIFs). As such, it has been allegedly used in human sports for increasing erythropoiesis. Krypton, another noble gas with reported narcosis effect, can also be expected to be a potential and less expensive erythropoiesis stimulating agent. This has raised concern about the misuse of noble gases as doping agents in equine sports. The aim of the present study is to establish a method for the simultaneous detection of xenon and krypton in equine plasma for the purpose of doping control. Xenon- or krypton-fortified equine plasma samples were prepared according to reported protocols. The target noble gases were simultaneously detected by gas chromatography-triple quadrupole mass spectrometry using headspace injection. Three xenon isotopes at m/z 129, 131, and 132, and four krypton isotopes at m/z 82, 83, 84, and 86 were targeted in selected reaction monitoring mode (with the precursor ions and product ions at identical mass settings), allowing unambiguous identification of the target analytes. Limits of detection for xenon and krypton were about 19 pmol/mL and 98 pmol/mL, respectively. Precision for both analytes was less than 15%. The method has good specificity as background analyte signals were not observed in negative equine plasma samples (n = 73). Loss of analytes under different storage temperatures has also been evaluated. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Erythropoietin: a multimodal neuroprotective agent

    OpenAIRE

    Byts, Nadiya; Sir?n, Anna-Leena

    2009-01-01

    Abstract The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and ...

  3. Forging ties between young People from CERN and ESA

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The CERN Student Club (CSC) is the official club for the community of young people at CERN. In addition to organizing regular activities for its members, the club serves as a platform for young people to come together and meet people from other backgrounds. On 11 and 12 April, the network for young people from the European Space Agency (YoungESA) organized an excursion to CERN, in which more than 30 young researchers participated. The CERN Student Club was happy to host several activities for the members of the two communities.   Some of the participants in the first meeting of the ESA-CERN student clubs. “One of the most amazing things about being a young researcher is the boundless opportunities for meeting people from all around the world, whether for the exchange of research ideas or for social purposes”, says Yi Ling Hwong, a member of the CMS experiment and Vice-president of the CERN Student Club. “In a place like CERN such occasions are abundant but t...

  4. The ESA Gaia Archive: Data Release 1

    Science.gov (United States)

    Salgado, J.; González-Núñez, J.; Gutiérrez-Sánchez, R.; Segovia, J. C.; Durán, J.; Hernández, J. L.; Arviset, C.

    2017-10-01

    The ESA Gaia mission is producing the most accurate source catalogue in astronomy to date. This represents a challenge in archiving to make the information and data accessible to astronomers in an efficient way, due to the size and complexity of the data. Also, new astronomical missions, taking larger and larger volumes of data, are reinforcing this change in the development of archives. Archives, as simple applications to access data, are evolving into complex data centre structures where computing power services are available for users and data mining tools are integrated into the server side. In the case of astronomy missions that involve the use of large catalogues, such as Gaia (or Euclid to come), the common ways to work on the data need to be changed to the following paradigm: "move the code close to the data". This implies that data mining functionalities are becoming a must to allow for the maximum scientific exploitation of the data. To enable these capabilities, a TAP+ interface, crossmatch capabilities, full catalogue histograms, serialisation of intermediate results in cloud resources, such as VOSpace etc., have been implemented for the Gaia Data Release 1 (DR1), to enable the exploitation of these science resources by the community without any bottlenecks in the connection bandwidth. We present the architecture, infrastructure and tools already available in the Gaia Archive DR1 (http://archives.esac.esa.int/gaia/) and we describe the capabilities and infrastructure.

  5. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Directory of Open Access Journals (Sweden)

    Seeley TW

    2017-03-01

    Full Text Available Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu Therapeutics R&D, FibroGen, Inc., San Francisco, CA, USA Abstract: The effects of pharmacological hypoxia-inducible factor (HIF stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF, using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs, FG-4497 or roxadustat (FG-4592. In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. Keywords: cancer progression, erythropoiesis, hypoxia-inducible factor, hypoxia-inducible factor prolyl hydroxylase inhibitors, vascular endothelial growth factor, MMTV-Neu breast cancer model

  6. Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

    Science.gov (United States)

    Langer, Arielle L; Ginzburg, Yelena Z

    2017-06-01

    Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

  7. IMPROVING THE SKILL AND THE INTEREST OF WRITING ADVERTISEMENTS AND POSTERS THROUGH ESA SEQUENCE

    Directory of Open Access Journals (Sweden)

    author Fatma Yuniarti

    2015-01-01

    Full Text Available The action reserach aims at improving the students’ writing skill especially to write advertsements and posters. Both are the short functional texts to be learned at the second semester. According to the data on pre cycle, the students of second semester got difficulties to write advertisements and posters. A treatment was necessary to help the students overcome their problem. To consider the related literature, the writer decided to implement ESA sequence (Harmer 2001 in the class. The elements of teaching in ESA Sequence are Engage (to arouse the students’ interests, Study (learn the language focus, and Activate (use the language freely and communicatively. The data were taken from the test of the linguistic competence mastery, the students writing, and the questionnaire. The students’ linguistic competence got increased as shown by the score (58 in pre-cycle, 66 in cycle 1, and 70 in cycle 2. The students’ ability to write the short functional texts also get improved as indicated by the average score on writing tasks (53 in pre-cycle, 63 in cycle 1, 72 in cycle 2. The interest also gets better as shown by the score of the questionnaire (22,3 in pre-cycle, 33,5 in cycle 1, and 37 in cycle 2. It means ESA Sequence can improve the studets’ ability to write advertisements and posters.Key words : advertisement, ESA (Engange Study Activate, poster

  8. ESA Parabolic Flight, Drop Tower and Centrifuge Opportunities for University Students

    Science.gov (United States)

    Callens, Natacha; Ventura-Traveset, Javier; Zornoza Garcia-Andrade, Eduardo; Gomez-Calero, Carlos; van Loon, Jack J. W. A.; Pletser, Vladimir; Kufner, Ewald; Krause, Jutta; Lindner, Robert; Gai, Frederic; Eigenbrod, Christian

    The European Space Agency (ESA) Education Office was established in 1998 with the purpose of motivating young people to study science, engineering and technology subjects and to ensure a qualified workforce for ESA and the European space sector in the future. To this end the ESA Education Office is supporting several hands-on activities including small student satellites and student experiments on sounding rockets, high altitude balloons as well as microgravity and hypergravity platforms. This paper is intended to introduce three new ESA Education Office hands-on activities called "Fly Your Thesis!", "Drop Your Thesis!" and "Spin Your Thesis!". These activities give re-spectively access to aircraft parabolic flight, drop tower and centrifuge campaigns to European students. These educational programmes offer university students the unique opportunity to design, build, and eventually perform, in microgravity or hypergravity, a scientific or techno-logical experiment which is linked to their syllabus. During the "Fly Your Thesis!" campaigns, the students accompany their experiments onboard the A300 Zero-G aircraft, operated by the company Novespace, based in Bordeaux, France, for a series of three flights of 30 parabolas each, with each parabola providing about 20s of microgravity [1]. "Drop Your Thesis!" campaigns are held in the ZARM Drop Tower, in Bremen, Germany. The installation delivers 4.74s of microgravity in dropping mode and 9.3s in the catapulting mode [2]. Research topics such as fluid physics, fundamental physics, combustion, biology, material sciences, heat transfer, astrophysics, chemistry or biochemistry can greatly benefit from using microgravity platforms. "Spin Your Thesis!" campaigns take place in the Large Diameter Centrifuge (LDC) facility, at ESTEC, Noordwijk, in the Netherlands. This facility offers an acceleration from 1 to 20 times Earth's gravity [3]. The use of hypergravity allows completing the scientific picture of how gravity has an

  9. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants

    Directory of Open Access Journals (Sweden)

    Weyandt LL

    2014-09-01

    characteristics such as sex, race, use of illicit drugs, and academic performance are associated with misuse of stimulant medications. Results also indicate that individuals both with and without ADHD are more likely to misuse short-acting agents than long-acting agents. These findings have implications for intervention, prevention, and future research. Keywords: ADHD symptomatology, pharmacotherapy, nonmedical stimulant use, lisdexamfetamine, methylphenidate, amphetamine

  10. The ESA Hubble 15th Anniversary Campaign: A Trans-European collaboration project

    Science.gov (United States)

    Zoulias, Manolis; Christensen, Lars Lindberg; Kornmesser, Martin

    2006-08-01

    On April 24th 2005, NASA/ESA Hubble Space Telescope had been in orbit for 15 years. The anniversary was celebrated by ESA with the production of an 83 min. scientific movie and a 120 pages book, both titled ``Hubble, 15 years of discovery''. In order to cross language and distribution barriers a network of 16 translators and 22 partners from more than 10 countries was established. The DVD was distributed in approximately 700,000 copies throughout Europe. The project was amongst the largest of its kind with respect to collaboration, distribution and audience impact. It clearly demonstrated how international collaboration can produce effective cross-cultural educational and outreach products for astronomy.

  11. Comparison of Three Sample Preparation Methods for Analysis of Chemical Warfare Agent Stimulants in Water

    International Nuclear Information System (INIS)

    Alessandro Sassolini

    2015-01-01

    Analytical chemistry in CBRNe (Chemical Biological Radiological Nuclear explosive) context requires not only high quality data; quickness, ruggedness and robustness are also mandatory. In this work, three samples preparation methods were compared using several organophosphorus pesticides as test compounds, used as stimulants of nerve CWA (Chemical Warfare Agents) to choose the one with best characteristics. Result was obtained better with the Dispersive Liquid-Liquid Micro Extraction (DLLME), relatively new in CBRNe field, obtaining uncertainty for different simulants between 8 and 15 % while a quantification limit between 0.01 and 0.08 μg/ l. To optimize this extraction method, different organo chlorinated solvents also tested but not relevant difference in these tests was obtained. In this work, all samples were analyzed by using a gas chromatography coupled with mass spectrometer (GC-MS) and also with Gas Chromatograph coupled with Nitrogen Phosphorous Detector (NPD) for DLLME samples to evaluate a low cost and rugged instrument adapt to field analytical methods with good performance in terms of uncertainty and sensibility even if poorer respect to the mass spectrometry. (author)

  12. The Arabidopsis defence response mutant esa1 as a tool to discover novel resistance traits against Fusarium diseases

    NARCIS (Netherlands)

    Hemelrijck, van W.; Wouters, P.F.J.; Brouwer, M.; Windelinckx, A.; Goderis, I.J.W.M.; Bolle, De M.F.C.; Thomma, B.P.H.J.; Cammue, B.P.A.; Delauré, S.L.

    2006-01-01

    The Arabidopsis thaliana mutant esa1 was previously shown to exhibit enhanced susceptibility to the necrotrophic fungal pathogens Alternaria brassicicola, Botrytis cinerea and Plectosphaerella cucumerina. In this work, we tried to elaborate on this susceptibility by investigating whether the esa1

  13. Improving accessibility and discovery of ESA planetary data through the new planetary science archive

    Science.gov (United States)

    Macfarlane, A. J.; Docasal, R.; Rios, C.; Barbarisi, I.; Saiz, J.; Vallejo, F.; Besse, S.; Arviset, C.; Barthelemy, M.; De Marchi, G.; Fraga, D.; Grotheer, E.; Heather, D.; Lim, T.; Martinez, S.; Vallat, C.

    2018-01-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific data sets through various interfaces at http://psa.esa.int. Mostly driven by the evolution of the PDS standards which all new ESA planetary missions shall follow and the need to update the interfaces to the archive, the PSA has undergone an important re-engineering. In order to maximise the scientific exploitation of ESA's planetary data holdings, significant improvements have been made by utilising the latest technologies and implementing widely recognised open standards. To facilitate users in handling and visualising the many products stored in the archive which have spatial data associated, the new PSA supports Geographical Information Systems (GIS) by implementing the standards approved by the Open Geospatial Consortium (OGC). The modernised PSA also attempts to increase interoperability with the international community by implementing recognised planetary science specific protocols such as the PDAP (Planetary Data Access Protocol) and EPN-TAP (EuroPlanet-Table Access Protocol). In this paper we describe some of the methods by which the archive may be accessed and present the challenges that are being faced in consolidating data sets of the older PDS3 version of the standards with the new PDS4 deliveries into a single data model mapping to ensure transparent access to the data for users and services whilst maintaining a high performance.

  14. Aspects of ESA s public outreach programme

    Science.gov (United States)

    Maree, H.

    The Science Programme Communication Service is currently implementing a new policy to increase the overall public interest in ESA Science Programme by adopting new ways of promoting its activities, accordingly to the simple principle that "different target audiences have different needs". It is clear that the general public (i.e. "the man in the street" / "the average tax- payer") rarely has the knowledge and the background to understand what exactly a space mission is, what it does and why it does it ("Mission oriented approach"). The experience has shown that a space mission becomes "popular" amongst this target audience when the relevant communication is done by passing generic/bas ic/simple messages ("Thematic oriented approach"). The careful selection of adequate supports together with efficient distribution and promotion networks are also key parameters for success of the latter approach. One should also note that the overall objective of this new policy, is to raise people's interest in space in general. By presenting the information under the ESA brand, the public will start more and more to associate this brand and Europe to space exploration. Within the next twelve months, four scientific missions will be launched. Interestingly, tree of them (SMART-1, ROSETTA and MARS EXPRESS) offer a unique opportunity to implement the new communication policy under the single thematic : Europe is exploring the Solar System. Nevertheless, the study of the various mission profiles and their potential communication impact lead us to choose to reach out the general public primarily via the sub-thematic : Europe goes to Mars.

  15. Neurologic Complications of Psychomotor Stimulant Abuse.

    Science.gov (United States)

    Sanchez-Ramos, Juan

    2015-01-01

    Psychomotor stimulants are drugs that act on the central nervous system (CNS) to increase alertness, elevate mood, and produce a sense of well-being. These drugs also decrease appetite and the need for sleep. Stimulants can enhance stamina and improve performance in tasks that have been impaired by fatigue or boredom. Approved therapeutic applications of stimulants include attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. These agents also possess potent reinforcing properties that can result in excessive self-administration and abuse. Chronic use is associated with adverse effects including psychosis, seizures, and cerebrovascular accidents, though these complications usually occur in individuals with preexisting risk factors. This chapter reviews the adverse neurologic consequences of chronic psychomotor stimulant use and abuse, with a focus on two prototypical stimulants methamphetamine and cocaine. © 2015 Elsevier Inc. All rights reserved.

  16. Hemoglobin levels and quality of life in patients with symptomatic chemotherapy-induced anemia: the eAQUA study

    Directory of Open Access Journals (Sweden)

    Mouysset JL

    2016-01-01

    Full Text Available Jean-Loup Mouysset,1 Beata Freier,2 Joan van den Bosch,3 Charles Briac Levaché,4 Alain Bols,5 Hans Werner Tessen,6 Laura Belton,7 G Chet Bohac,8 Jan-Henrik Terwey,9 Giuseppe Tonini101Department of Medical Oncology, Clinique Rambot Provencale, Aix en Provence, France; 2Clinical Oncology, Wojewodzki Szpital Specjalistyczny, Wroclaw, Poland; 3Department of Internal Medicine/Oncology, Albert Schweitzer Ziekenhuis locatie Dordwijk, Dordrecht, the Netherlands; 4Radiotherapy Service, Medical Oncology, Polyclinique Francheville, Périgueux, France; 5Central Pharmacy, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium; 6Private Oncology Practice. Goslar, Germany; 7LB Biostatistics, London, UK; 8Clinical Research, Amgen Inc., Thousand Oaks, CA, USA; 9Medical Development – Oncology, Amgen (Europe GmbH, Zug, Switzerland; 10Department of Medical Oncology, Università Campus Bio-Medico, Roma, ItalyPurpose: To assess hemoglobin (Hb outcomes and fatigue-related quality-of-life (QoL (electronic assessment in patients with solid tumors and symptomatic chemotherapy-induced anemia receiving cytotoxic chemotherapy and darbepoetin alfa (DA or another erythropoiesis-stimulating agent according to European indication.Methods: eAQUA was a Phase IV prospective observational study. The primary outcome (assessed in the primary analysis set [PAS]: patients receiving one or more DA dose who had baseline and week 9 assessments for Hb and QoL was the proportion of patients receiving DA having both Hb increases ≥1 g/dL and improved QoL between baseline and week 9. Functional Assessment of Cancer Therapy-Fatigue (FACT-F subscale scores were anchored to fatigue visual analog scale scores to determine the minimally important difference for improved QoL. Overall data/data over time are reported for the full analysis set (patients receiving one or more erythropoiesis-stimulating agent dose, n=1,158; week 9 data (ie, data relating to the primary and secondary outcomes are reported

  17. NASA and ESA Collaboration on Hexavalent Chrome Alternatives: Pretreatments Only Final Test Report

    Science.gov (United States)

    Kessel, Kurt R.

    2015-01-01

    Hexavalent chromium (hex chrome or CR(VI)) is a widely used element within applied coating systems because of its self-healing and corrosion-resistant properties. The replacement of hex chrome in the processing of aluminum for aviation and aerospace applications remains a goal of great significance. Aluminum is the major manufacturing material of structures and components in the space flight arena. The National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) are engaged in a collaborative effort to test and evaluate alternatives to hexavalent chromium containing corrosion coating systems. NASA and ESA share common risks related to material obsolescence associated with hexavalent chromium used in corrosion-resistant coatings.

  18. Strengthening the Security of ESA Ground Data Systems

    Science.gov (United States)

    Flentge, Felix; Eggleston, James; Garcia Mateos, Marc

    2013-08-01

    A common approach to address information security has been implemented in ESA's Mission Operations (MOI) Infrastructure during the last years. This paper reports on the specific challenges to the Data Systems domain within the MOI and how security can be properly managed with an Information Security Management System (ISMS) according to ISO 27001. Results of an initial security risk assessment are reported and the different types of security controls that are being implemented in order to reduce the risks are briefly described.

  19. Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

    International Nuclear Information System (INIS)

    Ramaseshan, Ramakrishnan; Sundarrajan, Subramanian; Liu, Yingjun; Barhate, R S; Lala, Neeta L; Ramakrishna, S

    2006-01-01

    A catalyst for the detoxification of nerve agents is synthesized from β-cyclodextrin (β-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with β-CD, IBA, a blend of β-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane

  20. Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

    Science.gov (United States)

    Ramaseshan, Ramakrishnan; Sundarrajan, Subramanian; Liu, Yingjun; Barhate, R. S.; Lala, Neeta L.; Ramakrishna, S.

    2006-06-01

    A catalyst for the detoxification of nerve agents is synthesized from β-cyclodextrin (β-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with β-CD, IBA, a blend of β-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane.

  1. Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

    Energy Technology Data Exchange (ETDEWEB)

    Ramaseshan, Ramakrishnan [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Sundarrajan, Subramanian [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Liu, Yingjun [Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore (Singapore); Barhate, R S [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Lala, Neeta L [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore); Ramakrishna, S [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore (Singapore)

    2006-06-28

    A catalyst for the detoxification of nerve agents is synthesized from {beta}-cyclodextrin ({beta}-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with {beta}-CD, IBA, a blend of {beta}-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane.

  2. Mida suudab muusikateraapia? / Melanie Voigt, Esa Ala-Ruona ; inetrvjueerinud Kristel Kossar

    Index Scriptorium Estoniae

    Voigt, Melanie

    2012-01-01

    Eesti Muusika- ja Teatriakadeemias toimunud Euroopa Muusikateraapia Konföderatsiooni peaassambleel ja sümpoosionil ettekannetega esinenud muusikaterapeudid Malanie Voigt Saksamaalt ja Esa Ala-Ruona Soomest räägivad tööst puuetega lastega ja tööstressist ning heliilmast

  3. Migration of polypotent hemopoietic stem cells from mouse bone marrow shielded during irradiation after hemorrhage and transfusion of syngeneic erythrocytes

    International Nuclear Information System (INIS)

    Kozlov, V.A.; Lozovoj, V.P.; Zhuravkin, I.N.

    1977-01-01

    CBA mice have been X-irradiated with a lethal dose of 850 R. The rate of migration of hemopoietic stem cells has been studied at varying times after hemorrhage and administration of syngeneic erythrocytes. Hemorrhage has been shown to enhance markedly the stem cell migration. Administration of syngeneic erythrocytes decreases considerably the rate of stem cell migaration. It is suggested that the erythropoiesis stimulation is responsible for the increased yield of stem cells from the bone marrow, and that the suppression of erythropoiesis inhibits migration of the stem cells

  4. The ESA climate change initiative: Satellite data records for essential climate variables

    DEFF Research Database (Denmark)

    Hollmann, R.; Merchant, C.J.; Saunders, R.

    2013-01-01

    The European Space Agency (ESA) has launched the Climate Change Initiative (CCI) to provide satellite-based climate data records (CDRs) that meet the challenging requirements of the climate community. The aim is to realize the full potential of the long-term Earth observation (EO) archives...... that both ESA and third parties have established. This includes aspects of producing a CDR, which involve data acquisition, calibration, algorithm development, validation, maintenance, and provision of the data to the climate research community. The CCI is consistent with several international efforts...... targeting the generation of satellite derived climate data records. One focus of the CCI is to provide products for climate modelers who increasingly use satellite data to initialize, constrain, and validate models on a wide range of space and time scales....

  5. ESA parabolic flights, drop tower and centrifuge opportunities for university students

    NARCIS (Netherlands)

    Callens, N; Ventura-Traveset, J.; de Lophem, T.L.; Lopez de Echazarreta, C.; Pletser, V.; van Loon, J.J.W.A

    2011-01-01

    "Fly Your Thesis!-An Astronaut Experience" is an educational programme launched by the ESA Education Office that aims to offer to European students the unique opportunity to design, build, and eventually fly, a scientific experiment as part of their Master or Ph.D. thesis. Selected teams accompany

  6. Evaluating ESA CCI Soil Moisture in East Africa

    Science.gov (United States)

    McNally, Amy; Shukla, Shraddhanand; Arsenault, Kristi R.; Wang, Shugong; Peters-Lidard, Christa D.; Verdin, James P.

    2016-01-01

    To assess growing season conditions where ground based observations are limited or unavailable, food security and agricultural drought monitoring analysts rely on publicly available remotely sensed rainfall and vegetation greenness. There are also remotely sensed soil moisture observations from missions like the European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) and NASAs Soil Moisture Active Passive (SMAP), however these time series are still too short to conduct studies that demonstrate the utility of these data for operational applications, or to provide historical context for extreme wet or dry events. To promote the use of remotely sensed soil moisture in agricultural drought and food security monitoring, we use East Africa as a case study to evaluate the quality of a 30+ year time series of merged active-passive microwave soil moisture from the ESA Climate Change Initiative (CCI-SM). Compared to the Normalized Difference Vegetation index (NDVI) and modeled soil moisture products, we found substantial spatial and temporal gaps in the early part of the CCI-SM record, with adequate data coverage beginning in 1992. From this point forward, growing season CCI-SM anomalies were well correlated (R greater than 0.5) with modeled, seasonal soil moisture, and in some regions, NDVI. We use correlation analysis and qualitative comparisons at seasonal time scales to show that remotely sensed soil moisture can add information to a convergence of evidence framework that traditionally relies on rainfall and NDVI in moderately vegetated regions.

  7. X-ray optics developments at ESA

    DEFF Research Database (Denmark)

    Bavdaz, M.; Wille, E.; Wallace, K.

    2013-01-01

    Future high energy astrophysics missions will require high performance novel X-ray optics to explore the Universe beyond the limits of the currently operating Chandra and Newton observatories. Innovative optics technologies are therefore being developed and matured by the European Space Agency (ESA......) in collaboration with research institutions and industry, enabling leading-edge future science missions. Silicon Pore Optics (SPO) [1 to 21] and Slumped Glass Optics (SGO) [22 to 29] are lightweight high performance X-ray optics technologies being developed in Europe, driven by applications in observatory class...... reflective coatings [30 to 35]. In addition, the progress with the X-ray test facilities and associated beam-lines is discussed [36]. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only....

  8. ESA parabolic flights, drop tower and centrifuge opportunities for university students

    NARCIS (Netherlands)

    Callens, N.; Ventura-Traveset, J.; de Lophem, T.L.; Lopez de Echazarreta, C.; Pletser, V.; van Loon, J.J.W.A.

    2011-01-01

    "Fly Your Thesis!—An Astronaut Experience" is an educational programme launched by the ESA Education Office that aims to offer to European students the unique opportunity to design, build, and eventually fly, a scientific experiment as part of their Master or Ph.D. thesis. Selected teams accompany

  9. Hubble gets new ESA-supplied solar arrays

    Science.gov (United States)

    1993-12-01

    Derek Eaton, ESA project manager, was overjoyed with the success of the day's spacewalk. "To build two such massive arrays some years apart to such tight tolerances and have one replace the other with so few problems is a tribute to the design and manufacturing skills of ESA and British Aerospace, the prime contractor for the arrays", he said. "The skill of Kathy and Tom contributed greatly to this success". The astronauts began their spacewalk at 09h30 p.m. CST (04h30 a.m. CET, Monday). Their first task was to jettison the troublesome solar array that failed to retract yesterday. Perched on the end of the shuttle's robot arm, 7.5 metres above the cargo bay, Thornton carefully released the array. ESA astronaut Claude Nicollier then pulled the arm away from the free-floating panel and mission commander Dick Covey fired the shuttle's thrusters to back away. Endeavour and the discarded array are moving apart at a rate of 18.5 kilometres each 90-minute orbit of the Earth. The array is expected to burn up in the Earth's atmosphere harmlessly within a year or so. The astronauts had no problems installing the new arrays and stowing the left-hand wing in the cargo bay for the return to Earth. The new arrays will remain rolled-up against the side of the telescope until the fifth spacewalk on Wednesday/Thursday. The telescope itself will be deployed on Saturday. The telescope's first set of arrays flexed in orbit because of the sudden swing in temperature as the craft moved in and out of sunlight. The movement, or "jitter", affected the telescope's pointing system and disrupted observations at times. The Space Telescope Operations Control Centre largely compensated for the problem with special software but this occupied a large amount of computer memory. The new arrays incorporate three major changes to eliminate the problem. The metal bi-stem booms, which support the solar blankets, is protected from extreme temperature changes by a concertina-style sleeve made up of one

  10. The Planetary Science Archive (PSA): Exploration and discovery of scientific datasets from ESA's planetary missions

    Science.gov (United States)

    Vallat, C.; Besse, S.; Barbarisi, I.; Arviset, C.; De Marchi, G.; Barthelemy, M.; Coia, D.; Costa, M.; Docasal, R.; Fraga, D.; Heather, D. J.; Lim, T.; Macfarlane, A.; Martinez, S.; Rios, C.; Vallejo, F.; Said, J.

    2017-09-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces at http://psa.esa.int. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA has started to implement a number of significant improvements, mostly driven by the evolution of the PDS standards, and the growing need for better interfaces and advanced applications to support science exploitation.

  11. Variations on agent-oriented programming

    Directory of Open Access Journals (Sweden)

    Dalia Baziukė

    2017-12-01

    Full Text Available Occurrence of the agent paradigm and its further applications have stimulated the emergence of new concepts and methodologies in computer science. Today terms like multi-agent system, agent-oriented methodology, and agent-oriented programming (AOP are widely used. The aim of this paper is to clarify the validity of usage of the terms AOP and AOP language. This is disclosed in two phases of an analysis process. Determining to which concepts, terms like agent, programming, object-oriented analysis and design, object-oriented programming, and agent-oriented analysis and design correspond is accomplished in the first phase. Analysis of several known agent system engineering methodologies in terms of key concepts used, final resulting artifacts, and their relationship with known programming paradigms and modern tools for agent system development is performed in the second phase. The research shows that in most cases in the final phase of agent system design and in the coding stage, the main artifact is an object, defined according to the rules of the object-oriented paradigm. Hence, we say that the computing society still does not have AOP owing to the lack of an AOP language. Thus, the term AOP is very often incorrectly assigned to agent system development frameworks that in most cases, transform agents into objects.DOI: 10.15181/csat.v5i1.1361

  12. ANALYTICAL METHOD DEVELOPMENT FOR ALACHLOR ESA AND OTHER ACETANILIDE HERBICIDE DEGRADATION PRODUCTS

    Science.gov (United States)

    In 1998, USEPA published a Drinking Water Contaminant Candidate List (CCL) of 50 chemicals and 10 microorganisms. "Alachlor ESA and other acetanilide herbicide degradation products" is listed on the the 1998 CCL. Acetanilide degradation products are generally more water soluble...

  13. Interstellar Neutral Helium in the Heliosphere from IBEX Observations. V. Observations in IBEX-Lo ESA Steps 1, 2, and 3

    Science.gov (United States)

    Swaczyna, Paweł; Bzowski, Maciej; Kubiak, Marzena A.; Sokół, Justyna M.; Fuselier, Stephen A.; Galli, André; Heirtzler, David; Kucharek, Harald; McComas, David J.; Möbius, Eberhard; Schwadron, Nathan A.; Wurz, P.

    2018-02-01

    Direct-sampling observations of interstellar neutral (ISN) He by the Interstellar Boundary Explorer (IBEX) provide valuable insight into the physical state of and processes operating in the interstellar medium ahead of the heliosphere. The ISN He atom signals are observed at the four lowest ESA steps of the IBEX-Lo sensor. The observed signal is a mixture of the primary and secondary components of ISN He and H. Previously, only data from one of the ESA steps have been used. Here, we extend the analysis to data collected in the three lowest ESA steps with the strongest ISN He signal, for the observation seasons 2009–2015. The instrument sensitivity is modeled as a linear function of the atom impact speed onto the sensor’s conversion surface separately for each ESA step of the instrument. We find that the sensitivity increases from lower to higher ESA steps, but within each of the ESA steps it is a decreasing function of the atom impact speed. This result may be influenced by the hydrogen contribution, which was not included in the adopted model, but seems to exist in the signal. We conclude that the currently accepted temperature of ISN He and velocity of the Sun through the interstellar medium do not need a revision, and we sketch a plan of further data analysis aiming at investigating ISN H and a better understanding of the population of ISN He originating in the outer heliosheath.

  14. Stimulation of NADH-dependent microsomal DNA strand cleavage by rifamycin SV.

    Science.gov (United States)

    Kukiełka, E; Cederbaum, A I

    1995-04-15

    Rifamycin SV is an antibiotic anti-bacterial agent used in the treatment of tuberculosis. This drug can autoxidize, especially in the presence of metals, and generate reactive oxygen species. A previous study indicated that rifamycin SV can increase NADH-dependent microsomal production of reactive oxygen species. The current study evaluated the ability of rifamycin SV to interact with iron and increase microsomal production of hydroxyl radical, as detected by conversion of supercoiled plasmid DNA into the relaxed open circular state. The plasmid used was pBluescript II KS(-), and the forms of DNA were separated by agarose-gel electrophoresis. Incubation of rat liver microsomes with plasmid plus NADH plus ferric-ATP caused DNA strand cleavage. The addition of rifamycin SV produced a time- and concentration-dependent increase in DNA-strand cleavage. No stimulation by rifamycin SV occurred in the absence of microsomes, NADH or ferric-ATP. Stimulation occurred with other ferric complexes besides ferric-ATP, e.g. ferric-histidine, ferric-citrate, ferric-EDTA, and ferric-(NH4)2SO4. Rifamycin SV did not significantly increase the high rates of DNA strand cleavage found with NADPH as the microsomal reductant. The stimulation of NADH-dependent microsomal DNA strand cleavage was completely blocked by catalase, superoxide dismutase, GSH and a variety of hydroxyl-radical-scavenging agents, but not by anti-oxidants that prevent microsomal lipid peroxidation. Redox cycling agents, such as menadione and paraquat, in contrast with rifamycin SV, stimulated the NADPH-dependent reaction; menadione and rifamycin SV were superior to paraquat in stimulating the NADH-dependent reaction. These results indicate that rifamycin SV can, in the presence of an iron catalyst, increase microsomal production of reactive oxygen species which can cause DNA-strand cleavage. In contrast with other redox cycling agents, the stimulation by rifamycin SV is more pronounced with NADH than with NADPH as the

  15. ESA unveils Spanish antenna for unique space mission

    Science.gov (United States)

    2000-05-01

    The newly refurbished antenna, which is located at the Villafranca del Castillo Satellite Tracking Station site (VILSPA) near Madrid, has been selected as the prime communication link with the Cluster II spacecraft. The VIL-1 antenna will play a vital role in ESA's Cluster mission by monitoring and controlling the four spacecraft and by receiving the vast amounts of data that will be returned to Earth during two years of operations. Scheduled for launch in summer 2000, the Cluster quartet will complete the most detailed investigation ever made into the interaction between our pl0anet's magnetosphere - the region of space dominated by Earth's magnetic field - and the continuous stream of charged particles emitted by the Sun - the solar wind. This exciting venture is now well under way, following completion of the satellite assembly and test programme and two successful verification flights by the newly developed Soyuz-Fregat launch vehicle. The ESA Flight Acceptance Review Board has accordingly given the go-ahead for final launch preparations at the Baikonur Cosmodrome in Kazakhstan. VILSPA, ESA and Cluster II Built in 1975, after an international agreement between the European Space Agency and the Spanish government, VILSPA is part of the European Space Operations Centre (ESOC) Tracking Station Network (ESTRACK). In the last 25 years, VILSPA has supported many ESA and international satellite programmes, including the International Ultraviolet Explorer (IUE), EXOSAT and the Infrared Space Observatory (ISO). In addition to supporting the Cluster II mission, it has been designated as the Science Operations Centre for ESA's XMM Newton mission and for the Far-Infrared Space Telescope (FIRST), which is due to launch in 2007. There are now more than half a dozen large dish antennae installed at VILSPA. One of these is the VIL-1 antenna, a 15 metre diameter dish which operates in the S-band radio frequency (1.8 - 2.7 GHz). This antenna has been modernised recently in order

  16. Homogeneity testing of the global ESA CCI multi-satellite soil moisture climate data record

    Science.gov (United States)

    Preimesberger, Wolfgang; Su, Chun-Hsu; Gruber, Alexander; Dorigo, Wouter

    2017-04-01

    ESA's Climate Change Initiative (CCI) creates a global, long-term data record by merging multiple available earth observation products with the goal to provide a product for climate studies, trend analysis, and risk assessments. The blending of soil moisture (SM) time series derived from different active and passive remote sensing instruments with varying sensor characteristics, such as microwave frequency, signal polarization or radiometric accuracy, could potentially lead to inhomogeneities in the merged long-term data series, undercutting the usefulness of the product. To detect the spatio-temporal extent of contiguous periods without inhomogeneities as well as subsequently minimizing their negative impact on the data records, different relative homogeneity tests (namely Fligner-Killeen test of homogeneity of variances and Wilcoxon rank-sums test) are implemented and tested on the combined active-passive ESA CCI SM data set. Inhomogeneities are detected by comparing the data against reference data from in-situ data from ISMN, and model-based estimates from GLDAS-Noah and MERRA-Land. Inhomogeneity testing is performed over the ESA CCI SM data time frame of 38 years (from 1978 to 2015), on a global quarter-degree grid and with regard to six alterations in the combination of observation systems used in the data blending process. This study describes and explains observed variations in the spatial and temporal patterns of inhomogeneities in the combined products. Besides we proposes methodologies for measuring and reducing the impact of inhomogeneities on trends derived from the ESA CCI SM data set, and suggest the use of inhomogeneity-corrected data for future trend studies. This study is supported by the European Union's FP7 EartH2Observe "Global Earth Observation for Integrated Water Resource Assessment" project (grant agreement number 331 603608).

  17. Hemoglobin stability in patients with anemia, CKD, and type 2 diabetes: an analysis of the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) placebo arm.

    Science.gov (United States)

    Skali, Hicham; Lin, Julie; Pfeffer, Marc A; Chen, Chao-Yin; Cooper, Mark E; McMurray, John J V; Nissenson, Allen R; Remuzzi, Giuseppe; Rossert, Jerome; Parfrey, Patrick S; Scott-Douglas, Nairne W; Singh, Ajay K; Toto, Robert; Uno, Hajime; Ivanovich, Peter

    2013-02-01

    Sparse data are available about the natural history of hemoglobin (Hb) level trends in contemporary patients with anemia, chronic kidney disease (CKD), and type 2 diabetes mellitus. We intended to describe Hb level trends over time with no or minimal administration of erythropoiesis-stimulating agents. Prospective clinical trial cohort. 2,019 individuals with type 2 diabetes, moderate anemia, and CKD from the placebo arm of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) followed up for 2.3 years with an average of 32 monthly Hb level determinations per patient. Darbepoetin alfa was administered only if Hb level decreased to protocol-directed doses of darbepoetin alfa received due to an Hb level decrease to protocol-directed darbepoetin alfa. The other patients received 1 (16%), 2-4 (16%), or 5 or more (13%) doses of darbepoetin alfa. Those who received no darbepoetin alfa doses had higher baseline Hb levels, higher estimated glomerular filtration rates (eGFRs), less proteinuria, and lower ferritin and transferrin saturation values. On average, Hb levels were stable or increased in all groups. Compared with individuals who received no darbepoetin alfa, those who received 5 or more doses were more likely to receive intravenous iron therapy and blood transfusions and progress to renal replacement therapy, but were not at higher risk of death. The strongest predictors of requiring 5 or more doses of darbepoetin alfa were lower baseline Hb level, lower eGFR, and higher proteinuria level. Post hoc analysis of a clinical trial of a specific population with diabetes, anemia, and non-dialysis-dependent CKD. In the TREAT placebo arm, Hb levels were stable with no or minimal protocol-directed darbepoetin alfa during 2.3 years of follow-up. Most patients with moderate anemia, non-dialysis-dependent CKD, and type 2 diabetes are able to maintain a stable Hb level without implementing long-term erythropoiesis-stimulating agent therapy. Copyright © 2013

  18. NASA and ESA Collaboration on Alternative to Nitric Acid Passivation: Parameter Optimization of Citric Acid Passivation for Stainless Steel Alloys

    Science.gov (United States)

    Kessel, Kurt R.

    2016-01-01

    reduced operational cost. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for the passivation of stainless steel alloys. While citric acid use has become more prominent in industry, there is little evidence that citric acid is a technically sound passivation agent, especially for the unique and critical applications encountered by NASA and ESA.

  19. Stability and Repeatability of the Distress Thermometer (DT and the Edmonton Symptom Assessment System-Revised (ESAS-r with Parents of Childhood Cancer Survivors.

    Directory of Open Access Journals (Sweden)

    Tatsiana Leclair

    Full Text Available Parents report psychological distress in association with their child's cancer. Reliable tools are needed to screen parental distress over the cancer trajectory. This study aimed to estimate the stability and repeatability of the Distress Thermometer (DT and the Depression and Anxiety items of the Edmonton Symptom Assessment System-revised (ESAS-r-D; -A in parents of children diagnosed with cancer.Fifty parents (28 mothers, median age = 44 of clinically stable survivors of childhood solid and brain tumours completed questionnaires about their own distress (DT, ESAS-r-D; -A, Brief Symptom Inventory-18: BSI-18, Patient Health Questionnaire-9: PHQ-9, Generalized Anxiety Disorder-7: GAD-7 and their children's quality of life (QoL; Peds Quality of Life: PedsQL twice, with a month interval between the two assessments. At retest, parents also evaluated life events that occurred between the two time points. Hierarchical regressions explored moderators for the temporal stability of test measures.Stability estimates were ICC = .78 for the DT, .55 for the ESAS-r-D, and .47 for the ESAS-r-A. Caseness agreement between test and retest was substantial for the DT, fair for the ESAS-r-D, and slight for the ESAS-r-A. Repeatability analyses indicated that the error range for the DT was more than 2 pts below/above actual measurement, whereas it was more than 3 pts for the ESAS-r-A, and 2.5 for the ESAS-r-D. Instability of the DT could be explained by changes in children's physical QoL, but not by other components of QoL or life events. No moderators of stability could be identified for the ESAS-r items.The DT appears to be a fairly stable measure when the respondent's condition is stable yet with a relatively wide error range. Fluctuations in distress-related constructs may affect the temporal stability of the DT. The lower stability of ESAS-r items may result from shorter time-lapse instructions resulting in a greater sensitivity to change. Findings support

  20. Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb

    DEFF Research Database (Denmark)

    Colquhoun, E Q; Hettiarachchi, M; Ye, J M

    1988-01-01

    Vasopressin and angiotensin II markedly stimulated oxygen uptake in the perfused rat hindlimb. The increase due to each agent approached 70% of the basal rate, and was greater than that produced by a maximal concentration of norepinephrine. Half-maximal stimulation occurred at 60 pM vasopressin, 0...

  1. ESA strategy for human exploration and the Lunar Lander Mission

    Science.gov (United States)

    Gardini, B.

    As part of ESAs Aurora Exploration programme, the Agency has defined, since 2001, a road map for exploration in which, alongside robotic exploration missions, the International Space Station (ISS) and the Moon play an essential role on the way to other destinations in the Solar System, ultimately to a human mission to Mars in a more distant future. In the frame of the Human Spaceflight programme the first European Lunar Lander Mission, with a launch date on 2018, has been defined, targeting the lunar South Pole region to capitalize on unique illumination conditions and provide the opportunity to carry out scientific investigations in a region of the Moon not explored so far. The Phase B1 industrial study, recently initiated, will consolidate the mission design and prepare the ground for the approval of the full mission development phase at the 2012 ESA Council at Ministerial. This paper describes the mission options which have been investigated in the past Phase A studies and presents the main activities foreseen in the Phase B1 to consolidate the mission design, including a robust bread-boards and technology development programme. In addition, the approach to overcoming the mission's major technical and environmental challenges and the activities to advance the definition of the payload elements will be described.

  2. Status of the ESA L1 mission candidate ATHENA

    Science.gov (United States)

    Rando, N.; Martin, D.; Lumb, D.; Verhoeve, P.; Oosterbroek, T.; Bavdaz, M.; Fransen, S.; Linder, M.; Peyrou-Lauga, R.; Voirin, T.; Braghin, M.; Mangunsong, S.; van Pelt, M.; Wille, E.

    2012-09-01

    ATHENA (Advanced Telescope for High Energy Astrophysics) was an L class mission candidate within the science programme Cosmic Vision 2015-2025 of the European Space Agency, with a planned launch by 2022. ATHENA was conceived as an ESA-led project, open to the possibility of focused contributions from JAXA and NASA. By allowing astrophysical observations between 100 eV and 10 keV, it would represent the new generation X-ray observatory, following the XMM-Newton, Astro-H and Chandra heritage. The main scientific objectives of ATHENA include the study of large scale structures, the evolution of black holes, strong gravity effects, neutron star structure as well as investigations into dark matter. The ATHENA mission concept would be based on focal length of 12m achieved via a rigid metering tube and a twoaperture, x-ray telescope. Two identical x-ray mirrors would illuminate fixed focal plane instruments: a cryogenic imaging spectrometer (XMS) and a wide field imager (WFI). The S/C is designed to be fully compatible with Ariane 5 ECA. The observatory would operate at SE-L2, with a nominal lifetime of 5 yr. This paper provides a summary of the reformulation activities, completed in December 2011. An overview of the spacecraft design and of the payload is provided, including both telescope and instruments. Following the ESA Science Programme Committee decision on the L1 mission in May 2012, ATHENA was not selected to enter Definition Phase.

  3. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin

    DEFF Research Database (Denmark)

    Robach, Paul; Recalcati, Stefania; Girelli, Domenico

    2009-01-01

    healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase...

  4. Joint European x-ray monitor (JEM-X): x-ray monitor for ESA's

    DEFF Research Database (Denmark)

    Schnopper, H.W.; Budtz-Joergensen, C.; Westergaard, Niels Jørgen Stenfeldt

    1996-01-01

    JEM-X will extend the energy range of the gamma ray instruments on ESA's INTEGRAL mission (SPI, IBIS) to include the x-ray band. JEM-X will provide images with arcminute angular resolution in the 2 - 60 keV band. The baseline photon detection system consists of two identical, high pressure, imagi...

  5. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

    Directory of Open Access Journals (Sweden)

    Davis-Ajami ML

    2014-04-01

    Full Text Available Mary Lynn Davis-Ajami,1 Jun Wu,2 Katherine Downton,3 Emilie Ludeman,3 Virginia Noxon4 1Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD, USA; 2South Carolina College of Pharmacy, University of South Carolina, Greenville, SC, USA; 3Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA; 4Department of Clinical Pharmacy and Outcomes Science, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA Abstract: Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L. This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility. Keywords: biosimilar, chronic kidney disease, epoetin alfa, erythropoiesis, renal anemia, Retacrit®

  6. Comparing NASA and ESA Cost Estimating Methods for Human Missions to Mars

    Science.gov (United States)

    Hunt, Charles D.; vanPelt, Michel O.

    2004-01-01

    To compare working methodologies between the cost engineering functions in NASA Marshall Space Flight Center (MSFC) and ESA European Space Research and Technology Centre (ESTEC), as well as to set-up cost engineering capabilities for future manned Mars projects and other studies which involve similar subsystem technologies in MSFC and ESTEC, a demonstration cost estimate exercise was organized. This exercise was a direct way of enhancing not only cooperation between agencies but also both agencies commitment to credible cost analyses. Cost engineers in MSFC and ESTEC independently prepared life-cycle cost estimates for a reference human Mars project and subsequently compared the results and estimate methods in detail. As a non-sensitive, public domain reference case for human Mars projects, the Mars Direct concept was chosen. In this paper the results of the exercise are shown; the differences and similarities in estimate methodologies, philosophies, and databases between MSFC and ESTEC, as well as the estimate results for the Mars Direct concept. The most significant differences are explained and possible estimate improvements identified. In addition, the Mars Direct plan and the extensive cost breakdown structure jointly set-up by MSFC and ESTEC for this concept are presented. It was found that NASA applied estimate models mainly based on historic Apollo and Space Shuttle cost data, taking into account the changes in technology since then. ESA used models mostly based on European satellite and launcher cost data, taking into account the higher equipment and testing standards for human space flight. Most of NASA's and ESA s estimates for the Mars Direct case are comparable, but there are some important, consistent differences in the estimates for: 1) Large Structures and Thermal Control subsystems; 2) System Level Management, Engineering, Product Assurance and Assembly, Integration and Test/Verification activities; 3) Mission Control; 4) Space Agency Program Level

  7. Radiation induced mitotic delay and stimulation of growth

    International Nuclear Information System (INIS)

    Feldmann, A.

    1974-01-01

    The mechanisms responsible for the radiation induced mitotic delay and stimulation of growth are discussed in connection with the results of studies in Lemna minor and Lepidium sativum. The action of temperature seems to be of major importance. As many authors suggest that various chemical agents and slight intoxications also affect mitosis in a way similar to that induced by ionizing radiation, the radiation induced stimulation has lost its specific character and approaches might be found for further investigations of this phenomenon. (MG) [de

  8. Virtual screening and pharmacophore design for a novel theoretical inhibitor of macrophage stimulating factor as a metastatic agent.

    Science.gov (United States)

    Torktaz, Ibrahim; Mohamadhashem, Faezeh; Esmaeili, Abolghasem; Behjati, Mohaddeseh; Sharifzadeh, Sara

    2013-01-01

    Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP) is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD) software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.

  9. Aromatase inhibitors in stimulated IVF cycles

    Directory of Open Access Journals (Sweden)

    Tournaye Herman

    2011-06-01

    Full Text Available Abstract Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels

  10. Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with KitWv Mutations

    Directory of Open Access Journals (Sweden)

    Ayano Yurino

    2016-09-01

    Full Text Available In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous KitWv mutations into C57BL/6.Rag2nullIl2rgnull mice with NOD-Sirpa (BRGS strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34+CD38− cord blood cells, these newly generated C57BL/6.Rag2nullIl2rgnullNOD-Sirpa KitWv/Wv (BRGSKWv/Wv mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow. Furthermore, depletion of host macrophages by clodronate administration resulted in the presence of human erythrocytes and platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly enhances the multi-lineage differentiation of human hematopoietic stem and progenitor cells (HSPCs in mouse bone marrow, presumably by outcompeting mouse HSPCs to occupy suitable microenvironments. The BRGSKWv/Wv mouse model is a useful tool to study human multi-lineage hematopoiesis.

  11. Onco-nephrology: an appraisal of the cancer and chronic kidney disease links.

    Science.gov (United States)

    Izzedine, Hassan; Perazella, Mark A

    2015-12-01

    A bidirectional relationship has been observed for kidney disease and cancer. On the one hand, cancer is an important complication noted in kidney disease as well as a major cause of morbidity and mortality in this group. On the other hand, improved cancer treatment has prolonged survival, but also increased the development of acute and chronic kidney disease. The combination of cancer and kidney disease makes it challenging for clinicians to provide comprehensive and safe therapies for this group of patients. As such, clinicians caring for this group must develop expertise and become competent in the practice of a newly evolving subspecialty of nephrology known as 'onco-nephrology'. This brief narrative review will focus on the cancer risk in patients with underlying kidney disease, the therapies such as erythropoiesis-stimulating agents on cancer progression and other outcomes, and the appropriate dosing of anti-cancer agents in patients with underlying kidney disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. The ESA/ESO/NASA Photoshop FITS Liberator 3: Have your say on new features

    Science.gov (United States)

    Nielsen, L. H.; Christensen, L. L.; Hurt, R. L.; Nielsen, K.; Johansen, T.

    2008-06-01

    The popular, free ESA/ESO/NASA Photoshop FITS Liberator image processing software (a plugin for Adobe Photoshop) is about to get simpler, faster and more user-friendly! Here we would like to solicit inputs from the community of users.

  13. Reduction of costs for anemia-management drugs associated with the use of ferric citrate

    Directory of Open Access Journals (Sweden)

    Thomas A

    2014-05-01

    Full Text Available Anila Thomas,1 Leif E Peterson2 1Clinical Pharmacy Services, Houston Methodist Hospital, Houston, TX, USA; 2Center for Biostatistics, Houston Methodist Research Institute, Houston, TX, USA Background: Ferric citrate is a novel phosphate binder which has the potential to reduce usage of erythropoietin-stimulating agents (ESAs and intravenous (IV iron used for anemia management during hemodialysis (HD among patients with end-stage renal disease (ESRD. Currently, the potential health care cost savings on a national scale due to the use of ferric citrate in ESRD are undetermined. Methods: Per-patient-per-year costs of ESAs (Epogen® and Aranesp® [Amgen Inc., CA, USA] and IV iron (Venofer® [American Regent, Inc., NY, USA] and Ferrlecit® [Sanofi US, Bridgewater, NJ, USA] were based on RED BOOK™ (Truven Health Analytics New York, NY, USA costs combined with the Centers for Medicare and Medicaid Services (CMS base rate and actual usage in 2011 for the four drugs. The annual number of outpatients undergoing HD in the US was based on frequencies reported by the USRDS (United States Renal Data System. Monte Carlo uncertainty analysis was performed to determine total annual costs and cost reduction based on ferric citrate usage. Results: Total annual cost of ESAs and IV iron for anemia management in ESRD determined by Monte Carlo analysis assuming CMS base rate value was 5.127 (3.664–6.260 billion USD. For actual utilization in 2011, total annual cost of ESAs and IV iron was 3.981 (2.780–4.930 billion USD. If ferric citrate usage reduced ESA utilization by 20% and IV iron by 40%, then total cost would be reduced by 21.2% to 4.038 (2.868–4.914 billion USD for the CMS base rate, and by 21.8% to 3.111 (2.148–3.845 billion USD, based on 2011 actual utilization. Conclusion: It is likely that US health care costs for anemia-management drugs associated with ESRD among HD patients can be reduced by using ferric citrate as a phosphate binder. Keywords

  14. Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose

    DEFF Research Database (Denmark)

    Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando

    2017-01-01

    BACKGROUND: Preclinical studies demonstrate renal proximal tubular injury after administration of some intravenous iron preparations but clinical data on renal effects of intravenous iron are sparse. METHODS: FIND-CKD was a 56-week, randomized, open-label, multicenter study in which patients...... with non-dialysis dependent chronic kidney disease (ND-CKD), anemia and iron deficiency without erythropoiesis-stimulating agent therapy received intravenous ferric carboxymaltose (FCM), targeting either higher (400-600 μg/L) or lower (100-200 μg/L) ferritin values, or oral iron. RESULTS: Mean (SD) e...... quartiles of FCM dose, change in ferritin or change in TSAT versus change in eGFR. Dialysis initiation was similar between groups. Renal adverse events were rare, with no indication of between-group differences. CONCLUSION: Intravenous FCM at doses that maintained ferritin levels of 100-200 μg/L or 400...

  15. The Promise of Neuroprotective Agents in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Judith ePotashkin

    2011-11-01

    Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

  16. Description of European Space Agency (ESA) Concept Development for a Mars Sample Receiving Facility (MSRF)

    Science.gov (United States)

    Vrublevskis, J.; Berthoud, L.; Guest, M.; Smith, C.; Bennett, A.; Gaubert, F.; Schroeven-Deceuninck, H.; Duvet, L.; van Winnendael, M.

    2018-04-01

    This presentation gives an overview of the several studies conducted for the European Space Agency (ESA) since 2007, which progressively developed layouts for a potential implementation of a Mars Sample Receiving Facility (MSRF).

  17. [Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].

    Science.gov (United States)

    Satoh, Jo

    2003-07-01

    Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, there has been indicated that these agents ameliorate metabolic syndrome beyond glucose-level lowering. Molecular targets of these agents have recently been revealed; AMP-activated protein kinase (AMPK) for metformin and adiponectin, while PPAR gamma for TZDs which induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs.

  18. Cell proliferation changes in hemopoietic tissue as a result of irradiation or drug administration: the control of cell proliferation in hemopoietic tissue

    International Nuclear Information System (INIS)

    Lord, B.I.

    1975-01-01

    The nature of the control processes operative on these cells is not completely understood. Erythropoietin has long been known as a direct stimulator of erythropoiesis at all levels. A similar compound has long been sought (unsuccessfully) to stimulate granulopoiesis. Currently the role of specific proliferation inhibitors of erythropoiesis and granulopoiesis are now attaining more prominence. In this respect, Patt and Maloney demonstrated an inverse relationship of cell concentration in the rabbit femur and the uptake of tritiated thymidine by the cells, and we have now established that extracts of mature blood cells do have specific effects on developing hemopoietic cells which are compatible with proliferation inhibition and which are completely reversible. Our current studies are showing that, used in vivo, these extracts are in fact capable of lowering the proliferation rates of the maturing hemopoietic cells (Lord- unpublished results). It is clear, therefore, that the maturing cell populations proliferate under a complex set of control processes

  19. The esa earth explorer land surface processes and interactions mission

    Science.gov (United States)

    Labandibar, Jean-Yves; Jubineau, Franck; Silvestrin, Pierluigi; Del Bello, Umberto

    2017-11-01

    The European Space Agency (ESA) is defining candidate missions for Earth Observation. In the class of the Earth Explorer missions, dedicated to research and pre-operational demonstration, the Land Surface Processes and Interactions Mission (LSPIM) will acquire the accurate quantitative measurements needed to improve our understanding of the nature and evolution of biosphere-atmosphere interactions and to contribute significantly to a solution of the scaling problems for energy, water and carbon fluxes at the Earth's surface. The mission is intended to provide detailed observations of the surface of the Earth and to collect data related to ecosystem processes and radiation balance. It is also intended to address a range of issues important for environmental monitoring, renewable resources assessment and climate models. The mission involves a dedicated maneuvering satellite which provides multi-directional observations for systematic measurement of Land Surface BRDF (BiDirectional Reflectance Distribution Function) of selected sites on Earth. The satellite carries an optical payload : PRISM (Processes Research by an Imaging Space Mission), a multispectral imager providing reasonably high spatial resolution images (50 m over 50 km swath) in the whole optical spectral domain (from 450 nm to 2.35 μm with a resolution close to 10 nm, and two thermal bands from 8.1 to 9.1 μm). This paper presents the results of the Phase A study awarded by ESA, led by ALCATEL Space Industries and concerning the design of LSPIM.

  20. Activation of Phosphoinositide Metabolism by Cholinergic Agents.

    Science.gov (United States)

    1992-03-15

    most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

  1. The first Spacelab payload - A joint NASA/ESA venture

    Science.gov (United States)

    Kennedy, R.; Pace, R.; Collet, J.; Sanfourche, J. P.

    1977-01-01

    Planning for the 1980 qualification flight of Spacelab, which will involve a long module and one pallet, is discussed. The mission will employ two payload specialists, one sponsored by NASA and the other by ESA. Management of the Spacelab mission functions, including definition and execution of the on-board experiments, development of the experimental hardware and training of the payload specialists, is considered; studies proposed in the areas of atmospheric physics, space plasma physics, solar physics, earth observations, astronomy, astrophysics, life sciences and material sciences are reviewed. Analyses of the Spacelab environment and the Spacelab-to-orbiter and Spacelab-to-experiment interactions are also planned.

  2. Insulin-releasing action of the novel antidiabetic agent BTS 67 582.

    Science.gov (United States)

    McClenaghan, N H; Flatt, P R; Bailey, C J

    1998-02-01

    1. BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate) is a novel antidiabetic agent with a short-acting insulin-releasing effect. This study examined its mode of action in the clonal B-cell line BRIN-BD11. 2. BTS 67582 increased insulin release from BRIN-BD11 cells in a concentration-dependent manner (10[-8] to 10[-4] M) at both non-stimulating (1.1 mM) and stimulating (16.7 mM) concentrations of glucose. 3. BTS 67582 (10[-4] M) potentiated the insulin-releasing effect of a depolarizing concentration of K+ (30 mM), whereas the K+ channel openers pinacidil (400 microM) and diazoxide (300 microM) inhibited BTS 67582-induced release. 4. Suppression of Ca+ channel activity with verapamil (20 microM) reduced the insulin-releasing effect of BTS 67582 (10[-4] M). 5. BTS 67582 (10[-4] M) potentiated insulin release induced by amino acids (10 mM), and enhanced the combined stimulant effects of glucose plus either the fatty acid palmitate (10 mM), or agents which raise intracellular cyclic AMP concentrations (25 microM forskolin and 1 mM isobutylmethylxanthine), or the cholinoceptor agonist carbachol (100 microM). 6. Inhibition of glucose-stimulated insulin release by adrenaline or noradrenaline (10 microM) was partially reversed by BTS 67582 (10[-4] M). 7. These data suggest that the insulin-releasing effect of BTS 67582 involves regulation of ATP-sensitive K+ channel activity and Ca2+ influx, and that the drug augments the stimulant effects of nutrient insulin secretagogues and agents which enhance adenylate cyclase and phospholipase C. BTS 67582 may also exert insulin-releasing effects independently of ATP-sensitive K+ channel activity.

  3. Nuclear interaction contribution to SEUs in heavy ion energy deposition in the ESA monitor

    CERN Document Server

    Bahamonde, Cristina

    2013-01-01

    The effects of nuclear interactions inducing Single Event Upsets in ESA SEU monitor are explored for heavy ion beams of different energies. The experimental and simulated results are compared, the possible causes of disagreement are suggested as well as the future steps to take.

  4. Luminescence optically stimulated: theory and applications; Luminiscencia opticamente estimulada: teoria y aplicaciones

    Energy Technology Data Exchange (ETDEWEB)

    Rivera M, T.; Azorin N, J. [Departamento de Fisica, Universidad Autonoma Metropolitana-Iztapalapa, 09340 Mexico D.F. (Mexico)

    2002-07-01

    The thermally stimulated luminescence (Tl) has occupied an important place in the Solid state physics (FES) by the flexibility of the phenomena, mainly for its applications in the fields of Radiation Physics (FR) and Medical Physics (MF). The reason of this phenomena lies in the fact of the electrons release by the action of heat. Under that same reason, it can be used the action of another stimulant agent for releasing the trapped electrons in the metastable states (EM), this agent is the light which has the same effect that the heat, giving as result the production of light photons at using light in the visible spectra, of different wavelength that the excitation light. This phenomena is called Luminescence optically stimulated (LOE). The LOE has a great impact in the Solid State Physics (FES), dating and now in the use of the phenomena as a dosimetric method, alternate to the Tl, for its use in the ionizing and non-ionizing radiations fields. (Author)

  5. Disease: H01642 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01642 Renal anemia Renal anemia is one of the most frequent complications of chro...sated for by tachycardia and cardiac hypertrophy, but eventually leads to the development of cardiovascular disease. Renal anemia... human erythropoietin has revolutionized the management of renal anemia, and erythropoiesis-stimulating agen

  6. SAR Processing on Demand Service for CryoSat-2 and Sentinel-3 at ESA G-POD

    Science.gov (United States)

    Benveniste, Jérôme; Ambrózio, Américo; Restano, Marco; Dinardo, Salvatore

    2016-04-01

    The scope of this presentation is to feature the G-POD SARvatore service to users for the exploitation of the CryoSat-2 and Sentniel-3 data, which was designed and developed by the Altimetry Team at ESA-ESRIN EOP-SER (Earth Observation - Exploitation, Research and Development). The G-POD service coined SARvatore (SAR Versatile Altimetric Toolkit for Ocean Research & Exploitation) is a web platform that allows any scientist to process on-line, on-demand and with user-selectable configuration CryoSat-2 SAR/SARIN data, from L1a (FBR) data products up to SAR/SARin Level-2 geophysical data products. The Processor takes advantage of the G-POD (Grid Processing On Demand) distributed computing platform (350 CPUs in ~70 Working Nodes) to timely deliver output data products and to interface with ESA-ESRIN FBR data archive (210'000 SAR passes and 120'000 SARin passes). The output data products are generated in standard NetCDF format (using CF Convention), therefore being compatible with the multi-mission Broadview Radar Altimetry Toolbox (BRAT) and other NetCDF tools. By using the G-POD graphical interface, it is straightforward to select a geographical area of interest within the time-frame related to the Cryosat-2 SAR/SARin FBR data products availability in the service catalogue. The processor prototype is versatile, allowing users to customize and to adapt the processing, according to their specific requirements, by setting a list of configurable options. After the task submission, users can follow, in real time, the status of the processing. From the web interface, users can choose to generate experimental SAR data products as stack data and RIP (Range Integrated Power) waveforms. The processing service, initially developed to support the development contracts awarded by confronting the deliverables to ESA's computations, has been made available to the worldwide SAR Altimetry Community for research & development experiments, for hands-on demonstrations/training in

  7. Diana H. Wall, ESA President 1999-2000

    Science.gov (United States)

    Baron, Jill S.; Parsons, A.

    2000-01-01

    A more polite term for workaholic is over-achiever, and Diana Harrison Wall could easily serve as the type specimen for both words. Her ability to multi-task is a great boon for the Ecological Society of America. That characteristic drive has also been essential to Wall’s own personal success, since it pushed her to persevere during the lean years when a woman’s place was NOT in the field or laboratory. Diana is a very strong role model for young ecologists through her enthusiasm for science, her remarkable scientific achievements, and her leadership skills. In addition to advising her many graduate students, Diana-as-role-model has been featured in many news media, including PBS TV shows such as “Horizons” and “Discovery,” National Geographic magazine, and the New York Times. She is highlighted on the ESA Web site: “What Do Ecologists Do? Focus on Ecologists.”

  8. Virtual Screening and Pharmacophore Design for a Novel Theoretical Inhibitor of Macrophage Stimulating Factor as a Metastatic Agent

    Directory of Open Access Journals (Sweden)

    Ibrahim Torktaz

    2013-09-01

    Full Text Available Introduction: Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Methods: Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. Results: The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Conclusion: Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.

  9. 78 FR 18585 - FIFRA Pesticide Registration Review and ESA Consultation Processes; Stakeholder Input; Notice of...

    Science.gov (United States)

    2013-03-27

    ... Review and ESA Consultation Processes; Stakeholder Input; Notice of Availability AGENCY: Environmental... describing enhanced opportunities for stakeholder input during its review of pesticide registrations under... announcing the availability of a document titled, ``Enhancing Stakeholder Input in the Pesticide Registration...

  10. The Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA): development, validity, reliability and sensitivity to change.

    Science.gov (United States)

    Price, Jonathan; Cole, Victoria; Doll, Helen; Goodwin, Guy M

    2012-09-01

    Some patients with major depression report a restricted range of emotions that may appear to arise as a side-effect of treatment with antidepressants. It is uncertain whether this phenomenon, sometimes called emotional blunting, represents residual symptoms of depression or side-effects of antidepressant treatment. There is currently no adequate instrument to measure this phenomenon. A draft questionnaire was developed from patient-derived qualitative data, refined using cognitive interviewing, and administered on three occasions to patients taking antidepressants. Statistical methods including factor analysis were used to reduce the size of the draft questionnaire, and to assess the performance of the resulting Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA). 207 patients completed the OQuESA on at least one occasion. Their BDI-II scores and self-reported emotional blunting were spread across the possible range. The factor analysis resulted in four dimensions: 'not caring', 'emotional detachment', 'reduction in positive emotions', and 'general reduction in emotions'. The OQuESA appears to be acceptable, valid, and reliable, with sensitivity to change. The OQuESA offers promise as an effective self-report measure of the symptoms of emotional blunting in patients with depression. It can be used as a clinical tool, to facilitate the identification of patients with the syndrome of emotional blunting. It should also be used in research studies, to advance our understanding of the nature, causes and treatment of this phenomenon. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The Hera Saturn Entry Probe Mission: a Proposal in Response to the ESA M5 Call

    Science.gov (United States)

    Mousis, Olivier; Atkinson, David; Amato, Michael; Aslam, Shahid; Atreya, Sushil; Blanc, Michel; Bolton, Scott; Brugger, Bastien; Calcutt, Simon; Cavalié, Thibault; Charnoz, Sébastien; Coustenis, Athena; Deleuil, Magali; Dobrijevic, Michel; Ferri, Francesca; Fletcher, Leigh; Gautier, Daniel; Guillot, Tristan; Hartogh, Paul; Holland, Andrew

    2017-04-01

    The Hera Saturn entry probe mission is proposed as an ESA M-class mission to be piggybacked on a NASA spacecraft sent to or past the Saturn system. Hera consists of an atmospheric probe built by ESA and released into the atmosphere of Saturn by its NASA companion Saturn Carrier-Relay spacecraft. Hera will perform in situ measurements of the chemical and isotopic composition as well as the structure and dynamics of Saturn's atmosphere using a single probe, with the goal of improving our understanding of the origin, formation, and evolution of Saturn, the giant planets and their satellite systems, with extrapolation to extrasolar planets. Hera will probe well into and possibly beneath the cloud-forming region of the troposphere, below the region accessible to remote sensing, to locations where certain cosmogenically abundant species are expected to be well mixed. The Hera probe will be designed from ESA elements with possible contributions from NASA, and the Saturn/Carrier-Relay Spacecraft will be supplied by NASA through its selection via the New Frontier 2016 call or in the form of a flagship mission selected by the NASA "Roadmaps to Ocean Worlds" (ROW) program. The Hera probe will be powered by batteries, and we therefore anticipate only one major subsystems to be possibly supplied by the United States, either by direct procurement by ESA or by contribution from NASA: the thermal protection system of the probe. Following the highly successful example of the Cassini-Huygens mission, Hera will carry European and American instruments, with scientists and engineers from both agencies and many affiliates participating in all aspects of mission development and implementation. A Saturn probe is one of the six identified desired themes by the Planetary Science Decadal Survey committee on the NASA New Frontier's list, providing additional indication that a Saturn probe is of extremely high interest and a very high priority for the international community.

  12. Aprendizaje de los roles de los agentes BIM en la organización de proyectos = Learning the roles of BIM agents in project management

    Directory of Open Access Journals (Sweden)

    Carolina Piña Ramirez

    2017-04-01

    Full Text Available Actualmente la metodología BIM se está desarrollando en todas las ramas de la construcción e ingeniería. La Unión Europea con la Directiva2014/24/UE marca un hito en el mercado, recomendando a los estados miembros el uso de BIM en sus proyectos, y España, por su parte está en fase de desarrollo de una transposición de esa directiva para implantar esa metodología, con el Ministerio de Fomento. Esta transformación del sector nos lleva a la necesidad de instituir profesionales de calidad cuya formación sea la competente para la inmersión en el mercado profesional existente. Por ello, el propósito de este artículo es exportar a la universidad el conocimiento de la relación entre las implicaciones de los agentes intervinientes en la metodología BIM y las fases de un proyecto. Este trabajo tiene como finalidad de conseguir una mejora en la enseñanza del Graduado en Ingeniería de la Edificación de la Universidad Politécnica de Madrid, hacia el cambio BIM. Abstract Currently the BIM methodology is being developed in all branches of construction and engineering. The European Union with the Directive2014/2/EU set a benchmark in the market, recommending to Member States the use of BIM in projects. Spain is actually in the process of developing a transposition of that directive to implement that methodology. This sector transformation makes it necessary to train professionals with adequate training to be immerse in the market. Therefore, the aim of this article is to export to the university the knowledge of the relationship between the implications of the intervening agents in the BIM methodology and the phases of a project. This has the purpose of obtaining an improvement in the teaching of the Graduate in Engineering of the Building of the Polytechnic University of Madrid, towards the BIM change.

  13. The New Planetary Science Archive (PSA): Exploration and Discovery of Scientific Datasets from ESA's Planetary Missions

    Science.gov (United States)

    Heather, David; Besse, Sebastien; Vallat, Claire; Barbarisi, Isa; Arviset, Christophe; De Marchi, Guido; Barthelemy, Maud; Coia, Daniela; Costa, Marc; Docasal, Ruben; Fraga, Diego; Grotheer, Emmanuel; Lim, Tanya; MacFarlane, Alan; Martinez, Santa; Rios, Carlos; Vallejo, Fran; Saiz, Jaime

    2017-04-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces at http://psa.esa.int. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA is currently implementing a number of significant improvements, mostly driven by the evolution of the PDS standard, and the growing need for better interfaces and advanced applications to support science exploitation. As of the end of 2016, the PSA is hosting data from all of ESA's planetary missions. This includes ESA's first planetary mission Giotto that encountered comet 1P/Halley in 1986 with a flyby at 800km. Science data from Venus Express, Mars Express, Huygens and the SMART-1 mission are also all available at the PSA. The PSA also contains all science data from Rosetta, which explored comet 67P/Churyumov-Gerasimenko and asteroids Steins and Lutetia. The year 2016 has seen the arrival of the ExoMars 2016 data in the archive. In the upcoming years, at least three new projects are foreseen to be fully archived at the PSA. The BepiColombo mission is scheduled for launch in 2018. Following that, the ExoMars Rover Surface Platform (RSP) in 2020, and then the JUpiter ICy moon Explorer (JUICE). All of these will archive their data in the PSA. In addition, a few ground-based support programmes are also available, especially for the Venus Express and Rosetta missions. The newly designed PSA will enhance the user experience and will significantly reduce the complexity for users to find their data promoting one-click access to the scientific datasets with more customized views when needed. This includes a better integration with Planetary GIS analysis tools and Planetary interoperability services (search and retrieve data, supporting e.g. PDAP, EPN-TAP). It will also be up

  14. Approach to technology prioritization in support of moon initiatives in the framework of ESA exploration technology roadmaps

    Science.gov (United States)

    Aleina, Sara Cresto; Viola, Nicole; Fusaro, Roberta; Saccoccia, Giorgio

    2017-10-01

    Exploration technology roadmaps have been developed by ESA in the past few years and the latest edition has been released in 2015. Scope of these technology roadmaps, elaborated in consultation with the different ESA stakeholders (e.g. European Industries and Research Entities), is to provide a powerful tool for strategic, programmatic and technical decisions in support of the European role within an International Space Exploration context. In the context of preparation for possible future European Moon exploration initiatives, the technology roadmaps have been used to highlight the role of technology within Missions, Building Blocks and Operational Capabilities of relevance. In particular, as part of reference missions to the Moon that would fit in the time frame 2020 to 2030, ESA has addressed the definition of lunar surface exploration missions in line with its space exploration strategy, with the common mission goals of returning samples from the Moon and Mars and expanding human presence to these destinations in a step-wise approach. The roadmaps for the procurement of technologies required for the first mission elements of the above strategy have been elaborated through their main building blocks, i.e. Visual navigation, Hazard detection and avoidance; Sample acquisition, processing and containment system; Surface mobility elements; Tele-robotic and autonomous control systems; and Storable propulsion modules and equipment. Technology prioritization methodologies have been developed in support of the ESA Exploration Technology Roadmaps, in order to provide logical and quantitative instruments to verify choices of prioritization that can be carried out based on important, but non-quantitative factors. These methodologies, which are thoroughly described in the first part of the paper, proceed through subsequent steps. First, technology prioritization's criteria are selected; then decision trees are developed to highlight all feasible paths of combination of

  15. A case study of desertification hazard mapping using the MEDALUS (ESAs methodology in southwest Iran

    Directory of Open Access Journals (Sweden)

    Shahabeddin Taghipour-Javi

    2016-01-01

    Full Text Available Understanding environmentally sensitive areas (ESAs prone to desertification can lead to substantial gains in the efficiency of land use planning and partly avoid negative outcomes. The main objectives of this research were the monitoring and mapping of ESAs to desertification in the agro-ecosystem of the Khanmirza plain, Iran, during two time series (2000 and 2013. In the current study, an adjusted “Mediterranean desertification and land use (MEDALUS” approach was applied to identify the most ESAs to desertification in the study area and monitorchanges inthe environmental sensitivity area indicator (ESAIbetween 2000 and 2013 over the studied area.Fivemain thematic indicators have been evaluated including, Soil quality indicator (SQI, Management quality indicator (MQI, Climate quality indicator (CQI, Vegetation quality indicator (VQI, and Irrigation water quality indicator (IWQI. Results show that the areas affected by the critical desertification status covered approximately 7% of the farmlands and the meadowlands in this agro-ecosystem region in the year 2000. Likewise, in 2013, almost 24% of the study area was sensitive to and affected by desertification, giving a rate of increase of approximately 1.3% per year.More than half of the land used for agriculture has been moderately to severely degraded. The results also show that the central places intheregionwere affected by farmlands and meadowlands degradingto barrenlands due to mismanagement and a lack ofeffective planning withland and water resources. However, rehabilitation of irreversibly degraded land requires serious measures that aim torestore the capability of those areas and increase resistance to degradation through effective planning in water and land in the region.

  16. Anaemia and fever in kidney transplant. The role of human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Yanet Parodis López

    2017-03-01

    We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

  17. ESA's Hipparcos finds rebels with a cause

    Science.gov (United States)

    2004-10-01

    hi-res Size hi-res: 20Kb Credits: S. Kerroudj, B. Famaey & A. Jorissen (Université Libre de Bruxelles) Artist's impression of the Milky Way Artist's impression of our galaxy, the Milky Way, an aggregate of thousands of millions of stars. The spiral arms are clearly visible. They are regions of enhanced density of stars and gas. The Sun is located near the edge of one arm, about half-way from the galactic centre. Spiral arms can impart a kick on stars orbiting close to them. These stars are then forced unto streams running inwards or outwards, whereas the bulk of stars in the Milky Way move in circular orbits around the galactic centre. Using data from ESA’s Hipparcos satellite, astronomers have now identified three such streams, reaching into the solar neighbourhood. High-resolution version (TIFF) Low-resolution version (JPG) The Sun and most stars near it follow an orderly, almost circular orbit around the centre of our galaxy, the Milky Way. Using data from ESA's Hipparcos satellite, a team of European astronomers has now discovered several groups of 'rebel' stars that move in peculiar directions, mostly towards the galactic centre or away from it, running like the spokes of a wheel. These rebels account for about 20% of the stars within 1000 light-years of the Sun, itself located about 25 000 light-years away from the centre of the Milky Way. The data show that rebels in the same group have little to do with each other. They have different ages so, according to scientists, they cannot have formed at the same time nor in the same place. Instead, they must have been forced together. "They resemble casual travel companions more than family members," said Dr Benoit Famaey, Université Libre de Bruxelles, Belgium. Famaey and his colleagues believe that the cause forcing the rebel stars together on their unusual trajectory is a 'kick' received from one of the Milky Way's spiral arms. The spiral arms are not solid structures but rather regions of higher density of

  18. Una manera de nombrar el deseo en Toda esa gran verdad

    OpenAIRE

    List Reyes, Mauricio

    2011-01-01

    Este artículo analiza la novela Toda esa gran verdad (2006) del mexicano Eduardo Montagner. El artículo centra su atención en el tema de la sexualidad, particularmente la del personaje principal. La idea es reflexionar acerca de formas disidentes de la sexualidad que rompen con las maneras normativas y que son sancionadas socialmente. En este caso en particular, unas botas de hule son el centro de la atención de un joven de una comunidad rural que dice estar enamorado del dueño de dicho calza...

  19. Infectious Agents as Stimuli of Trained Innate Immunity

    Directory of Open Access Journals (Sweden)

    Paulina Rusek

    2018-02-01

    Full Text Available The discoveries made over the past few years have modified the current immunological paradigm. It turns out that innate immunity cells can mount some kind of immunological memory, similar to that observed in the acquired immunity and corresponding to the defense mechanisms of lower organisms, which increases their resistance to reinfection. This phenomenon is termed trained innate immunity. It is based on epigenetic changes in innate immune cells (monocytes/macrophages, NK cells after their stimulation with various infectious or non-infectious agents. Many infectious stimuli, including bacterial or fungal cells and their components (LPS, β-glucan, chitin as well as viruses or even parasites are considered potent inducers of innate immune memory. Epigenetic cell reprogramming occurring at the heart of the phenomenon may provide a useful basis for designing novel prophylactic and therapeutic strategies to prevent and protect against multiple diseases. In this article, we present the current state of art on trained innate immunity occurring as a result of infectious agent induction. Additionally, we discuss the mechanisms of cell reprogramming and the implications for immune response stimulation/manipulation.

  20. Which benefits and limits derive from ESA membership for European Countries owning ;medium-sized; space agencies?

    Science.gov (United States)

    Petroni, Giorgio; Bigliardi, Barbara; Galati, Francesco; Petroni, Alberto

    2018-01-01

    This study investigates the benefits and limits deriving from membership with ESA of six medium-sized space agencies in terms of strengthening and development (or not) of space technologies, as well as their contribution to the growth of productive activities and to the increase of services for citizens. This research contributes to the more general issue of the usefulness of space activities, not only for scientific or military-political purposes but also for economic and social development. Results show that, on the one hand, the membership with ESA has allowed smaller Countries to access space programs, to develop advanced technologies and to support the growth of their firms in some significant markets, but, on the other hand, the membership has also limited the access to space to few companies, without encouraging the broad dissemination of technological knowledge.

  1. ESA's Gaia Satellite and data processing status

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Gaia, ESA's astrometric surveyor, was launched on Dec 19th 2013 from Kourou. This exciting mission intends to probe the formation history of our galaxy among other things. We will briefly describe the mission and its goals. An overview of Gaia Data Processing Analysis Consortium and the status of the on ground processing will be provided as this is intimately linked to mission performance and goals. The commissioning phase ended in July 2015, this was longer than planned due to in-flight issues. Now we are well into nominal operations and learning to deal with the Gaia we have (it is a great piece of hardware). We will share the current status of Gaia at L2 and the current end of mission performance estimates. About the speaker Since April 2014 William O'Mullane is head of the Operations Development Division in the Science and Robotic Exploration (SRE) directorate of the the European Space Agency. Based in Madrid, he was Gaia Science Operations Development manager from 2005 to launc...

  2. APEX - the Hyperspectral ESA Airborne Prism Experiment

    Directory of Open Access Journals (Sweden)

    Koen Meuleman

    2008-10-01

    Full Text Available The airborne ESA-APEX (Airborne Prism Experiment hyperspectral mission simulator is described with its distinct specifications to provide high quality remote sensing data. The concept of an automatic calibration, performed in the Calibration Home Base (CHB by using the Control Test Master (CTM, the In-Flight Calibration facility (IFC, quality flagging (QF and specific processing in a dedicated Processing and Archiving Facility (PAF, and vicarious calibration experiments are presented. A preview on major applications and the corresponding development efforts to provide scientific data products up to level 2/3 to the user is presented for limnology, vegetation, aerosols, general classification routines and rapid mapping tasks. BRDF (Bidirectional Reflectance Distribution Function issues are discussed and the spectral database SPECCHIO (Spectral Input/Output introduced. The optical performance as well as the dedicated software utilities make APEX a state-of-the-art hyperspectral sensor, capable of (a satisfying the needs of several research communities and (b helping the understanding of the Earth’s complex mechanisms.

  3. N° 15-2000: ESA, CERN and ESO launch "Physics on Stage"

    Science.gov (United States)

    2000-03-01

    But how much do the citizens of Europe really know about physics? Here is a unique opportunity to learn more about this elusive subject! Beginning in February 2000, three major European research establishments [1] are organising a unique Europe-wide programme to raise the public awareness of physics and related sciences. "Physics on Stage" is launched by the European Space Agency (ESA), the European Laboratory for Particle Physics (CERN), and the European Southern Observatory (ESO), with support from the European Union (EU). Other partners include the European Physical Society (EPS) and the European Association for Astronomy Education (EAAE). This exciting programme is part of the European Week for Science and Technology and will culminate in a Science Festival during November 6-11, 2000, at CERN, Geneva. Why "Physics on Stage"? The primary goal of "Physics on Stage" is to counteract the current decline in interest and knowledge of physics among Europe's citizens by means of a series of highly visible promotional activities. It will bring together leading scientists and educators, government bodies and the media, to confront the diminishing attraction of physics to young people and to develop strategies to reverse this trend. The objective in the short term is to infuse excitement and to provide new educational materials. In the longer term, "Physics on Stage" will generate new developments by enabling experts throughout Europe to meet, exchange and innovate. "Physics on Stage" in 22 European Countries. "Physics on Stage" has been initiated in 22 European countries [2]. In each country, a dedicated National Steering Committee (NSC) is being formed which will be responsible for their own national programme. A list of contact addresses is attached below. "Physics on Stage" is based on a series of high-profile physics-related activities that will inform the European public in general, and European high school physics teachers and media representatives in particular

  4. ESA's Integral detects closest cosmic gamma-ray burst

    Science.gov (United States)

    2004-08-01

    5 August 2004 A gamma-ray burst detected by ESA's Integral gamma-ray observatory on 3 December 2003 has been thoroughly studied for months by an armada of space and ground-based observatories. Astronomers have now concluded that this event, called GRB 031203, is the closest cosmic gamma-ray burst on record, but also the faintest. This also suggests that an entire population of sub-energetic gamma-ray bursts has so far gone unnoticed... Gamma ray burst model hi-res Size hi-res: 22 KB Credits: CXC/M. Weiss Artist impression of a low-energy gamma-ray burst This illustration describes a model for a gamma-ray burst, like the one detected by Integral on 3 December 2003 (GRB 031203). A jet of high-energy particles from a rapidly rotating black hole interacts with surrounding matter. Observations with Integral on 3 December 2003 and data on its afterglow, collected afterwards with XMM-Newton, Chandra and the Very Large Array telescope, show that GRB 031203 radiated only a fraction of the energy of normal gamma-ray bursts. Like supernovae, gamma-ray bursts are thought to be produced by the collapse of the core of a massive star. However, while the process leading to supernovae is relatively well understood, astronomers still do not know what happens when a core collapses to form a black hole. The discovery of 'under-energetic' gamma-ray bursts, like GRB 031203, should provide valuable clues as to links between supernovae, black holes and gamma-ray bursts. Lo-res JPG (22 Kb) Hi-res TIFF (5800 Kb) Cosmic gamma-ray bursts (GRBs) are flashes of gamma rays that can last from less than a second to a few minutes and occur at random positions in the sky. A large fraction of them is thought to result when a black hole is created from a dying star in a distant galaxy. Astronomers believe that a hot disc surrounding the black hole, made of gas and matter falling onto it, somehow emits an energetic beam parallel to the axis of rotation. According to the simplest picture, all GRBs

  5. Assessing ESA on What It Is Designed For: A Reply to Cooper and Glaesser

    Science.gov (United States)

    Schneider, Carsten Q.; Wagemann, Claudius

    2016-01-01

    We appreciate Barry Cooper and Judith Glaesser's (henceforth CG) energy and effort put into reflecting on parts of our proposals laid out in "Set-theoretic Methods for the Social Sciences" (2012). We use our response to explain what enhanced standard analysis (ESA) is meant to achieve and what not, an issue about which CG hold erroneous…

  6. Cobalt chloride administration in athletes: a new perspective in blood doping?

    Science.gov (United States)

    Lippi, G; Franchini, M; Guidi, G C

    2005-11-01

    Blood doping is an illegal and unfair way of enhancing athletic performance by increasing the oxygen carrying capacity of the blood. Currently used methods usually involve stimulation of erythropoiesis. Gene therapy targeting the hypoxia inducible factor pathway may be an attractive alternative to traditional blood doping techniques. Hypoxia activates a large number of genes with essential roles in cell and tissue adaptation to low oxygen. Cobalt chloride is a well established chemical inducer of hypoxia-like responses such as erythropoiesis. Cobalt supplementation is not banned and therefore would not be detected by current anti-doping testing. Although there is as yet no direct or anecdotal evidence of cobalt chloride administration to athletes, its use should be warned against as being not only unfair but potentially dangerous.

  7. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  8. Injectable agents affecting subcutaneous fats.

    Science.gov (United States)

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.

  9. Beta-blocking agents during electroconvulsive therapy: a review.

    Science.gov (United States)

    Boere, E; Birkenhäger, T K; Groenland, T H N; van den Broek, W W

    2014-07-01

    Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Effect of bleaching agent extracts on murine macrophages.

    Science.gov (United States)

    Fernandes, Aletéia M M; Vilela, Polyana G F; Valera, Marcia C; Bolay, Carola; Hiller, Karl Anton; Schweikl, Helmut; Schmalz, Gottfried

    2018-05-01

    The aim of this study was to evaluate the cytotoxicity and the influence of bleaching agents on immunologically cell surface antigens of murine macrophages in vitro. RAW 264.7 cells were exposed to bleaching gel extracts (40% hydrogen peroxide or 20% carbamide peroxide) and different H 2 O 2 concentrations after 1 and 24-h exposure periods and 1-h exposure and 23-h recovery. Tests were performed with and without N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO). Cell viability was determined by MTT assay. The expression of surface markers CD14, CD40, and CD54 with and without LPS stimulation was detected by flow cytometry, while the production of TNF-α was measured by ELISA. Statistical analysis was performed using the Mann-Whitney U test (α = 0.05). Extracts of bleaching agents were cytotoxic for cells after a 1-h exposure; cells could not recover after 24 h. This effect can be mitigated by the antioxidant NAC and increased by BSO, an inhibitor of glutathione (GSH) synthesis. LPS stimulated expression of all surface markers and TNF-α production. Exposure to bleaching agent extracts and H 2 O 2 leads to a reduction of TNF-α, CD14, and CD40 expression, while the expression of CD54 was upregulated at non-cytotoxic concentrations. Whereas NAC reduced this effect, it was increased in the presence of BSO. Extracts of bleaching agents were irreversibly cytotoxic to macrophages after a 1-h exposure. Only the expression of CD54 was upregulated. The reactions are mediated by the non-enzymatic antioxidant GSH. The addition of an antioxidant can downregulate unfavorable effects of dental bleaching.

  11. Results of the ESA study on psychological selection of astronaut candidates for Columbus missions II: Personality assessment

    Science.gov (United States)

    Goeters, Klaus-Martin; Fassbender, Christoph

    A unique composition of personality assessment methods was applied to a group of 97 ESA scientists and engineers. This group is highly comparable to real astronaut candidates with respect to age and education. The list of used tests includes personality questionnaires, problem solving in groups as well as a projective technique. The study goals were: 1. Verification of psychometric qualities and applicability of tests to the target group; 2. Search for culture-fair tests by which multi-national European groups can be examined; 3. Identification of test methods by which the adaptability of the candidates to the psycho-social stress of long-duration space flights can be assessed. Based on the empirical findings, a test battery was defined which can be used in the selection of ESA space personnel.

  12. Gross and net land cover changes in the main plant functional types derived from the annual ESA CCI land cover maps (1992-2015)

    Science.gov (United States)

    Li, Wei; MacBean, Natasha; Ciais, Philippe; Defourny, Pierre; Lamarche, Céline; Bontemps, Sophie; Houghton, Richard A.; Peng, Shushi

    2018-01-01

    Land-use and land-cover change (LULCC) impacts local energy and water balance and contributes on global scale to a net carbon emission to the atmosphere. The newly released annual ESA CCI (climate change initiative) land cover maps provide continuous land cover changes at 300 m resolution from 1992 to 2015, and can be used in land surface models (LSMs) to simulate LULCC effects on carbon stocks and on surface energy budgets. Here we investigate the absolute areas and gross and net changes in different plant functional types (PFTs) derived from ESA CCI products. The results are compared with other datasets. Global areas of forest, cropland and grassland PFTs from ESA are 30.4, 19.3 and 35.7 million km2 in the year 2000. The global forest area is lower than that from LUH2v2h (Hurtt et al., 2011), Hansen et al. (2013) or Houghton and Nassikas (2017) while cropland area is higher than LUH2v2h (Hurtt et al., 2011), in which cropland area is from HYDE 3.2 (Klein Goldewijk et al., 2016). Gross forest loss and gain during 1992-2015 are 1.5 and 0.9 million km2 respectively, resulting in a net forest loss of 0.6 million km2, mainly occurring in South and Central America. The magnitudes of gross changes in forest, cropland and grassland PFTs in the ESA CCI are smaller than those in other datasets. The magnitude of global net cropland gain for the whole period is consistent with HYDE 3.2 (Klein Goldewijk et al., 2016), but most of the increases happened before 2004 in ESA and after 2007 in HYDE 3.2. Brazil, Bolivia and Indonesia are the countries with the largest net forest loss from 1992 to 2015, and the decreased areas are generally consistent with those from Hansen et al. (2013) based on Landsat 30 m resolution images. Despite discrepancies compared to other datasets, and uncertainties in converting into PFTs, the new ESA CCI products provide the first detailed long-term time series of land-cover change and can be implemented in LSMs to characterize recent carbon dynamics

  13. A new 25 years Arctic Sea level record from ESA satellites

    DEFF Research Database (Denmark)

    Andersen, Ole Baltazar; Cheng, Yongcun; Knudsen, Per

    The Arctic is an extremely challenging region for the use of remote sensing for ocean studies. One is the fact that despite 25 years of altimetry only very limited sea level observations exists in the interior of the Arctic Ocean. However, with Cryosat-2 SAR altimetry the situation is changing...... the ESA GOCE mission we are now able to derive a mean dynamic topography of the Arctic Ocean with unprecedented accuracy to constrain the ocean circulation. We present both a new estimation of the mean ocean circulation and new estimates of large scale sea level changes based on satellite data and perform...

  14. Detection of Chemical/Biological Agents and Stimulants using Quadrupole Ion Trap Mass Spectrometry

    International Nuclear Information System (INIS)

    Harmon, S.H.; Hart, K.J.; Vass, A.A.; Wise, M.B.; Wolf, D.A.

    1999-01-01

    Detection of Chemical/Biological Agents and Simulants A new detector for chemical and biological agents is being developed for the U. S. Army under the Chemical and Biological Mass Spectrometer Block II program. The CBMS Block II is designed to optimize detection of both chemical and biological agents through the use of direct sampling inlets[I], a multi- ported sampling valve and a turbo- based vacuum system to support chemical ionization. Unit mass resolution using air as the buffer gas[2] has been obtained using this design. Software to control the instrument and to analyze the data generated from the instrument has also been newly developed. Detection of chemical agents can be accomplished. using the CBMS Block II design via one of two inlets - a l/ I 6'' stainless steel sample line -Chemical Warfare Air (CW Air) or a ground probe with enclosed capillary currently in use by the US Army - CW Ground. The Block II design is capable of both electron ionization and chemical ionization. Ethanol is being used as the Cl reagent based on a study indicating best performance for the Biological Warfare (BW) detection task (31). Data showing good signal to noise for 500 pg of methyl salicylate injected into the CW Air inlet, 50 ng of dimethylmethylphosphonate exposed to the CW Ground probe and 5 ng of methyl stearate analyzed using the pyrolyzer inlet were presented. Biological agents are sampled using a ''bio-concentrator'' unit that is designed to concentrate particles in the low micron range. Particles are collected in the bottom of a quartz pyrolyzer tube. An automated injector is being developed to deliver approximately 2 pL of a methylating reagent, tetramethylamonium- hydroxide to 'the collected particles. Pyrolysis occurs by rapid heating to ca. 55OOC. Biological agents are then characterized by their fatty acid methyl ester profiles and by other biomarkers. A library of ETOH- Cl/ pyrolysis MS data of microorganisms used for a recently published study[3] has been

  15. Recent Advances in Antenna Measurement Techniques at the DTU-ESA Spherical Near-Field Antenna Test Facility

    DEFF Research Database (Denmark)

    Breinbjerg, Olav; Pivnenko, Sergey; Kim, Oleksiy S.

    2014-01-01

    This paper reports recent antenna measurement projects and research at the DTU-ESA Spherical Near-Field Antenna Test Facility at the Technical University of Denmark. High-accuracy measurement projects for the SMOS, SENTINEL-1, and BIOMASS missions of the European Space Agency were driven...

  16. Studies on chemotherapy of parasitic helminths (VI) effects of various neuropharmacological agents on the motility of Dipylidium caninum.

    Science.gov (United States)

    Terada, M; Ishii, A I; Kino, H; Sano, M

    1982-06-01

    Effects of various neuropharmacological agents on the motility of Dipylidium caninum was studied. 5-HT stimulated the motility of D. caninum, while other drugs such as GABA, adrenaline, phenylephrine, isoproterenol, dibenamine, and propranolol showed little effect. The stimulatory action of 5-HT was antagonized by tryptophol. Stibnal caused paralysis which was blocked by the pretreatment with 5-HT. Paralytic effects were caused by eserine, dichlorovos, ACh, carbachol and DMPP, but not by pilocarpine and McN-A-343. d-Tubocurarine, hexamethonium, and atropine all showed little effect on the motility and on the paralytic action of eserine. Though guanidine showed little effect, strychnine remarkably stimulated the motility. The action of strychnine was stimulated by 5-HT but partially inhibited by tryptophol. Morphine and picrate slightly stimulated the motility, but showed little influence on the paralytic action of eserine. These two agents stimulated the paralyzed preparation by tryptophol transiently and sustainedly, respectively. These results on the cholinergic and serotonergic drugs basically showed good agreement with those reported in trematodes such as Schistosoma mansoni and Fasciola hepatica.

  17. In Vivo Microdialysis and Electroencephalographic Activity in Freely Moving Guinea Pigs Exposed to Organophosphorus Nerve Agents Sarin and VX: Analysis of Acetylcholine and Glutamate

    Science.gov (United States)

    2011-01-01

    support the idea that there is a triphasic NT model for onset and progression of seizures and subsequent brain damage upon acute exposure to nerve agent...col- umn reactor (ACH-SPR Part No. 70-0640), and analytical cell (Model 5040) were all obtained from ESA Biosci- ences, Inc. (Chelmsford, MA...injection volume was 10 ll. To facilitate EC detection, a post-column reactor was utilized to convert ACh and Ch to hydrogen peroxide. The signal from

  18. DNA-damaging agents stimulate gene expression at specific loci in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Kenyon, C.J.; Walker, G.C.

    1988-05-01

    Operon fusions in Escherichia coli were obtained that showed increased beta-galactosidase expression in response to treatment with the DNA-damaging agent mitomycin C. These fusions were generated by using the Mud(ApR, lac) vector to insert the lactose structural genes randomly into the bacterial chromosome. Induction of beta-galactosidase in these strains, which carried fusions of lac to these din (damage-inducible) loci, was (i) triggered by UV light as well as by mitomycin C and (ii) abolished by either a recA- or a lexA- mutation. Similar characteristics of induction were observed when the lactose genes were fused to a prophage lambda promoter by using Mud(ApR, lac). These results indicate that E. coli contains a set of genes that, like prophage lambda genes, are expressed in response to DNA-damaging agents and regulated by the recA and lexA gene products. These din genes map at five bacterial loci. One din::Mud(ApR, lac) insertion results in a UV-sensitive phenotype and may be within the uvrA transcriptional unit.

  19. Study of the erythropoiesis activity of nano-encapsulated forms of erythropoietin

    Directory of Open Access Journals (Sweden)

    Zhanagul Khasenbekova

    2014-01-01

    Full Text Available Introduction: The recombinant human erythropoietin (rhEPO is used in the treatment of anemia. In order to improve its pharmacokinetic properties, nanoparticles of biodegradable polymers of natural or synthetic origin were used. The aim of this study was to investigate the effect of new nano-encapsulated forms of recombinant human erythropoietin for oral use on the erythropoiesis in the cyclophosphamide immunosuppression model. Material and methods: The CHOpE immortalized cells culture (a primary producer of rhEPO "Vector" in Russia was used. The following biodegradable polymers were chosen: 0.05% and 0.005% carbopol, 0.05% and 0.005% kollidon, and 0.05% and 0.005% pectin. Immunosuppression was obtained by a single dose of i.p. injection of cyclophosphamide (250 mg/kg in white mice (18-20 g. During the next 5 days, the nano-encapsulated erythropoietin (100 ED/mouse was administered orally to each mouse. After 5 and 10 days, the cell count of the number of blood reticulocytes and the myelogram of bone marrow were performed. The control group of mice received injections of Eprex. Results: On the 5th day of the experiment, the highest level of reticulocyte was observed in the samples of erythropoietin with kollidon (0.05% and pectin (0.005% nanoparticles. On the 10th day, the highest activity was observed in the samples of erythropoietin substance with pectin at 0.05% and 0.005% concentrations. The levels of reticulocytes in these groups reached 13.53% and 14.55%, respectively. The results of the myelogram during immunosuppression showed some activity of erythropoietin in conjunction with both concentrations of pectin when a two-fold increase in the number of erythroblasts was observed on the 5th day. High degrees of erythrokaryocytes in the state of mitosis were observed in the 0.05% pectin samples. Similar results were observed in equivalent groups of control animals on the 10th day of the experiment, which is compatible with the data on Eprex

  20. Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.

    Directory of Open Access Journals (Sweden)

    Michelle Erin Miller

    Full Text Available Meis1 is recognized as an important transcriptional regulator in hematopoietic development and is strongly implicated in the pathogenesis of leukemia, both as a Hox transcription factor co-factor and independently. Despite the emerging recognition of Meis1's importance in the context of both normal and leukemic hematopoiesis, there is not yet a full understanding of Meis1's functions and the relevant pathways and genes mediating its functions. Recently, several conditional mouse models for Meis1 have been established. These models highlight a critical role for Meis1 in adult mouse hematopoietic stem cells (HSCs and implicate reactive oxygen species (ROS as a mediator of Meis1 function in this compartment. There are, however, several reported differences between these studies in terms of downstream progenitor populations impacted and effectors of function. In this study, we describe further characterization of a conditional knockout model based on mice carrying a loxP-flanked exon 8 of Meis1 which we crossed onto the inducible Cre localization/expression strains, B6;129-Gt(ROSA26Sor(tm1(Cre/ERTNat/J or B6.Cg-Tg(Mx1-Cre1Cgn/J. Findings obtained from these two inducible Meis1 knockout models confirm and extend previous reports of the essential role of Meis1 in adult HSC maintenance and expansion and provide new evidence that highlights key roles of Meis1 in both megakaryopoiesis and erythropoiesis. Gene expression analyses point to a number of candidate genes involved in Meis1's role in hematopoiesis. Our data additionally support recent evidence of a role of Meis1 in ROS regulation.

  1. Definition of accurate reference pattern for the DTU-ESA VAST12 antenna

    DEFF Research Database (Denmark)

    Pivnenko, Sergey; Breinbjerg, Olav; Burgos, Sara

    2009-01-01

    In this paper, the DTU-ESA 12 GHz validation standard (VAST12) antenna and a dedicated measurement campaign carried out in 2007-2008 for the definition of its accurate reference pattern are first described. Next, a comparison between the results from the three involved measurement facilities...... is presented. Then, an accurate reference pattern of the VAST12 antenna is formed by averaging the three results taking into account the estimated uncertainties of each result. Finally, the potential use of the reference pattern for benchmarking of antenna measurement facilities is outlined....

  2. Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants.

    Science.gov (United States)

    O'Connor, Ayrn D; Padilla-Jones, Angie; Gerkin, Richard D; Levine, Michael

    2015-06-01

    Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42) years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10

  3. Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Foged, Eva M; Krogh-Madsen, Rikke

    2010-01-01

    administration of EPO. We recorded exercise capacity, transcranial ultrasonography-derived middle cerebral artery blood velocity, and arterial-internal jugular venous concentration differences of glucose and lactate. In addition, cognitive function, ratings of perceived exertion, ventilation and voluntary......Recombinant human erythropoietin (EPO) increases exercise capacity by stimulating erythropoiesis and subsequently enhancing oxygen delivery to the working muscles. In a large dose, EPO cross the blood brain barrier and may reduce central fatigue and improve cognition. In turn, this would augment...... exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young males (18-34 yo., 74 +/- 7 kg) received either 3 days of high dose (30,000 IU day(-1), N=7) double-blinded placebo controlled or 3 months of low dose (5,000 IU week(-1), N=8) counter-balanced open but controlled...

  4. Stimulation of DNA synthesis by 340nm/ 351nm UV laser irradiation

    International Nuclear Information System (INIS)

    Meldrum, R.A.; Wharton, C.W.

    1991-01-01

    During preliminary experiments designed to test the feasibility of using a 'caged' DNA break trapping agent, the authors observed a stimulation of incorporation of 3 H-thymidine into DNA when cells were irradiated with low doses (100-1000J/m 2 ) of 351nm UV laser irradiation. This wavelength is used to photolyse 'caged' dideoxynucleotides in our fast time course measurements of DNA repair in mammalian cells. The dose at which this stimulation was observed is well below that at which measurable damage is detected. (author)

  5. Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation.

    Science.gov (United States)

    Liu, Yuguan; Weisberg, Lawrence S; Langman, Craig B; Logan, Amanda; Hunter, Krystal; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Berns, Jeffrey S; Handelman, Garry J; Sirover, William D

    2016-10-01

    Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100μM may be supratherapeutic, levels of at least 30μM may be needed to improve wound healing and levels may need to reach 70μM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30μM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels HD patients. A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1μM to 6.4±3.2μM, PHD plasma AA levels ≤100μM were not associated with a pre-HD plasma Ox level≥30μM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30μM were not associated with lower cumulative 4-year survival. Pre-HD plasma AA levels up to 100μM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. Modernization of the electrostatic accelerator ESA-2 used for fundamental and applied investigations

    International Nuclear Information System (INIS)

    Komarov, F.F.; Kamyshan, A.S.; Lagutin, A.E.

    2005-01-01

    The directions of indispensable modernization of the Van de Graaff electrostatic accelerator ESA-2 are indicated. Design and results of reconstruction of the electrostatic accelerator are described and discussed. The ion source constructed is described too. Design of the new acceleration tube with flat electrodes was investigated. There are many characteristics for the electrostatic accelerator tube presented. The main attention was paid to the upgrading of the charging system. There are many characteristics for the electrostatic accelerator charging belt discussed as well. (authors)

  7. Simulated experiment for elimination of chemical and biological warfare agents by making use of microwave plasma torch

    International Nuclear Information System (INIS)

    Hong, Yong C.; Kim, Jeong H.; Uhm, Han S.

    2004-01-01

    The threat of chemical and biological warfare agents in a domestic terrorist attack and in military conflict is increasing worldwide. Elimination and decontamination of chemical and biological warfare (CBW) agents are immediately required after such an attack. Simulated experiment for elimination of CBW agents by making use of atmospheric-pressure microwave plasma torches is carried out. Elimination of biological warfare agents indicated by the vitrification or burnout of sewage sludge powders and decomposition of toluene gas as a chemical agent stimulant are presented. A detailed characterization for the elimination of the simulant chemicals using Fourier transform infrared and gas chromatography is also presented

  8. Simulated experiment for elimination of chemical and biological warfare agents by making use of microwave plasma torch

    Science.gov (United States)

    Hong, Yong C.; Kim, Jeong H.; Uhm, Han S.

    2004-02-01

    The threat of chemical and biological warfare agents in a domestic terrorist attack and in military conflict is increasing worldwide. Elimination and decontamination of chemical and biological warfare (CBW) agents are immediately required after such an attack. Simulated experiment for elimination of CBW agents by making use of atmospheric-pressure microwave plasma torches is carried out. Elimination of biological warfare agents indicated by the vitrification or burnout of sewage sludge powders and decomposition of toluene gas as a chemical agent stimulant are presented. A detailed characterization for the elimination of the simulant chemicals using Fourier transform infrared and gas chromatography is also presented.

  9. Reduced discomfort during High-Definition transcutaneous stimulation using 6% benzocaine

    Directory of Open Access Journals (Sweden)

    Berkan eGuleyupoglu

    2014-07-01

    Full Text Available AbstractBackground High-Definition transcranial Direct Current Stimulation (HD-tDCS allows for non-invasive neuromodulation using an array of compact (approximately 1 cm2 contact area High-Definition (HD electrodes, as compared to conventional tDCS (which uses two large pads that are approximately 35cm2. In a previous transcutaneous study, we developed and validated designs for HD electrodes that reduce discomfort over >20 min session with 2 mA electrode current.ObjectiveThe purpose of this study was to investigate the use of a chemical pretreatment with 6% benzocaine (topical numbing agent to further reduce subjective discomfort during transcutaneous stimulation and to allow for better sham controlled studies.MethodsPre-treatment with 6% benzocaine was compared with control (no pretreatment for 22 minutes 2 mA of stimulation, with either CCNY-4 or Lectron II electroconductive gel, for both cathodal and anodal transcutaneous (forearm stimulation (8 different combinations.Results Results show that for all conditions and polarities tested, stimulation with HD electrodes is safe and well tolerated and that pretreatment further reduced subjective discomfort. ConclusionPretreatment with a mild analgesic reduces discomfort during HD-tDCS.

  10. Simulating Heavy Ion SEUs in the ESA Monitor

    CERN Document Server

    Noordeh, Emil

    2014-01-01

    This study analyzed SEU measurements made of the ESA Monitor at GSI, RADEF, UCL, and TAMU. An IRPP model was implemented through the use of FLUKA that was calibrated to the measurements of ions above the LET threshold. The model proved successful in reproducing proton measurements that are entirely independent of the calibration. When applied to the sub-threshold region, experimental measurements were underestimated by a factor of $\\sim$3 for the high energy ions at GSI, a factor of $\\sim$10 for the ions at UCL/RADEF, and an anomalous factor of $\\sim$300 for the ion at TAMU. Several possible sources of systematic uncertainty were investigated including sensitive volume size, BEOL thickness, and substrate thickness. Additionally, the impact of including air between the beam and the DUT as well as side effects due to the simulated geometry were explored. It was found that none of these sources can provide a substantial enough impact on the SEU cross-section to reconcile the anomalous measurement made at TAMU.

  11. ESA's Food Security Thematic Exploitation Platform "Supporting Sustainable Food Production from Space"

    Science.gov (United States)

    Gilliams, S. J.

    2017-12-01

    In line with the paradigm shift in Earth Observation of "Bringing the users to the data", ESA provides collaborative, virtual work environments giving access to EO data and tools, processors, and ICT resources through coherent interfaces. These coherent interfaces are categorized thematically, tailored to the related user communities and named Thematic Exploitation Platforms (TEP). The Food Security Thematic Exploitation Platform (FS-TEP) is the youngest out of seven TEPs and is developed in an agile mode in close coordination with its users. It will provide a "one stop platform" for the extraction of information from EO data for services in the food security sector mainly in Europe & Africa, allowing both access to EO data and processing of these data sets. Thereby it will foster smart, data-intensive agricultural and aquacultural applications in the scientific, private and public domain. The FS-TEP builds on a large and heterogeneous user community, spanning from application developers in agriculture to aquaculture, from small-scale farmers to agricultural industry, from public science to the finance and insurance sectors, from local and national administration to international agencies. To meet the requirements of these groups, the FS-TEP will provide different frontend interfaces. Service pilots will demonstrate the platform's ability to support agriculture and aquaculture with tailored EO based information services.The project team developing the FS-TEP and implementing pilot services during a 30 months period (started in April 2017) is led by Vista GmbH, Germany, supported by CGI Italy, VITO, Belgium, and Hatfield Consultants, Canada. It is funded by ESA under contract number 4000120074/17/I-EF.

  12. Efficacy and safety of iorEPOCIM for chemotherapy- or radiotherapy-induced anemia in pediatric cancer patients.

    Science.gov (United States)

    Vargas, Alicia; Mendoza, Ivis; Uranga, Rolando; González, Alejandro; Martínez, Liliana; Caballero, Iraida; Piedra, Patricia; Saurez, Giselle; Verdecia, Manuel; Cabanas, Ricardo

    2010-07-01

    Recombinant human erythropoietin (RHuEPO) is an erythropoiesis stimulating agent (ESA) used to treat anemia in patients with total or relative erythropoietin deficit. In cancer patients, it is administered to optimize hemoglobin (Hb) levels, correct anemia and reduce the need for transfusions. Cuba produces a RHuEPO, registered in 1998 as iorEPOCIM, that is widely used in the national public health system, mainly to treat patients with anemia due to chronic kidney disease (CKD). Evaluate the efficacy and safety of iorEPOCIM in pediatric cancer patients with anemia following chemotherapy or radiotherapy. The working hypothesis posed an Hb increase>or=15 g/l in 70% of patients receiving iorEPOCIM for 8 weeks. A Phase IV, multicenter, open clinical trial was conducted. Participants were 157 patients aged 1-19 years with anemia and cyto-histological diagnosis of cancer in any location. Patients received either 600 U/kg iorEPOCIM intravenously, once weekly, or 150 U/kg iorEPOCIM subcutaneously, 3 times a week, for 8 weeks. All patients had blood tests every week to determine hemoglobin and hematocrit, and reticulocyte and platelet counts. Mean number of transfusions required by patients during the treatment period was compared to the mean number of transfusions received in the preceding 8 weeks. Adverse events (AE) were recorded at the 4th and 8th weeks and classified by intensity and causality. Hb levels rose>or=15 g/l in 68.8% of patients, and transfusion requirements decreased 17%. The most frequent adverse events were fever (19.3%), vomiting (10.2%) and flu-like syndrome (9.6%). Intensity of AE was predominantly mild. Only 7 AE were classified as very probably related to the product and none of those was severe. iorEPOCIM proved to be safe and effective at the doses and frequencies used in this patient population. As a result, this medication was recommended for use in all pediatric oncology and hematology services in the country.

  13. Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Damián Hernández

    2016-01-01

    Full Text Available Background. Human induced pluripotent stem cells (iPSCs are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

  14. Effect of iodide on glucose oxidation and 32P incorporation into phospholipids stimulated by different agents in dog thyroid slices

    International Nuclear Information System (INIS)

    Tseng, F.Y.; Rani, C.S.; Field, J.B.

    1989-01-01

    Since iodide (I-) inhibits TSH stimulation of cAMP formation, which mediates most of the effects of the hormone, it has been assumed that this accounts for the inhibitory action of iodide on the thyroid. However, TSH stimulation of 32P incorporation into phospholipids and stimulation of thyroid metabolism by other agonists, such as carbachol, phorbol esters, and ionophore A23187, is not cAMP mediated. The present studies examined the effect of iodide on stimulation of glucose oxidation and 32P incorporation into phospholipids by TSH and other agonists to determine if the inhibition of cAMP formation was responsible for the action of iodide. Preincubation of dog thyroid slices for 1 h with iodide (10(-4) M) inhibited TSH-, (Bu)2cAMP-, carbachol-, methylene blue-, 12-O-tetradecanoyl phorbol-13-acetate-, ionophore A23187-, prostaglandin E1-, and cholera toxin-stimulated glucose oxidation. I- also inhibited the stimulation by TSH, 12-O-tetradecanoyl phorbol-13-acetate, carbachol, and ionophore A23187 of 32P incorporation into phospholipids. The inhibition was similar whether iodide was added 2 h before or simultaneously with the agonist. I- itself sometimes stimulated basal glucose oxidation, but had no effect on basal 32P incorporation into phospholipids. The effects of iodide on basal and agonist-stimulated thyroid metabolism were blocked by methimazole (10(-3) M). When dog thyroid slices were preloaded with 32PO4 or [1-14C]glucose, the iodide inhibition of agonist stimulation disappeared, suggesting that the effect of iodide involves the transport process. In conclusion, I- inhibited stimulation of glucose oxidation and 32P incorporation into phospholipids by all agonists, indicating that the effect is independent of the cAMP system and that iodide autoregulation does not only involve this system. Oxidation and organification of iodide are necessary for the inhibition

  15. ESA's spaceborne lidar mission ADM-Aeolus; project status and preparations for launch

    Science.gov (United States)

    Straume, Anne Grete; Elfving, Anders; Wernham, Denny; de Bruin, Frank; Kanitz, Thomas; Schuettemeyer, Dirk; Bismarck, Jonas von; Buscaglione, Fabio; Lecrenier, O.; McGoldrick, Phil

    2018-04-01

    ESA's Doppler Wind lidar mission, the Atmospheric Dynamics Mission (ADM-Aeolus, hereafter abbreviated to Aeolus), was chosen as an Earth Explorer Core mission within the Living Planet Programme in 1999. It shall demonstrate the potential of space-based Doppler Wind lidars for operational measurements of wind profiles and their use in Numerical Weather Prediction (NWP) and climate research. Spin-off products are profiles of cloud and aerosol optical properties. Aeolus carries the novel Doppler Wind lidar instrument ALADIN. The mission prime is Airbus Defence & Space UK (ADS-UK), and the instrument prime is Airbus Defence & Space France (ADS-F).

  16. Thermal simulations of the STIX instrument for ESA Solar Orbiter mission

    Science.gov (United States)

    Białek, Agata; Severyn, Karol; Grassmann, Kamil; Orleańskii, Piotr; Skup, Konrad R.; Arnold, Nicolas; Gröbelbauer, Hans-Peter; Hurford, Gordon J.; Krucker, Samuel; Bauer, Svend-Marian; Mann, Gottfied; Önel, Hakan; Bernet, Adeline; Blecha, Luc; Grimm, Oliver; Limousin, Olivier; Martignac, Jerome; Meuris, Aline

    2013-07-01

    The ESA Solar Orbiter mission, planned to be launched in 2017, is going to study the Sun with ten different instruments including the Spectrometer/Telescope for Imaging X-rays - STIX. The thermal environment on the elliptical orbit around the Sun - 0.28 AU at perihelion and 0.952 AU at aphelion - is extreme, where at one point of the orbit is very hot, while on another very cold. That makes the requirements for the heat fluxes exchanged between each instrument and the spacecraft, as well as between the instrument - subsystems, very restrictive. Here the authors discuss the thermal design with respect to the defined requirements and present the results of the thermal analyses performed with ESATAN TMS software.

  17. Una manera de nombrar el deseo en Toda esa gran verdad

    Directory of Open Access Journals (Sweden)

    Mauricio List

    2011-01-01

    Full Text Available Este artículo analiza la novela Toda esa gran verdad (2006 del mexicano Eduardo Montagner. El artículo centra su atención en el tema de la sexualidad, particularmente la del personaje principal. La idea es reflexionar acerca de formas disidentes de la sexualidad que rompen con las maneras normativas y que son sancionadas socialmente. En este caso en particular, unas botas de hule son el centro de la atención de un joven de una comunidad rural que dice estar enamorado del dueño de dicho calzado. Él va aprendiendo que un sujeto fetichista requiere de su objeto para disfrutar del placer erótico.

  18. ESA's Multi-mission Sentinel-1 Toolbox

    Science.gov (United States)

    Veci, Luis; Lu, Jun; Foumelis, Michael; Engdahl, Marcus

    2017-04-01

    The Sentinel-1 Toolbox is a new open source software for scientific learning, research and exploitation of the large archives of Sentinel and heritage missions. The Toolbox is based on the proven BEAM/NEST architecture inheriting all current NEST functionality including multi-mission support for most civilian satellite SAR missions. The project is funded through ESA's Scientific Exploitation of Operational Missions (SEOM). The Sentinel-1 Toolbox will strive to serve the SEOM mandate by providing leading-edge software to the science and application users in support of ESA's operational SAR mission as well as by educating and growing a SAR user community. The Toolbox consists of a collection of processing tools, data product readers and writers and a display and analysis application. A common architecture for all Sentinel Toolboxes is being jointly developed by Brockmann Consult, Array Systems Computing and C-S called the Sentinel Application Platform (SNAP). The SNAP architecture is ideal for Earth Observation processing and analysis due the following technological innovations: Extensibility, Portability, Modular Rich Client Platform, Generic EO Data Abstraction, Tiled Memory Management, and a Graph Processing Framework. The project has developed new tools for working with Sentinel-1 data in particular for working with the new Interferometric TOPSAR mode. TOPSAR Complex Coregistration and a complete Interferometric processing chain has been implemented for Sentinel-1 TOPSAR data. To accomplish this, a coregistration following the Spectral Diversity[4] method has been developed as well as special azimuth handling in the coherence, interferogram and spectral filter operators. The Toolbox includes reading of L0, L1 and L2 products in SAFE format, calibration and de-noising, slice product assembling, TOPSAR deburst and sub-swath merging, terrain flattening radiometric normalization, and visualization for L2 OCN products. The Toolbox also provides several new tools for

  19. First Prototype of a Web Map Interface for ESA's Planetary Science Archive (PSA)

    Science.gov (United States)

    Manaud, N.; Gonzalez, J.

    2014-04-01

    We present a first prototype of a Web Map Interface that will serve as a proof of concept and design for ESA's future fully web-based Planetary Science Archive (PSA) User Interface. The PSA is ESA's planetary science archiving authority and central repository for all scientific and engineering data returned by ESA's Solar System missions [1]. All data are compliant with NASA's Planetary Data System (PDS) Standards and are accessible through several interfaces [2]: in addition to serving all public data via FTP and the Planetary Data Access Protocol (PDAP), a Java-based User Interface provides advanced search, preview, download, notification and delivery-basket functionality. It allows the user to query and visualise instrument observations footprints using a map-based interface (currently only available for Mars Express HRSC and OMEGA instruments). During the last decade, the planetary mapping science community has increasingly been adopting Geographic Information System (GIS) tools and standards, originally developed for and used in Earth science. There is an ongoing effort to produce and share cartographic products through Open Geospatial Consortium (OGC) Web Services, or as standalone data sets, so that they can be readily used in existing GIS applications [3,4,5]. Previous studies conducted at ESAC [6,7] have helped identify the needs of Planetary GIS users, and define key areas of improvement for the future Web PSA User Interface. Its web map interface shall will provide access to the full geospatial content of the PSA, including (1) observation geometry footprints of all remote sensing instruments, and (2) all georeferenced cartographic products, such as HRSC map-projected data or OMEGA global maps from Mars Express. It shall aim to provide a rich user experience for search and visualisation of this content using modern and interactive web mapping technology. A comprehensive set of built-in context maps from external sources, such as MOLA topography, TES

  20. Improved oceanographic measurements fom SAR altimetry: Results and scientific roadmap from ESA cryosat plus for oceans project

    DEFF Research Database (Denmark)

    Cotton, P. D.; Andersen, Ole Baltazar; Stenseng, Lars

    The ESA CryoSat mission is the first space mission to carry a radar altimeter that can operate in Synthetic Aperture Radar (SAR) mode. It thus provides the first opportunity to test and evaluate, using real data, the significant potential benefits of SAR altimetry for ocean applications. The obje...

  1. An improved and homogeneous altimeter sea level record from the ESA Climate Change Initiative

    Science.gov (United States)

    Legeais, Jean-François; Ablain, Michaël; Zawadzki, Lionel; Zuo, Hao; Johannessen, Johnny A.; Scharffenberg, Martin G.; Fenoglio-Marc, Luciana; Joana Fernandes, M.; Baltazar Andersen, Ole; Rudenko, Sergei; Cipollini, Paolo; Quartly, Graham D.; Passaro, Marcello; Cazenave, Anny; Benveniste, Jérôme

    2018-02-01

    Sea level is a very sensitive index of climate change since it integrates the impacts of ocean warming and ice mass loss from glaciers and the ice sheets. Sea level has been listed as an essential climate variable (ECV) by the Global Climate Observing System (GCOS). During the past 25 years, the sea level ECV has been measured from space by different altimetry missions that have provided global and regional observations of sea level variations. As part of the Climate Change Initiative (CCI) program of the European Space Agency (ESA) (established in 2010), the Sea Level project (SL_cci) aimed to provide an accurate and homogeneous long-term satellite-based sea level record. At the end of the first phase of the project (2010-2013), an initial version (v1.1) of the sea level ECV was made available to users (Ablain et al., 2015). During the second phase of the project (2014-2017), improved altimeter standards were selected to produce new sea level products (called SL_cci v2.0) based on nine altimeter missions for the period 1993-2015 (https://doi.org/10.5270/esa-sea_level_cci-1993_2015-v_2.0-201612; Legeais and the ESA SL_cci team, 2016c). Corresponding orbit solutions, geophysical corrections and altimeter standards used in this v2.0 dataset are described in detail in Quartly et al. (2017). The present paper focuses on the description of the SL_cci v2.0 ECV and associated uncertainty and discusses how it has been validated. Various approaches have been used for the quality assessment such as internal validation, comparisons with sea level records from other groups and with in situ measurements, sea level budget closure analyses and comparisons with model outputs. Compared with the previous version of the sea level ECV, we show that use of improved geophysical corrections, careful bias reduction between missions and inclusion of new altimeter missions lead to improved sea level products with reduced uncertainties on different spatial and temporal scales. However, there

  2. CryoSat: ESA's Ice Explorer Mission: status and achievements

    Science.gov (United States)

    Parrinello, Tommaso; Mardle, Nicola; Hoyos Ortega, Berta; Bouzinac, Catherine; Badessi, Stefano; Frommknecht, Bjorn; Davidson, Malcolm; Fornari, Marco; Cullen, Robert

    2013-04-01

    CryoSat-2 was launched on the 8th April 2010 and it is the first European ice mission dedicated to monitoring precise changes in the thickness of polar ice sheets and floating sea ice over a 3-year period. Cryosat-2 carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL) with two antennas and with extended capabilities to meet the measurement requirements for ice-sheets elevation and sea-ice freeboard. Experimental evidence have shown that data is of high quality thanks to an altimeter that is behaving exceptional well within its design specifications. In April 2012, the first winter [2010 -2011] sea-ice variation map of the Arctic was released to the scientific community. Scope of this paper is to describe the current mission status and the main scientific achievements in the last twelve months. Topics will also include programmatic highlights and information on accessing Cryosat products following the new ESA Earth Observation Data Policy.

  3. ESA remote-sensing programme - Present activities and future plans

    Energy Technology Data Exchange (ETDEWEB)

    Plevin, J [ESA, Directorate of Planning and Future Programmes, Paris, France; Pryke, I [ESA, Directorate of Applications Programmes, Toulouse, France

    1979-02-01

    The present activities and future missions of the ESA program of spaceborne remote sensing of earth resources and environment are discussed. Program objectives have been determined to be the satisfaction of European regional needs by agricultural, land use, water resources, coastal and polar surveys, and meeting the requirements of developing nations in the areas of agricultural production, mineral exploration and disaster warning and assessment. The Earthnet system of data processing centers presently is used for the distribution of remote sensing data acquired by NASA satellites. Remote sensing experiments to be flown aboard Spacelab are the Metric Camera, to test high resolution mapping capabilities of a large format camera, and the Microwave Remote-Sensing Experiment, which operates as a two-frequency scatterometer, a synthetic aperture radar and a passive microwave radiometer. Studies carried out on the definition of future remote sensing satellite systems are described, including studies of system concepts for land applications and coastal monitoring satellites.

  4. Nutritional support in the tertiary care of patients affected by chronic renal insufficiency: report of a step-wise, personalized, pragmatic approach.

    Science.gov (United States)

    Cupisti, Adamasco; D'Alessandro, Claudia; Di Iorio, Biagio; Bottai, Anna; Zullo, Claudia; Giannese, Domenico; Barsotti, Massimiliano; Egidi, Maria Francesca

    2016-09-06

    Dietary treatment is helpful in CKD patients, but nutritional interventions are scarcely implemented. The main concern of the renal diets is its feasibility with regards to daily clinical practice especially in the elderly and co-morbid patients. This study aimed to evaluate the effects of a pragmatic, step-wise, personalized nutritional support in the management of CKD patients on tertiary care. This is a case-control study. It included 823 prevalent out-patients affected by CKD stage 3b to 5 not-in-dialysis, followed by tertiary care in nephrology clinics; 305 patients (190 males, aged 70 ± 12 years) received nutritional support (nutritional treatment Group, NTG); 518 patients (281 males, aged 73 ± 13 years) who did not receive any dietary therapy, formed the control group (CG). In the NTG patients the dietary interventions were assigned in order to prevent or correct abnormalities and to maintain a good nutritional status. They included manipulation of sodium, phosphate, energy and protein dietary intakes while paying special attention to each patient's dietary habits. Phosphate and BUN levels were lower in the NTG than in the CG, especially in stage 4 and 5. The prevalence of hyperphosphatemia was lower in the NTG than in CG in stage 5 (13.3 % vs 53.3 %, p < 001, respectively), in stage 4 (4.1 % vs 18.3 % vs, p < 0.001) and stage 3b (2.8 % vs 9.5 % p < 0.05). Serum albumin was higher in NTG than in CG especially in stage 5 . The use of calcium-free intestinal phosphate binders was significantly lower in NTG than in CG (11 % vs 19 % p < 0.01), as well as that of Erythropoiesis stimulating agents (11 % vs 19 %, p < 0.01), and active Vitamin D preparations (13 % vs 21 %, p < 0.01). This case-control study shows the usefulness of a nutritional support in addition to the pharmacological good practice in CKD patients on tertiary care. Lower phosphate and BUN levels are obtained together with maintenance of serum albumin

  5. Machine Learning Approach to Deconvolution of Thermal Infrared (TIR) Spectrum of Mercury Supporting MERTIS Onboard ESA/JAXA BepiColombo

    Science.gov (United States)

    Varatharajan, I.; D'Amore, M.; Maturilli, A.; Helbert, J.; Hiesinger, H.

    2018-04-01

    Machine learning approach to spectral unmixing of emissivity spectra of Mercury is carried out using endmember spectral library measured at simulated daytime surface conditions of Mercury. Study supports MERTIS payload onboard ESA/JAXA BepiColombo.

  6. IMPROVING THE SKILL AND THE INTEREST OF WRITING ADVERTISEMENTS AND POSTERS THROUGH ESA SEQUENCE

    OpenAIRE

    author Fatma Yuniarti

    2015-01-01

    The action reserach aims at improving the students’ writing skill especially to write advertsements and posters. Both are the short functional texts to be learned at the second semester. According to the data on pre cycle, the students of second semester got difficulties to write advertisements and posters. A treatment was necessary to help the students overcome their problem. To consider the related literature, the writer decided to implement ESA sequence (Harmer 2001) in the class. The elem...

  7. Competitive agents in a market: Statistical physics of the minority game

    Science.gov (United States)

    Sherrington, David

    2007-10-01

    A brief review is presented of the minority game, a simple frustrated many-body system stimulated by considerations of a market of competitive speculative agents. Its cooperative behaviour exhibits phase transitions and both ergodic and non-ergodic regimes. It provides novel challenges to statistical physics, reminiscent of those of mean-field spin glasses.

  8. The role indigenous bacterial isolates for bioremediation agent in the uranium contaminated aquatic environment

    International Nuclear Information System (INIS)

    Mochd Yazid

    2014-01-01

    A Research on the role of indigenous bacterial isolates for bio-remediation agent of the uranium contaminated in the aquatic environment has been conducted. The objective of the research is to study the role of Pseudomonas sp and Bacillus sp. have been isolated from low level uranium waste for bioremediation agent in their environment, such as the determination of efficiency of the uranium binding compared by the non indigenous bacterial, location of these binding and the influences of added acethyl acid stimulant. The uranium reduction studied was measured by weighting bacterial biomass and uranium concentration was measured by spectrophotometer. The acethyl acid stimulant addition has been done with the variation of concentration and volume. The efficiency of the uranium reduction by indigenous bacterial isolate such as Pseudomonas sp were 84.99 % and Bacillus sp were 52.70 %, so the reduction efficiency by non indigenous bacterial such as Pseudomonas aerogenes were 78.47 % and Bacillus subtilis were 45.22 % for 54 hours incubation time. The result of this research can be concluded that Pseudomonas sp and Bacillus sp. Indigenous bacterial have been isolates from the liquid uranium waste can contributed in bioremediation agent for uranium radionuclide in the environment for 60 ppm concentration with reduction efficiency 52.70 %-84.99 %, that is higher non indigenous bacterial for 54 hours incubation time, the stimulant addition of acethyl acid, the efficiency can be increased up to 99.8 %. (author)

  9. Outsourcing the development of specific application software using the ESA software engineering standards the SPS software Interlock System

    CERN Document Server

    Denis, B

    1995-01-01

    CERN is considering outsourcing as a solution to the reduction of staff. To need to re-engineer the SPS Software Interlock System provided an opportunity to explore the applicability of outsourcing to our specific controls environment and the ESA PSS-05 standards were selected for the requirements specification, the development, the control and monitoring and the project management. The software produced by the contractor is now fully operational. After outlining the scope and the complexity of the project, a discussion on the ESA PSS-05 will be presented: the choice, the way these standards improve the outsourcing process, the quality induced but also the need to adapt them and their limitation in the definition of the customer-supplier relationship. The success factors and the difficulties of development under contract will also be discussed. The maintenance aspect and the impact on in-house developments will finally be addressed.

  10. Anemia of chronic kidney disease: novel physiological approaches to therapy based on simulation of hypoxic response

    Directory of Open Access Journals (Sweden)

    K. A. Aitbaev

    2017-01-01

    Full Text Available Anemia is a modifiable risk factor for the progression of chronic kidney disease (CKD and is characterized by a  decrease in the hemoglobin level, the hematocrit, and the number of circulating red blood cells. In the pre-erythropoietin era blood transfusion was a  common practice for the adequate correction of anemia in patients with CKD. However, a  recombinant human erythropoietin, that was developed and implemented into a clinical practice three decades ago, made a revolution in the renal anemia treatment. Today the management of anemia is based on the use of exogenous erythropoiesis-stimulating agents, such as erythropoietin and its analogues, as well as an oral or parenteral administration of iron. Nevertheless, despite of the high efficacy in the majority of patients this approach has a  negative side. The hemoglobin excursions, increased risk of cardiovascular complications, as well as the development of iron deficiency and chronic inflammation become additional factors in the pathogenesis of anemia associated with the renal failure. In this regard, the development of effective and safe methods of anemia management in CKD is of immediate interest. New medications based mainly on physiological approach are developed. A pharmacological activation of hypoxia-inducible factor (HIF response is one of them. HIF is the main hormonal regulator of erythropoiesis that stimulates the production of endogenous erythropoietin. It is known that in patients with renal failure, the activation of this factor in response to hypoxia is compromised, resulting in a lack of erythropoietin production. This review covers the new mechanistic views on the hypoxic regulation of erythropoiesis and the production of erythropoietin by the kidneys, and presents the newly discovered interactions between the synthesis of erythropoietin, iron metabolism, and the chronic inflammation. Besides that, ongoing clinical trials of pharmacological HIF activators, such as

  11. Bioactive natural constituents from lemongrass tea and erythropoiesis boosting effects: potential use in prevention and treatment of anemia.

    Science.gov (United States)

    Ekpenyong, Christopher E; Daniel, Nyebuk E; Antai, Atim B

    2015-01-01

    This study assessed the effects of lemongrass (Cymbopogon citratus) tea on hematologic indices in human volunteers. One hundred five subjects (55 men and 50 women), aged 18 to 35 years, were randomly assigned to groups set to orally receive infusion prepared from 2, 4, or 8 g of C. citratus leaves once daily for 30 days. Assessment of hematologic indices (hemoglobin concentration [Hb], packed cell volume [PCV], red blood cell [RBC] count, mean cell Hb [MCH], mean cell volume [MCV], mean cell Hb concentration [MCHC], total white blood cell [WBC-total] and differentials, and platelets) were performed 1 day before (baseline), and at 10 (acute) and 30 days (subchronic phase) after the initiation of treatment. Results obtained on days 10 and 30 were compared with baseline values. Infusions prepared from C. citratus leaf powder, which tested positive for tannins, saponins, alkaloids, flavonoids, macro- and micronutrients, significantly increased PCV, Hb, and RBC (P<.05) in all subjects, particularly in the subchronic phase of the study. MCH, MCV, and MCHC were not significantly different from baseline values in both the sexes. WBCs and differentials significantly decreased (P<.05) with the exception of neutrophils and lymphocytes, which significantly increased in some or all groups (P<.05), respectively. C. citratus leaf infusion appears to exert an erythropoiesis boosting effect, likely due to some nutritional constituents and its antioxidant and pharmacologic properties.

  12. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

    Directory of Open Access Journals (Sweden)

    Stavrinou Lampis C

    2011-06-01

    Full Text Available Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. Case presentation We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. Conclusion The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  13. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

    Science.gov (United States)

    Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

    2011-06-29

    The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  14. ESA's XMM-Newton gains deep insights into the distant Universe

    Science.gov (United States)

    2003-07-01

    First image from the XMM-LSS survey hi-res Size hi-res: 87 kb Credits: ESA First image from the XMM-LSS survey The first image from the XMM-LSS survey is actually a combination of fourteen separate 'pointings' of the space observatory. It represents a region of the sky eight times larger than the full Moon and contains around 25 clusters. The circles represent the sources previously known from the 1991 ROSAT All-Sky Survey. A computer programme zooms in on an interesting region hi-res Size hi-res: 86 kb Credits: ESA A computer programme zooms in on an interesting region A computer programme zooms in on an interesting region of the image and identifies the possible cluster. Each point on this graph represents a single X-ray photons detected by XMM-Newton. Most come from distant actie galaxies and the computer must perform a sophisticated, statistical computation to determine which X-ray come from clusters. Contour map of clusters hi-res Size hi-res: 139 kb Credits: ESA Contour map of clusters The computer programme transforms the XMM-Newton data into a contour map of the cluster's probable extent and superimposes it over the CFHT snapshot, allowing the individual galaxies in the cluster to be targeted for further observations with ESO's VLT, to measure its distance and locate the cluster in the universe. Unlike grains of sand on a beach, matter is not uniformly spread throughout the Universe. Instead, it is concentrated into galaxies like our own which themselves congregate into clusters. These clusters are 'strung' throughout the Universe in a web-like structure. Astronomers have studied this large-scale structure of the nearby Universe but have lacked the instruments to extend the search to the large volumes of the distant Universe. Thanks to its unrivalled sensitivity, in less than three hours, ESA's X-ray observatory XMM-Newton can see back about 7000 million years to a cosmological era when the Universe was about half its present size, and clusters of galaxies

  15. The assessment of GRASP as a prospective ESA gamma ray astronomy mission

    International Nuclear Information System (INIS)

    Bignami, G.; Villa, G.; Dean, A.J.

    1987-01-01

    The GRASP mission - Gamma-Ray Astronomy with Spectroscopy and Positioning was originally proposed as a prospective European astronomy mission by the representatives of a wide European community. The project was selected by ESA for a detailed assessment study which was duly completed in December 1986. The telescope has been designed as a high quality spectral imager (E/ΔE∼1000, Δθ∼6') which operates over a wide spectral range (15 keV to >∼100 MeV) with a (3σ) sensitivity of typically 10 m Crab or better over the entire operational range within an observation period of 10 5 s. Two principal mission scenarios were considered

  16. The sensitivity of the ESA DELTA model

    Science.gov (United States)

    Martin, C.; Walker, R.; Klinkrad, H.

    Long-term debris environment models play a vital role in furthering our understanding of the future debris environment, and in aiding the determination of a strategy to preserve the Earth orbital environment for future use. By their very nature these models have to make certain assumptions to enable informative future projections to be made. Examples of these assumptions include the projection of future traffic, including launch and explosion rates, and the methodology used to simulate break-up events. To ensure a sound basis for future projections, and consequently for assessing the effectiveness of various mitigation measures, it is essential that the sensitivity of these models to variations in key assumptions is examined. The DELTA (Debris Environment Long Term Analysis) model, developed by QinetiQ for the European Space Agency, allows the future projection of the debris environment throughout Earth orbit. Extensive analyses with this model have been performed under the auspices of the ESA Space Debris Mitigation Handbook and following the recent upgrade of the model to DELTA 3.0. This paper draws on these analyses to present the sensitivity of the DELTA model to changes in key model parameters and assumptions. Specifically the paper will address the variation in future traffic rates, including the deployment of satellite constellations, and the variation in the break-up model and criteria used to simulate future explosion and collision events.

  17. Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Joshua M. Kaplan

    2018-01-01

    Full Text Available Hypoxia-inducible factor (HIF plays a crucial role in the response to hypoxia at the cellular, tissue, and organism level. New agents under development to pharmacologically manipulate HIF may provide new and exciting possibilities in the treatment of anemia of chronic kidney disease (CKD as well as in multiple other disease states involving ischemia–reperfusion injury. This article provides an overview of recent studies describing current standards of care for patients with anemia in CKD and associated clinical issues, and those supporting the clinical potential for targeting HIF stabilization with HIF prolyl-hydroxylase inhibitors (HIF-PHI in these patients. Additionally, articles reporting the clinical potential for HIF-PHIs in ‘other’ putative therapeutic areas, the tissue and intracellular distribution of HIF- and prolyl-hydroxylase domain (PHD isoforms, and HIF isoforms targeted by the different PHDs, were identified. There is increasing uncertainty regarding the optimal treatment for anemia of CKD with poorer outcomes associated with treatment to higher hemoglobin targets, and the increasing use of iron and consequent risk of iron imbalance. Attainment and maintenance of more physiologic erythropoietin levels associated with HIF stabilization may improve the management of patients resistant to treatment with erythropoiesis-stimulating agents and improve outcomes at higher hemoglobin targets.

  18. Nitrogen-containing bisphosphonate induces a newly discovered hematopoietic structure in the omentum of an anemic mouse model by stimulating G-CSF production.

    Science.gov (United States)

    Otsuka, Hirotada; Yagi, Hideki; Endo, Yasuo; Soeta, Satoshi; Nonaka, Naoko; Nakamura, Masanori

    2017-02-01

    We previously reported that the injection of nitrogen-containing bisphosphonate (NBP) induced the site of erythropoiesis to shift from the bone marrow (BM) to the spleen. Our previous study established a severely anemic mouse model that was treated with a combination of NBP with phenylhydrazine (PHZ), which induced newly discovered hematopoietic organs in the omentum. No reports have shown that new hematopoietic organs form under any condition. We characterized the structures and factors related to the formation of these new organs. Splenectomized mice were treated with NBP to inhibit erythropoiesis in the BM and then injected with PHZ to induce hemolytic anemia. The mice showed severe anemia and wine-colored structures appeared in the omentum. Some hematopoietic cells, including megakaryocytes, and well-developed sinuses were observed in these structures. Numerous TER119-positive erythroblasts were located with cells positive for PCNA, a cell proliferation marker. C-kit-positive cells were detected and mRNAs related to hematopoiesis were expressed in these structures. Moreover, TER119-positive erythroblasts emerged and formed clusters and hematopoiesis-related factors were detected in the omentum of mice treated with NBP and PHZ. The levels of G-CSF in the serum and hematopoietic progenitor cells (HPCs) in the peripheral blood were increased upon treatment with both NBP and PHZ. These results suggest that the induced hematopoietic structures act as the sites of erythropoiesis and that NBP-induced G-CSF production causes HPC mobilization, homing and colonization in the omentum because they constitutively express some factors, including SDF-1; thus, the newly discovered hematopoietic structure in this study might be formed.

  19. Is there life out there ? - A new series for the ESA's Web TV

    Science.gov (United States)

    Clervoy, J. F.; Coliolo, F.

    2012-09-01

    The European Space Agency, ESA, is preparing a new outreach project: a series of short videos for the ESA's Web TV dedicated to the search for life in the Universe. The rationale behind this pilot project is to use stunning images to attract the attention together with a scientific content accessible to people of varying ages, education levels and cultural outlook. We intent to work with scientists across Europe in order to bring the public on a journey from the boundaries of the Cosmos to the core of the Earth looking for the ingredients necessary for life to form and evolve. Our main objectives are: to share discovery, curiosity and sense of adventure in order to make the public a player in the quest of knowledge about who we are, and where do we come from; to educate and engage different target audiences about European space science and exploration activities; encourage international partnerships. I will present you the first trailer that we have realised with two scientists: André Brack, Astrobiologist, Honorary Director of Research at the CNRS, Orleans, France and Gian Gabriele Ori, Research professor in Geology, and Director of the IRSPS, International Reaserch School of Planetary Science, Pescara, Italy. This first presentation gives an overview of the « exobiological » places beyond the Earth and highlights the importance of comparative planetology for better understand our planet. We would like to share with you ideas and advices in order to produce and diffuse this series in the most efficient way.

  20. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Science.gov (United States)

    Seeley, Todd W; Sternlicht, Mark D; Klaus, Stephen J; Neff, Thomas B; Liu, David Y

    2017-01-01

    The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. PMID:28331872

  1. Tubulin polymerization-stimulating activity of Ganoderma triterpenoids.

    Science.gov (United States)

    Kohno, Toshitaka; Hai-Bang, Tran; Zhu, Qinchang; Amen, Yhiya; Sakamoto, Seiichi; Tanaka, Hiroyuki; Morimoto, Satoshi; Shimizu, Kuniyoshi

    2017-04-01

    Tubulin polymerization is an important target for anticancer therapies. Even though the potential of Ganoderma triterpenoids against various cancer targets had been well documented, studies on their tubulin polymerization-stimulating activity are scarce. This study was conducted to evaluate the effect of Ganoderma triterpenoids on tubulin polymerization. A total of twenty-four compounds were investigated using an in vitro tubulin polymerization assay. Results showed that most of the studied triterpenoids exhibited microtuble-stabilizing activity to different degrees. Among the investigated compounds, ganoderic acid T-Q, ganoderiol F, ganoderic acid S, ganodermanontriol and ganoderic acid TR were found to have the highest activities. A structure-activity relationship (SAR) analysis was performed. Extensive investigation of the SAR suggests the favorable structural features for the tubulin polymerization-stimulating activity of lanostane triterpenes. These findings would be helpful for further studies on the potential mechanisms of the anticancer activity of Ganoderma triterpenoids and give some indications on the design of tubulin-targeting anticancer agents.

  2. CarbonSat: ESA's Earth Explorer 8 Candidate Mission

    Science.gov (United States)

    Meijer, Y. J.; Ingmann, P.; Löscher, A.

    2012-04-01

    The CarbonSat candidate mission is part of ESA's Earth Explorer Programme. In 2010, two candidate opportunity missions had been selected for feasibility and preliminary definition studies. The missions, called FLEX and CarbonSat, are now in competition to become ESA's eighth Earth Explorer, both addressing key climate and environmental change issues. In this presentation we will provide a mission overview of CarbonSat with a focus on science. CarbonSat's primary mission objective is the quantification and monitoring of CO2 and CH4 sources and sinks from the local to the regional scale for i) a better understanding of the processes that control carbon cycle dynamics and ii) an independent estimate of local greenhouse gas emissions (fossil fuel, geological CO2 and CH4, etc.) in the context of international treaties. A second priority objective is the monitoring/derivation of CO2 and CH4 fluxes on regional to global scale. These objectives will be achieved by a unique combination of frequent, high spatial resolution (2 x 2 km2) observations of XCO2 and XCH4 coupled to inverse modelling schemes. The required random error of a single measurement at ground-pixel resolution is of the order of between 1 and 3 ppm for XCO2 and between 9 and 17 ppb for XCH4. High spatial resolution is essential in order to maximize the probability for clear-sky observations and to identify flux hot spots. Ideally, CarbonSat shall have a wide swath allowing a 6-day global repeat cycle. The CarbonSat observations will enable CO2 emissions from coal-fired power plants, localized industrial complexes, cities, and other large emitters to be objectively assessed at a global scale. Similarly, the monitoring of natural gas pipelines and compressor station leakage will become feasible. The detection and quantification of the substantial geological greenhouse gas emission sources such as seeps, volcanoes and mud volcanoes will be achieved for the first time. CarbonSat's Greenhouse Gas instrument will

  3. The ESA Space Environment Information System (SPENVIS)

    Science.gov (United States)

    Heynderickx, D.; Quaghebeur, B.; Evans, H. D. R.

    2002-01-01

    The ESA SPace ENVironment Information System (SPENVIS) provides standardized access to models of the hazardous space environment through a user-friendly WWW interface. The interface includes parameter input with extensive defaulting, definition of user environments, streamlined production of results (both in graphical and textual form), background information, and on-line help. It is available on-line at http://www.spenvis.oma.be/spenvis/. SPENVIS Is designed to help spacecraft engineers perform rapid analyses of environmental problems and, with extensive documentation and tutorial information, allows engineers with relatively little familiarity with the models to produce reliable results. It has been developed in response to the increasing pressure for rapid-response tools for system engineering, especially in low-cost commercial and educational programmes. It is very useful in conjunction with radiation effects and electrostatic charging testing in the context of hardness assurance. SPENVIS is based on internationally recognized standard models and methods in many domains. It uses an ESA-developed orbit generator to produce orbital point files necessary for many different types of problem. It has various reporting and graphical utilities, and extensive help facilities. The SPENVIS radiation module features models of the proton and electron radiation belts, as well as solar energetic particle and cosmic ray models. The particle spectra serve as input to models of ionising dose (SHIELDOSE), Non-Ionising Energy Loss (NIEL), and Single Event Upsets (CREME). Material shielding is taken into account for all these models, either as a set of user-defined shielding thicknesses, or in combination with a sectoring analysis that produces a shielding distribution from a geometric description of the satellite system. A sequence of models, from orbit generator to folding dose curves with a shielding distribution, can be run as one process, which minimizes user interaction and

  4. Radioprotection: mechanism and radioprotective agents including honeybee venom

    Energy Technology Data Exchange (ETDEWEB)

    Varanda, E.A.; Tavares, D.C. [UNESP, Araraquara, SP (Brazil). Escola de Ciencias Farmaceuticas. Dept. de Ciencias Biologicas

    1998-07-01

    Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

  5. Radioprotection: mechanism and radioprotective agents including honeybee venom

    International Nuclear Information System (INIS)

    Varanda, E.A.; Tavares, D.C.

    1998-01-01

    Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

  6. An Enhanced MWR-Based Wet Tropospheric Correction for Sentinel-3: Inheritance from Past ESA Altimetry Missions

    Science.gov (United States)

    Lazaro, Clara; Fernandes, Joanna M.

    2015-12-01

    The GNSS-derived Path Delay (GPD) and the Data Combination (DComb) algorithms were developed by University of Porto (U.Porto), in the scope of different projects funded by ESA, to compute a continuous and improved wet tropospheric correction (WTC) for use in satellite altimetry. Both algorithms are mission independent and are based on a linear space-time objective analysis procedure that combines various wet path delay data sources. A new algorithm that gets the best of each aforementioned algorithm (GNSS-derived Path Delay Plus, GPD+) has been developed at U.Porto in the scope of SL_cci project, where the use of consistent and stable in time datasets is of major importance. The algorithm has been applied to the main eight altimetric missions (TOPEX/Poseidon, Jason-1, Jason-2, ERS-1, ERS-2, Envisat and CryoSat-2 and SARAL). Upcoming Sentinel-3 possesses a two-channel on-board radiometer similar to those that were deployed in ERS-1/2 and Envisat. Consequently, the fine-tuning of the GPD+ algorithm to these missions datasets shall enrich it, by increasing its capability to quickly deal with Sentinel-3 data. Foreseeing that the computation of an improved MWR-based WTC for use with Sentinel-3 data will be required, this study focuses on the results obtained for ERS-1/2 and Envisat missions, which are expected to give insight into the computation of this correction for the upcoming ESA altimetric mission. The various WTC corrections available for each mission (in general, the original correction derived from the on-board MWR, the model correction and the one derived from GPD+) are inter-compared either directly or using various sea level anomaly variance statistical analyses. Results show that the GPD+ algorithm is efficient in generating global and continuous datasets, corrected for land and ice contamination and spurious measurements of instrumental origin, with significant impacts on all ESA missions.

  7. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels

    International Nuclear Information System (INIS)

    Cotten, M.; Laengle-Rouault, F.; Kirlappos, H.; Wagner, E.; Mechtler, K.; Zenke, M.; Beug, H.; Birnstiel, M.L.

    1990-01-01

    The authors have subverted a receptor-mediated endocytosis event to transport genes into human leukemic cells. By coupling the natural iron-delivery protein transferrin to the DNA-binding polycations polylysine or protamine, they have created protein conjugates that bind nucleic acids and carry them into the cell during the normal transferrin cycle. They demonstrate here that this procedure is useful for a human leukemic cell line. They enhanced the rate of gene delivery by (i) increasing the transferrin receptor density through treatment of the cells with the cell permeable iron chelator desferrioxamine, (ii) interfering with the synthesis of heme with succinyl acetone treatment, or (iii) stimulating the degradation of heme with cobalt chloride treatment. Consistent with gene delivery as an endocytosis event, they show that the subsequent expression in K-562 cells of a gene included in the transported DNA depends upon the cellular presence of the lysosomotropic agent chloroquine. By contrast, monensin blocks transferrinfection, as does incubation of the cells at 18 degree C

  8. Nanosecond UV lasers stimulate transient Ca2+ elevations in human hNT astrocytes.

    Science.gov (United States)

    Raos, B J; Graham, E S; Unsworth, C P

    2017-06-01

    Astrocytes respond to various stimuli resulting in intracellular Ca 2+ signals that can propagate through organized functional networks. Recent literature calls for the development of techniques that can stimulate astrocytes in a fast and highly localized manner to emulate more closely the characteristics of astrocytic Ca 2+ signals in vivo. In this article we demonstrate, for the first time, how nanosecond UV lasers are capable of reproducibly stimulating Ca 2+ transients in human hNT astrocytes. We report that laser pulses with a beam energy of 4-29 µJ generate transient increases in cytosolic Ca 2+ . These Ca 2+ transients then propagate to adjacent astrocytes as intercellular Ca 2+ waves. We propose that nanosecond laser stimulation provides a valuable tool for enabling the study of Ca 2+ dynamics in human astrocytes at both a single cell and network level. Compared to previously developed techniques nanosecond laser stimulation has the advantage of not requiring loading of photo-caged or -sensitising agents, is non-contact, enables stimulation with a high spatiotemporal resolution and is comparatively cost effective.

  9. Radiation, hypoxia and genetic stimulation: implications for future therapies

    International Nuclear Information System (INIS)

    Adams, Gerald E.; Hasan, Na'il M.; Joiner, Michael C.

    1997-01-01

    The cellular stress response, whereby very low doses of cytotoxic agents induce resistance to much higher doses, is an evolutionary defence mechanism and is stimulated following challenges by numerous chemical, biological and physical agents including particularly radiation, drugs, heat and hypoxia. There is much homology in the effects of these agents which are manifest through the up-regulation of various genetic pathways. Low-dose radiation stress influences processes involved in cell-cycle control, signal transduction pathways, radiation sensitivity, changes in cell adhesion and cell growth. There is also homology between radiation and other cellular stress agents, particularly hypoxia. Whereas traditionally, hypoxia was regarded mainly as an agent conferring resistance to radiation, there is now much evidence illustrating the cytokine-like properties of hypoxia as well as radiation. Stress phenomena are likely to be important in risks arising from low doses of radiation. Conversely, exploitation of the stress response in settings appropriate to therapy can be particularly beneficial not only in regard to radiation alone but in combinations of radiation and drugs. Similarly, tissue hypoxia can be exploited in novel ways of enhancing therapeutic efficacy. Bioreductive drugs, which are cytotoxically activated in hypoxic regions of tissue, can be rendered even more effective by hypoxia-induced increased expression of enzyme reductases. Nitric oxide pathways are influenced by hypoxia thereby offering possibilities for novel vascular based therapies. Other approaches are discussed

  10. Direct targets of pSTAT5 signalling in erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Kevin R Gillinder

    Full Text Available Erythropoietin (EPO acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25, epigenetic regulation (Suv420h2, and EpoR turnover (Clint1/EpsinR. Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors.

  11. Fetal plasma erythropoietin concentration in severe growth retardation.

    Science.gov (United States)

    Snijders, R J; Abbas, A; Melby, O; Ireland, R M; Nicolaides, K H

    1993-02-01

    The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. The plasma erythropoietin concentration in blood samples from 33 small-for-gestational-age fetuses at 26 to 38 weeks' gestation was measured. Measurements were compared with the reference range for gestation, and associations with PO2, pH, and erythroblast and erythrocyte counts were examined. The mean plasma erythropoietin concentration in the small-for-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks' gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.

  12. The Potential Role of Recombinant Hematopoietic Colony-Stimulating Factors in Preventing Infections in the Immunocompromised Host

    Directory of Open Access Journals (Sweden)

    James Rusthoven

    1991-01-01

    Full Text Available Hematopoietic colony-stimulating factors coordinate the proliferation and maturation of bone marrow and peripheral blood cells during normal hematopoiesis. Most of these factors are now available as recombinant human colony-stimulating factors, and preclinical and clinical testing is proceeding rapidly. Granulocyte and granulocyte/macrophage colony-stimulating factors have been the most extensively studied to date. In human clinical trials, granulocyte colony-stimulating factor improves neutrophil counts and function, reduces episodes of febrile neutropenia, improves neutrophil recovery after disease- or treatment-induced myelosuppression, and reduces the number of serious infections in several neutropenic disease states. Granulocyte/macrophage colony-stimulating factor has similar biological properties but may also improve eosinophil proliferation and function, and platelet cell recovery after myelotoxic bone marrow injury, Interleukin-1 boosts the effects of granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, but also may promote the resolution of established infections in conjunction with antibiotics. The therapeutic realities and future therapeutic implications of these agents for the therapy of infections, cancer and hemopoietic disorders are discussed.

  13. Numerical simulation support to the ESA/THOR mission

    Science.gov (United States)

    Valentini, F.; Servidio, S.; Perri, S.; Perrone, D.; De Marco, R.; Marcucci, M. F.; Daniele, B.; Bruno, R.; Camporeale, E.

    2016-12-01

    THOR is a spacecraft concept currently undergoing study phase as acandidate for the next ESA medium size mission M4. THOR has been designedto solve the longstanding physical problems of particle heating andenergization in turbulent plasmas. It will provide high resolutionmeasurements of electromagnetic fields and particle distribution functionswith unprecedented resolution, with the aim of exploring the so-calledkinetic scales. We present the numerical simulation framework which is supporting the THOR mission during the study phase. The THOR teamincludes many scientists developing and running different simulation codes(Eulerian-Vlasov, Particle-In-Cell, Gyrokinetics, Two-fluid, MHD, etc.),addressing the physics of plasma turbulence, shocks, magnetic reconnectionand so on.These numerical codes are being used during the study phase, mainly withthe aim of addressing the following points:(i) to simulate the response of real particle instruments on board THOR, byemploying an electrostatic analyser simulator which mimics the response ofthe CSW, IMS and TEA instruments to the particle velocity distributions ofprotons, alpha particle and electrons, as obtained from kinetic numericalsimulations of plasma turbulence.(ii) to compare multi-spacecraft with single-spacecraft configurations inmeasuring current density, by making use of both numerical models ofsynthetic turbulence and real data from MMS spacecraft.(iii) to investigate the validity of the Taylor hypothesis indifferent configurations of plasma turbulence

  14. The BIOMASS mission — An ESA Earth Explorer candidate to measure the BIOMASS of the earth's forests

    DEFF Research Database (Denmark)

    Scipal, K.; Arcioni, M.; Chave, J.

    2010-01-01

    The European Space Agency (ESA) released a Call for Proposals for the next Earth Explorer Core Mission in March 2005, with the aim to select the 7th Earth Explorer (EE-7) mission for launch in the next decade. Twenty-four proposals were received and subject to scientific and technical assessment...... of any current space systems capable of addressing this need....

  15. NASA-ESA Joint Mission to Explore Two Worlds of Great Astrobiological Interest - Titan and Enceladus

    Science.gov (United States)

    Reh, K.; Coustenis, A.; Lunine, J.; Matson, D.; Lebreton, J.-P.; Erd, C.; Beauchamp, P.

    2009-04-01

    Rugged shorelines, laced with canyons, leading to ethane/methane seas glimpsed through an organic haze, vast fields of dunes shaped by alien sciroccos… An icy moon festooned with plumes of water-ice and organics, whose warm watery source might be glimpsed through surface cracks that glow in the infrared… The revelations by Cassini-Huygens about Saturn's crown jewels, Titan and Enceladus, have rocked the public with glimpses of new worlds unimagined a decade before. The time is at hand to capitalize on those discoveries with a broad mission of exploration that combines the widest range of planetary science disciplines—Geology, Geophysics, Atmospheres, Astrobiology,Chemistry, Magnetospheres—in a single NASA/ESA collaboration. The Titan Saturn System Mission will explore these exciting new environments, flying through Enceladus' plumes and plunging deep into Titan's atmosphere with instruments tuned to find what Cassini could only hint at. Exploring Titan with an international fleet of vehicles; from orbit, from the surface of a great polar sea, and from the air with the first hot air balloon to ride an extraterrestrial breeze, TSSM will turn our snapshot gaze of these worlds into an epic film. This paper will describe a collaborative NASA-ESA Titan Saturn System Mission that will open a new phase of planetary exploration by projecting robotic presence on the land, on the sea, and in the air of an active, organic-rich world.

  16. The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

    Science.gov (United States)

    Albertson, T E; Walby, W F; Allen, R P; Tharratt, R S

    1995-01-01

    Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

  17. LIDAR technology developments in support of ESA Earth observation missions

    Science.gov (United States)

    Durand, Yannig; Caron, Jérôme; Hélière, Arnaud; Bézy, Jean-Loup; Meynart, Roland

    2017-11-01

    Critical lidar technology developments have been ongoing at the European Space Agency (ESA) in support of EarthCARE (Earth Clouds, Aerosols, and Radiation Explorer), the 6th Earth Explorer mission, and A-SCOPE (Advanced Space Carbon and Climate Observation of Planet Earth), one of the candidates for the 7th Earth Explorer mission. EarthCARE is embarking an Atmospheric backscatter Lidar (ATLID) while A-SCOPE is based on a Total Column Differential Absorption Lidar. As EarthCARE phase B has just started, the pre-development activities, aiming at validating the technologies used in the flight design and at verifying the overall instrument performance, are almost completed. On the other hand, A-SCOPE pre-phase A has just finished. Therefore technology developments are in progress, addressing critical subsystems or components with the lowest TRL, selected in the proposed instrument concepts. The activities described in this paper span over a broad range, addressing all critical elements of a lidar from the transmitter to the receiver.

  18. ESA CryoVEx 2014 - Airborne ASIRAS radar and laser scanner measurements during 2014 CryoVEx campaign in the Arctic

    DEFF Research Database (Denmark)

    Hvidegaard, S. M.; Nielsen, J. E.; Sørensen, L. Sandberg

    the penetration depth of the ASIRAS radar. An opportunity site on the Greenland Ice Sheet was surveyed near Jakobshavn Isbræ. No other ground experiments were coordinated with the CryoVEx campaing on the Greenland Ice Sheet. The CryoVEx 2014 campaign was a success and the processed data is of high quality......This report outlines the airborne field operations with the ESA airborne Ku‐band interferometric radar (ASIRAS), coincident airborne laser scanner (ALS) and vertical photography to acquire data over sea‐ and land ice along validation sites and CryoSat‐2 ground tracks. The airborne campaign...... in the Beaufort Sea lead by US office of Naval Research (ONR) and north of Greenland as a dedicated ESA CryoVEx initiative. In addition, selected CryoSat‐2 ground tracks were under‐flown in the Lincoln Sea from CFS Alert, North of Greenland and Svalbard from St. Nord and Longyearbyen. Several of the flights...

  19. ESA's Rosetta mission and the puzzles that Hale-Bopp left behind

    Science.gov (United States)

    1997-04-01

    The scientific payload was confirmed by ESA's Science Programme Committee in February. Now the scientists must perfect the full range of ultra-sensitive yet spaceworthy instruments in good time for Rosetta's despatch by an Ariane 5 launcher in January 2003. And even as most of the world was admiring Comet Hale-Bopp at its brightest, dedicated astronomers were examining the comet that will be Rosetta's target. Although too faint to be seen with the naked eye, Comet Wirtanen made its closest approach to the Sun on 14 March and a fairly close approach to the Earth on 24 March. This comet comes back every 5.5 years. Rosetta will dance attendance on Comet Wirtanen, not at the next return in 2002, nor even in 2008, but in 2013. The project is an ambitious and patient effort to achieve the most thorough investigation of a comet ever attempted. As the successor to ESA's highly successful Giotto mission to Halley's Comet and Comet Grigg-Skjellerup (which took seven years) Rosetta will spend eight years positioning itself. It will manoeuvre around the planets until it is shadowing Comet Wirtanen far beyond Mars, on nearly the same path around the Sun. In 2011 it will rendezvous with the comet and fly near it. In April 2012 Rosetta will go into a near orbit around Comet Wirtanen, and escort it for 17 busy months, as it flies in to make its closest approach to the Sun in September 2013, at the climax of the mission. "The Giotto mission placed us at the forefront of cometary exploration," comments Roger Bonnet, ESA's director of science. "The motivation came from European scientists with a sharp sense of the special importance of comets for understanding the Solar System. The same enthusiasm drives us onward to Rosetta, which will ensure our continued leadership in this important branch of space science." Scientific tasks During its prolonged operations in very close company with the comet's nucleus, Rosetta will map and examine its entire surface from distances of 10 to 50

  20. Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis.

    Science.gov (United States)

    Kastberger, Gerald; Weihmann, Frank; Hoetzl, Thomas

    2010-03-01

    The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes.

  1. Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis

    OpenAIRE

    Kastberger, Gerald; Weihmann, Frank; Hoetzl, Thomas

    2010-01-01

    The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes.

  2. The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine.

    Science.gov (United States)

    Mikami, M; Llewellyn-Jones, C G; Stockley, R A

    1998-08-14

    Neutrophils isolated from patients with chronic bronchitis and emphysema have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is currently unclear whether the observed differences are due to a 'priming' effect by a second agent in vivo, or whether this is a primary difference in the neutrophils. We have studied the effects of interleukin-8, which is thought to be one of the major pro-inflammatory cytokines in chronic lung disease and granulocyte macrophage colony stimulating factor (GMCSF), in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effect of preincubation of these agents with neutrophils for 30 min followed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possible 'priming' effect that may be relevant to our clinical data. We report suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed an additive effect of IL-8 and FMLP for neutrophil degranulation leading to fibronectin degradation. The results suggest that IL-8 does not 'prime' neutrophils for subsequent FMLP stimulation as observed in vivo. Although the results for GMCSF were similar for the chemotactic response, the agent also had a synergistic effect on connective tissue degradation. However, it is concluded that neither agent could explain the enhanced neutrophil responses seen in our patients.

  3. Assimilation of the ESA CCI Soil Moisture ACTIVE and PASSIVE Product into the SURFEX Land Surface Model using the Ensemble Transform Kalman Filter

    Science.gov (United States)

    Blyverket, J.; Hamer, P.; Bertino, L.; Lahoz, W. A.

    2017-12-01

    The European Space Agency Climate Change Initiative for soil moisture (ESA CCI SM) was initiated in 2012 for a period of six years, the objective for this period was to produce the most complete and consistent global soil moisture data record based on both active and passive sensors. The ESA CCI SM products consist of three surface soil moisture datasets: The ACTIVE product and the PASSIVE product were created by fusing scatterometer and radiometer soil moisture data, respectively. The COMBINED product is a blended product based on the former two datasets. In this study we assimilate globally both the ACTIVE and PASSIVE product at a 25 km spatial resolution. The different satellite platforms have different overpass times, an observation is mapped to the hours 00.00, 06.00, 12.00 or 18.00 if it falls within a 3 hour window centred at these times. We use the SURFEX land surface model with the ISBA diffusion scheme for the soil hydrology. For the assimilation routine we apply the Ensemble Transform Kalman Filter (ETKF). The land surface model is driven by perturbed MERRA-2 atmospheric forcing data, which has a temporal resolution of one hour and is mapped to the SURFEX model grid. Bias between the land surface model and the ESA CCI product is removed by cumulative distribution function (CDF) matching. This work is a step towards creating a global root zone soil moisture product from the most comprehensive satellite surface soil moisture product available. As a first step we consider the period from 2010 - 2016. This allows for comparison against other global root zone soil moisture products (SMAP Level 4, which is independent of the ESA CCI SM product).

  4. The Elbow Self-Assessment Score (ESAS): development and validation of a new patient-reported outcome measurement tool for elbow disorders.

    Science.gov (United States)

    Beirer, Marc; Friese, Henrik; Lenich, Andreas; Crönlein, Moritz; Sandmann, Gunther H; Biberthaler, Peter; Kirchhoff, Chlodwig; Siebenlist, Sebastian

    2017-07-01

    To develop and validate an elbow self-assessment score considering subjective as well as objective parameters. Each scale of the American Shoulder and Elbow Surgeons-Elbow Score, the Broberg and Morrey rating system (BMS), the Patient-Rated Elbow Evaluation (PREE) Questionnaire, the Mayo Elbow Performance Score (MEPS), the Oxford Elbow Score (OES) and the Quick Disabilities of the Arm, Shoulder and Hand (Quick-DASH) was analysed, and after matching of the general topics, the dedicated items underwent a fusion to the final ESAS's item and a score containing 22 items was created. In a prospective clinical study, validity, reliability and responsiveness in physically active patients with traumatic as well as degenerative elbow disorders were evaluated. Validation study included 103 patients (48 women, 55 men; mean age 43 years). A high test-retest reliability was found with intraclass correlation coefficients of at least 0.71. Construct validity and responsiveness were confirmed by correlation coefficients of -0.80 to -0.84 and 0.72-0.84 (p Self-Assessment Score (ESAS), a valid and reliable instrument for a qualitative self-assessment of subjective and objective parameters (e.g. range of motion) of the elbow joint is demonstrated. Quantitative measurement of elbow function may not longer be limited to specific elbow disorders or patient groups. The ESAS seems to allow for a broad application in clinical research studying elbow patients and may facilitate the comparison of treatment results in elbow disorders. The treatment efficacy can be easily evaluated, and treatment concepts could be reviewed and revised. Diagnostic study, Level III.

  5. Strengthening the management of ESA - the Inter-Directorate Reform of Corporate and Risk Management

    Science.gov (United States)

    Feustel-Büechl, Jörg; Arend, Harald; Derio, Eric; Infante, Giovanni; Kreiner, Gerhard; Phaler, Jesse; Tabbert, Michael

    2007-02-01

    ESA has undertaken the Inter-Directorate Reform of Corporate and Risk Management to strengthen the Agency's internal operations. The reform was completed at the end of 2006, encompassing five dedicated projects on Risk Management, Agency-Wide Controlling System, Project Plan and Integrated Project Review, General Budget Structure and Charging Policy, and Corporate Information Systems. It has contributed to improved management of the Agency's internal operations by engaging all internal stakeholders in a common objective, introducing improvements to planning and management methods, elaborating consolidated information structures and tools, contributing to enhanced transparency and accountability, and by providing qualified new policies, processes and tools.

  6. [Variability of the sensitivity of human lymphocytes to the antiproliferative action of alkylating agents].

    Science.gov (United States)

    Veremko, L N; Telegin, L Iu; Pevnitskii, L A

    1983-05-01

    A study was made of variability of the sensitivity of peripheral blood lymphocytes from different donors to an antiproliferative action of cyclophosphamide and thiophosphamide. A similar degree of the sensitivity was revealed to alkylating agents differing in the action mode, with this degree being independent of the "stimulation index" magnitude.

  7. Appetite stimulants for people with cystic fibrosis.

    Science.gov (United States)

    Chinuck, Ruth; Dewar, Jane; Baldwin, David R; Hendron, Elizabeth

    2014-07-27

    , this is based upon moderate quality data from a small number of trials and so this therapy cannot be conclusively recommended based upon the findings in the review. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any patients prescribed these medications accordingly.Research is needed to determine meaningful surrogate measures for appetite and define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.

  8. A vista of new knowledge from ESA's Hipparcos astronomy mission

    Science.gov (United States)

    1997-05-01

    Hipparcos is a milestone in the history of astronomy. In 1985 the American physicist Freeman J. Dyson hailed Hipparcos as the first major new development in space science to come from outside the United States. The spacecraft operated in orbit 1989-93, measuring the angles between stars in the sky. Over a further three years, computing teams across Europe generated a consistent, high-precision plot of 118,000 stars in the Hipparcos Catalogue and somewhat less accurate (but still unprecedented) data on a million stars in the Tycho Catalogue. The distances, motions, pairings and variability of stars are now known far more accurately than ever before. Hipparcos will make an impact on every branch of astronomy, from the Solar System to the history of the Universe, and especially on theories of stars and their evolution. For almost a year, astronomers most closely associated with the mission have had an early view of the completed catalogues and in Venice they will summarize their initial results. The Hipparcos data will be published in June, as an extraordinary contribution from Europe to astronomy all around the world. The success of Hipparcos has created problems for the organizers of Venice symposium. Altogether 190 scientific papers were offered for presentation by various groups of astronomers. With three mornings and three afternoons available for the main scientific sessions, 67 oral presentations are accommodated, by restricting speakers to 10-15 minutes each. For the rest, there will a generous display of results in the form of posters. Thus Hipparcos will be celebrated by a vista of new knowledge. The stars are looking younger Already Hipparcos seems to cure a headache concerning the ages of stars. As recently as last year, astronomers were perplexed by a contradiction between their estimates of the age of the Universe, and stars that seemed to be older. An early Hipparcos result announced in February 1997 (ESA Information Note 04/97) concerned the winking

  9. Dobutamine use for arrhythmia induction during electrical programmed heart stimulation

    International Nuclear Information System (INIS)

    Vanegas, Diego I; Perez, Climaco de J; Montenegro, Juan de J; Orjuela, Alejandro

    2006-01-01

    isoproterenol is the traditionally used drug for incrementing arrhythmia induction when this induction is not achieved during electric programmed heart stimulation under basal conditions. Dobutamine is an adrenergic agent, chemical precursor of isoproterenol, which can be an alternative for inducing arrhythmia during electrical programmed heart stimulation (PES). Patients and methods: a retrospective comparative study of the experience with dobutamine for inducing arrhythmia during electrical programmed heart stimulation was performed. The following data were collected: number of studies, data about the patient (medical record, age, gender, and study indication) protocol of programmed electrical stimulation, basal and under dobutamine or isoproterenol, and result of the study. Isoproterenol was used in doses of 1 to 3 micrograms per minute until the basal heart rate was incremented at least in 25%. Dobutamine was used in doses of 10 to 40 micrograms per kg of body weight, until obtaining the same increment in the basal heart rate. Results: 1054 electrophysiological studies were evaluated. In 144 patients (group A) isoproterenol was used and in 140, dobutamine (group B). In A group the mean age was 39.2 ± 16.2 and 58.3% were females. In-group B, mean age was 41.9 ± 18.6 and 51% were females. The most frequent symptom was palpitation and the most commonly induced arrhythmia was AV nodal reentry tachycardia in both groups. The induction of arrhythmia during the electrical programmed heat stimulation under drugs was similar in-group A (isoproterenol) respect to group B (dobutamine). Conclusions: There were no statistical significant differences in the induction of arrhythmia during electrical programmed heart stimulation using dobutamine or isoproterenol. Dobutamine may be safe and may be successfully used as an alternative to isoproterenol for arrhythmia induction during electrical programmed stimulation

  10. Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

    Science.gov (United States)

    Doulatov, Sergei; Vo, Linda T.; Macari, Elizabeth R.; Wahlster, Lara; Kinney, Melissa A.; Taylor, Alison M.; Barragan, Jessica; Gupta, Manav; McGrath, Katherine; Lee, Hsiang-Ying; Humphries, Jessica M.; DeVine, Alex; Narla, Anupama; Alter, Blanche P.; Beggs, Alan H.; Agarwal, Suneet; Ebert, Benjamin L.; Gazda, Hanna T.; Lodish, Harvey F.; Sieff, Colin A.; Schlaeger, Thorsten M.; Zon, Leonard I.; Daley, George Q.

    2017-01-01

    Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA. PMID:28179501

  11. Click Chemistry-based Discovery of [3-Hydroxy-5-(1H-1,2,3-triazol-4-yl)picolinoyl]glycines as Orally Active Hypoxia Inducing Factor Prolyl Hydroxylase Inhibitors with Favorable Safety Profiles for the Treatment of Anemia.

    Science.gov (United States)

    Wu, Yue; Jiang, Zhensheng; Li, Zhihong; Gu, Jing; You, Qi-Dong; Zhang, Xiaojin

    2018-06-01

    As a gene associated with anemia, the erythropoiesis gene is physiologically expressed under hypoxia regulated by hypoxia-inducing factor-α (HIF-α). Thus, stabilizing HIF-α is a potent strategy to stimulate the expression and secretion of erythropoiesis. In this study we applied click chemistry to the discovery of HIF prolyl hydroxylase 2 (HIF-PHD2) inhibitors for the first time and a series of triazole compounds showed preferable inhibitory activity in fluorescence polarization assay. Of particular note was the orally active HIF-PHD inhibitor 15i (IC50 = 62.23 nM), which was almost ten times more active than the phase III drug FG-4592 (IC50 = 591.4 nM). Furthermore, it can upregulate the hemoglobin of cisplatin induced anemia mice (120 g/L) to normal levels (160 g/L) with no apparent toxicity observed in vivo. These results confirm that triazole compound 15i is a promising candidate for the treatment of renal anemia.

  12. Protective, restorative, and therapeutic properties of recombinant colony-stimulating factors

    International Nuclear Information System (INIS)

    Talmadge, J.E.; Tribble, H.; Pennington, R.; Bowersox, O.; Schneider, M.A.; Castelli, P.; Black, P.L.; Abe, F.

    1989-01-01

    Pretreatment of mice with recombinant murine (rM) colony-stimulating factor-granulocyte-macrophage (CSF-gm) or recombinant human (rH) CSF-g provides partial protection from the lethal effects of ionizing radiation or the alkylating agent cyclophosphamide (CTX). In addition, these agents can significantly prolong survival if administered following lethal doses of irradiation or CTX. To induce protective activity, cytokines were injected 20 hours before lethal irradiation or CTX administration. To accelerate recovery from lethal irradiation, the cytokines must be administered shortly following irradiation, and the induction of maximal levels of activity is dependent on chronic administration. In contrast, because of their longer half-lives, accelerated recovery from alkylating agents requires a delay of at least 24 to 48 hours to allow complete clearance of CTX before administration of a CSF. Studies quantitating peripheral blood leukocytes and bone marrow cellularity as well as colony-forming units per culture (CFU-C) frequency and CFU-C per femur revealed a significant correlation between these parameters and the ability to survive lethal irradiation

  13. Erythropoietin between therapy and doping : Two sides of the same coin

    Directory of Open Access Journals (Sweden)

    Ostojić Ana

    2016-01-01

    Full Text Available Erythropoietin is a hormone that promotes the formation of red blood cells by the bone marrow. In adults it is mainly produced by the kidneys as a response to hypoxia. Besides its main role, it also acts as antiapoptotic, anti-inflammatory and cytoprotective agent. Furthermore, it is produced in many non-hematopoietic tissues where it acts locally, stimulating angiogenesis. Erythropoietin binds cytokine receptors on target cells, such as erythrocyte precursor cells, neurons, glial and endothelial cells, cardiomyocytes, myocytes etc. The discovery of synthetic erythropoietin forms, in the late eighties of the last century, has significantly improved treatment outcome of patients with anaemia related to chronic diseases, especially chronic renal failure. Renal anaemia is multifactorial, but predominantly a consequence of erythropoietin deficiency. Today, three generations of erythropoiesis stimulating agents are available, differing in glycosylation pattern, molecular size, half-life and modes of administration and dosage. In anaemic patients this therapy significantly improves their quality of life, but may also have serious, potentially dangerous adverse effects. Synthesis of recombinant human erythropoietin, on the other hand, has improved possibilities for manipulations in sport, in the field of blood doping. Erythropoietin administration in athletes increases their maximum oxygen consumption capacity, improves endurance and performance, especially in aerobic exercise. This seriously undermines the spirit of sport, and also endangers athletes' health. Different anti-doping tests have been developed and used, still with limited success. At the same time, new illicit ways of malpractice are developing, such as variuos models of gene doping. Therefore, providing new models of anti-doping tests and strategies, together with better health control of athletes, still remains a considerable challenge.

  14. Electrical stimulation for physiologic measurement of neuromuscular function and respiratory support during anticholinesterase poisoning. Annual report, October 1983-September 1984

    Energy Technology Data Exchange (ETDEWEB)

    Yodlowski, E.H.

    1984-10-01

    The purpose of this research is to develop the techniques necessary for providing short-term respiratory support for personnel poisoned by organophosphate agents. Following acute exposure to organophosphate compounds, respiration ceases before cardiovascular collapse occurs. Military personnel exposed to these compounds in the field are most likely to die from asphyxiation. By virtue of their ability to cross the blood-brain barrier and inhibit cholinesterase activity the organophosphates are capable of interrupting control of respiration either centrally (i.e. within the central nervous system) or peripherally by blocking neuromuscular transmission or contraction coupling at the peripheral muscles. We hypothesize that it will be possible to overcome organophosphate induced respiratory arrest by providing artificial respiratory pacing. This research is aimed at producing a means of respiratory support via electronic stimulation of the phrenic nerve (s) that can be used when central respiratory drive has become blocked by organophosphate agents. Animal experiments have been conducted to implement and evaluate the transesophageal electrophrenic stimulation technique (TEST) for respiratory pacing and to determine appropriate stimulation parameters to produce effective and efficient respirations.

  15. Agent 2003 Conference on Challenges in Social Simulation

    Energy Technology Data Exchange (ETDEWEB)

    Margaret Clemmons, ed.

    2003-01-01

    difficult social issues. Among the resources that give us the prospect of success is the innovative and transdisciplinary research community being built. We believe that Agent 2003 contributes to further progress in computational modeling of social processes, and we hope that you find these Proceedings to be stimulating and rewarding. As the horizons of this transdiscipline continue to emerge and converge, we hope to provide similar forums that will promote development of agent simulation modeling in the years to come.

  16. An improved and homogeneous altimeter sea level record from the ESA Climate Change Initiative

    DEFF Research Database (Denmark)

    Legeais, Jean-Francois; Ablain, Michael; Zawadzki, Lionel

    2018-01-01

    , the sea level ECV has been measured from space by different altimetry missions that have provided global and regional observations of sea level variations. As part of the Climate Change Initiative (CCI) program of the European Space Agency (ESA) (established in 2010), the Sea Level project (SL_cci) aimed...... to provide an accurate and homogeneous long-term satellite-based sea level record. At the end of the first phase of the project (2010-2013), an initial version (v1.1) of the sea level ECV was made available to users (Ablain et al., 2015). During the second phase of the project (2014-2017), improved altimeter...

  17. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  18. Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

    Directory of Open Access Journals (Sweden)

    Magteld Zeitler

    2018-05-01

    Full Text Available A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on

  19. Methylquercetins stimulate melanin biosynthesis in a three-dimensional skin model.

    Science.gov (United States)

    Yamauchi, Kosei; Mitsunaga, Tohru

    2018-03-01

    In a previous study, we found that both synthetic 3-O-methylquercetin (3MQ) and 3,4',7-O-trimethylquercetin (34'7TMQ) increased extracellular melanin content. 34'7TMQ increased the activity of melanogenic enzymes by stimulating the p38 pathway and the expression of microphthalmia-associated transcription factor (MITF). In contrast, 3MQ increased the activity of melanogenic enzymes without the involvement of MITF, which suggests that 3MQ inhibits the degradation of melanogenic enzymes. In the present study, we investigated the effects of 3MQ and 34'7TMQ on melanogenesis in normal human melanocytes and using a commercial three-dimensional (3D) skin model system. Both 3MQ and 34'7TMQ elongated the dendrites of normal human melanocytes from a Caucasian donor, but did not stimulate melanogenesis in the melanocytes. In the 3D skin model, which included melanocytes from an Asian donor, 3MQ and 34'7TMQ increased and elongated the melanocytes and showed a tendency to stimulate melanogenesis. These results suggest that 3MQ and 34'7TMQ could be put to practical use in skin care products and agents aimed at preventing hair graying.

  20. Ficus Deltoidea: A potential source for new oral antidiabetic agent

    International Nuclear Information System (INIS)

    Zainah Adam; Juliana Mahamad Napiah; Shafii Khamis; Muhajir Hamid

    2012-01-01

    Ficus deltoidea or locally known as Mas Cotek is one of the common medicinal plant used in Malaysia. Ethno botanical approaches showed that this plant possess antidiabetic property. Previous study had shown that F. deltoidea reduced hyperglycemia in type I diabetic rats at different prandial state. This study was done to elucidate the possible antihyperglycemic mechanisms of F. deltoidea. The results showed that F. deltoidea significantly stimulated insulin secretion from pancreatic β-cells with the highest magnitude of stimulation was 7.31-fold (p 50 value was 4.15±0.25 mg/ml. Kinetic analysis of the enzyme activity revealed the F. deltoidea exhibited a mixed-type inhibition mechanism against sucrase activity. Such observations showed that F. deltoidea has the potential to be developed as new oral antidiabetic agent for the treatment of diabetes mellitus. (author)

  1. Ristocetin induces phosphorylated-HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti-platelet agent-effect on the release.

    Science.gov (United States)

    Tokuda, Haruhiko; Kuroyanagi, Gen; Onuma, Takashi; Enomoto, Yukiko; Doi, Tomoaki; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

    2018-04-01

    It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group). Ristocetin potently induced the aggregation of platelets in the two groups. Ristocetin-induced changes of the area under the curve of light transmittance and the ratio of the size of platelet aggregates in the anti-platelet group were slightly different from those in the control group. On the other hand, the levels of phosphorylated-HSP27 induced by ristocetin in the platelets from a patient of the anti-platelet group taking ASA were significantly lower than those from a patient of the control group. The levels of HSP27 release from the ristocetin-stimulated platelets were significantly correlated with the levels of phosphorylated-HSP27 in the platelets from patients in the two groups. The levels of HSP27 release and those of platelet-derived growth factor-AB (PDGF-AB) secretion stimulated by ristocetin in the anti-platelet group were lower than those in the control group. In addition, the levels of HSP27 release and those of PDGF-AB secretion stimulated by ADP in the anti-platelet group were lower than those in the control group. These results strongly suggest that anti-platelet agents inhibit the HSP27 release from platelets stimulated by ristocetin but not the aggregation in type 2 DM patients.

  2. ESA CAMELOT study: Challenges in future operational missions for GMES atmospheric monitoring, sentinel 4 and 5

    Science.gov (United States)

    Levelt, P.; Veefkind, P.

    2009-04-01

    Dedicated atmospheric chemistry observations from space have been made for over 30 years now, starting with the SBUV and TOMS measurements of the ozone layer. Since then huge progress has been made, improving the accuracy of the measurements, extending the amount of constituents, and by sensing not only the stratosphere, but the last five to ten years also the troposphere. The potential to operational monitor the atmosphere, following the meteorological community, came within reach. At the same time, the importance for society of regular operational environmental measurements, related to the ozone layer, air quality and climate change, became apparent, amongst others resulting in the EU initiative Global Monitoring for Environment and Security (GMES) In order to prepare the operational missions in the context of the GMES, ESA took the initiative to further study the user requirements for the Sentinel 4 and 5 (precursor) missions. The Sentinel 4 and 5 (precursor) missions are dedicated operational missions to monitor the atmospheric composition in the 2013-2020 timeframe and onward. The user requirements for the sentinel missions focus on monitoring the atmosphere from an environmental point of view (ozone layer, air quality and climate). ESA's CAMELOT (Composition of the Atmospheric Mission concEpts and SentineL Observation Techniques) study is the follow-on study to ESA's CAPACITY study finished in 2005. The general objective of the CAMELOT study is to further contribute to the definition of the air quality and climate protocol monitoring parts of the GMES Sentinel 4 and 5 missions. Key issues in the CAMELOT study are: • trade-offs between different observation strategies (spectral ranges, polarisation, direction etc) for aerosols and several trace gases • a quantitative assessment of the requirements for spatio-temporal sampling taking into account the contamination of nadir-viewing observations by cloud • optimising several orbit scenario's (leo, inclined

  3. Geophysical validation of temperature retrieved by the ESA processor from MIPAS/ENVISAT atmospheric limb-emission measurements

    Directory of Open Access Journals (Sweden)

    M. Ridolfi

    2007-08-01

    Full Text Available The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS has been operating since March 2002 onboard of the ENVIronmental SATellite of the European Space Agency (ESA. The high resolution (0.035 cm−1 full width half maximum, unapodized limb-emission measurements acquired by MIPAS in the first two years of operation have very good geographical and temporal coverage and have been re-processed by ESA with the most recent versions (4.61 and 4.62 of the inversion algorithms. The products of this processing chain are pressures at the tangent points and geolocated profiles of temperature and of the volume mixing ratios of six key atmospheric constituents: H2O, O3, HNO3, CH4, N2O and NO2. As for all the measurements made with innovative instruments and techniques, this data set requires a thorough validation. In this paper we present a geophysical validation of the temperature profiles derived from MIPAS measurements by the ESA retrieval algorithm. The validation is carried-out by comparing MIPAS temperature with correlative measurements made by radiosondes, lidars, in-situ and remote sensors operated either from the ground or stratospheric balloons.

    The results of the intercomparison indicate that the bias of the MIPAS profiles is generally smaller than 1 or 2 K depending on altitude. Furthermore we find that, especially at the edges of the altitude range covered by the MIPAS scan, the random error estimated from the intercomparison is larger (typically by a factor of two to three than the corresponding estimate derived on the basis of error propagation.

    In this work we also characterize the discrepancies between MIPAS temperature and the temperature fields resulting from the analyses of the European Centre for Medium-range Weather Forecasts (ECMWF. The bias and the standard deviation of these discrepancies are consistent with those obtained when

  4. Growth stimulation of Porphyromonas endodontalis by hemoglobin and protoporphyrin IX.

    Science.gov (United States)

    Zerr, M A; Cox, C D; Johnson, W T; Drake, D R

    2000-12-01

    Porphyromonas endodontalis, like other Porphyromonas species, has a complex set of nutritional requirements. In addition to being an obligate anaerobe, the bacterium must be grown in a complex medium consisting of amino acids, reducing agents and heme compounds. P. endodontalis accumulates high concentrations of heme pigments to the extent that colonies appear black on blood agar. This accumulation of heme and the need for these compounds has been characterized as iron requirements by these species. However, in our studies, P. endodontalis demonstrated growth dependence on hemoglobin or protoporphyrin IX but not on free iron. Iron added to other heme compounds actually decreased growth stimulation by porphyrin-containing compounds. P. endodontalis actively transported free iron, but this process did not appear to be critical for growth. The maximum stimulation of growth by protoporphyrin IX, under conditions of iron deprivation, suggests that P. endodontalis requires the porphyrin moiety as a growth factor.

  5. Rosetta performs ESA's closest-ever Earth fly-by

    Science.gov (United States)

    2005-03-01

    Rosetta’s unique instruments, such as its ultraviolet light instrument ALICE, should be able to make critical contributions to the American mission. About Rosetta Rosetta is the first mission designed to both orbit and land on a comet, and consists of an orbiter and a lander. The spacecraft carries 11 scientific experiments and will be the first mission to undertake long-term exploration of a comet at close quarters. After entering orbit around Comet 67P/Churyumov-Gerasimenko in 2014, the spacecraft will release a small lander onto the icy nucleus. Rosetta will orbit the comet for about a year as it heads towards the Sun, remaining in orbit for another half-year past perihelion (closest approach to the Sun). Comets hold essential information about the origin of our Solar System because they are the most primitive objects in the Solar System and their chemical composition has changed little since their formation. By orbiting and landing on Comet 67P/Churyumov-Gerasimenko, Rosetta will help us reconstruct the history of our own neighbourhood in space. Note for broadcasters: The ESA TV Service will transmit a TV exchange with images of the fly-by, together with science results/images from observations as far as available on 11 March. For further details : http://television.esa.int

  6. ESA NEOCC effort to eliminate high Palermo Scale virtual impactors

    Science.gov (United States)

    Micheli, M.; Koschny, D.; Hainaut, O.; Bernardi, F.

    2014-07-01

    At the moment of this writing about 4 % of the known near-Earth objects are known to have at least one future close approach scenario with a non-negligible collision probability within the next century, as routinely computed by the NEODyS and Sentry systems. The most straightforward way to improve the knowledge of the future dynamics of an NEO in order to exclude (or possibly confirm) some of these possible future impact is to obtain additional astrometric observations of the object as soon as it becomes observable again. In particular, since a large fraction (>98 %) of the known objects currently recognized as possible future impactors have been observed during a single opposition, this usually corresponds to obtaining a new set of observations during a second opposition, a so called ''recovery''. However, in some cases the future observability windows for the target after the discovery apparition may be very limited, either because the object is intrinsically small (and therefore requires a very close and consequently rare approach to become observable) or because its orbital dynamic prevents the observability from the ground for a long timespan (as in the case of quasi-resonant objects with a long synodic period). When this happens, the only short-term way to clarify an impact scenario is to look toward the past, and investigate the possibility that unrecognized detections of the object are already present in the databases of old astronomical images, which are often archived by professional telescopes and made available to the community a few months to years after they are exposed. We will here present an effort lead by the newly formed ESA NEO Coordination Centre (NEOCC) in Frascati to pursue both these avenues with the intent of improving the orbital knowledge of the highest-rated possible impactors, as defined by the Palermo Technical Impact Hazard Scale (PS in the following). As an example of our ongoing observational activities, we will first present our

  7. Performance and technical feasibility comparison of reusable launch systems: A synthesis of the ESA winged launcher studies

    Science.gov (United States)

    Berry, W.; Grallert, H.

    1996-02-01

    The paper presents a synthesis of the performance and technical feasibility assessment of 7 reusable launcher types, comprising 13 different vehicles, studied by European Industry for ESA in the ESA Winged Launcher Study in the period January 1988 to May 1994. The vehicles comprised single-stage-to-orbit (SSTO) and two-stage-to-orbit (TSTO) vehicles, propelled by either air-breathing/rocket propulsion or entirely by rocket propulsion. The results showed that an SSTO vehicle of the HOTOL-type, propelled by subsonic combustion air-breathing/rocket engines could barely deliver the specified payload mass and was aerodynamically unstable; that a TSTO vehicle of the Saenger type, employing subsonic combustion airbreathing propulsion in its first stage and rocket propulsion in its second stage, could readily deliver the specified payload mass and was found to be technically feasible and versatile; that an SSTO vehicle of the NASP type, propelled by supersonic combustion airbreathing/rocket propulsion was able to deliver a reduced payload mass, was very complex and required very advanced technologies; that an air-launched rocket propelled vehicle of the Interim HOTOL type, although technically feasible, could deliver only a reduced payload mass, being constrained by the lifting capability of the carrier airplane; that three different, entirely rocket-propelled vehicles could deliver the specified payload mass, were technically feasible but required relatively advanced technologies.

  8. ESA's high-energy observatories spot doughnut-shaped cloud with a black-hole filling

    Science.gov (United States)

    2004-07-01

    hi-res Size hi-res: 7265 KB Credits: ESA, V. Beckmann (GSFC) Doughnut-shaped cloud surrounds black hole This artist's impression shows the thick dust torus that astronomers believe surrounds supermassive black holes and their accretion discs, like the one harboured in the nucleus of the spiral galaxy NGC 4388. When the torus is seen `edge-on’ as in this case, the visible light emitted by the accretion disc is partially blocked. However, the sharp X-ray and gamma-ray eyes of XMM-Newton and Integral can peer through the thick dust and see how the energy released by the accretion disc interacts with and is absorbed by the torus. Black holes are objects so compact and with gravity so strong that not even light can escape from them. Scientists think that `supermassive’ black holes are located in the cores of most galaxies, including our Milky Way galaxy. They can contain the mass of thousands of millions of suns, confined within a region no larger than our Solar System. They appear to be surrounded by a hot, thin disk of accreting gas and, farther out, the thick doughnut-shaped torus. Depending on the inclination of the torus, it can hide the black hole and the hot accretion disc from the line of sight. Galaxies in which a torus blocks the light from the central accretion disc are called `Seyfert 2’ types and are usually faint to optical telescopes. Another theory, however, is that these galaxies appear rather faint because the central black hole is not actively accreting gas and the disc surrounding it is therefore faint. An international team of astronomers led by Dr Volker Beckmann, Goddard Space Flight Center (Greenbelt, USA) has studied one of the nearest objects of this type, a spiral galaxy called NGC 4388, located 65 million light years away in the constellation Virgo. Since NGC 4388 is relatively close, and therefore unusually bright for its class, it is easier to study. Astronomers often study black holes that are aligned face-on, thus avoiding the

  9. Development Of Electro-Spark Alloying (ESA) And Thermo-Reactive Electro-Spark Surface Strengthening (TRESS) Technologies And Set Of Equipment With Attachments For Mechanization

    National Research Council Canada - National Science Library

    Levashov, Evgeny A

    2006-01-01

    ... (Technological University) as follows: The main goal of the project is to develop advanced ESA and TRESS coating technologies for application on Ti and superalloys substrates to resist high-cycle fatigue failure initiated at the blade roots...

  10. Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

    Science.gov (United States)

    Vidal, Jose; Ghovanloo, Maysam

    2013-01-01

    We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

  11. ESA BRAT (Broadview Radar Altimetry Toolbox) and GUT (GOCE User Toolbox) toolboxes

    Science.gov (United States)

    Benveniste, J.; Ambrozio, A.; Restano, M.

    2016-12-01

    's variance-covariance matrices. BRAT and GUT toolboxes can be freely downloaded, along with ancillary material, at https://earth.esa.int/brat and https://earth.esa.int/gut.

  12. Ultrasound stimulation on bone healing. The optimization of stimulation time

    International Nuclear Information System (INIS)

    Rosim, R.C.; Paulin, J.B.P.; Goncalves, R.P.

    1990-01-01

    Previous works in ultrasonic simulation of bone healing dealt with parameters optimization. Albertin (1983) studied the stimulation time and found forty minutes as ideal. However, this stimulation time was the largest one employed and remained some doubt about the most appropriated value. 30, 40, 50 and 60 minutes of stimulation time were selected, while others parameters were held constant with: pulse width in 200 μs, repetition rate in 1000 pulses per second and amplitude in 30 V. Partial incomplete transverse osteotomies were done in the middle third of radio in the right forearm of rabbits. Twenty four animals divided in four subgroups, with 6 animals each were stimulated. The daily stimulation time for each subgroup was 30, 40, 50 and minutes respectively, during 15 consecutive days. The stimulation procedure started 24 hours after surgery. After the stimulation period, radiological, histological and morphometric evaluations were done and greater bone healing was found for the 50 minutes stimulation subgroup, in them new bone was also prominent. (author)

  13. Impact of Global Economic Disparities on Practices and Outcomes of Chronic Peritoneal Dialysis in Children: Insights from the International Pediatric Peritoneal Dialysis Network Registry

    Science.gov (United States)

    Schaefer, Franz; Borzych-Duzalka, Dagmara; Azocar, Marta; Munarriz, Reyner Loza; Sever, Lale; Aksu, Nejat; Barbosa, Lorena Sànchez; Galan, Yajaira Silva; Xu, Hong; Coccia, Paula A.; Szabo, Attila; Wong, William; Salim, Rosana; Vidal, Enrico; Pottoore, Stephen; Warady, Bradley A.

    2012-01-01

    ♦ Background, Objectives, and Methods: The number of patients on chronic peritoneal dialysis (CPD) is increasing rapidly on a global scale. We analyzed the International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global database active in 33 countries spanning a wide range in gross national income (GNI), to identify the impact of economic conditions on CPD practices and outcomes in children and adolescents. ♦ Results: We observed close associations of GNI with the fraction of very young patients on dialysis, the presence and number of comorbidities, the prevalence of patients with unexplained causes of end-stage kidney disease, and the rate of culture-negative peritonitis. The prevalence of automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The GNI stratum also affected the use of biocompatible peritoneal dialysis fluids, enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs, and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to 5.5) independently of young patient age and the number of comorbidities present. Patients from low-income countries tended to die more often from infections unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong independent predictor of standardized height (p < 0.0001), adding to the impact of congenital renal disease, anuria, age at PD start, and dialysis vintage. Patients from the lower economic strata (GNI < $18 000) had higher serum parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin concentrations. No impact of GNI was observed with regard to CPD technique survival or peritonitis incidence. ♦ Conclusions: We conclude that CPD is practiced successfully, albeit with major regional variation related to economic differences, in children around the globe. The variations encompass the acceptance of very young patients and

  14. Dual Functions of the C5a Receptor as a Connector for the K562 Erythroblast-Like Cell-THP-1 Macrophage-Like Cell Island and as a Sensor for the Differentiation of the K562 Erythroblast-Like Cell during Haemin-Induced Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2012-01-01

    Full Text Available The transcriptional nuclear factor binding to the Y box of human leukocyte antigen genes (NF-Y for the C5a receptor (C5aR gene is active in erythroblasts. However, the roles of the C5aR in erythropoiesis are unclear. We have previously demonstrated that apoptotic cell-derived ribosomal protein S19 (RP S19 oligomers exhibit extraribosomal functions in promoting monocyte chemotaxis and proapoptosis via the C5aR without receptor internalisation. In contrast to the extraribosomal functions of the RP S19, a proapoptotic signal in pro-EBs, which is caused by mutations in the RP S19 gene, is associated with the inherited erythroblastopenia, Diamond-Blackfan anaemia. In this study, we detected C5aR expression and RP S19 oligomer generation in human erythroleukemia K562 cells during haemin-induced erythropoiesis. Under monocell culture conditions, the differentiation into K562 erythrocyte-like cells was enhanced following the overexpression of Wild-type RP S19. Conversely, the differentiation was repressed following the overexpression of mutant RP S19. An RP S19 oligomer inhibitor and a C5aR inhibitor blocked the association of the K562 basophilic EB-like cells and the THP-1 macrophage-like cells under coculture conditions. When bound to RP S19 oligomers, the C5aR may exhibit dual functions as a connector for the EB-macrophage island and as a sensor for EB differentiation in the bone marrow.

  15. The effect of different physical agents in the behaviour of bss-13 Lettuce variety

    International Nuclear Information System (INIS)

    Perez, C.; Calderon, S.; Mendoza, M.; Perez, M.; Perez, G.; Labrada, A.

    1999-01-01

    The objective of this study was to evaluate and compare the effect of two physical agents in their physiological answer the BSS-13 lettuce variety. Rays gamma Co 60 and rays laser (He-Ne) were the physiological agents utilised. A group of seed were irradiated with gamma in a dose of 10 and 100Grey, and the other group with a time of exposure of 15 sec and 15 min., and power density of 0,4mW/cm2, the rest was no irradiated and was considered like witness. The seed were planted in the protected cultural where remained until of transplantation in field conditions. In the harvest was measured the height, diameter and weight of lettuce. The results show that both agents were presented with an outstanding stimulating with laser with a good efficiency respect to control

  16. Development of pretreatment compounds against nerve-gas agents. Annual report (Final), 16 May 88-30 Sep 90

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, F.I.; Abraham, P.

    1990-09-30

    The U. S. Army Medical Research and Development Command is interested in research directed toward the development of countermeasures to chemical warfare (CW) agents such as the nerve gas poison soman. Soman and other nerve gas poisons are extremely potent cholinesterase inhibitors. This inhibition leads to a buildup of excess acetylcholine resulting in over-stimulation of both the peripheral and central nervous system and can lead to death. Standard therapy for organophosphate nerve agent poisoning is based on co-administration of an anticholinergic agent such as atropine to antagonize the effects of accumulated acetylcholine and a cholinesterase reactivator such as 2-PAM to dephosphorylate the inhibited enzyme. However, since many problems remain in the treatment of organophosphate nerve agent poisoning, there is considerable interest and need to develop new pretreatment and treatment drugs, particularly for soman poisoning.

  17. Differences in the stimulation of repair replication by 3-aminobenzamide in lymphoblastoid cells damaged by methylmethanesulfonate or ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Cleaver, J.E.; Morgan, W.F.

    1987-09-01

    Human lymphoblastoid cells damaged by u.v. light accumulated DNA breaks in the presence of cytosine arabinoside and hydroxyurea at a frequency similar to that of cells damaged by methylmethanesulfonate. 3-Aminobenzamide (1 mM) reduced the net strand-break frequency detected after either kind of damage. Repair replication, however, was stimulated only in methylmethanesulfonate-damaged cells. This stimulation is therefore not related directly to the DNA strand-break frequencies and concomitant poly(ADP-ribose) synthesis, but depends on some other cellular response specific to alkylating agents.

  18. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Lanza, Francesco; Balleari, Enrico

    2005-01-01

    Thirty-seven anaemic subjects with low-to-intermediate risk myelodysplastic syndrome (MDS) received the highly glycosylated, long-acting erythropoiesis-stimulating molecule darbepoetin-alpha (DPO) at the single, weekly dose of 150 microg s.c. for at least 12 weeks. Fifteen patients (40.5%) achieved......, no excess of blasts and hypoplastic bone marrow. This study suggests that DPO, at the dose and schedule used, can be safely given in low-intermediate risk MDS and may be effective in a significant proportion of these patients....

  19. Detection of Stimulants and Narcotics by Liquid Chromatography-Tandem Mass Spectrometry and Gas Chromatography-Mass Spectrometry for Sports Doping Control.

    Science.gov (United States)

    Ahrens, Brian D; Kucherova, Yulia; Butch, Anthony W

    2016-01-01

    Sports drug testing laboratories are required to detect several classes of compounds that are prohibited at all times, which include anabolic agents, peptide hormones, growth factors, beta-2 agonists, hormones and metabolic modulators, and diuretics/masking agents. Other classes of compounds such as stimulants, narcotics, cannabinoids, and glucocorticoids are also prohibited, but only when an athlete is in competition. A single class of compounds can contain a large number of prohibited substances and all of the compounds should be detected by the testing procedure. Since there are almost 70 stimulants on the prohibited list it can be a challenge to develop a single screening method that will optimally detect all the compounds. We describe a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) testing method for detection of all the stimulants and narcotics on the World Anti-Doping Agency prohibited list. Urine for LC-MS/MS testing does not require sample pretreatment and is a direct dilute and shoot method. Urine samples for the GC-MS method require a liquid-liquid extraction followed by derivatization with trifluoroacetic anhydride.

  20. Stimulating at the right time: phase-specific deep brain stimulation.

    Science.gov (United States)

    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  1. Electron transport and precipitation at Mercury during the MESSENGER flybys: Implications for electron-stimulated desorption

    Czech Academy of Sciences Publication Activity Database

    Schriver, D.; Trávníček, Pavel M.; Ashour-Abdalla, M.; Richard, R. L.; Hellinger, Petr; Slavin, J.A.; Anderson, B.J.; Baker, D. N.; Benna, M.; Boardsen, S.A.; Gold, R.E.; Ho, G.C.; Korth, H.; Krimigis, S.M.; McClintock, W.E.; McLain, J.L.; Orlando, T.M.; Sarantos, M.; Sprague, A.L.; Starr, R.D.

    2011-01-01

    Roč. 59, č. 15 (2011), s. 2026-2036 ISSN 0032-0633 R&D Projects: GA MŠk ME09009 Grant - others:ESA(XE) ESA- PECS project No. 98068 Institutional research plan: CEZ:AV0Z10030501 Keywords : Mercury * magnetosphere * numerical simulations Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 2.224, year: 2011

  2. The ESA Lunar Lander and the search for Lunar Volatiles

    Science.gov (United States)

    Morse, A. D.; Barber, S. J.; Pillinger, J. M.; Sheridan, S.; Wright, I. P.; Gibson, E. K.; Merrifield, J. A.; Waltham, N. R.; Waugh, L. J.; Pillinger, C. T.

    2011-10-01

    Following the Apollo era the moon was considered a volatile poor body. Samples collected from the Apollo missions contained only ppm levels of water formed by the interaction of the solar wind with the lunar regolith [1]. However more recent orbiter observations have indicated that water may exist as water ice in cold polar regions buried within craters at concentrations of a few wt. % [2]. Infrared images from M3 on Chandrayaan-1 have been interpreted as showing the presence of hydrated surface minerals with the ongoing hydroxyl/water process feeding cold polar traps. This has been supported by observation of ephemeral features termed "space dew" [3]. Meanwhile laboratory studies indicate that water could be present in appreciable quantities in lunar rocks [4] and could also have a cometary source [5]. The presence of sufficient quantities of volatiles could provide a resource which would simplify logistics for long term lunar missions. The European Space Agency (ESA's Directorate of Human Spaceflight and Operations) have provisionally scheduled a robotic mission to demonstrate key technologies to enable later human exploration. Planned for launch in 2018, the primary aim is for precise automated landing, with hazard avoidance, in zones which are almost constantly illuminated (e.g. at the edge of the Shackleton crater at the lunar south pole). These regions would enable the solar powered Lander to survive for long periods > 6 months, but require accurate navigation to within 200m. Although landing in an illuminated area, these regions are close to permanently shadowed volatile rich regions and the analysis of volatiles is a major science objective of the mission. The straw man payload includes provision for a Lunar Volatile and Resources Analysis Package (LVRAP). The authors have been commissioned by ESA to conduct an evaluation of possible technologies to be included in L-VRAP which can be included within the Lander payload. Scientific aims are to demonstrate the

  3. Erythropoiesis- and Thrombopoiesis-Characterizing Parameters in Adenosine A(3) Receptor Knock-Out Mice

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Weiterová, Lenka

    2013-01-01

    Roč. 62, č. 3 (2013), s. 305-311 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : ELEVATING EXTRACELLULAR ADENOSINE * COLONY-STIMULATING FACTOR * HEMATOPOIETIC PROGENITOR CELLS Subject RIV: BO - Biophysics Impact factor: 1.487, year: 2013

  4. [Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

    Science.gov (United States)

    Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

    2012-12-01

    Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

  5. Combined Dextroamphetamine and Transcranial Direct Current Stimulation in Poststroke Aphasia.

    Science.gov (United States)

    Keser, Zafer; Dehgan, Michelle Weber; Shadravan, Shaparak; Yozbatiran, Nuray; Maher, Lynn M; Francisco, Gerard E

    2017-10-01

    There is a growing need for various effective adjunctive treatment options for speech recovery after stroke. A pharmacological agent combined with noninvasive brain stimulation has not been previously reported for poststroke aphasia recovery. In this "proof of concept" study, we aimed to test the safety of a combined intervention consisting of dextroamphetamine, transcranial direct current stimulation, and speech and language therapy in subjects with nonfluent aphasia. Ten subjects with chronic nonfluent aphasia underwent two experiments where they received dextroamphetamine or placebo along with transcranial direct current stimulation and speech and language therapy on two separate days. The Western Aphasia Battery-Revised was used to monitor changes in speech performance. No serious adverse events were observed. There was no significant increase in blood pressure with amphetamine or deterioration in speech and language performance. Western Aphasia Battery-Revised aphasia quotient and language quotient showed a statistically significant increase in the active experiment. Comparison of proportional changes of aphasia quotient and language quotient in active experiment with those in placebo experiment showed significant difference. We showed that the triple combination therapy is safe and implementable and seems to induce positive changes in speech and language performance in the patients with chronic nonfluent aphasia due to stroke.

  6. Enhancement of cell-cell contact by a nonmitogenic lectin increases blastogenic response and IL-2 release by mitogen-stimulated mouse thymocytes.

    Science.gov (United States)

    Favero, J; Marti, J; Dornand, J; Bonnafous, J C; Mani, J C

    1986-03-01

    We have examined the influence of peanut agglutinin (PNA), a lectin which agglutinates but does not stimulate mouse thymocytes, on the responsiveness of these cells to concanavalin A (Con A) or galactose oxidase stimulation. Binding low amounts of PNA on unseparated mouse thymocytes pretreated with neuraminidase highly enhances the mitogenic response and the level of interleukin 2 release in the culture medium upon Con A stimulation. We have shown that PNA present on the cell surface acts as a crosslinking agent which favors intercellular binding between accessory cells (macrophages) and thymocytes, leading through this enhanced cooperation by cell-cell contact to an enhanced blastogenic response.

  7. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    Science.gov (United States)

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-01-01

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

  8. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    2015-07-01

    Full Text Available Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  9. CD28 co-stimulation down regulates Th17 development.

    Directory of Open Access Journals (Sweden)

    Salim Bouguermouh

    Full Text Available Th17 cells are implicated in host defence and autoimmune diseases. CD28/B7 co-stimulation is involved in the induction and progression of autoimmune diseases, but its role in controlling murine Th17 cell fate remains to be clarified. We here report that soluble anti-CD28 mAb suppressed the differentiation of anti-CD3-stimulated naïve CD4(+ T cells into IL-17-producing cells. CD28 co-stimulation reduced the frequency of proliferating cells that produce IL-17. We provide evidence for an IL-2 and IFN-gamma-dependent mechanism of CD28-mediated IL-17 suppression. CD28 blockade of Th17 development was correlated with a decrease rather than an increase in the percentage of Foxp3(+ T cells. In APC/T cell co-cultures, mature dendritic cells (DC were less efficient than immature DC in their ability to support Th17 cell differentiation, while CTLA4-Ig, an agent blocking CD28/B7 and CTLA4/B7 interactions, facilitated both murine and human Th17 differentiation. This study identifies the importance of B7 co-stimulatory molecules in the negative regulation of Th17 development. These unexpected results caution targeting the CD28/B7 pathways in the treatment of human autoimmune diseases.

  10. An Agent-Based Model of New Venture Creation: Conceptual Design for Simulating Entrepreneurship

    Science.gov (United States)

    Provance, Mike; Collins, Andrew; Carayannis, Elias

    2012-01-01

    There is a growing debate over the means by which regions can foster the growth of entrepreneurial activity in order to stimulate recovery and growth of their economies. On one side, agglomeration theory suggests the regions grow because of strong clusters that foster knowledge spillover locally; on the other side, the entrepreneurial action camp argues that innovative business models are generated by entrepreneurs with unique market perspectives who draw on knowledge from more distant domains. We will show you the design for a novel agent-based model of new venture creation that will demonstrate the relationship between agglomeration and action. The primary focus of this model is information exchange as the medium for these agent interactions. Our modeling and simulation study proposes to reveal interesting relationships in these perspectives, offer a foundation on which these disparate theories from economics and sociology can find common ground, and expand the use of agent-based modeling into entrepreneurship research.

  11. A Reference Implementation of the OGC CSW EO Standard for the ESA HMA-T project

    Science.gov (United States)

    Bigagli, Lorenzo; Boldrini, Enrico; Papeschi, Fabrizio; Vitale, Fabrizio

    2010-05-01

    This work was developed in the context of the ESA Heterogeneous Missions Accessibility (HMA) project, whose main objective is to involve the stakeholders, namely National space agencies, satellite or mission owners and operators, in an harmonization and standardization process of their ground segment services and related interfaces. Among HMA objectives was the specification, conformance testing, and experimentation of two Extension Packages (EPs) of the ebRIM Application Profile (AP) of the OGC Catalog Service for the Web (CSW) specification: the Earth Observation Products (EO) EP (OGC 06-131) and the Cataloguing of ISO Metadata (CIM) EP (OGC 07-038). Our contributions have included the development and deployment of Reference Implementations (RIs) for both the above specifications, and their integration with the ESA Service Support Environment (SSE). The RIs are based on the GI-cat framework, an implementation of a distributed catalog service, able to query disparate Earth and Space Science data sources (e.g. OGC Web Services, Unidata THREDDS) and to expose several standard interfaces for data discovery (e.g. OGC CSW ISO AP). Following our initial planning, the GI-cat framework has been extended in order to expose the CSW.ebRIM-CIM and CSW.ebRIM-EO interfaces, and to distribute queries to CSW.ebRIM-CIM and CSW.ebRIM-EO data sources. We expected that a mapping strategy would suffice for accommodating CIM, but this proved to be unpractical during implementation. Hence, a model extension strategy was eventually implemented for both the CIM and EO EPs, and the GI-cat federal model was enhanced in order to support the underlying ebRIM AP. This work has provided us with new insights into the different data models for geospatial data, and the technologies for their implementation. The extension is used by suitable CIM and EO profilers (front-end mediator components) and accessors (back-end mediator components), that relate ISO 19115 concepts to EO and CIM ones. Moreover

  12. Payload operations management of a planned European SL-Mission employing establishments of ESA and national agencies

    Science.gov (United States)

    Joensson, Rolf; Mueller, Karl L.

    1994-01-01

    Spacelab (SL)-missions with Payload Operations (P/L OPS) from Europe involve numerous space agencies, various ground infrastructure systems and national user organizations. An effective management structure must bring together different entities, facilities and people, but at the same time keep interfaces, costs and schedule under strict control. This paper outlines the management concept for P/L OPS of a planned European SL-mission. The proposal draws on the relevant experience in Europe, which was acquired via the ESA/NASA mission SL-1, by the execution of two German SL-missions and by the involvement in, or the support of, several NASA-missions.

  13. The Neuroprotective Benefits of Central Adenosine Receptor Stimulation in a Soman Nerve Agent Rat Model

    Science.gov (United States)

    2014-04-01

    where treatment is delayed and nerve agent-induced status epilepticus develops. New therapeutic targets are required to improve survivability and...Exp Ther 304(3): 1307-1313. Compton, J. R. (2004). Adenosine Receptor Agonist Pd 81,723 Protects Against Seizure/ Status Epilepticus and...Dragunow (1994). " Status epilepticus may be caused by loss of adenosine anticonvulsant mechanisms." Neuroscience 58(2): 245-261. Youssef, A. F. and B. W

  14. Una ciudad de los vascones en el yacimiento de Campo Real/Fillera (Sos del Rey Católico-Sangüesa

    Directory of Open Access Journals (Sweden)

    Andreu Pintado, Javier

    2008-12-01

    Full Text Available The following paper deals with the detailed and preliminary study of the archaeological site of Campo Real/Fillera (Sos del Rey Católico/Sangüesa, between today Zaragoza and Navarra provinces specially focusing in its Roman period. The paper exposes a review of the archeological and epigraphical material from the site, proposes an urban condition for it and raises some hypothesis on its identification with one of the cities that ancient sources tribued to Vascones.El presente trabajo aborda el estudio detallado y preliminar del yacimiento arqueológico de Campo Real/Fillera (Sos del Rey Católico/Sangüesa, en el límite entre las actuales provincias de Zaragoza y Navarra con especial atención a su etapa romana. Se procede a la revisión del material arqueológico y epigráfico procedente del lugar, se defiende la condición de enclave urbano del yacimiento y se plantea una hipótesis respecto de su identificación con las ciudades que las fuentes antiguas atribuyen a los Vascones.

  15. Leukemogenic Ptpn11 allele causes defective erythropoiesis in mice.

    Directory of Open Access Journals (Sweden)

    Tatiana Usenko

    Full Text Available Src homology 2 (SH2 domain-containing phosphatase 2 (SHP2, encoded by PTPN11, regulates signaling networks and cell fate in many tissues. Expression of oncogenic PTPN11 in the hematopoietic compartment causes myeloproliferative neoplasm (MPN in humans and mice. However, the stage-specific effect(s of mutant Ptpn11 on erythroid development have remained unknown. We found that expression of an activated, leukemogenic Ptpn11 allele, Ptpn11D61Y, specifically in the erythroid lineage causes dyserythropoiesis in mice. Ptpn11D61Y progenitors produce excess cKIT+ CD71+ Ter119- cells and aberrant numbers of cKITl° CD71+ erythroblasts. Mutant erythroblasts show elevated activation of ERK, AKT and STAT3 in response to EPO stimulation, and MEK inhibitor treatment blocks Ptpn11D61Y-evoked erythroid hyperproliferation in vitro. Thus, the expression of oncogenic Ptpn11 causes dyserythropoiesis in a cell-autonomous manner in vivo.

  16. Agent Programming Languages and Logics in Agent-Based Simulation

    DEFF Research Database (Denmark)

    Larsen, John

    2018-01-01

    and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI...

  17. Thoracoscopic patch insulation to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy.

    Science.gov (United States)

    Mediratta, Neeraj; Barker, Diane; McKevith, James; Davies, Peter; Belchambers, Sandra; Rao, Archana

    2012-07-01

    Cardiac resynchronization therapy is an established therapy for heart failure, improving quality of life and prognosis. Despite advances in technique, available leads and delivery systems, trans-venous left ventricular (LV) lead positioning remains dependent on the patient's underlying venous anatomy. The left phrenic nerve courses over the surface of the pericardium laterally and may be stimulated by the LV pacing lead, causing uncomfortable diaphragmatic twitch. This paper describes a video-assisted thoracoscopic (VATS) procedure to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy. Most current ways of avoiding phrenic stimulation involve either electronic reprogramming to distance the phrenic nerve from the stimulation circuit or repositioning the lead. We describe a case where the phrenic nerve was surgically insulated from the stimulating current by insinuating a patch of bovine pericardium between the epicardium and native pericardium of the heart thus completely resolving previously intolerable and incessant diaphragmatic twitch. The procedure was performed under general anaesthesia with single-lung ventilation and minimal use of neuromuscular blocking agents. Surgical patch insulation of the phrenic nerve was performed using minimally invasive VATS surgery, as a short-stay procedure, with no complications. No diaphragmatic twitch occurred post-surgery and the patient continued to gain symptomatic benefit from cardiac synchronization therapy (New York Heart Association Class III to II), enabling return to work. In cases where the trans-venous position of a LV lead is limited by troublesome phrenic nerve stimulation, thoracoscopic surgical patch insulation of the phrenic nerve could be considered to allow beneficial cardiac resynchronization therapy.

  18. Reflections on multiple strategies to reduce transfusion in cancer patients: A joint narrative.

    Science.gov (United States)

    Goubran, Hadi; Seghatchian, Jerard; Prokopchuk-Gauk, Oksana; Radosevic, Julia; Sabry, Waleed; Iqbal, Nayyer; Burnouf, Thierry

    2017-06-01

    Transfusion of red blood cells, platelets and plasma is widely used in the management of anemia and coagulopathy in cancer patients undergoing surgery, chemotherapy, and radiation. The decision to transfuse should not be made lightly as exposure to transfused blood, whether from an allogeneic or even autologous source, is not without risk and the long-term effect of blood transfusion on cancer outcomes remains questionable. Recognition of anemia associated with nutritional deficiency should be promptly corrected while avoiding the use of erythropoiesis stimulating agents. Minimizing blood loss and the prompt control of bleeding, coupled with a restrictive transfusion strategy, seem to be a reasonable approach that does not appear to be associated with long-term sequelae. Limiting platelet transfusion to patients with severe hypo-proliferative thrombocytopenia, and implementation of local hemostatic measures, together with the use of fractionated coagulation factor concentrates, as an alternative to frozen plasma transfusion, may reduce the exposure of cancer patients to potentially harmful thrombogenic and pro-inflammatory cellular microparticles. This joint narrative highlights current opinions for minimizing blood usage in patients with cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  19. Erythroid cells in vitro: from developmental biology to blood transfusion products.

    Science.gov (United States)

    Migliaccio, Anna Rita; Whitsett, Carolyn; Migliaccio, Giovanni

    2009-07-01

    Red blood cells (RBCs) transfusion plays a critical role in numerous therapies. Disruption of blood collection by political unrest, natural disasters and emerging infections and implementation of restrictions on the use of erythropoiesis-stimulating agents in cancer may impact blood availability in the near future. These considerations highlight the importance of developing alternative blood products. Knowledge about the processes that control RBC production has been applied to the establishment of culture conditions allowing ex-vivo generation of RBCs in numbers close to those (2.5 x 10 cells/ml) present in a transfusion, from cord blood, donated blood units or embryonic stem cells. In addition, experimental studies demonstrate that such cells protect mice from lethal bleeding. Therefore, erythroid cells generated ex vivo may be suitable for transfusion provided they can be produced safely in adequate numbers. However, much remains to be done to translate a theoretical production of approximately 2.5 x 10 RBCs in the laboratory into a 'clinical grade production process'. This review summarizes the state-of-the-art in establishing ex-vivo culture conditions for erythroid cells and discusses the most compelling issues to be addressed to translate this progress into a clinical grade transfusion product.

  20. Idiopathic erythrocytosis in a patient on chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Dong Hyun Lee

    2015-03-01

    Full Text Available A 78-year-old man on hemodialysis presented to our hospital with erythrocytosis. He had started hemodialysis 4 years previously, with a hemoglobin level of 9.8 g/dL, and was administered erythropoiesis stimulating agents and ferrous sulfate. Two years previously, his hemoglobin level increased to 14.5 g/dL and the treatment for anemia was discontinued. He continued hemodialysis thrice weekly; however, the hemoglobin level had increased to 17.0 g/dL at the time of presenting to our hospital. His serum erythropoietin level was 31.4 mIU/mL (range, 3.7–31.5 mIU/mL, carboxyhemoglobin level was 0.6% (range, 0–1.5%, and oxygen saturation in ambient air was 95.4%. The JAK2 V617F mutation was not observed and other bone marrow abnormalities were not identified. The patient was diagnosed with bladder cancer and a transurethral resection was performed. Eight months after the treatment of bladder cancer, his hemoglobin level was 15.1 g/dL, and he was diagnosed with idiopathic erythrocytosis.

  1. Do Different Stimulation Protocols Effect Oocyte Quality and IVF Outcomes in IVF-ET?

    Directory of Open Access Journals (Sweden)

    Nafiye Yilmaz

    2016-04-01

    Full Text Available Aim: This study was planned to compare the effect of different stimulation protocols (hMG and uFSH on oocyte maturation and in vitro fertilization outcomes. Material and Method: Eighty-two patients admitted Ankara University Obstetrics and Gynecology Clinic- IVF Department were included in this retrospective study. All patients used long GnRH agonist protocol. Fifty-nine patients used human menopausal gonadotropin (hMG (Group 1 and 23 patients used urine derived follicle-stimulating hormone (uFSH (Group 2 for ovulation induction. Maximum follicle diameter, dominant follicle number, endometrial thickness at human chorionic gonadotropin day, duration of induction, dose of gonadotropin, oocyte number and quality, fertilization rate, embryo number and quality, pregnancy rate per cycles and transfer were reported. Results: Maximum follicle diameter, dominant follicle number, immature oocyte number were significantly higher in hMG group vs. uFSH group (p0.05. Discussion: Clinical pregnancy rate was not significantly different in hMG vs. uFSH group. In developing countries, ovarian stimulation agents should be chosen based on patient characteristics and cost.

  2. An evaluation of the MEDALUS ESA index (environmental sensitivity to land degradation), from regional to plot scale

    International Nuclear Information System (INIS)

    Lavado Contador, J. J.; Schnabel, S.; Gomez Gutierrez, A.

    2009-01-01

    An assessment of the sensitivity to land degradation have been carried out for the region of Extramadura, Sw Spain, by means of the modelling approach developed in the European Commission funded MEDALUS project (Mediterranean Desertification and Land Use) which identifies such areas on the basis of an index (ESA index) that incorporates data on environmental quality (climate, vegetation, soil) as well as on anthropogenic factors (management). Two maps of environmental sensitivity to degradation with different legend resolution (4 and 8 classes of sensitivity) have been made. (Author) 6 refs.

  3. Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1.

    Science.gov (United States)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

    2015-02-01

    Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30-50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40-50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30-40% in tension developing muscle but did not affect contraction-stimulated glucose transport in

  4. Agents unleashed a public domain look at agent technology

    CERN Document Server

    Wayner, Peter

    1995-01-01

    Agents Unleashed: A Public Domain Look at Agent Technology covers details of building a secure agent realm. The book discusses the technology for creating seamlessly integrated networks that allow programs to move from machine to machine without leaving a trail of havoc; as well as the technical details of how an agent will move through the network, prove its identity, and execute its code without endangering the host. The text also describes the organization of the host's work processing an agent; error messages, bad agent expulsion, and errors in XLISP-agents; and the simulators of errors, f

  5. Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Jae Meen Lee

    2016-02-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS surgery in a cerebral palsy (CP patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

  6. Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Kimberly B. Hoang

    2017-10-01

    Full Text Available The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs, and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs, and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.

  7. Effect of bioremediation agents on oil biodegradation in medium-fine sand

    International Nuclear Information System (INIS)

    Croft, B.C.; Swannell, R.P.J.; Grant, A.L.; Lee, K.

    1995-01-01

    A spill of weathered Arabian light crude oil on an intertidal sand zone was simulated in the laboratory. Respirometry, chemical, and microbiological methods were employed to assess the effectiveness of two bioremediation agents: a slow-release inorganic (Max Bac) and an oleophilic organic fertilizer (Inipol EAP22). Inipol EAP22 stimulated additional CO 2 evolution, and significantly increased both the total chemoheterotrophic population and the number of hydrocarbon-degrading microorganisms. At the end of the experiment, the residual oil extracted from the Inipol-treated sand was significantly more biodegraded, based on the application of the conserved biomarkers (phytane and 17α, 21β hopane), than that removed from the other sand columns, albeit by a relatively small amount. The results suggested that Inipol EAP22 stimulated the chemoheterotrophic and hydrocarbon-degrading microbial population and, after a lag phase, encouraged oil biodegradation in fine sandy sediments subjected to a vertical tidal cycle

  8. Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACE

    Directory of Open Access Journals (Sweden)

    Miguel Cavadas

    2017-10-01

    Full Text Available Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme, is responsible for cleavage (“shedding” of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents. Here, we report a role for iRhom2 in TACE stimulation on the cell surface. TACE shedding stimuli trigger MAP kinase-dependent phosphorylation of iRhom2 N-terminal cytoplasmic tail. This recruits 14-3-3 proteins, enforcing the dissociation of TACE from complexes with iRhom2, promoting the cleavage of TACE substrates. Our data reveal that iRhom2 controls multiple aspects of TACE biology, including stimulated shedding on the cell surface.

  9. Mobile Agent Data Integrity Using Multi-Agent Architecture

    National Research Council Canada - National Science Library

    McDonald, Jeffrey

    2004-01-01

    .... Security issues for mobile agents continue to produce research interest, particularly in developing mechanisms that guarantee protection of agent data and agent computations in the presence of malicious hosts...

  10. Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use.

    Science.gov (United States)

    Briden, M Elizabeth

    2004-02-01

    Chemical peeling is an in-office procedure that involves the application of a chemical agent to the skin to induce controlled destruction or exfoliation of old skin and stimulation of new epidermal growth with more evenly distributed melanin. When peel agents reach the dermal layer, important wound-healing activities occur that cause skin remodeling and skin smoothing, both antiaging benefits. There are a number of key factors in selecting a peeling agent and procedure, and each is discussed. Variables to consider are the peeling agent and its formulation, the concentration of the agent, the patient's skin type, the site to be peeled, the skin preparation procedure prior to and immediately preceding the application of the agent, the application method, the duration of contact, and the patient's medical history and lifestyle. Various types of peels are discussed. Of particular interest are superficial chemical peels, which offer great flexibility over a range of skin types and conditions with minimal to no "downtime." Alpha-hydroxyacid (AHA) peels are superficial and can be combined with other cosmetic procedures in the office to maximize benefits. In addition, AHA peels work well when combined with supportive homecare products including AHAs or polyhydroxy acids (PHAs), topical retinoids, and antiacne/antirosacea treatments. Case studies are presented of patients using AHA peels for the treatment of acne and hyperpigmentation in a variety of skin types, including Asian skin.

  11. Greenhouse gas observations from space: The GHG-CCI project of ESA's Climate Change Initiative

    Science.gov (United States)

    Buchwitz, Michael; Noël, Stefan; Bergamaschi, Peter; Boesch, Hartmut; Bovensmann, Heinrich; Notholt, Justus; Schneising, Oliver; Hasekamp, Otto; Reuter, Maximilian; Parker, Robert; Dils, Bart; Chevallier, Frederic; Zehner, Claus; Burrows, John

    2012-07-01

    The GHG-CCI project (http://www.esa-ghg-cci.org) is one of several projects of ESA's Climate Change Initiative (CCI), which will deliver various Essential Climate Variables (ECVs). The goal of GHG-CCI is to deliver global satellite-derived data sets of the two most important anthropogenic greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4) suitable to obtain information on regional CO2 and CH4 surface sources and sinks as needed for better climate prediction. The GHG-CCI core ECV data products are column-averaged mole fractions of CO2 and CH4, XCO2 and XCH4, retrieved from SCIAMACHY on ENVISAT and TANSO on GOSAT. Other satellite instruments will be used to provide constraints in upper layers such as IASI, MIPAS, and ACE-FTS. Which of the advanced algorithms, which are under development, will be the best for a given data product still needs to be determined. For each of the 4 GHG-CCI core data products - XCO2 and XCH4 from SCIAMACHY and GOSAT - several algorithms are being further developed and the corresponding data products are inter-compared to identify which data product is the most appropriate. This includes comparisons with corresponding data products generated elsewhere, most notably with the operational data products of GOSAT generated at NIES and the NASA/ACOS GOSAT XCO2 product. This activity, the so-called "Round Robin exercise", will be performed in the first two years of this project. At the end of the 2 year Round Robin phase (end of August 2012) a decision will be made which of the algorithms performs best. The selected algorithms will be used to generate the first version of the ECV GHG. In the last six months of this 3 year project the resulting data products will be validated and made available to all interested users. In the presentation and overview about this project will be given focussing on the latest results.

  12. The new Planetary Science Archive: A tool for exploration and discovery of scientific datasets from ESA's planetary missions

    Science.gov (United States)

    Heather, David

    2016-07-01

    Introduction: The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces (e.g. FTP browser, Map based, Advanced search, and Machine interface): http://archives.esac.esa.int/psa All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. Updating the PSA: The PSA is currently implementing a number of significant changes, both to its web-based interface to the scientific community, and to its database structure. The new PSA will be up-to-date with versions 3 and 4 of the PDS standards, as PDS4 will be used for ESA's upcoming ExoMars and BepiColombo missions. The newly designed PSA homepage will provide direct access to scientific datasets via a text search for targets or missions. This will significantly reduce the complexity for users to find their data and will promote one-click access to the datasets. Additionally, the homepage will provide direct access to advanced views and searches of the datasets. Users will have direct access to documentation, information and tools that are relevant to the scientific use of the dataset, including ancillary datasets, Software Interface Specification (SIS) documents, and any tools/help that the PSA team can provide. A login mechanism will provide additional functionalities to the users to aid / ease their searches (e.g. saving queries, managing default views). Queries to the PSA database will be possible either via the homepage (for simple searches of missions or targets), or through a filter menu for more tailored queries. The filter menu will offer multiple options to search for a particular dataset or product, and will manage queries for both in-situ and remote sensing instruments. Parameters such as start-time, phase angle, and heliocentric distance will be emphasized. A further

  13. A distributed current stimulator ASIC for high density neural stimulation.

    Science.gov (United States)

    Jeong Hoan Park; Chaebin Kim; Seung-Hee Ahn; Tae Mok Gwon; Joonsoo Jeong; Sang Beom Jun; Sung June Kim

    2016-08-01

    This paper presents a novel distributed neural stimulator scheme. Instead of a single stimulator ASIC in the package, multiple ASICs are embedded at each electrode site for stimulation with a high density electrode array. This distributed architecture enables the simplification of wiring between electrodes and stimulator ASIC that otherwise could become too complex as the number of electrode increases. The individual ASIC chip is designed to have a shared data bus that independently controls multiple stimulating channels. Therefore, the number of metal lines is determined by the distributed ASICs, not by the channel number. The function of current steering is also implemented within each ASIC in order to increase the effective number of channels via pseudo channel stimulation. Therefore, the chip area can be used more efficiently. The designed chip was fabricated with area of 0.3 mm2 using 0.18 μm BCDMOS process, and the bench-top test was also conducted to validate chip performance.

  14. Transcranial magnetic stimulation and sleep disorders: pathophysiologic insights.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Brigo, Francesco; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

    2013-11-01

    The neural mechanisms underlying the development of the most common intrinsic sleep disorders are not completely known. Therefore, there is a great need for noninvasive tools which can be used to better understand the pathophysiology of these diseases. Transcranial magnetic stimulation (TMS) offers a method to noninvasively investigate the functional integrity of the motor cortex and its corticospinal projections in neurologic and psychiatric diseases. To date, TMS studies have revealed cortical and corticospinal dysfunction in several sleep disorders, with cortical hyperexcitability being a characteristic feature in some disorders (i.e., the restless legs syndrome) and cortical hypoexcitability being a well-established finding in others (i.e., obstructive sleep apnea syndrome narcolepsy). Several research groups also have applied TMS to evaluate the effects of pharmacologic agents, such as dopaminergic agent or wake-promoting substances. Our review will focus on the mechanisms underlying the generation of abnormal TMS measures in the different types of sleep disorders, the contribution of TMS in enhancing the understanding of their pathophysiology, and the potential diagnostic utility of TMS techniques. We also briefly discussed the possible future implications for improving therapeutic approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Reactions of human dental pulp cells to capping agents in the presence or absence of bacterial exposure.

    Science.gov (United States)

    Cai, Shiwei; Zhang, Wenjian; Tribble, Gena; Chen, Wei

    2017-01-01

    An ideal pulp-capping agent needs to have good biocompatibility and promote reparative dentinogenesis. Although the effects of capping agents on healthy pulp are known, limited data regarding their effects on bacterial contaminated pulp are available. This study aimed to evaluate the reaction of contaminated pulps to various capping agents to assist clinicians in making informed decisions. Human dental pulp (HDP) cell cultures were developed from extracted human molars. The cells were exposed to a bacterial cocktail comprising Porphyromonas gingivalis, Prevotella intermedia, and Streptococcus gordonii before being cocultured with capping agents such as mineral trioxide aggregate (MTA) Portland cement (PC), and Dycal. HDP cell proliferation was assayed by MTS colorimetric cell proliferation assay, and its differentiation was evaluated by real-time PCR for detecting alkaline phosphatase, dentin sialophosphoprotein, and osteocalcin expressions. MTA and PC had no apparent effect, whereas Dycal inhibited HDP cell proliferation. PC stimulated HDP cell differentiation, particularly when they were exposed to bacteria. MTA and Dycal inhibited differentiation, regardless of bacterial infection. In conclusion, PC was the most favorable agent, followed by MTA, and Dycal was the least favorable agent for supporting the functions of bacterial compromised pulp cells.

  16. Transcranial brain stimulation: closing the loop between brain and stimulation

    DEFF Research Database (Denmark)

    Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

    2016-01-01

    -related and state-related variability. Fluctuations in brain-states can be traced online with functional brain imaging and inform the timing or other settings of transcranial brain stimulation. State-informed open-loop stimulation is aligned to the expression of a predefined brain state, according to prespecified......PURPOSE OF REVIEW: To discuss recent strategies for boosting the efficacy of noninvasive transcranial brain stimulation to improve human brain function. RECENT FINDINGS: Recent research exposed substantial intra- and inter-individual variability in response to plasticity-inducing transcranial brain...... stimulation. Trait-related and state-related determinants contribute to this variability, challenging the standard approach to apply stimulation in a rigid, one-size-fits-all fashion. Several strategies have been identified to reduce variability and maximize the plasticity-inducing effects of noninvasive...

  17. Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate in vitro hematopoietic stem cell migration effectively comparable to beta-adrenergic stimulation.

    Science.gov (United States)

    Köse, Sevil; Aerts-Kaya, Fatima; Köprü, Çağla Zübeyde; Nemutlu, Emirhan; Kuşkonmaz, Barış; Karaosmanoğlu, Beren; Taşkıran, Ekim Zihni; Altun, Belgin; Uçkan Çetinkaya, Duygu; Korkusuz, Petek

    2018-01-01

    Granulocyte colony-stimulating factor (G-CSF) is a well-known hematopoietic stem cell (HSC)-mobilizing agent used in both allogeneic and autologous transplantation. However, a proportion of patients or healthy donors fail to mobilize a sufficient number of cells. New mobilization agents are therefore needed. Endocannabinoids (eCBs) are endogenous lipid mediators generated in the brain and peripheral tissues and activate the cannabinoid receptors CB1 and CB2. We suggest that eCBs may act as mobilizers of HSCs from the bone marrow (BM) under stress conditions as beta-adrenergic receptors (Adrβ). This study demonstrates that BM mesenchymal stem cells (MSCs) secrete anandamide (AEA) and 2-arachidonylglycerol (2-AG) and the peripheral blood (PB) and BM microenvironment contain AEA and 2-AG. 2-AG levels are significantly higher in PB of the G-CSF-treated group compared with BM plasma. BM mononuclear cells (MNCs) and CD34 + HSCs express CB1, CB2, and Adrβ subtypes. CD34 + HSCs had higher CB1 and CB2 receptor expression in G-CSF-untreated and G-CSF-treated groups compared with MSCs. MNCs but not MSCs expressed CB1 and CB2 receptors based on qRT-PCR and flow cytometry. AEA- and 2-AG-stimulated HSC migration was blocked by eCB receptor antagonists in an in vitro migration assay. In conclusion, components of the eCB system and their interaction with Adrβ subtypes were demonstrated on HSCs and MSCs of G-CSF-treated and G-CSF-untreated healthy donors in vitro, revealing that eCBs might be potential candidates to enhance or facilitate G-CSF-mediated HSC migration under stress conditions in a clinical setting. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  18. Evaluation of a Petition Requesting National Marine Fisheries Service (NMFS) to List the Smooth Hammerhead Shark (Sphryna zygaena) as a Threatened or Endangered Species Under the Endangered Species Act (ESA)

    Science.gov (United States)

    Sturm, A. B.

    2016-12-01

    The wildlife conservation organization, Defenders of Wildlife, petitioned NMFS to list the smooth hammerhead shark, Sphryna zygaena, as endangered or threatened throughout its range under the ESA. The petition was critically evaluated to determine if the petitioners presented substantial scientific or commercial information indicating that the smooth hammerhead shark may warrant listing under the ESA. The petition and the cited scientific literature (as well as scientific literature readily available in NMFS files) were evaluated to determine if the smooth hammerhead shark may be threatened or endangered because of any one or a combination of the following five ESA section 4(a)(1) factors: (1) present or threatened destruction, modification, or curtailment of its habitat or range; (2) over utilization for commercial, recreational, scientific, or educational purposes; (3) disease or predation; (4) inadequacy of existing regulatory mechanisms; (5) or other natural or manmade factors affecting its continued existence. The available scientific literature indicates that the smooth hammerhead shark populations have declined in multiple regions. Smooth hammerhead sharks may warrant listing due to ongoing threats of over utilization for commercial purposes by global fisheries that target and retain incidental catch of these species to obtain their high-value fins, possible inadequacies in global regulatory mechanisms to control this level of exploitation, and natural factors (such as inherent biological vulnerabilities) that may be exacerbating these threats. Based on these findings, the smooth hammerhead shark may warrant listing as a threatened or endangered species under the ESA and a status review of the species is currently being conducted.

  19. Airborne direct-detection and coherent wind lidar measurements over the North Atlantic in 2015 supporting ESA's aeolus mission

    Science.gov (United States)

    Marksteiner, Uwe; Reitebuch, Oliver; Lemmerz, Christian; Lux, Oliver; Rahm, Stephan; Witschas, Benjamin; Schäfler, Andreas; Emmitt, Dave; Greco, Steve; Kavaya, Michael J.; Gentry, Bruce; Neely, Ryan R.; Kendall, Emma; Schüttemeyer, Dirk

    2018-04-01

    The launch of the Aeolus mission by the European Space Agency (ESA) is planned for 2018. The satellite will carry the first wind lidar in space, ALADIN (Atmospheric Laser Doppler INstrument). Its prototype instrument, the ALADIN Airborne Demonstrator (A2D), was deployed during several airborne campaigns aiming at the validation of the measurement principle and optimization of algorithms. In 2015, flights of two aircraft from DLR & NASA provided the chance to compare parallel wind measurements from four airborne wind lidars for the first time.

  20. SCOSII: ESA's new generation of mission control systems: The user's perspective

    Science.gov (United States)

    Kaufeler, P.; Pecchioli, M.; Shurmer, I.

    1994-01-01

    In 1974 ESOC decided to develop a reusable Mission Control System infrastructure for ESA's missions operated under its responsibility. This triggered a long and successful product development line, which started with the Multi Mission Support System (MSSS) which entered in service in 1977 and is still being used today by the MARECS and ECS missions; it was followed in 1989 by a second generation of systems known as SCOS-I, which was/is used by the Hipparcos, ERS-1 and EURECA missions and will continue to support all future ESCO controlled missions until approximately 1995. In the meantime the increasing complexity of future missions together with the emergence of new hardware and software technologies have led ESOC to go for the development of a third generation of control systems, SCOSII, which will support their future missions up to at least the middle of the next decade. The objective of the paper is to present the characteristics of the SCOSII system from the perspective of the mission control team; i.e. it will concentrate on the improvements and advances in the performance, functionality and work efficiency of the system.

  1. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  2. ESA Unveils Its New Comet Chaser.

    Science.gov (United States)

    1999-07-01

    The objective is to study one of these primordial objects at close quarters by placing a lander on its surface and chasing, with an orbiter, the comet for millions of kilometres through space. Comets - among the oldest (4.6 billion years!) and last altered objects in the solar system - are regarded as the building blocks from which the planets formed. Thus the Rosetta's discoveries will allow the scientists to learn more about birth and evolution of the planets and about the origin of life on the Earth. The final design of the Rosetta orbiter will be revealed for the first time at the Royal Society in London on 1 July when a 1:4 scale model will be unveiled by ESA's Director of Science, Prof.. Roger Bonnet. (The full size version of the spacecraft is 32 metres across, so large that it would stretch the entire width of a football pitch. Almost 90 of this is accounted for by the giant solar panels which are needed to provide electrical power in the dark depths of the Solar System). "Rosetta is a mission of major scientific importance," said Prof. Bonnet. "It will build on the discoveries made by Giotto and confirm ESA's leading role in the exploration of the Solar System and the Universe as a whole." The timing of this event has been chosen to coincide with the London meeting of the Rosetta Science Working Team and the second Earth flyby of the now non-operational Giotto spacecraft. In addition, the opening of the British Museum's 'Cracking Codes' Exhibition, for which the Rosetta Stone is the centrepiece, is set to take place on 10 July. The Rosetta mission. Rosetta is the third Cornerstone in ESA's 'Horizon 2000' long-term scientific programme. It will be launched by Ariane 5 rocket from Kourou spaceport in French Guiana in January 2003. In order to gain sufficient speed to reach the distant comet, Rosetta will require gravity assists from the Earth (twice) and Mars. After swinging around Mars in May 2005, Rosetta will return to Earth's vicinity in October 2005 and

  3. Results of the ESA study on psychological selection of astronaut applicants for Columbus missions I: Aptitude testing

    Science.gov (United States)

    Fassbender, Christoph; Goeters, Klaus-Martin

    European participation in the Space Station Freedom brought about new challenges for the psychological selection of astronaut candidates, particularly in respect to specific demands of long duration space flights. For this reason existing selection criteria and methods were reassessed. On these grounds a study was undertaken applying a unique composition of aptitude tests to a group of 97 ESA scientists and engineers who are highly comparable to the expected astronaut applicants with respect to age and education. The tests assessed operational aptitudes such as logical reasoning, memory function, perception, spatial orientation, attention, psychomotor function, and multiple task capacity. The study goals were: 1) Verification of psychometric qualities and applicability of tests in a normative group; 2) Search for culture-fair tests by which multi-national groups can be examined; 3) Identification of test methods which consider general and special operational demands of long duration space flights. Based on the empirical findings a test battery was arranged for use in the selection of ESA astronaut applicants. Results showed that 16 out of the 18 employed tests have good psychometric qualities and differentiate reliably in the special group of testees. The meta structure of the test battery as described by a factorial analysis is presented. Applicability of tests was generally high. Tests were culture-fair, however, a relation between English language skills and test results was identified. Since most item material was language-free, this was explained with the importance of English language skills for the understanding of test instructions. Solutions to this effect are suggested.

  4. Vagal nerve stimulation therapy: what is being stimulated?

    Science.gov (United States)

    Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

    2014-01-01

    Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

  5. Vagal nerve stimulation therapy: what is being stimulated?

    Directory of Open Access Journals (Sweden)

    Guy Kember

    Full Text Available Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

  6. Biological study on the effect of an anabolic steroidal agent administration pre-exposure to whole body gamma irradiated male mice

    International Nuclear Information System (INIS)

    Aly, S.M.; Eldawy, H.A.E.; Ragab, E.A.

    2002-01-01

    The present study was prepared to evaluate the potency of methoxy dimethylamino phenyl epiandrosterone (an anabolic agent animal in origin with an additive side chain) in a dose of 35 μ/g/kg b.wt in male albino mice as a radio-protective agent pre-exposure to gamma irradiation. This was accomplished through measuring follicular stimulating hormone (FSH), luteinizing hormone (LH) and prostaglandin-E 2 (PGE 2 ) and endothelin in plasma of mice. Meanwhile, observations of the chromosomal aberrations and sperm head abnormalities were recorded. The administration of the anabolic agent pre-irradiation resulted in slightly non-significant amelioration in the pituitary hormone levels and in levels of PGE 2 and endothelin

  7. Fiber-optic sensor demonstrator (FSD) for the monitoring of spacecraft subsystems on ESA's PROBA-2

    Science.gov (United States)

    Kruzelecky, Roman V.; Zou, Jing; Mohammed, Najeeb; Haddad, Emile; Jamroz, Wes; Ricci, Francesco; Lamorie, Joshua; Edwards, Eric; McKenzie, Iain; Vuilleumier, Pierrik

    2017-11-01

    MPB Communications (MPBC) is developing solutions to the monitoring requirements of spacecraft based on its fiber-laser and Fiber Bragg Grating expertise. This is cumulating in the Fiber Sensor Demonstrator for ESA's Proba-2 that is scheduled for launch in 2007. The advantages of the MPBC approach include a central interrogation system that can be used to control a variety of different fiber-optic sensors including temperature, pressure, actuator status, and propellant leakage. This paper reviews the design and ground qualification of the FSD system in preparation for integration with Proba-2. The FSD will provide monitoring for various Proba-2 subsystems, including a hybrid propulsion system. Some of the challenges associated with using fiber-optics in space are discussed.

  8. ESA 86: proceedings for the second annual conference of the Ergonomics Society of Southern Africa

    International Nuclear Information System (INIS)

    1986-01-01

    The proceedings contain presentations from ESA 86 which reflect most of the major areas of Ergonomics as it is researched and practised internationally. Highlights include presentations dealing with transport and computer system ergonomics, office furniture and other consumer products, safety at work and executive health. One seminar 'Ergonomics and nuclear power generation', looks at the control systems and its safety in a nuclear power plant. Ergonomics is concerned with the relationship between people and technology: specifically the design of the user interface. Its objective is to enhance efficiency, usability and safety and it is applied to the design of a wide range of industrial and consumer products. However not the least consideration is to achieve as near as possible total wellbeing for the Human Factor

  9. Avaliação dos instrumentos do projeto “nossas crianças: janelas de oportunidades”, segundo agentes comunitários de saúde

    Directory of Open Access Journals (Sweden)

    Juliana Martins

    2008-01-01

    Full Text Available La cartilla y el manual de apoyo "Toda hora es hora de cuidar" constituyen tecnologías del Proyecto "Nuestros niños: ventanas de oportunidades" para promover el desarrollo infantil. Esta investigación de carácter evaluativo, realizada en 2005/2006, con agentes comunitarios de salud, tuvo como objetivos: evaluar la aceptación y el uso de la cartilla y del manual de apoyo; identificar opiniones acerca de sus contenidos, formatos y redacción; identificar las dificultades y facilidades para su implantación. La recolección de los datos ocurrió en 17 centros de salud comunitaria en la ciudad de Sao Paulo; 29 agentes participaron de grupos focales y 125 respondieron cuestionarios estructurados. El análisis temático indica que los participantes consideran los instrumentos adecuados y de buena calidad, pero destacan como barreras a su utilización, dificultades propias de las familias y del proceso de trabajo. Ellos priorizan estrategias educativas tradicionales y los programas de formación influencian de manera positiva a esa evaluación

  10. Gastric electrical stimulation: a report of two cases.

    LENUS (Irish Health Repository)

    Sibartie, V

    2012-02-03

    Gastroparesis refractory to prokinetic agents poses a major challenge to the physician and patient, alike. In the past 5 years, electrical methods to treat gastroparesis have emerged from animal and human experiments to a potentially valuable tool in clinical gastroenterology. One of these methods, known as gastric electrical stimulation (GES), is being increasingly used in specialized centres worldwide, but had never been tried in Ireland. We describe here our experience with the first two implantations of gastric neurostimulators performed in Ireland and the outcome with these 2 patients. Our results at 6 months show reduction in symptoms and improvement in quality of life, which is encouraging and should prompt further evaluation of GES for patients with gastroparesis refractory to medical therapy.

  11. Reference payload of the ESA L1 mission candidate ATHENA

    Science.gov (United States)

    Martin, Didier; Rando, Nicola; Lumb, David; Verhoeve, Peter; Oosterbroek, Tim; Bavdaz, Marcos

    2012-09-01

    The Advanced Telescope for High ENergy Astrophysics (ATHENA) is one of the three candidates that competed for the first large-class mission (L1) in ESA’s Cosmic Vision 2015-2025 programme, with a launch planned by 2022 and is the result of the IXO reformulation activities. ATHENA is an ESA-led project and is conceived as the next generation X-ray observatory. It is meant to address fundamental questions about accretion around black-holes, reveal the physics underpinning cosmic feedback, trace the large scale structure of baryons in galaxy clusters and the cosmic as well as a large number of astrophysics and fundamental physics phenomena. The observatory consists of two identical mirrors each illuminating a fixed focal plane instrument, providing collectively 1 m2 effective area at 1 keV. The reference payload consists of a medium resolution wide field imager (WFI) and a high resolution X-ray micro-calorimeter spectrometer (XMS). The WFI is based on a monolithic Si DepFET array providing imaging over a 24 × 24 arcmin2 field of view and a good PSF oversampling. The sensor will measure X-rays in the range 0.1-15 keV and provides near Fano limited energy resolution (150eV at 6keV). The XMS is based on a micro-calorimeter array operating at its transition temperature of ~100mK and provides Definition Phase.

  12. Incorporating BDI Agents into Human-Agent Decision Making Research

    Science.gov (United States)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  13. Chemical warfare agents.

    Science.gov (United States)

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  14. ESA' s novel gravitational modeling of irregular planetary bodies

    Science.gov (United States)

    Ortega, Guillermo

    A detailed understanding and modeling of the gravitational modeling is required for realistic investigation of the dynamics of orbits close to irregularly shaped bodies. Gravity field modelling up to a certain maximum spherical harmonic degree N involves N2 unkown spherical harmonic coefficients or complex harmonics. The corresponding number of matrix entries reaches till N4 . For missions like CHAMP, GRACE or GOCE, the maximum degree of resolution is 75, 150 and 300 respectively. Therefore, the number of unknowns for a satellite like GOCE will be around 100.000. Since these missions usually fly for a period of time of several years, the number of observations is huge. Hence, gravity field recovery from these missions is a high demanding task. The classical approaches like spherical expansion of the potential lead generally to a high number of coefficients, which reduce the software computational efficiency of the orbit propagation and which have mostly a limited physical meaning. One of the main targets of the activity is the modelling of asteroids, small moons, and cometary bodies. All celestial bodies are irregular by definition. However, the scope of the activity is broad enough as to be able to use the models and the software in quasy-regular bodies as well. Therefore the models and tools could be used for bodies such as the Moon, Mars, Venus, Deimos, Europa, Eros, Mathilda, and Churyumov-Gerasimenko, etc., being these applications relevant for scientific (Rosetta, Bepi Colombo), exploration (Exo-Mars), NEO mitigation (Don Quijote) and Earth observation (GOCE) missions of ESA.

  15. Surface elevation changes of the greenland ice sheet - results from ESA'S ice sheet CCI

    DEFF Research Database (Denmark)

    Fredenslund Levinsen, Joanna; Khvorostovky, Kirill; Meister, Rakia

    2013-01-01

    In order to ensure long-term climate data records for the Greenland Ice Sheet (GIS), ESA have launched the Climate Change Initiative (CCI). This work presents the preliminary steps towards the Ice Sheet CCI's surface elevation change (SEC) derivation using radar altimeter data. In order to find...... the most optimal method, a Round Robin exercise was conducted in which the scientific community was asked to provide their best SEC estimate over the Jakobshavn Isbr drainage basin. The participants used both repeat-track (RT), overlapping footprints, and the cross-over (XO) methods, and both ICESat laser...... and Envisat radar altimeter data were used. Based on this and feedback sheets describing their methods we found that a combination of the RT and XO techniques yielded the best results. In the following, the obtained results will be presented and discussed....

  16. Logics for Intelligent Agents and Multi-Agent Systems

    NARCIS (Netherlands)

    Meyer, John-Jules Charles

    2014-01-01

    This chapter presents the history of the application of logic in a quite popular paradigm in contemporary computer science and artificial intelligence, viz. the area of intelligent agents and multi-agent systems. In particular we discuss the logics that have been used to specify single agents, the

  17. Plasma kinetics issues in an ESA study for a plasma laboratory in space

    International Nuclear Information System (INIS)

    Annaratone, B M; Biancalani, A; Ceccherini, F; Pegoraro, F; Bruno, D; Capitelli, M; Pascale, O de; Longo, S; Daly, E; Hilgers, A; Diomede, P; D'Ammando, G; Marcuccio, S; Mendonca, J T; Nagnibeda, V; Sanmartin, J R

    2008-01-01

    A study supported by the European Space Agency (ESA), in the context of its General Studies Programme, performed an investigation of the possible use of space for studies in pure and applied plasma physics, in areas not traditionally covered by 'space plasma physics'. A set of experiments have been identified that can potentially provide access to new phenomena and to allow advances in several fields of plasma science. These experiments concern phenomena on a spatial scale (10 1 -10 4 m) intermediate between what is achievable on the ground and the usual solar system plasma observations. Detailed feasibility studies have been performed for three experiments: active magnetic experiments, large-scale discharges and long tether-plasma interactions. The perspectives opened by these experiments are discussed for magnetic reconnection, instabilities, MHD turbulence, atomic excited states kinetics, weakly ionized plasmas, plasma diagnostics, artificial auroras and atmospheric studies. The discussion is also supported by results of numerical simulations and estimates

  18. Integrating adaptive behaviour in large-scale flood risk assessments: an Agent-Based Modelling approach

    Science.gov (United States)

    Haer, Toon; Aerts, Jeroen

    2015-04-01

    Between 1998 and 2009, Europe suffered over 213 major damaging floods, causing 1126 deaths, displacing around half a million people. In this period, floods caused at least 52 billion euro in insured economic losses making floods the most costly natural hazard faced in Europe. In many low-lying areas, the main strategy to cope with floods is to reduce the risk of the hazard through flood defence structures, like dikes and levees. However, it is suggested that part of the responsibility for flood protection needs to shift to households and businesses in areas at risk, and that governments and insurers can effectively stimulate the implementation of individual protective measures. However, adaptive behaviour towards flood risk reduction and the interaction between the government, insurers, and individuals has hardly been studied in large-scale flood risk assessments. In this study, an European Agent-Based Model is developed including agent representatives for the administrative stakeholders of European Member states, insurers and reinsurers markets, and individuals following complex behaviour models. The Agent-Based Modelling approach allows for an in-depth analysis of the interaction between heterogeneous autonomous agents and the resulting (non-)adaptive behaviour. Existing flood damage models are part of the European Agent-Based Model to allow for a dynamic response of both the agents and the environment to changing flood risk and protective efforts. By following an Agent-Based Modelling approach this study is a first contribution to overcome the limitations of traditional large-scale flood risk models in which the influence of individual adaptive behaviour towards flood risk reduction is often lacking.

  19. A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

    Science.gov (United States)

    Dong, Xiaoxi; Liu, Tianjun; Wang, Han; Yang, Jichun; Chen, Zhuying; Hu, Yong; Li, Yingxin

    2017-07-01

    This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order

  20. Stimulation of JNK Phosphorylation by the PTTH in Prothoracic Glands of the Silkworm, Bombyx mori

    Directory of Open Access Journals (Sweden)

    Shi-Hong Gu

    2018-02-01

    Full Text Available In this study, phosphorylation of c-Jun N-terminal kinase (JNK by the prothoracicotropic hormone (PTTH was investigated in prothoracic glands (PGs of the silkworm, Bombyx mori. Results showed that JNK phosphorylation was stimulated by the PTTH in time- and dose-dependent manners. In vitro activation of JNK phosphorylation in PGs by the PTTH was also confirmed in an in vivo experiment, in which a PTTH injection greatly increased JNK phosphorylation in PGs of day-6 last instar larvae. JNK phosphorylation caused by PTTH stimulation was greatly inhibited by U73122, a potent and specific inhibitor of phospholipase C (PLC and an increase in JNK phosphorylation was also detected when PGs were treated with agents (either A23187 or thapsigargin that directly elevated the intracellular Ca2+ concentration, thereby indicating involvement of PLC and Ca2+. Pretreatment with an inhibitor (U0126 of mitogen-activated protein kinase (MAPK/extracellular signal-regulated kinase (ERK kinase (MEK and an inhibitor (LY294002 of phosphoinositide 3-kinase (PI3K failed to significantly inhibit PTTH-stimulated JNK phosphorylation, indicating that ERK and PI3K were not related to JNK. We further investigated the effect of modulation of the redox state on JNK phosphorylation. In the presence of either an antioxidant (N-acetylcysteine, NAC or diphenylene iodonium (DPI, PTTH-stimulated JNK phosphorylation was blocked. The JNK kinase inhibitor, SP600125, markedly inhibited PTTH-stimulated JNK phosphorylation and ecdysteroid synthesis. The kinase assay of JNK in PGs confirmed its stimulation by PTTH and inhibition by SP600125. Moreover, PTTH treatment did not affect JNK or Jun mRNA expressions. Based on these findings, we concluded that PTTH stimulates JNK phosphorylation in Ca2+- and PLC-dependent manners and that the redox-regulated JNK signaling pathway is involved in PTTH-stimulated ecdysteroid synthesis in B. mori PGs.

  1. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  2. [Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

    Science.gov (United States)

    Ruszczak, Z; Ciborska, L; Kaszuba, A

    1988-12-01

    The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

  3. Profile of peginesatide and its potential for the treatment of anemia in adults with chronic kidney disease who are on dialysis.

    Science.gov (United States)

    Mikhail, Ashraf

    2012-01-01

    Peginesatide is a synthetic, dimeric peptide that is covalently linked to polyethylene glycol (PEG). The amino acid sequence of peginesatide is unrelated to that of erythropoietin (EPO) and is not immunologically cross-reactive with EPO. Peginesatide binds to and activates the human EPO receptor, stimulating the proliferation and differentiation of human red cell precursors in vitro in a manner similar to other EPO-stimulating agents (ESAs). In Phase II and III studies in dialysis and predialysis patients, peginesatide administered once monthly was as effective as epoetin alfa given thrice weekly (dialysis patients) or darbepoetin given once weekly (nondialysis patients), in correcting anemia of chronic kidney disease as well as maintaining hemoglobin within the desired target range. In the dialysis population, the reported side-effect profile of peginesatide was comparable to that known with other marketed ESAs. In the nondialysis studies, compared with those treated with darbepoetin, patients treated with peginesatide experienced a higher adverse-effect profile. Peginesatide is likely to be licensed for treatment of renal anemia in dialysis patients and not in nondialysis patients. Despite this limitation, peginesatide is likely to prove valuable in treating dialysis patients because of its infrequent mode of administration, thereby allowing for a reduced number of injections, with associated better compliance, reduced cold storage requirement, and improved stock accountability. PEGylated therapeutic proteins can elicit immunological response to the PEG moiety of the therapeutic complex. Only long-term experience and post-marketing surveillance will address whether this immunological response will have any impact on the clinical efficacy or safety of peginesatide in clinical practice.

  4. Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity

    NARCIS (Netherlands)

    Bazuine, Merlijn; Ouwens, D. Margriet; Gomes de Mesquita, Daan S.; Maassen, J. Antonie

    2003-01-01

    The protein-modifying agent arsenite stimulates glucose uptake in 3T3-L1 adipocytes. In the current study we have analysed the signalling pathways that contribute to this response. By subcellular fractionation we observed that arsenite, like insulin, induces translocation of the GLUT1 and GLUT4

  5. Risco de infecção tuberculosa em agentes comunitários de saúde Riesgo de infección tuberculosa en agentes comunitarios de salud Risk of tuberculosis infection among community health agents

    Directory of Open Access Journals (Sweden)

    Tiago Ricardo Moreira

    2010-04-01

    ínica, utilizando la tuberculina PPD RT23. Fue calculado el riesgo relativo e intervalo con 95% de confianza y fue evaluada la correlación entre el viraje tuberculínico y la historia ocupacional de los agentes por medio del coeficiente de correlación de Pearson. RESULTADOS: La incidencia del viraje fue de 41,7% en el grupo de los expuestos y 13,5% en el grupo de los no expuestos. El riesgo anual de infección fue de 52,8% en el grupo de los expuestos y de 14,4% en el grupo de los no expuestos (p=0,013. Se observó asociación entre viraje tuberculínico y exposición a paciente con tuberculosis (RR = 3,08; IC 95%: 1,201;7,914. CONCLUSIONES: Los agentes que acompañaron pacientes con tuberculosis en sus rutinas de servicio presentaron riesgo de infección mayor que aquellos que no acompañaron pacientes con esa enfermedad. La implementación de medidas administrativas de bioseguridad de rutina, entre ellas la prueba tuberculínica, deben ser priorizadas, considerando el alto riesgo de infección tuberculosa entre los agentes comunitarios de salud.OBJECTIVE: To estimate the risk of tuberculosis infection among community health agents involved in disease control. METHODS: A prospective cohort was followed up from April 2007 to May 2008 in the municipality of Cachoeiro de Itapemirim, Southeastern Brazil. The cohort was composed of 61 community agents, divided between unexposed individuals (n = 37 and exposed individuals (who were following up tuberculosis patients; n = 24. Over the 12-month follow-up, the tuberculin test was performed, using the tuberculin PPD RT23. The relative risk and 95% confidence interval were calculated, and the correlation between tuberculin response and the agents' occupational history was evaluated by means of Pearson's correlation. RESULTS: The incidence of the response was 41.7% in the exposed group and 13.5% in the unexposed group. The annual risk of infection was 52.8% in the exposed group and 14.4% in the unexposed group (p = 0.013. An association

  6. Cognitive stimulation in healthy older adults: a cognitive stimulation program using leisure activities compared to a conventional cognitive stimulation program.

    Science.gov (United States)

    Grimaud, Élisabeth; Taconnat, Laurence; Clarys, David

    2017-06-01

    The aim of this study was to compare two methods of cognitive stimulation for the cognitive functions. The first method used an usual approach, the second used leisure activities in order to assess their benefits on cognitive functions (speed of processing; working memory capacity and executive functions) and psychoaffective measures (memory span and self esteem). 67 participants over 60 years old took part in the experiment. They were divided into three groups: 1 group followed a program of conventional cognitive stimulation, 1 group a program of cognitive stimulation using leisure activities and 1 control group. The different measures have been evaluated before and after the training program. Results show that the cognitive stimulation program using leisure activities is as effective on memory span, updating and memory self-perception as the program using conventional cognitive stimulation, and more effective on self-esteem than the conventional program. There is no difference between the two stimulated groups and the control group on speed of processing. Neither of the two cognitive stimulation programs provides a benefit over shifting and inhibition. These results indicate that it seems to be possible to enhance working memory and to observe far transfer benefits over self-perception (self-esteem and memory self-perception) when using leisure activities as a tool for cognitive stimulation.

  7. Role of Mesenchymal Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases

    Science.gov (United States)

    2017-07-01

    Clinical Metastases PRINCIPAL INVESTIGATOR: Jeffrey Green CONTRACTING ORGANIZATION: The Geneva Foundation Tacoma, WA 98402 REPORT DATE: July 2017 TYPE...2016 - 14 June 2017 4. TITLE AND SUBTITLE Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical ...and/or select agents. Nothing to report. 6. PRODUCTS: • publications, conference papers, and presentations ; Jennifer Zhu submitted an abstract and will

  8. Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study.

    Science.gov (United States)

    Terraneo, Alberto; Leggio, Lorenzo; Saladini, Marina; Ermani, Mario; Bonci, Antonello; Gallimberti, Luigi

    2016-01-01

    Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Trial name: Repetitive transcranial magnetic stimulation (rTMS) in cocaine abusers, URL:〈http://www.isrctn.com/ISRCTN15823943?q=&filters=&sort=&offset=8&totalResults=13530&page=1&pageSize=10&searchType=basic-search〉, ISRCTN15823943. Published by Elsevier B.V.

  9. Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

    Directory of Open Access Journals (Sweden)

    Michal Hofer

    2014-04-01

    Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

  10. Solar system science with ESA Euclid

    Science.gov (United States)

    Carry, B.

    2018-01-01

    Context. The ESA Euclid mission has been designed to map the geometry of the dark Universe. Scheduled for launch in 2020, it will conduct a six-year visible and near-infrared imaging and spectroscopic survey over 15 000 deg2 down to VAB 24.5. Although the survey will avoid ecliptic latitudes below 15°, the survey pattern in repeated sequences of four broadband filters seems well-adapted to detect and characterize solar system objects (SSOs). Aims: We aim at evaluating the capability of Euclid of discovering SSOs and of measuring their position, apparent magnitude, and spectral energy distribution. We also investigate how the SSO orbits, morphology (activity and multiplicity), physical properties (rotation period, spin orientation, and 3D shape), and surface composition can be determined based on these measurements. Methods: We used the current census of SSOs to extrapolate the total amount of SSOs that will be detectable by Euclid, that is, objects within the survey area and brighter than the limiting magnitude. For each different population of SSO, from neighboring near-Earth asteroids to distant Kuiper-belt objects (KBOs) and including comets, we compared the expected Euclid astrometry, photometry, and spectroscopy with the SSO properties to estimate how Euclid will constrain the SSOs dynamical, physical, and compositional properties. Results: With the current survey design, about 150 000 SSOs, mainly from the asteroid main-belt, should be observable by Euclid. These objects will all have high inclination, which is a difference to many SSO surveys that focus on the ecliptic plane. Euclid may be able to discover several 104 SSOs, in particular, distant KBOs at high declination. The Euclid observations will consist of a suite of four sequences of four measurements and will refine the spectral classification of SSOs by extending the spectral coverage provided by Gaia and the LSST, for instance, to 2 microns. Combined with sparse photometry such as measured by Gaia

  11. Health and taste related compounds in strawberries under various irrigation regimes and bio-stimulant application.

    Science.gov (United States)

    Kapur, Burcak; Sarıdaş, Mehmet Ali; Çeliktopuz, Eser; Kafkas, Ebru; Paydaş Kargı, Sevgi

    2018-10-15

    Strawberry has a unique status within the fruit species in terms of health and taste related compounds. This experimental study concerned the application of a bio-stimulant at various drip irrigation levels (IR125, IR100, IR75 and IR50). The effects of the bio-stimulant (seaweed extract) on the eating quality, i.e., the taste-related (TSS, fructose, glucose, sucrose and citric, malic, l-ascorbic acid), and health-related (antioxidant activity, total phenol, myricetin and quercetin) compounds were studied in two strawberry cultivars. The 'Rubygem' with its higher sugar and lower acid content has been more preferable than the 'Kabarla' cultivar. The bio-stimulant contributes to taste by improving the TSS, fructose, sucrose and also to health by increasing the quercetin content of the fruit which is associated to the cardiovascular properties and cancer reducing agents. The experiment conducted revealed significant increases only in the TSS contents and antioxidant activity under the IR50 and IR75 deficit irrigation treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.

    Science.gov (United States)

    Shrestha, Aarajana; Jin Oh, Hye; Kim, Mi Jin; Pun, Nirmala Tilija; Magar, Til Bahadur Thapa; Bist, Ganesh; Choi, Hongseok; Park, Pil-Hoon; Lee, Eung-Seok

    2017-06-16

    As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Mechanism of orientation of stimulating currents in magnetic brain stimulation (abstract)

    Science.gov (United States)

    Ueno, S.; Matsuda, T.

    1991-04-01

    We made a functional map of the human motor cortex related to the hand and foot areas by stimulating the human brain with a focused magnetic pulse. We observed that each functional area in the cortex has an optimum direction for which stimulating currents can produce neural excitation. The present report focuses on the mechanism which is responsible for producing this anisotropic response to brain stimulation. We first obtained a functional map of the brain related to the left ADM (abductor digiti minimi muscles). When the stimulating currents were aligned in the direction from the left to the right hemisphere, clear EMG (electromyographic) responses were obtained only from the left ADM to magnetic stimulation of both hemisphere. When the stimulating currents were aligned in the direction from the right to the left hemisphere, clear EMG signals were obtained only from the right ADM to magnetic stimulation of both hemisphere. The functional maps of the brain were sensitive to changes in the direction of the stimulating currents. To explain the phenomena obtained in the experiments, we developed a model of neural excitation elicited by magnetic stimulation. When eddy currents which are induced by pulsed magnetic fields flow in the direction from soma to the distal part of neural fiber, depolarized area in the distal part are excited, and the membrane excitation propagates along the nerve fiber. In contrast, when the induced currents flow in the direction from the distal part to soma, hyperpolarized parts block or inhibit neural excitation even if the depolarized parts near the soma can be excited. The model explains our observation that the orientation of the induced current vectors reflect both the functional and anatomical organization of the neural fibers in the brain.

  14. A Heliospheric Weather Expert Service Centre for ESA's Space Situational Awareness Space Weather Activities

    Science.gov (United States)

    Barnes, D.; Perry, C. H.

    2017-12-01

    The Heliospheric Weather Expert Service Centre (H-ESC) is one of five thematic virtual centres that are currently being developed as part of ESA's Space Situational Awareness pre-operational Space Weather service. In this presentation we introduce the current products and service that the H-ESC is providing. The immediate and downstream user groups that the centre is aiming to support are discussed. A description is provided on how the H-ESC is largely built on adoption and tailoring of federated products from expert groups around Europe and how these can be used to add value to the overall system. Having only recently been established the H-ESC is continuing to address gaps in its capabilities. Some of the priorities for products, their assessment, validation and integration into the system are discussed together with plans for bespoke development activities tailored to specific end-user group needs.

  15. http://www.esa.int/esaSC/Pr_11_2004_s_en.html

    Science.gov (United States)

    2004-06-01

    surface of the moon and, most importantly, the presence of layers of dark material at the top of crater walls. "The imaging team is in hot debate at the moment on the interpretations of our findings," said Dr Carolyn Porco, Cassini imaging team leader at the Space Science Institute in Boulder, USA. "Based on our images, some of us are leaning towards the view that has been promoted recently, that Phoebe is probably ice-rich and may be an object originating in the outer solar system, more related to comets and Kuiper Belt objects than to asteroids." The high-resolution images of Phoebe show a world of dramatic landforms, with landslides and linear structures such as grooves, ridges and chains of pits. Craters are ubiquitous, with many smaller than one kilometre. "This means, besides the big ones, lots of projectiles smaller than 100 metres must have hit Phoebe," said Prof. Gerhard Neukum, Freie Universitaet Berlin, Germany, and a member of the imaging team. Whether these projectiles came from outside or within the Saturn system is debatable. There is a suspicion that Phoebe, the largest of Saturn's outer moons, might be parent to the other, much smaller retrograde outer moons that orbit Saturn. They could have resulted from the impact ejecta that formed the many craters on Phoebe. Besides these stunning images, the instruments on board Cassini collected a wealth of other data, which will allow scientists to study the surface structures, determine the mass and composition of Phoebe and create a global map of it. "If these additional data confirm that Phoebe is mostly ice, covered by layers of dust, this may well mean that we are looking at a 'leftover' from the formation of the Solar System about 4600 million years ago," said Dr Jean-Pierre Lebreton, ESA Huygens Project Scientist. Phoebe might indeed be an icy wanderer from the distant outer reaches of the Solar System, which, like a comet, was dislodged from the Kuiper Belt and captured by Saturn when the planet was

  16. Validation and inter-comparison of surface elevation changes derived from altimetry over the Jakobshavn Isbræ drainage basin, Greenland – Round Robin results from ESA's Ice_Sheets_CCI (ID #EGU2013-6007)

    DEFF Research Database (Denmark)

    Fredenslund Levinsen, Joanna; Khvorostovsky, Kirill; Ticconi, Francesca

    elevation changes (SEC), surface velocities, calving front locations, and grounding line locations. This work focuses on SEC, and the goal is to develop the best routine for estimating this by means of radar altimetry. In order to find the most optimal approach we have completed a Round Robin experiment (RR......In order to ensure long-term climate records, ESA has launched the Climate Change Initiative (ESA CCI), which puts focus on 13 different Essential Climate Variables, one of them being Ice Sheets. In this program, four selected key parameters will be determined for the Greenland Ice Sheet: Surface...

  17. Contrast agents for cardiac angiography: effects of a nonionic agent vs. a standard ionic agent

    International Nuclear Information System (INIS)

    Bettmann, M.A.; Bourdillon, P.D.; Barry, W.H.; Brush, K.A.; Levin, D.C.

    1984-01-01

    The effects on cardiac hemodynamics and of a standard contrast agent, sodium methylglucamine diatrizoate [Renografin 76] were compared with the effects of a new nonionic agent (iohexol) in a double-blind study in 51 patietns undergoing coronary angiography and left ventriculography. No significant alteration in measured blood parameters occurred with either contrast agent. Hemodynamic changes occurred with both, but were significantly greater with the standard renografin than with the low-osmolality, nonionic iohexol. After left ventriculography, heart rate increased and peripheral arterial pressure fell with both agents, but less with iohexol. It is concluded that iohexol causes less alteration in cardiac function than does the agent currently most widely used. Nonionic contrast material is likely to improve the safety of coronary angiography, particularly in those patients at greatest risk

  18. Methodological novelties applied to the anthropology of food: agent-based models and social networks analysis

    Directory of Open Access Journals (Sweden)

    Diego Díaz Córdova

    2016-12-01

    Full Text Available En este artículo presentamos dos modalidades metodológicas que aún no han sido muy utilizadas en la antropología alimentaria. Por un lado, nos referimos al análisis de redes sociales y, por otro, a los modelos basados en agentes. Para ilustrar los métodos, tomaremos dos casos de materiales clásicos de la antropología alimentaria. Para el primero usaremos los platos de comida de un relevamiento hecho en la Quebrada de Humahuaca (provincia de Jujuy, Argentina y, para el segundo, utilizaremos algunos elementos del concepto aplicado por Aguirre de “estrategias domésticas de consumo”. La idea subyacente es que, dado que la alimentación se reconoce como un “hecho social total” y, por lo tanto, como un fenómeno complejo, el abordaje metodológico debe seguir necesariamente esa misma característica. Mientras más métodos utilicemos (con el grado de rigor adecuado mejor estaremos preparados para comprender la dinámica alimentaria en el medio social.

  19. An afocal telescope configuration for the ESA ARIEL mission

    Science.gov (United States)

    Da Deppo, Vania; Focardi, Mauro; Middleton, Kevin; Morgante, Gianluca; Pascale, Enzo; Grella, Samuele; Pace, Emanuele; Claudi, Riccardo; Amiaux, Jérôme; Colomé Ferrer, Josep; Hunt, Thomas; Rataj, Miroslaw; Sierra-Roig, Carles; Ficai Veltroni, Iacopo; Eccleston, Paul; Micela, Giuseppina; Tinetti, Giovanna

    2017-12-01

    Atmospheric Remote-Sensing Infrared Exoplanet Large Survey (ARIEL) is a candidate as an M4 ESA mission to launch in 2026. During its 3.5 years of scientific operations, ARIEL will observe spectroscopically in the infrared (IR) a large population of known transiting planets in the neighbourhood of the solar system. ARIEL aims to give a breakthrough in the observation of exoplanet atmospheres and understanding of the physics and chemistry of these far-away worlds. ARIEL is based on a 1 m class telescope feeding a collimated beam into two separate instrument modules: a spectrometer module covering the waveband between 1.95 and 7.8 μm and a combined fine guidance system/visible photometer/NIR spectrometer. The telescope configuration is a classic Cassegrain layout used with an eccentric pupil and coupled to a tertiary off-axis paraboloidal mirror. To constrain the thermo-mechanically induced optical aberrations, the primary mirror (M1) temperature will be monitored and finely tuned using an active thermal control system based on thermistors and heaters. They will be switched on and off to maintain the M1 temperature within ± 1 K by the telescope control unit (TCU). The TCU is a payload electronics subsystem also responsible for the thermal control of the spectrometer module detectors as well as the secondary mirror mechanism and IR calibration source management. The TCU, being a slave subsystem of the instrument control unit, will collect the housekeeping data from the monitored subsystems and will forward them to the master unit. The latter will run the application software, devoted to the main spectrometer management and to the scientific data on-board processing.

  20. Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

    International Nuclear Information System (INIS)

    Hohmann, J.; Albrecht, T.; Hoffmann, C.W.; Wolf, K.-J.

    2003-01-01

    Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet