WorldWideScience

Sample records for agents stimulating erythropoiesis

  1. Pharmacovigilance in practice: erythropoiesis-stimulating agents

    International Nuclear Information System (INIS)

    Pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or other problems related to medical products after they have been licensed for marketing. The purpose of PV is to advance the safe use of marketed medical products. Regulatory agencies and license holders collaborate to collect data reported by health care providers, patients, and the public as well as data from systematic reviews, meta-analyses, and individual clinical and nonclinical studies. They validate and analyze the data to determine whether safety signals exist, and if warranted, develop an action plan to mitigate the identified risk. Erythropoiesis-stimulating agents (ESAs) provide an example of how PV is applied in reality. Among other approved indications, ESAs may be used to treat anemia in patients with chemotherapy-induced anemia. ESAs increase hemoglobin levels and reduce the need for transfusions; they are also associated with a known increased risk of thromboembolic events. Starting in 2003, emerging data suggested that ESAs might reduce survival. As a result of PV activities by regulatory agencies and license holders, labeling for ESAs addresses these risks. Meta-analyses and individual clinical studies have confirmed that ESAs increase the risk of thromboembolic events, but when used as indicated, ESAs have not been shown to have a significant effect on survival or disease progression. Ongoing safety studies will provide additional data in the coming years to further clarify the risks and benefits of ESAs

  2. 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...

  3. Erythropoiesis-stimulating agents in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2012-04-01

    Full Text Available Anemia is a frequent complication of chronic kidney disease (CKD due to the inability of the kidneys to release sufficient erythropoietin to regulate the production of red blood cells. Administration of erythropoiesis-stimulating agents (ESAs is highly effective in correcting anemia of CKD. The ESAs currently approved in Italy are epoetin alfa, epoetin beta, epoetin theta, darbepoetin alfa, CERA and biosimilars epoetin alfa and epoetin zeta. All the ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues. However, regarding the optimal use of ESAs an issue that remains controversial is the most appropriate dose conversion between epoetin alfa and darbepoetin alfa. In fact clinical experience demonstrates that the dose relationship between epoetin alfa and darbepoetin alfa is non proportional across the dosing spectrum. In this review is presented an update on the latest available evidence in the treatment of anemia in CKD patients, with particular reference to the definition of the correct conversion ratio EPO:DARB.

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

    Science.gov (United States)

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

    2016-02-01

    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.

  5. Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats.

    Science.gov (United States)

    Theurl, Milan; Nairz, Manfred; Schroll, Andrea; Sonnweber, Thomas; Asshoff, Malte; Haschka, David; Seifert, Markus; Willenbacher, Wolfgang; Wilflingseder, Doris; Posch, Wilfried; Murphy, Anthony T; Witcher, Derrick R; Theurl, Igor; Weiss, Günter

    2014-09-01

    Anemia of chronic disease is a multifactorial disorder, resulting mainly from inflammation-driven reticuloendothelial iron retention, impaired erythropoiesis, and reduced biological activity of erythropoietin. Erythropoiesis-stimulating agents have been used for the treatment of anemia of chronic disease, although with varying response rates and potential adverse effects. Serum concentrations of hepcidin, a key regulator of iron homeostasis, are increased in patients with anemia of chronic disease and linked to the pathogenesis of this disease, because hepcidin blocks cellular iron egress, thus limiting availability of iron for erythropoiesis. We tested whether serum hepcidin levels can predict and affect the therapeutic efficacy of erythropoiesis-stimulating agent treatment using a well-established rat model of anemia of chronic disease. We found that high pre-treatment hepcidin levels correlated with an impaired hematologic response to an erythropoiesis-stimulating agent in rats with anemia of chronic disease. Combined treatment with an erythropoiesis-stimulating agent and an inhibitor of hepcidin expression, LDN-193189, significantly reduced serum hepcidin levels, mobilized iron from tissue stores, increased serum iron levels and improved hemoglobin levels more effectively than did the erythropoiesis-stimulating agent or LDN-193189 monotherapy. In parallel, both the erythropoiesis-stimulating agent and erythropoiesis-stimulating agent/LDN-193189 combined reduced the expression of cytokines known to inhibit erythropoiesis. We conclude that serum hepcidin levels can predict the hematologic responsiveness to erythropoiesis-stimulating agent therapy in anemia of chronic disease. Pharmacological inhibition of hepcidin formation improves the erythropoiesis-stimulating agent's therapeutic efficacy, which may favor a reduction of erythropoiesis-stimulating agent dosages, costs and side effects.

  6. Safety and clinical outcome of erythropoiesis-stimulating agents in patients with ST-elevation myocardial infarction : A meta-analysis of individual patient data

    NARCIS (Netherlands)

    Fokkema, Marieke L.; van der Meer, Peter; Rao, Sunil V.; Belonje, Anne M.; Ferrario, Maurizio; Hillege, Hans L.; Katz, Stuart D.; Lipsic, Erik; Ludman, Andrew J.; Ott, Ilka; Prunier, Fabrice; Choi, Dong-Ju; Toba, Ken; van Veldhuisen, Dirk J.; Voors, Adriaan A.

    2014-01-01

    Background Erythropoiesis-stimulating agents (ESAs) have been investigated in small studies in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Erythropoiesis-stimulating agents did not show a clear effect on left ventricular funct

  7. Intersecting Guidelines: Administering Erythropoiesis-Stimulating Agents to Chronic Kidney Disease Patients with Cancer

    Science.gov (United States)

    Bennett, Charles L.; Becker, Pamela S.; Kraut, Eric H.; Samaras, Athena T.; West, Dennis P.

    2009-01-01

    There has been a dramatic sea change in the use of erythropoiesis-stimulating agents (ESAs) for anemic persons with chronic kidney disease (CKD) or cancer patients undergoing chemotherapy. An important area that has not been addressed previously is a CKD patient who also has a malignancy. Clinical guidelines exist that outline recommended treatments for each disease, but the intersection of the two disease processes presents difficult decisions for patients and physicians. Herein, we review the background underlying recent revisions in clinical alerts and guidelines for ESAs, and provide guidance for treating anemia among CKD patients who are receiving no therapy, chemotherapy with curative intent, or chemotherapy with palliative intent. The guiding principle is that comprehensive assessment of risks and benefits in the relevant clinical setting is imperative. PMID:19175532

  8. Detection of erythropoiesis-stimulating agents in human anti-doping control: past, present and future.

    Science.gov (United States)

    Leuenberger, Nicolas; Reichel, Christian; Lasne, Françoise

    2012-07-01

    Stimulation of erythropoiesis is one of the most efficient ways of doping. This type of doping is advantageous for aerobic physical exercise and of particular interest to endurance athletes. Erythropoiesis, which takes place in bone marrow, is under the control of EPO, a hormone secreted primarily by the kidneys when the arterial oxygen tension decreases. In certain pathological disorders, such as chronic renal failure, the production of EPO is insufficient and results in anemia. The pharmaceutical industry has, thus, been very interested in developing drugs that stimulate erythropoiesis. With this aim, various strategies have been, and continue to be, envisaged, giving rise to an expanding range of drugs that are good candidates for doping. Anti-doping control has had to deal with this situation by developing appropriate methods for their detection. This article presents an overview of both the drugs and the corresponding methods of detection, and thus follows a roughly chronological order. PMID:22831473

  9. Associations among Erythroferrone and Biomarkers of Erythropoiesis and Iron Metabolism, and Treatment with Long-Term Erythropoiesis-Stimulating Agents in Patients on Hemodialysis.

    Directory of Open Access Journals (Sweden)

    Hirokazu Honda

    Full Text Available We aimed to identify associations between erythroferrone (ERFE, a regulator of hepcidin 25, and biomarkers of erythropoiesis and iron metabolism. We also aimed to determine the effects of erythropoiesis-stimulating agents (ESA, continuous erythropoietin receptor activator (CERA and darbepoetin-α (DA on ERFE production in patients on hemodialysis (HD.Blood samples were obtained from 59 patients before HD sessions on day 0 (baseline. Twenty patients who were injected with either CERA (N = 10 or DA (N = 10 at the end of the dialysis week (day 0, who had ferritin ≥ 100 ng/mL and/or transferrin saturation ≥ 20%, and hemoglobin > 9 g/dL were selected from among the 59 patients. Blood was sampled serially before HD sessions on days 3, 5, 7 from patients on DA and on the same days plus day 14 from those on CERA.Levels of ERFE correlated inversely with those of hepcidin 25 and ferritin, and positively with those of soluble transferrin receptor. The hepcidin 25: ERFE ratio and hepcidin 25 levels positively correlated with ferritin levels. Levels of ERFE significantly increased from day 3 of treatment with DA and CERA and decreased by days 7 and 14, respectively. Erythropoiesis-stimulating agents concomitantly decreased levels of hepcidin 25 as those of ERFE increased.We identified a novel association between ESA and ERFE in patients on HD. Both DA and CERA increased levels of ERFE that regulated hepcidin 25 and led to iron mobilization from body stores during erythropoiesis.

  10. Managing chemotherapy induced anemia with darbepoetin alfa and other erythropoiesis stimulating agents: a nurse's perspective

    Directory of Open Access Journals (Sweden)

    Derbyshire L

    2013-11-01

    Full Text Available Loraine Derbyshire, Colin W Thain School of Health, University of Central Lancashire, Preston, United Kingdom Abstract: Chemotherapy induced anemia (CIA is a frequent complication of anticancer treatment, but often remains untreated. The main presenting symptom of CIA is fatigue, and this can have profound implications upon chemotherapy treatment compliance and patients' quality of life (QoL. Nevertheless, a tendency has been seen in both patients and physicians to underestimate the consequences of fatigue. As nurses are taking on greater responsibilities for identifying, monitoring, and in some cases even treating CIA, it is important that they have a clear understanding of the treatment options at their disposal. Erythropoiesis stimulating agents (ESAs have been available as a tool for the treatment of CIA for many years. However, the vast majority of literature on this topic has been targeted towards physicians. Hence, the purpose of this review is to summarize the key ESA studies, with an emphasis on material that is of interest to the nursing community. Herein we present a brief chronological review of the development of ESAs to illustrate how the currently available treatment options for anemia arose. For conciseness, darbepoetin alfa (DA has been used as a model to represent all ESAs; however, important findings from studies of other ESAs have also been included for completeness. We also discuss the management of CIA, based on the available literature and our experience of routine clinical practice in the UK. In conclusion, CIA is important in the context of maintaining QoL in patients undergoing chemotherapy and its effective management needs to be considered as part of their holistic care. Available studies show that ESA treatment can decrease fatigue levels and reduce the need for transfusions. ESAs, such as DA, may therefore be an important treatment option for patients with CIA. DA is well tolerated when used according to current

  11. Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

    Science.gov (United States)

    McVicar, Carmel M.; Colhoun, Liza M.; Abrahams, Jodie L.; Kitson, Claire L.; Hamilton, Ross; Medina, Reinhold J.; Durga, Dash; Gardiner, Tom A.; Rudd, Pauline M.; Stitt, Alan W.

    2010-01-01

    Background Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. Methodology/Principal Findings The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1–20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFα and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001). Conclusions This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs. PMID:20686695

  12. Responsiveness to erythropoiesis-stimulating agents in chronic kidney disease: does geography matter?

    Science.gov (United States)

    De Nicola, Luca; Locatelli, Francesco; Conte, Giuseppe; Minutolo, Roberto

    2014-02-01

    Management of renal anemia in the large and at-risk population of non-dialysis chronic kidney disease (CKD) patients is a critical issue. In particular, definition of the optimal hemoglobin (Hb) target for therapy is controversial but highly warranted by physicians and patients worldwide. Recently, international clinical practice guidelines have recommended delayed initiation of erythropoiesis-stimulating agents (ESA) and lower Hb target levels during maintenance therapy. However, geographical differences in terms of ESA dose needed to achieve a given Hb value can be evidenced, with US patients showing higher prevalence of ESA resistance. On the other hand, non-US patients are often maintained in a higher Hb range by means of low ESA doses. This critical point has never been addressed. Nevertheless, outside of the US, translating the restrictive recommendations of new guidelines, which are essentially based on trials in US patients, can lead to negative effects, such as an increased need for a blood transfusion, and worsening of quality of life. In this article we provide a reappraisal of current recommendations on anemia management in non-dialysis CKD in light of the geographical differences in individual responsiveness to ESA.

  13. Costs of managing anemia with erythropoiesis-stimulating agents during hemodialysis: a time and motion study.

    Science.gov (United States)

    Schiller, Brigitte; Doss, Sheila; DE Cock, Erwin; Del Aguila, Michael A; Nissenson, Allen R

    2008-10-01

    Use of erythropoiesis-stimulating agents (ESAs) presents a significant time and cost burden in the management of anemia of chronic kidney disease (CKD). We conducted a prospective, observational, activity-based costing study to estimate the health care personnel time and resulting direct medical costs associated with administering epoetin 3 times weekly to patients with end-stage renal disease on dialysis. The study was conducted at 5 US hemodialysis centers. The personnel time and costs were derived from time and motion observations. Predicted time and cost savings were modeled for switching patients to once-monthly ESA therapy. Patients also completed a survey questionnaire to assess their level of CKD knowledge and information needs. Total per-patient-per-year (PPPY) time expended on anemia management with epoetin averaged 608 minutes (range 512-915 minutes), with an average PPPY cost of $548 (range $342-$651). Use of a once-monthly ESA, compared with epoetin, could decrease average PPPY time expenditure by 79% (127 minutes [range 96-173 minutes]) and reduce PPPY costs by 81% ($104 [range $79-$136]). The patient questionnaire reported insufficient education on CKD. Use of a once-monthly ESA to correct anemia in dialysis patients may provide substantial time, resource, and cost savings compared with current treatment practices. PMID:19090867

  14. Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy.

    Directory of Open Access Journals (Sweden)

    Carmel M McVicar

    Full Text Available BACKGROUND: Erythropoiesis stimulating agents (ESAs are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDINGS: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml. ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal neovascularisation in comparison to controls (p<0.05. Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05. This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05. Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001. CONCLUSIONS: This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs.

  15. Effects of Funding Policy Changes and Health Warnings on the Use of Erythropoiesis-Stimulating Agents

    Science.gov (United States)

    Weir, Matthew A.; Gomes, Tara; Winquist, Eric; Juurlink, David N.; Cuerden, Meaghan S.; Mamdani, Muhammad

    2012-01-01

    Purpose: To characterize the effects of formulary changes and governmental safety warnings on use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Patients and Methods: We conducted a cross-sectional time-series analysis using health administrative data from Ontario, Canada. From January 1997 to December 2009 we identified all ESA initiations among patients diagnosed with cancer. We explored the effects of two formulary changes that progressively liberalized coverage for ESAs, first by rescinding the requirement for blood transfusion in 2003 and then by removing all restrictions in 2007. We also explored the effect of US Food and Drug Administration and Health Canada warnings issued in the second quarter of 2007. To assess regional variability in ESA use, we determined prescription rates for each of Ontario's 14 regional cancer centers. Results: After the first formulary change, the ESA initiation rate increased to 1.66 new users per 1,000 patients with cancer, 374% more than predicted (P < .001). After the second formulary change, the initiation rate increased to 3.97 new users per 1,000 patients with cancer, 73% more than predicted (P < .001). After the safety warnings, this rate declined 81% by study end (P < .001). We found significant regional variation in ESA use. Conclusion: Formulary access and safety warnings had significant impacts on the new use of ESA drugs in patients with cancer. This suggests that both are effective means of influencing the use of these drugs. Variable ESA prescription rates across our region may reflect a lack of consensus regarding their utility. PMID:22942813

  16. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease

    Science.gov (United States)

    Seliger, Stephen L.; Zhang, Amy D.; Weir, Matthew R.; Walker, Loreen; Hsu, Van Doren; Parsa, Afshin; Diamantidis, Clarissa; Fink, Jeffrey C.

    2013-01-01

    Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). However, a recent trial in diabetic CKD patients suggested a greater stroke risk associated with full correction of anemia using ESAs. We performed a case-control study examining the association of incident ESA use with acute stroke in CKD patients, using national Veterans Affairs data. Patients with eGFR<60 cc/min/1.73m2 and outpatient hemoglobin (Hb)<12g/dL were included. Acute hospitalized stroke cases (N=2071) were identified using diagnosis codes and matched 1:5 to controls without stroke. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use (N=1026, 8.3%) was associated with 30% greater odds of stroke (odds ratio[OR]=1.30, 95% confidence interval[CI]: 1.06, 1.58). There was significant interaction (p=.015) between ESA use and cancer; ESA use was associated with 85% greater odds of stroke in cancer patients (95% CI: 1.26, 2.65), but not associated with stroke in patients without cancer (OR=1.07, 95% CI: 0.85, 1.35). ESA-treated patients with cancer received a median initial dose 2.5 to 4 times greater than ESA patients without cancer, but pre-ESA Hb and rate of Hb change did not differ between groups. Among a large national sample of anemic CKD patients, ESA treatment is associated with an increased risk of acute stroke, with the greatest effect among patients with cancer. PMID:21389972

  17. Erythropoiesis-stimulating Agents and Anemia in Patients with Non-dialytic Chronic Kidney Disease.

    Science.gov (United States)

    Kim, Sun Moon; Kim, Kyeong Min; Kwon, Soon Kil; Kim, Hye-Young

    2016-01-01

    Anemia is common in patients with advanced chronic kidney disease (CKD). Though erythropoiesis-stimulating agents (ESAs) have been strongly endorsed in guidelines, it is of particular financial interest. Recently, the reimbursement of ESAs in non-dialytic patients was started by the Korean National Health Insurance System. Thus, we investigated the impact of the reimbursement of ESAs on the anemia care in non-dialytic CKD patients. Medical records of patients with advanced CKD (estimated GFR <30 mL/min/1.73 m(2)) were reviewed. Use of ESAs, blood transfusion, and hemoglobin concentrations were analyzed from one year prior to reimbursement to three years following. We used multivariable modified Poisson regression to estimate the utilization prevalence ratio (PRs). A total of 1,791 medical records were analyzed. The proportion of patients receiving ESAs increased from 14.8% before reimbursement to a peak 33.6% in 1 yr after reimbursement; thereafter, ESA use decreased to 22.4% in 3 yr after reimbursement (compared with baseline; PR, 2.19 [95% CI, 1.40-3.42]). In patients with Hb <10 g/dL, the proportion of receiving ESAs increased from 32.1% before reimbursement to 66.7% in 3 yr after reimbursement (compared with baseline; PR, 2.04 [95% CI, 1.25-3.32]). Mean hemoglobin concentrations were 10.06±1.54 g/dL before reimbursement and increased to 10.78±1.51 g/dL in 3 yr after the reimbursement change (P=0.001). However, the requirement of blood transfusion was not changed over time. With the reimbursement of ESAs, the advanced CKD patients were more likely to be treated with ESAs, and the hemoglobin concentrations increased.

  18. The Safety of Erythropoiesis-Stimulating Agents for the Treatment of Anemia Resulting from Chronic Kidney Disease.

    Science.gov (United States)

    Robles, Nicolas Roberto

    2016-06-01

    Chronic kidney disease (CKD) anemia treatment was revolutionized in the late 1980s with the introduction of recombinant human erythropoietin. This and related erythropoiesis-stimulating agents (ESAs) greatly benefited patients by decreasing debilitating symptoms, improving their quality of life, and freeing them from dependence on blood transfusions with their associated complications such as infections, sensitization impeding transplantation, and secondary iron overload. However, even in the initial studies, untoward effects were noted in patients receiving ESAs, including worsening hypertension, seizures, and dialysis access clotting. Later, increased mortality, malignancy progression and even stroke were reported in renal patients. This review focuses on the safety issues of ESAs in CKD patients. PMID:26894799

  19. Erythropoiesis-stimulating agents for the treatment of chemotherapy-induced anemia: comparisons from real-world clinical experience

    Directory of Open Access Journals (Sweden)

    Rodriguez Garzotto A

    2014-04-01

    Full Text Available Analia Rodriguez Garzotto,1 Oliver Heine,2 Matthew Turner,3 Francisco Rebollo Laserna,4 Andreas Lorenz5 1Hospital Universitario 12 de Octubre, Ctra Andalucía, Madrid, Spain; 2Zentralklinikum Suhl, Suhl, 3Sandoz International GmbH, Holzkirchen, Germany; 4Sandoz Farmaceutica SA, Madrid, Spain; 5Frauenarztpraxis, Hildburghausen, GermanyBackground: The purpose of this paper is to report real-world data on the relative effectiveness of a biosimilar erythropoiesis-stimulating agent (ESA; Binocrit®, and other available ESAs for the treatment of chemotherapy-induced anemia.Methods: Data were collected retrospectively from single centers in Spain (n=284 and Germany (n=145. Hemoglobin outcomes, transfusion requirements, and serious drug-related adverse events were assessed for each ESA.Results: Hemoglobin outcomes and transfusion requirements were generally similar in the different ESA treatment groups assessed. No serious drug-related adverse events were recorded in any of the treatment groups.Conclusion: These data confirm the real-world effectiveness and safety of a biosimilar ESA (Binocrit® for the treatment of cancer patients with chemotherapy-induced anemia.Keywords: erythropoiesis-stimulating agents, chemotherapy-induced anemia, biosimilar

  20. Correction of anemia in multiple myeloma patients by erythropoiesis-stimulating agents

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available In this paper analysis of anemia correction efficacy in multiple myeloma patients was shown. Patients (n = 68 treated with epoetin alfa (recombinant erythropoietin (rEPO 150 IU/kg subcutaneously three times per week (no more 20 weeks were included in the study group. Patients who did not receive erythropoiesis-stimulating therapy were included in the control group (n = 31. Patients in both groups received at least 3 courses of chemotherapy and continued to receive anticancer treatment during follow-up. Baseline hemoglobin level was 5.3 g/dl – 10.0 g/dl. The increase in hemoglobin level to normal range (≥ 12.0 g/dl during ≤ 20 weeks was considered as positive therapy response. Positive response rate was higher in patients received epoetin alfa comparing with control group (64.7 % and 25.8 %, respectively; p < 0.05. Transfusion dependence persisted in 6 from 19 study patients who received RBC transfusions along with rEPO therapy (31.6 %, whereas in 5 from 9 control group patients (55.6 %. In epoetin alfa group significant increase in reticulocytes count at 2–3 weeks of therapywas revealed: from 27.3 × 109/l to 64.9 × 109/l (in patients with positive response and from 13.3 × 109/l to 25.1 × 109/l (in patients without response. Changes in the reticulocytes count in the control group were not revealed. Thus in patients with positive response reticulocytes level significantly increased to 3 weeks of therapy compared with negative response patients (37.6 × 109/l versus 11.8 × 109/l, respectively; p < 0,05, it can be used as prognostic factors of rEPO response.

  1. Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients.

    Science.gov (United States)

    Marcelli, Daniele; Bayh, Inga; Merello, José I; Ponce, Pedro; Heaton, Alex; Kircelli, Fatih; Chazot, Charles; Di Benedetto, Attilio; Marelli, Cristina; Ladanyi, Erzsebet; Kroczak, Miroslaw; Stuard, Stefano; Grassmann, Aileen; Scatizzi, Laura; Brand, Katharina; Canaud, Bernard

    2016-07-01

    Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients. PMID:27178833

  2. Hepcidin-25 in chronic hemodialysis patients is related to residual kidney function and not to treatment with erythropoiesis stimulating agents.

    Directory of Open Access Journals (Sweden)

    Neelke C van der Weerd

    Full Text Available Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7 ± 13.9 [mean SD] enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556 were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001, hsCRP (p<0.001 and the presence of diabetes (p = 0.02 and inversely with the estimated glomerular filtration rate (p = 0.01, absolute reticulocyte count (p = 0.02 and soluble transferrin receptor (p<0.001. Men had lower hepcidin-25 levels as compared to women (p = 0.03. Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but

  3. Recent advances and clinical application of erythropoietin and erythropoiesis-stimulating agents.

    Science.gov (United States)

    Tanaka, Tetsuhiro; Nangaku, Masaomi

    2012-05-15

    Erythropoietin (EPO) is an essential glycoprotein that facilitates red blood cell maturation from erythroid progenitors and mediates erythropoiesis. The use of recombinant human EPO (rhEPO) dramatically changed management of anemic patients with chronic kidney disease and improved their quality of life. EPO is mainly produced in the fetal liver and the postnatal kidney, although the molecular determinants for tissue-specific expression are elusive. Meanwhile, recent advances established a role of hypoxia-inducible factors (HIF) in transcriptionally upregulating EPO in hypoxia. Out of three HIF- isoforms, HIF-2 appears to play a central role. Prolyl hydroxylase domain-containing protein (PHD), a key regulator connecting oxygen availability and HIF-α expression, is also involved in hypoxic induction of EPO mRNA and the precise roles of PHD paralogs in erythropoiesis are now beginning to be uncovered. On the other hand, widespread expression of EPO receptors (EPOR) beyond erythroid progenitors led to the discovery of non-hematopoietic, pleiotropic roles of EPO in the brain, the heart and the kidney. The precise signal transduction pathways of pleiotropic EPO remain unclear, but carbamylated EPO, which fails to bind to the canonical EPOR homodimers or transduce the JAK2-STAT5 signaling, conferred organ protection through multimeric receptors composed of EPO-R and the common β subunit (βCR). The clinical benefit of normalization of anemia in pre-dialysis CKD by EPO therapy is controversial and recent large-scale, randomized-controlled trials do not favor normalization of anemia by EPO in improving cardiovascular as well as renal outcomes. The optimal EPO therapy should be determined based on the clinical context of individual patients. PMID:22414872

  4. 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.

  5. 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.

  6. Effects of erythropoiesis-stimulating agents on heart failure patients with anemia: a meta-analysis

    Science.gov (United States)

    Zhang, Pei; Zhang, Yaheng; Yan, Junqiang; Dong, Pingshuan; Wang, Yanyu; Niu, Xiaowei

    2016-01-01

    Introduction Heart failure (HF) is always complicated with anemia and is associated with bad prognosis in this patient population. Several studies have assessed the potential role of erythropoietin-stimulating agent (ESA) in improving cardiac function and reducing the number of hospitalizations in anemic patients with HF. Aim We performed a meta-analysis to assess the potential role of ESA in the treatment of anemic patients with HF. Material and methods A literature and Medline search was performed to identify studies with control groups that examined the efficacy of ESA therapy in patients with HF and anemia. Results A total of 11 studies were included (n = 3044 subjects) in the final analysis. Compared to placebo, ESA therapy was associated with increased hemoglobin levels (1.89 g/dl; 95% CI: 1.64–2.14, p < 0.00001), increased left ventricular ejection fraction (LVEF) to 6.88 (95% CI: 0.49–13.28, p = 0.03), decreased B-type natriuretic protein (–272.20; 95% CI: (–444.52)–(–99.89), p = 0.002), improvement in New York Heart Association functional class to –0.33 mean difference (95% CI: (–0.44)–(–0.23), p < 0.00001), and decreased hospitalization (OR = 0.61, 95% CI: 0.39–0.94, p = 0.02). There was no significant between-group difference in all-cause mortality (OR = 0.78, 95% CI: 0.51–1.21, p = 0.27). Conclusions The treatment of anemia with ESA therapy did not reduce the rate of all-cause mortality among patients with heart failure, but ESA therapy made a potential important contribution to patients’ symptomatic improvement. PMID:27625688

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Erythropoiesis-stimulating agents and other methods to enhance oxygen transport.

    Science.gov (United States)

    Elliott, S

    2008-06-01

    Oxygen is essential for life, and the body has developed an exquisite method to collect oxygen in the lungs and transport it to the tissues. Hb contained within red blood cells (RBCs), is the key oxygen-carrying component in blood, and levels of RBCs are tightly controlled according to demand for oxygen. The availability of oxygen plays a critical role in athletic performance, and agents that enhance oxygen delivery to tissues increase aerobic power. Early methods to increase oxygen delivery included training at altitude, and later, transfusion of packed RBCs. A breakthrough in understanding how RBC formation is controlled included the discovery of erythropoietin (Epo) and cloning of the EPO gene. Cloning of the EPO gene was followed by commercial development of recombinant human Epo (rHuEpo). Legitimate use of this and other agents that affect oxygen delivery is important in the treatment of anaemia (low Hb levels) in patients with chronic kidney disease or in cancer patients with chemotherapy-induced anaemia. However, competitive sports was affected by illicit use of rHuEpo to enhance performance. Testing methods for these agents resulted in a cat-and-mouse game, with testing labs attempting to detect the use of a drug or blood product to improve athletic performance (doping) and certain athletes developing methods to use the agents without being detected. This article examines the current methods to enhance aerobic performance and the methods to detect illicit use. PMID:18362898

  9. Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact.

    Science.gov (United States)

    Kiss, Zoltán; Elliott, Steven; Jedynasty, Kinga; Tesar, Vladimír; Szegedi, János

    2010-04-01

    Cloning of the human erythropoietin (EPO) gene and development of the first recombinant human erythropoietin (rHuEPO) drug were truly breakthroughs. This allowed a deeper understanding of the structure and pharmacology of rHuEpo, which in turn inspired the discovery and development of additional erythropoiesis-stimulating agents (ESAs). In vivo specific activity and serum half-life of rHuEPO are influenced by the amount and structure of the attached carbohydrate. Increased numbers of sialic acids on carbohydrate attached to rHuEPO correlated with a relative increase in in-vivo-specific activity and increased serum half-life. The effect of increasing the number of sialic-acid-containing carbohydrates on in-vivo-specific activity was explored. Initial research focused on solving the problem of how the protein backbone could be engineered so a cell would add more carbohydrate to it. Additional work resulted in darbepoetin alfa, a longer-acting molecule with two additional carbohydrate chains. PMID:20127232

  10. 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

    OpenAIRE

    Kirtan Nautiyal; Rui Li; Sarvari Yellapragada; Perumal Thiagarajan; Martha Mims; Gustavo Rivero

    2014-01-01

    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 gro...

  11. Measurement of Anti-Erythropoiesis-Stimulating Agent IgG4 Antibody as an Indicator of Antibody-Mediated Pure Red Cell Aplasia

    Science.gov (United States)

    Weeraratne, Dohan K.; Kuck, Andrew J.; Chirmule, Narendra

    2013-01-01

    Patients treated with erythropoietin-based erythropoiesis-stimulating agents (ESAs) can develop a rare but life-threatening condition called antibody-mediated pure red cell aplasia (amPRCA). The antibody characteristics in a nephrology patient with amPRCA include high antibody concentrations with neutralizing activity and a mixed IgG subclass including anti-ESA IgG4 antibodies. In contrast, anti-ESA IgG4 antibody is generally not detected in baseline samples and antibody-positive non-PRCA patients. Therefore, we validated a highly sensitive immunoassay on the ImmunoCAP 100 instrument to quantitate anti-ESA IgG4 antibodies using a human recombinant anti-epoetin alfa (EPO) IgG4 antibody as a calibrator. The biotinylated ESA was applied to a streptavidin ImmunoCAP, and bound anti-ESA IgG4 antibodies were detected using a β-galactosidase-conjugated mouse anti-human IgG4 antibody. The validated assay was used to detect anti-ESA IgG4 in amPRCA and non-PRCA patients. The immunoassay detected 15 ng/ml of human anti-EPO IgG4 antibody in the presence of a 200 M excess of human anti-ESA IgG1, IgG2, or IgM antibody and tolerated 2 μg/ml of soluble erythropoietin. All patient samples with confirmed amPRCA had measurable anti-ESA IgG4 antibodies. In addition, 94% (17/18) of non-PRCA patient samples were antibody negative or had below 15 ng/ml of anti-ESA IgG4 antibodies. This novel immunoassay can measure low-nanogram quantities of human anti-ESA IgG4 antibodies in the presence of other anti-ESA antibodies. An increased concentration of anti-ESA IgG4 antibody is associated with the development of amPRCA. We propose that the measurement of anti-ESA specific IgG4 antibodies may facilitate early detection of amPRCA in patients receiving all ESAs structurally related to human erythropoietin. PMID:23114696

  12. Switching patients with non-dialysis chronic kidney disease from oral iron to intravenous ferric carboxymaltose: effects on erythropoiesis-stimulating agent requirements, costs, hemoglobin and iron status.

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Toblli

    Full Text Available Patients with non-dialysis-dependent chronic kidney disease (ND-CKD often receive an erythropoiesis-stimulating agent (ESA and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD.This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min, hemoglobin 11-12 g/dL and iron deficiency (ferritin 20%. Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint; number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints. Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study.Thirty patients were enrolled (age 70.1±11.4 years; mean±SD. Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01. Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 μg/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01. No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study.Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study.ClinicalTrials.gov NCT02232906.

  13. Switching Patients with Non-Dialysis Chronic Kidney Disease from Oral Iron to Intravenous Ferric Carboxymaltose: Effects on Erythropoiesis-Stimulating Agent Requirements, Costs, Hemoglobin and Iron Status

    Science.gov (United States)

    Toblli, Jorge Eduardo; Di Gennaro, Federico

    2015-01-01

    Background Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD. Methods This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min), hemoglobin 11–12 g/dL and iron deficiency (ferritin 20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study. Results Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01). Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 μg/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01). No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study. Conclusion Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study. Trial Registration ClinicalTrials.gov NCT02232906 PMID

  14. The Korean Clinical Research Center for End-Stage Renal Disease Study Validates the Association of Hemoglobin and Erythropoiesis-Stimulating Agent Dose with Mortality in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Owen Kwon

    Full Text Available Anemia is an important risk factor for mortality in hemodialysis (HD patients. However, higher hemoglobin (Hb is not necessarily better, as seen in several studies. This study aimed to validate the clinical use of an Hb target of 10-11 g/dL in Korean HD patients.A total of 1,276 HD patients from the Clinical Research Center (CRC for End-Stage Renal Disease (ESRD were investigated in a prospective observational study. Cox proportional hazard analysis was conducted for each category of time-dependent Hb level and erythropoiesis-stimulating agent (ESA dose, with subgroup analysis stratified by age and diabetes status.Using a reference Hb level of 10-11 g/dL, the hazard ratios (HRs of death were 5.12 (95% confidence interval [CI], 2.62-10.02, P <0.05 for Hb level <9.0 g/dL, and 2.03 (CI, 1.16-3.69, P <0.05 for Hb level 9.0-10.0 g/dL, after adjustment for multiple clinical variables. However, an Hb level ≥11 g/dL was not associated with decreased mortality risk. In an adjusted model categorized by Hb and ESA dose, the risk of death at an Hb level <10 g/dL and a higher dose of ESA (≥126 U/kg/week had an HR of 2.25 (CI, 1.03-4.92, P <0.05, as compared to Hb level 10-11 g/dL and a lower dose of ESA. In subgroup analysis, those older than 65 years or who were diabetic had greater risk for mortality only in Hb category <9.0 g/dL. However, there was no significant interaction between age or diabetes status and Hb.Using CRC-ESRD data, we validated the association between Hb and ESA dose and mortality in Korean HD patients. The clinical practice target of an Hb of 10-11 g/dL before the new KDIGO guideline era seems reasonable considering its survival benefit in HD patients.

  15. 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.

  16. Definition and cause of hyporesponsiveness to erythropoiesis-stimulating agent%红细胞生成刺激剂治疗低反应定义及原因分析

    Institute of Scientific and Technical Information of China (English)

    林攀; 丁小强

    2012-01-01

    Hyporesponsiveness to erythropoiesis-stimulating agent ( ESA) has been a common issue in the treatment of renal anemia and is one of the major contributors of cardiovascular events and mortality and an independent risk factor of the prognosis in patients receiving hemodialysis. Factors leading to ESA hyporesponsiveness consisted of iron deficiency, hyper-parathyroidism,inflammation and (or) infection,increased C-reactive protein (CRP) ,malnutrition,vitamin B12 or folic acid deficiency,insufficient dialysis,catheter implantation and frequent hospitalizations.%红细胞生成刺激剂(ESA)治疗低反应是目前肾性贫血治疗中的一个常见问题,是患者心血管事件和病死率的重要影响因素之一,是血液透析患者预后的独立危险因素.造成ESA低反应的常见原因有铁缺乏、甲状旁腺功能亢进、炎症和(或)感染状态、C反应蛋白(CRP)水平增高、营养不良、维生素B12(VitB12)或叶酸缺乏、透析不充分、导管植入以及频繁住院等.

  17. Erythropoiesis-Stimulating Agents and Heart Failure

    NARCIS (Netherlands)

    Lipsic, Erik; van der Meer, Peter; van Veldhuisen, Dirk J.

    2011-01-01

    Anemia is a common comorbidity in heart failure (HF) patients. Its occurrence and severity are associated with worse prognosis. Although the etiology of anemia is multifactorial, inappropriate erythropoietin (EPO) production and/or bone-marrow resistance to EPO appear crucial in majority of anemic H

  18. 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

  19. Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, A.; Zapf, J.; Eckardt, K.U.; Clemons, G.; Froesch, E.R.; Bauer, C. (Universitaet Zurich (Switzerland))

    1988-10-01

    Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. The authors have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 {mu}g of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, {sup 59}Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and {sup 59}Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production.

  20. Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats

    International Nuclear Information System (INIS)

    Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. The authors have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 μg of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, 59Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and 59Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production

  1. The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model.

    Science.gov (United States)

    Crathorne, Louise; Huxley, Nicola; Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Hoyle, Martin; Briscoe, Simon; Coelho, Helen; Long, Linda; Medina-Lara, Antonieta; Mujica-Mota, Ruben; Napier, Mark; Hyde, Chris

    2016-01-01

    BACKGROUND Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed

  2. A dimeric peptide with erythropoiesis-stimulating activity uniquely affects erythropoietin receptor ligation and cell surface expression.

    Science.gov (United States)

    Verma, Rakesh; Green, Jennifer M; Schatz, Peter J; Wojchowski, Don M

    2016-08-01

    Erythropoiesis-stimulating agents (ESAs) that exert long-acting antianemia effects have been developed recently, but their mechanisms are poorly understood. Analyses reveal unique erythropoietin receptor (EPOR)-binding properties for one such ESA, the synthetic EPOR agonist peginesatide. Compared with recombinant human EPO and darbepoietin, peginesatide exhibited a slow on rate, but sustained EPOR residency and resistant displacement. In EPO-dependent human erythroid progenitor UT7epo cells, culture in peginesatide unexpectedly upmodulated endogenous cell surface EPOR levels with parallel increases in full-length EPOR-68K levels. These unique properties are suggested to contribute to the durable activity of this (and perhaps additional) dimeric peptide hematopoietic growth factor receptor agonist. PMID:27174804

  3. Drug Safety Communication: Erythropoiesis-Stimulating Agents (ESAs)

    Science.gov (United States)

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... it was archived. Search Archive Submit archive search Drugs Home Drugs Drug Safety and Availability Postmarket Drug ...

  4. Influence of melatonin on erythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Walmer, D.K.; Berkut, M.K.; O' Shea, M.D.

    Estrogens are known to inhibit erythropoiesis in mice. Melatonin inhibits growth of ovary and disrupts the estrous cycle. This report is of studies on the action of melatonin in preventing estrogen inhibition of erythropoiesis. Female mice were given melatonin or its precursor, tryptophan, subjected to hypobaria and finally given either saline, erythropoietin or cobalt salt injections. As expected, melatonin adversely affected development of sex organs. Stimulation of erythropoiesis was measured by Fe-59 incorporation into red cells. Erythropoiesis in melatonin-treated mice was increasingly stimulated with increasing doses of cobalt. The animals also showed greater response to erythropoietin treatment than did mice treated with tryptophan. Thus, the antigonadal action of melatonin suppressed inhibitory action of estrogen on erythropoiesis. Without estrogen influence, the mice were more sensitive to stimulatory action of erythropoietin and cobalt.

  5. Quantitative analysis of dietary iron utilization for erythropoiesis in response to body iron status.

    Science.gov (United States)

    Matsuo-Tezuka, Yukari; Noguchi-Sasaki, Mariko; Kurasawa, Mitsue; Yorozu, Keigo; Shimonaka, Yasushi

    2016-06-01

    Erythropoiesis requires large amounts of iron for hemoglobin synthesis. There are two sources of iron for erythropoiesis, dietary and stored iron; however, their relative contributions to erythropoiesis remain unknown. In this study, we used the stable iron isotope (57)Fe to quantify synthesis of hemoglobin derived from dietary iron. Using this method, we investigated the activities of dietary iron absorption and the utilization of dietary iron for erythropoiesis in responses to stimulated erythropoiesis and to interventions to alter body iron status. Under iron-loaded conditions, the activity of dietary iron absorption was clearly lowered in response to up-regulation of hepcidin, although the estimated activity of iron release from stored iron was not compared with that under control conditions. This result was supported by the observation that two duodenal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin, were downregulated by iron loading, although the levels of expression of ferroportin in iron storage tissues were not changed by iron loading under erythropoietic stimulation by epoetin-β pegol (C.E.R.A., a long-acting erythropoiesis-stimulating agent). These results indicate that the dietary iron absorption system is more sensitive to body iron status than are reticuloendothelial iron- release mechanisms. Our data indicated that there could be a regulatory mechanism favoring use of stored iron over dietary iron under iron-loaded conditions. PMID:26911670

  6. MUTUAL INHIBITION OF MURINE ERYTHROPOIESIS AND GRANULOPOIESIS DURING COMBINED ERYTHROPOIETIN, GRANULOCYTE-COLONY-STIMULATING FACTOR, AND STEM-CELL FACTOR ADMINISTRATION - IN-VIVO INTERACTIONS AND DOSE-RESPONSE SURFACES

    NARCIS (Netherlands)

    DEHAAN, G; ENGEL, C; DONTJE, B; NIJHOF, W; LOEFFLER, M

    1994-01-01

    We investigated the in vivo effects of erythropoietin (EPO) on granulopoiesis and, conversely, the effect of granulocyte colony-stimulating factor (G-CSF) treatment on erythropoiesis. Recombinant human EPO at four different doses in combination with recombinant human G-CSF also at four different dos

  7. Erythropoiesis-stimulating agents for anaemia in chronic heart failure patients

    NARCIS (Netherlands)

    Ngo, Katherine; Kotecha, Dipak; Walters, Julia A. E.; Manzano, Luis; Palazzuoli, Alberto; van Veldhuisen, Dirk J.; Flather, Marcus

    2010-01-01

    Background Chronic heart failure (CHF) is a leading cause of morbidity and mortality worldwide. Anaemia is a common (12-55%) co-morbid condition and is associated with worsening symptoms and increased mortality. Anaemia is treatable and can be targeted in the treatment of patients with CHF. Erythrop

  8. Eighteen days of "living high, training low" stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners

    DEFF Research Database (Denmark)

    Brugniaux, Julien V; Schmitt, Laurent; Robach, Paul;

    2005-01-01

    at 2,500 m and 12 nights at 3,000 m), whereas the control group (CON, n = 6) slept in normoxia (1,200 m). Both LHTL and CON trained at 1,200 m. Maximal oxygen uptake and maximal aerobic power were improved at Post1 and Post2 for LHTL only (+7.1 and +3.4% for maximal oxygen uptake, +8.4 and +4.......7% for maximal aerobic power, respectively). Similarly oxygen uptake and ventilation at ventilatory threshold increased in LHTL only (+18.1 and +12.2% at Post1, +15.9 and +15.4% at Post2, respectively). Heart rate during a 10-min run at 19.5 km/h decreased for LHTL at Post2 (-4.4%). Despite the stimulation...

  9. Improvement in Erythropoieis-stimulating Agent-induced Pure Red-cell Aplasia by Introduction of Darbepoetin-α When the Anti-erythropoietin Antibody Titer Declines Spontaneously

    OpenAIRE

    Lee, Hajeong; Yang, Jaeseok; Kim, Hyosang; Kwon, Ju Won; Oh, Kook-Hwan; Joo, Kwon Wook; Kim, Yon Su; Ahn, Curie; Han, Jin Suk; Kim, Suhnggwon

    2010-01-01

    Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-α. The patient developed progressive, severe anemia after the use of erythropoietin-α. As the anemia did not imp...

  10. 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

  11. 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.

  12. A Review of Natural Stimulant and Non-stimulant Thermogenic Agents.

    Science.gov (United States)

    Stohs, Sidney J; Badmaev, Vladimir

    2016-05-01

    Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p-synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd. PMID:26856274

  13. A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents

    Science.gov (United States)

    Badmaev, Vladimir

    2016-01-01

    Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non‐stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non‐stimulatory thermogenic agents include p‐synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd. PMID:26856274

  14. MECHANISTIC OPTIONS OF ERYTHROPOIETIN-STIMULATED ERYTHROPOIESIS

    NARCIS (Netherlands)

    NIJHOF, W; DEHAAN, G; PIETENS, J; DONTJE, B

    1995-01-01

    The in vivo mechanism of hematopoietic growth factor-induced cell multiplication is in debate. Several options can be examined: 1) growth factors can reduce the cycling time of their dividing target cells, 2) growth factors can add extra cell divisions within the differentiation pathway, 3) the comb

  15. Androgens and erythropoiesis: past and present.

    Science.gov (United States)

    Shahani, S; Braga-Basaria, M; Maggio, M; Basaria, S

    2009-09-01

    Association between androgens and erythropoiesis has been known for more than seven decades. Androgens stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells. Before the discovery of recombinant erythropoietin (rhEpo), androgens were used in the treatment of anemia associated with renal disease, bone marrow suppression, and hypopituitarism. Anabolism is an additional advantage of androgen therapy. Furthermore, in light of recent reports regarding adverse effects of rhEpo, the role of androgen therapy in various types of anemias should be readdressed. Polycythemia remains a known side effect of androgen therapy. In this review, we will briefly discuss the initial animal and human studies which demonstrated the role of androgens in the treatment of anemia, their mechanism of action, a detailed account of the efficacy of androgens in the treatment of various anemias, the erythropoietic side effects of androgens and finally, the relationship between hematocrit levels and cardiovascular disease. PMID:19494706

  16. Advances in understanding erythropoiesis: evolving perspectives.

    Science.gov (United States)

    Nandakumar, Satish K; Ulirsch, Jacob C; Sankaran, Vijay G

    2016-04-01

    Red blood cells (RBCs) are generated from haematopoietic stem and progenitor cells (HSPCs) through the step-wise process of differentiation known as erythropoiesis. In this review, we discuss our current understanding of erythropoiesis and highlight recent advances in this field. During embryonic development, erythropoiesis occurs in three distinct waves comprising first, the yolk sac-derived primitive RBCs, followed sequentially by the erythro-myeloid progenitor (EMP) and HSPC-derived definitive RBCs. Recent work has highlighted the complexity and variability that may exist in the hierarchical arrangement of progenitors responsible for erythropoiesis. Using recently defined cell surface markers, it is now possible to enrich for erythroid progenitors and precursors to a much greater extent than has been possible before. While a great deal of knowledge has been gained on erythropoiesis from model organisms, our understanding of this process is currently being refined through human genetic studies. Genes mutated in erythroid disorders can now be identified more rapidly by the use of next-generation sequencing techniques. Genome-wide association studies on erythroid traits in healthy populations have also revealed new modulators of erythropoiesis. All of these recent developments have significant promise not only for increasing our understanding of erythropoiesis, but also for improving our ability to intervene when RBC production is perturbed in disease. PMID:26846448

  17. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  18. Engineering a human bone marrow model: a case study on ex vivo erythropoiesis.

    Science.gov (United States)

    Mantalaris, A; Keng, P; Bourne, P; Chang, A Y; Wu, J H

    1998-01-01

    Bone marrow, with its intricate, three-dimensional tissue structure facilitating cell-cell interactions, provides a microenvironment supporting the production of hundreds of billions of multilineal blood cells everyday. We have developed a three-dimensional bone marrow culture system in which marrow cells are cultured in a reactor packed with porous microspheres. The culture supports a three-dimensional growth configuration and multilineal hemopoiesis mimicking the bone marrow in vivo. We studied ex vivo human erythropoiesis using the three-dimensional culture system. The system sustained extensive erythropoiesis at low erythropoietin concentrations (0.2 U/mL), plus stem cell factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and insulin-like growth factor-I. Erythroid cell production lasted for more than 5 weeks, and the percentage of erythroid cells in the nonadherent cell population was approximately 60%. Flow cytometric analysis using cell surface markers specific for erythroid cells (CD71 and glycophorin-A) indicated that the culture produced early, intermediate, and late erythroid cells. As the culture progressed, the erythroid cell population shifted gradually toward mature cell types. When compared to the three-dimensional culture, the traditional flask cultures failed to support extensive erythropoiesis under the same conditions. This indicates that the three-dimensional bone marrow culture system provides a microenvironment conducive to erythropoiesis under more physiological conditions and is a better bone marrow model.

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

    Energy Technology Data Exchange (ETDEWEB)

    Beguin, Y.; Fillet, G.; Bury, J.; Fairon, Y. (Univ. of Liege (Belgium))

    1989-10-01

    Splenic erythropoiesis was demonstrated by surface counting of {sup 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.

  20. Cell-surface remodelling during mammalian erythropoiesis.

    Science.gov (United States)

    Wraith, D C; Chesterton, C J

    1982-10-15

    Current evidence suggests that the major cell-surface modification occurring during mammalian erythropoiesis could be generated by two separate mechanisms: either selective loss of membrane proteins during enucleation or endocytosis at the subsequent reticulocyte and erythrocyte stages. The former idea was tested by collecting developing rabbit erythroid cells before and after the enucleation step and comparing their cell-surface protein composition via radiolabelling and electrophoresis. Few changes were observed. Our data thus lend support to the endocytosis mechanism.

  1. Quantitation of erythropoiesis in myelomatosis

    DEFF Research Database (Denmark)

    Birgens, H S; Hansen, O P; Henriksen, Jens Henrik Sahl;

    1979-01-01

    ) and the Red Blood Cell Iron Turnover (RBCIT) varied from subnormal to values markedly increased above upper normal limit. The calculated average Mean Red Cell Life time (MRCL) of erythrocytes was just below normal range. The mean Marrow Transit Time (MTT) was normal in the patients, despite subnormal venous...... haematocrit, indicating insufficient stimulation of the bone marrow. The renal function, measured as 51Cr-EDTA clearance, was found positively correlated to the RBCIT (r = 0.78, P less than 0.05). The results suggest that the previously demonstrated relationship between anaemia and renal failure in patients...

  2. Induction of megakaryocytic colony-stimulating activity in mouse skin by inflammatory agents and tumor promoters

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.A.; Dessypris, E.N.; Koury, M.J.

    1987-03-01

    The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with US -methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by US -methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

  3. Iron supply for erythropoiesis in the rabbit.

    OpenAIRE

    Celada, A; Stray, S; Sivarajan, M; Finch, C

    1984-01-01

    Marrow radioiron uptake and marrow blood flow were measured in order to evaluate iron supply for erythropoiesis. Normal, phenylhydrazine-treated and bled animals were studied. The plasma iron turnover of seven normal rabbits was 1.49 +/- 0.22 mg/dl whole blood per d, of 11 rabbits treated 4 d before with phenylhydrazine was 5.16 +/- 1.81, and of four bled animals the plasma iron turnover was 3.75 +/- 1.61. The cardiac output and the percentage of blood flow to the marrow was increased in phen...

  4. Macrophage migration inhibitory factor is an endogenous regulator of stress-induced extramedullary erythropoiesis.

    Science.gov (United States)

    Vignjević Petrinović, Sanja; Budeč, Mirela; Marković, Dragana; Gotić, Mirjana; Mitrović Ajtić, Olivera; Mojsilović, Slavko; Stošić-Grujičić, Stanislava; Ivanov, Milan; Jovčić, Gordana; Čokić, Vladan

    2016-09-01

    Macrophage migration inhibitory factor is a well-known proinflammatory cytokine that is released during systemic stress response. Although MIF can affect erythrocyte production, the role of this cytokine in stress-induced erythropoiesis is completely unknown. To extend our previous findings showing that chronic psychological stress stimulates extramedullary erythropoiesis, here we examined whether MIF is involved in the control of stress-induced erythropoietic response. Adult male C57BL/6 wild-type (WT) and MIF-KO (knock-out) mice were subjected to 2-h daily restraint stress for either 7 or 14 consecutive days. The number of erythroid progenitors and CD71/Ter119 profile of erythroid precursors were analyzed in the bone marrow and spleen. Additionally, MIF protein expression was assessed in WT mice. Our results demonstrated that chronic restraint stress enhanced the number of both erythroid progenitors and precursors in the spleen. Stress-induced increase in the number of splenic late erythroid progenitors as well as in the percentage of CD71(+)Ter119(+)-double-positive precursors was significantly more pronounced in MIF-KO mice compared to WT animals. Furthermore, repeatedly stressed WT animals demonstrated an augmented MIF expression in the spleen. Unlike the spleen, the bone marrow of chronically stressed WT mice exhibited less prominent changes in erythropoietic stress response and no significant alteration in MIF expression. In addition, MIF deficiency did not influence the bone marrow erythropoiesis in stressed animals. These findings suggest that MIF regulates extramedullary erythropoiesis by inhibiting an overexpansion of splenic immature erythroid cells during chronic stress and indicate a novel role for this cytokine under chronic stress conditions. PMID:27129368

  5. 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.

  6. Stimulating erythropoiesis in inflammatory bowel disease associated anemia

    Institute of Scientific and Technical Information of China (English)

    Georgia Tsiolakidou; Ioannis E Koutroubakis

    2007-01-01

    Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBDassociated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation.However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.

  7. Iron Loading and Overloading due to Ineffective Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Toshihiko Tanno

    2010-01-01

    Full Text Available Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.

  8. Roles of transferrin receptors in erythropoiesis.

    Science.gov (United States)

    Kawabata, Hiroshi; Sakamoto, Soichiro; Masuda, Taro; Uchiyama, Tatsuki; Ohmori, Katsuyuki; Koeffler, H Phillip; Takaori-Kondo, Akifumi

    2016-07-01

    Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form. Bone marrow erythroblasts incorporate Tf through endocytosis, which is mediated by transferrin receptor 1 (TFR1). Recently, human TFR1, aside from its role as a Tf receptor, was also found to be a receptor for the H-subunit of ferritin (FTH). In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin). H-ferritin inhibits the formation of burst forming unit-erythroid colonies in vitro. TFR2, which is also a Tf receptor, is predominantly expressed in hepatocytes and erythroid precursor cells. In the liver, TFR2 forms a complex with HFE, a hereditary hemochromatosis-associated protein, and acts as an iron sensor. In mice, hepatocyte-specific knockout of the TFR2 gene has been shown to cause systemic iron-overload with decreased expression of hepcidin, the central regulator of iron homeostasis. In erythroid cells, TFR2 forms a complex with the erythropoietin receptor and facilitates its trafficking to the cell membrane. Moreover, hematopoietic cell-specific knockout of the TFR2 gene causes microcytic erythrocytosis in mice. This review focuses on the molecular evolution and functions of these TFRs and their ligands. PMID:27498743

  9. Cardio-renal-anemia syndromeとErythropoietin Stimulating Agents(ESA)

    OpenAIRE

    成宮, 博理; 山田, 博之; 北川, 功幸; 原山, 拓也; 熱田, 晴彦; 井上, 衛; 出口, 雅子

    2011-01-01

     近年の様々な疫学調査や大規模臨床試験により,慢性腎臓病(CKD)が心血管疾患(CVD)の独立した危険因子であることが明らかになった.さらに,CKD のCVD へのリスクとなる間に介在する要因として,貧血が大きな役割を果たしていることが証明されてきた.このようにCKD,CVD,貧血がお互いに悪影響を及ぼし合い,悪循環を形成するという考えをcardio-renal-anemia syndromeと呼ぶようになった.保存期CKD やうっ血性心不全に対する介入は困難が予想される.一方で,Erythropoietin stimulating agents と呼ばれるrHuEPO などを使用した腎性貧血の治療は,心機能を改善し腎機能増悪を抑制させることが報告されている.ここでは,cardio-renal-anemia syndrome の概念と新しいESA について紹介する....

  10. Negative autoregulation by Fas stabilizes adult erythropoiesis and accelerates its stress response.

    Directory of Open Access Journals (Sweden)

    Miroslav Koulnis

    Full Text Available Erythropoiesis maintains a stable hematocrit and tissue oxygenation in the basal state, while mounting a stress response that accelerates red cell production in anemia, blood loss or high altitude. Thus, tissue hypoxia increases secretion of the hormone erythropoietin (Epo, stimulating an increase in erythroid progenitors and erythropoietic rate. Several cell divisions must elapse, however, before Epo-responsive progenitors mature into red cells. This inherent delay is expected to reduce the stability of erythropoiesis and to slow its response to stress. Here we identify a mechanism that helps to offset these effects. We recently showed that splenic early erythroblasts, 'EryA', negatively regulate their own survival by co-expressing the death receptor Fas, and its ligand, FasL. Here we studied mice mutant for either Fas or FasL, bred onto an immune-deficient background, in order to avoid an autoimmune syndrome associated with Fas deficiency. Mutant mice had a higher hematocrit, lower serum Epo, and an increased number of splenic erythroid progenitors, suggesting that Fas negatively regulates erythropoiesis at the level of the whole animal. In addition, Fas-mediated autoregulation stabilizes the size of the splenic early erythroblast pool, since mutant mice had a significantly more variable EryA pool than matched control mice. Unexpectedly, in spite of the loss of a negative regulator, the expansion of EryA and ProE progenitors in response to high Epo in vivo, as well as the increase in erythropoietic rate in mice injected with Epo or placed in a hypoxic environment, lagged significantly in the mutant mice. This suggests that Fas-mediated autoregulation accelerates the erythropoietic response to stress. Therefore, Fas-mediated negative autoregulation within splenic erythropoietic tissue optimizes key dynamic features in the operation of the erythropoietic network as a whole, helping to maintain erythroid homeostasis in the basal state, while

  11. The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis

    OpenAIRE

    McMullin, Mary Frances; Harrison, Claire N; Niederwieser, Dietger; Demuynck, Hilde; Jäkel, Nadja; Gopalakrishna, Prashanth; McQuitty, Mari; Stalbovskaya, Viktoriya; Recher, Christian; Theunissen, Koen; Gisslinger, Heinz; Kiladjian, Jean-Jacques; Al-Ali, Haifa-Kathrin

    2015-01-01

    BACKGROUND: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of actio...

  12. Photo-stimulated electro-optic response of liquid-crystalline system with trans-cis photo-isomerizable agent

    International Nuclear Information System (INIS)

    A rather strong photo-stimulated enhancement of photo-induced bend flexoelectric effect based on trans-cis photoisomerization of azo bond was found in a guest-host system formed from the nematic liquid crystal (LC) N-(4-methoxybenzylidene)-4-butylaniline (MBBA) as a host, and the azobenzene LC 4-hexyloxybenzoloxy-4'-cyanoazobenzene, as a guest photoactive agent at 1 wt.% concentration. Upon application of electric field, thin homeotropic layers of thickness 100 pm containing this photo-sensitized LC mixture were investigated as subjected to a relatively weak illumination with UV light (λ = 375 nm, from narrow-band light-emitting diode, LED). The stimulation of the photoactive electro-optic response of azobenzene-doped MBBA (owing to enhanced photo-induced bend flexoelectric effect driven by the photo-isomerizable dopants) was achieved by pre-resonant excitation of the photoactive agent. The degree of the effect measured is of potential interest for thin-film photoactive electro-optic applications. The UV light-induced effect in azobenzene-doped MBBA was reversible; the back (relaxation) process was stimulated by light in the blue from a LED with broadband spectrum centered at 455 nm

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

    NARCIS (Netherlands)

    Crielaard, Bart J; Rivella, Stefano

    2014-01-01

    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 erythrocyte

  14. Transcriptional divergence and conservation of human and mouse erythropoiesis.

    Science.gov (United States)

    Pishesha, Novalia; Thiru, Prathapan; Shi, Jiahai; Eng, Jennifer C; Sankaran, Vijay G; Lodish, Harvey F

    2014-03-18

    Mouse models have been used extensively for decades and have been instrumental in improving our understanding of mammalian erythropoiesis. Nonetheless, there are several examples of variation between human and mouse erythropoiesis. We performed a comparative global gene expression study using data from morphologically identical stage-matched sorted populations of human and mouse erythroid precursors from early to late erythroblasts. Induction and repression of major transcriptional regulators of erythropoiesis, as well as major erythroid-important proteins, are largely conserved between the species. In contrast, at a global level we identified a significant extent of divergence between the species, both at comparable stages and in the transitions between stages, especially for the 500 most highly expressed genes during development. This suggests that the response of multiple developmentally regulated genes to key erythroid transcriptional regulators represents an important modification that has occurred in the course of erythroid evolution. In developing a systematic framework to understand and study conservation and divergence between human and mouse erythropoiesis, we show how mouse models can fail to mimic specific human diseases and provide predictions for translating findings from mouse models to potential therapies for human disease.

  15. Enzymatic Debriding Agents Are Safe in Wounds With High Bacterial Bioburdens and Stimulate Healing

    OpenAIRE

    Payne, Wyatt G.; Salas, R. Emerick; Ko, Francis; Naidu, Deepak K.; Donate, Guillermo; Wright, Terry E.; Robson, Martin C.

    2008-01-01

    Background: Debridement is essential for successful wound management. Enzymatic debridement is commonly utilized in wound care but has been reported to be unsafe in wounds with significant bacterial bioburden, unless used in conjunction with topical antimicrobials. We examine this hypothesis with 2 commercially available, commonly used preparations of enzymatic debriding agents. Materials and Methods: Using a standard rodent model of a chronically infected granulating wound with bacterial lev...

  16. In-vitro studies of ineffective erythropoiesis in rheumatoid arthritis

    OpenAIRE

    Williams, R A; Samson, Diana; Tikerpae, J.; Crowne, Helen; Gumpel, J M

    1982-01-01

    Ineffective erythropoiesis was assessed in a series of 32 patients with rheumatoid arthritis by means of a new in-vitro method which measures the release of haem from a labelled cohort of erythroblasts in culture. Haem release was significantly increased in patients with the anaemia of chronic disorders but was normal in those who were not anaemic or who had an iron-deficiency anaemia. In 2 patients with anaemia of chronic disorders haem release returned to normal after successful antirheumat...

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

    OpenAIRE

    Crielaard, Bart J.; Rivella, Stefano

    2014-01-01

    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 erythropoi...

  18. 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.

  19. Pregnancy-secreted Acid phosphatase, uteroferrin, enhances fetal erythropoiesis.

    Science.gov (United States)

    Ying, Wei; Wang, Haiqing; Bazer, Fuller W; Zhou, Beiyan

    2014-11-01

    Uteroferrin (UF) is a progesterone-induced acid phosphatase produced by uterine glandular epithelia in mammals during pregnancy and targeted to sites of hematopoiesis throughout pregnancy. The expression pattern of UF is coordinated with early fetal hematopoietic development in the yolk sac and then liver, spleen, and bone to prevent anemia in fetuses. Our previous studies suggested that UF exerts stimulatory impacts on hematopoietic progenitor cells. However, the precise role and thereby the mechanism of action of UF on hematopoiesis have not been investigated previously. Here, we report that UF is a potent regulator that can greatly enhance fetal erythropoiesis. Using primary fetal liver hematopoietic cells, we observed a synergistic stimulatory effect of UF with erythropoietin and other growth factors on both burst-forming unit-erythroid and colony-forming unit-erythroid formation. Further, we demonstrated that UF enhanced erythropoiesis at terminal stages using an in vitro culture system. Surveying genes that are crucial for erythrocyte formation at various stages revealed that UF, along with erythropoietin, up-regulated transcription factors required for terminal erythrocyte differentiation and genes required for synthesis of hemoglobin. Collectively, our results demonstrate that UF is a cytokine secreted by uterine glands in response to progesterone that promotes fetal erythropoiesis at various stages of pregnancy, including burst-forming unit-erythroid and colony-forming unit-erythroid progenitor cells and terminal stages of differentiation of hematopoietic cells in the erythroid lineage. PMID:25093463

  20. Effects of Testosterone on Erythropoiesis in a Female Mouse Model of Anemia of Inflammation.

    Science.gov (United States)

    Guo, Wen; Schmidt, Paul J; Fleming, Mark D; Bhasin, Shalender

    2016-07-01

    The anemia of inflammation is a common problem in inflammatory and autoimmune diseases. We characterized a mouse model of anemia of chronic inflammation induced by repeated injections of low doses of heat-killed Brucella abortus (HKBA), and determined the effects of T administration on erythropoiesis in this model. Female C57BL/6NCrl mice were injected weekly with HKBA for 10 wk. Weekly injections of T or vehicle oil were started 4 wk later. Control mice were injected with saline and vehicle oil in parallel. HKBA-injected mice had significantly lower hemoglobin, hematocrit, mean corpuscular volume, reticulocyte hemoglobin, transferrin saturation (TSAT), and tissue nonheme iron in liver and spleen, enlarged spleen, and up-regulated hepatic expression of inflammatory markers, serum amyloid A1, and TNFα, but down-regulated IL-6, bone morphogenic protein 6, and hepcidin compared with saline controls. HKBA also reduced serum hepcidin and increased serum erythropoietin. Bone marrow erythroid precursors were substantially reduced in HKBA-injected mice. Cotreatment with T increased the percentage of late-stage erythroid precursors in the bone marrow relative to HKBA-injected and saline controls and reversed HKBA-induced suppression of hemoglobin and hematocrit. T also normalized serum erythropoietin, TSAT, and reticulocyte hemoglobin without correcting the expression of the hepatic inflammation markers. Conclusions are that low-dose HKBA induces moderate anemia characterized by chronic inflammation, decreased iron stores, and suppression of erythroid precursors in the bone marrow. T administration reverses HKBA-induced anemia by stimulating erythropoiesis, which is associated with a shift toward accelerated maturation of erythroid precursors in the bone marrow. PMID:27074351

  1. BEBIDAS ENERGIZANTES: ¿HIDRATANTES O ESTIMULANTES? Energy drinks: rehydrating agents or stimulants?

    Directory of Open Access Journals (Sweden)

    Miguel Cote-Menéndez

    2011-09-01

    .Background. Energy drinks can be found almost everywhere; their consumption has increased due to ease of access to them, their stimulant properties and the idea that they are harmless. Scarce knowledge about their characteristics has led to them being confused with rehydrating drinks and thus their indiscriminate use, even though rehydrating drinks seek to prevent dehydration and energy drinks have a stimulant effect. Objective. Describing energy drinks' components and analysing their effects, undesired reactions and precautions regarding their use. Materials and methods. The literature in Pubmed was reviewed using the MeSH terms «caffeine» OR «taurine» OR «gluconates» combined with the term «energy drinks» with specifiers, 42 articles being found. The summaries were analysed and 29 articles were included in the study. Results. Energy drinks contain methylxanthines, carbohydrates, taurine, vitamins and/or guaraná (caffeine source from an Amazon region berry. Most stimulant effects happen at the expense of high concentrations of methylxanthines such as caffeine. Such high concentrations increase the risk of poisoning and caffeine dependence. Cases of arrhythmia, heart attack, exacerbation of psychiatric symtomatology and convulsions associated with their consumption have been reported. Furthermore, mixing them with alcohol increases alcohol poisoning-related damage. They are not recommended for sportspeople due to their diuretic and cardiovascular effects. Conclusions. It has been shown that energy drink components are not completely innocuous. Even though their chronic effects remain unknown, the literature does warn about the damage to health which could be caused by strong acute consumption or frequent consumption. Measures must thus be implemented which are aimed at broadcasting the consequences of these substances and restricting their consumption by atrisk populations.

  2. 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

    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...

  3. 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.

  4. Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis.

    Science.gov (United States)

    da Cunha, Marcela S B; Siqueira, Egle M A; Trindade, Luciano S; Arruda, Sandra F

    2014-10-01

    Vitamin A modulates inflammatory status, iron metabolism and erythropoiesis. Given that these factors modulate the expression of the hormone hepcidin (Hamp), we investigated the effect of vitamin A deficiency on molecular biomarkers of iron metabolism, the inflammatory response and the erythropoietic system. Five groups of male Wistar rats were treated: control (AIN-93G), the vitamin A-deficient (VAD) diet, the iron-deficient (FeD) diet, the vitamin A- and iron-deficient (VAFeD) diet or the diet with 12 mg atRA/kg diet replacing all-trans-retinyl palmitate by all-trans retinoic acid (atRA). Vitamin A deficiency reduced serum iron and transferrin saturation levels, increased spleen iron concentrations, reduced hepatic Hamp and kidney erythropoietin messenger RNA (mRNA) levels and up-regulated hepatic and spleen heme oxygenase-1 gene expression while reducing the liver HO-1 specific activity compared with the control. The FeD and VAFeD rats exhibited lower levels of serum iron and transferrin saturation, lower iron concentrations in tissues and lower hepatic Hamp mRNA levels compared with the control. The treatment with atRA resulted in lower serum iron and transferrin concentrations, an increased iron concentration in the liver, a decreased iron concentration in the spleen and in the gut, and decreased hepatic Hamp mRNA levels. In summary, these findings suggest that vitamin A deficiency leads to ineffective erythropoiesis by the down-regulation of renal erythropoietin expression in the kidney, resulting in erythrocyte malformation and the consequent accumulation of the heme group in the spleen. Vitamin A deficiency indirectly modulates systemic iron homeostasis by enhancing erythrophagocytosis of undifferentiated erythrocytes.

  5. 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.

  6. Potential Manipulations to Restore Aberrant Myelopoiesis: The Role of New Colony-Stimulating Factors and other Agents

    OpenAIRE

    1992-01-01

    A rapidly growing number of new recombinant human colony-stimulating factors (CSFs) are entering various phases of clinical testing. With the recent approval of granulocyte colony-stimulating factor (G-CSF) and granulocytemacrophage colony-stimulating factor (GM-CSF) for clinical use, newer CSFs will be developed for a widening spectrum of disease states singularly and in combination with other CSFs. Interleukin (IL)-3 is being tested in early clinical trials, and combination studies with G-C...

  7. Dexamethasone facilitates erythropoiesis in murine embryonic stem cells differentiating into hematopoietic cells in vitro

    International Nuclear Information System (INIS)

    Differentiating embryonic stem (ES) cells are increasingly emerging as an important source of hematopoietic progenitors with a potential to be useful for both basic and clinical research applications. It has been suggested that dexamethasone facilitates differentiation of ES cells towards erythrocytes but the mechanism responsible for sequential expression of genes regulating this process are not well-understood. Therefore, we in vitro induced differentiation of murine ES cells towards erythropoiesis and studied the sequential expression of a set of genes during the process. We hypothesized that dexamethasone-activates its cognate nuclear receptors inducing up-regulation of erythropoietic genes such as GATA-1, Flk-1, Epo-R, and direct ES cells towards erythropoietic differentiation. ES cells were cultured in primary hematopoietic differentiation media containing methyl-cellulose, IMDM, IL-3, IL-6, and SCF to promote embryoid body (EB) formation. Total RNA of day 3, 5, and 9-old EBs was isolated for gene expression studies using RT-PCR. Cells from day 9 EBs were subjected to secondary differentiation using three different cytokines and growth factors combinations: (1) SCF, EPO, dexamethasone, and IGF; (2) SCF, IL-3, IL-6, and TPO; and (3) SCF IL-3, IL-6, TPO, and EPO. Total RNA from day 12 of secondary differentiated ES cells was isolated to study the gene expression pattern during this process. Our results demonstrate an up-regulation of GATA-1, Flk-1, HoxB-4, Epo-R, and globin genes (α-globin, βH-1 globin, β-major globin, ε -globin, and ζ-globin) in the 9-day-old EBs, whereas, RNA from 5-day-old EBs showed expression of HoxB-4, ε-globin, γ-globin, βH1-globin, and Flk-1. Three-day-old EBs showed only HoxB-4 and Flk-1 gene expression and lacked expression of all globin genes. These findings indicate that erythropoiesis-specific genes are activated later in the course of differentiation. Gene expression studies on the ES cells of secondary EB origin cultured

  8. Macrophages support pathological erythropoiesis in Polycythemia Vera and Beta-Thalassemia

    OpenAIRE

    Ramos, Pedro; Casu, Carla; Gardenghi, Sara; Breda, Laura; Crielaard, Bart J.; Guy, Ella; Marongiu, Maria Franca; Gupta, Ritama; Levine, Ross L; Abdel-Wahab, Omar; Benjamin L Ebert; van Rooijen, Nico; Ghaffari, Saghi; Grady, Robert W.; Giardina, Patricia J.

    2013-01-01

    Regulation of erythropoiesis is achieved by integration of distinct signals. Among these, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages for physiological and pathological conditions of enhanced erythropoiesis. We utilized mouse models of induced anemia, Polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that mac...

  9. 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

    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

  10. Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase C.

    Science.gov (United States)

    McConkey, D J; Hartzell, P; Jondal, M; Orrenius, S

    1989-08-15

    Glucocorticoid hormones and Ca2+ ionophores stimulate a suicide process in immature thymocytes, known as apoptosis or programmed cell death, that involves extensive DNA fragmentation. We have recently shown that a sustained increase in cytosolic Ca2+ concentration stimulates DNA fragmentation and cell killing in glucocorticoid- or ionophore-treated thymocytes. However, a sustained increase in the cytosolic Ca2+ level also mediates lymphocyte proliferation, suggesting that apoptosis is blocked in proliferating thymocytes. In this study we report that phorbol esters, which selectively stimulate protein kinase C (PKC), blocked DNA fragmentation and cell death in thymocytes exposed to Ca2+ ionophore or glucocorticoid hormone. The T cell mitogen, concanavalin A, which stimulates thymocytes by a mechanism that involves PKC activation, caused concentration-dependent increases in the cytosolic Ca2+ level that did not result in DNA fragmentation, but incubation with concanavalin A and the PKC inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) resulted in both DNA fragmentation and cell death. Phorbol ester directly inhibited Ca2+-dependent DNA fragmentation in isolated thymocyte nuclei. Our results strongly suggest that PKC activation blocks thymocyte apoptosis by preventing Ca2+-stimulated endonuclease activation. PMID:2503500

  11. Herpesvirus entry mediator regulates hypoxia-inducible factor–1α and erythropoiesis in mice

    Science.gov (United States)

    Sakoda, Yukimi; Anand, Sudarshan; Zhao, Yuming; Park, Jang-June; Liu, Yingjia; Kuramasu, Atsuo; van Rooijen, Nico; Chen, Ling; Strome, Scott E.; Hancock, Wayne W.; Chen, Lieping; Tamada, Koji

    2011-01-01

    Erythropoiesis, the production of red blood cells, must be tightly controlled to ensure adequate oxygen delivery to tissues without causing thrombosis or stroke. Control of physiologic and pathologic erythropoiesis is dependent predominantly on erythropoietin (EPO), the expression of which is regulated by hypoxia-inducible factor (HIF) activity in response to low oxygen tension. Accumulating evidence indicates that oxygen-independent mediators, including inflammatory stimuli, cytokines, and growth factors, also upregulate HIF activity, but it is unclear whether these signals also result in EPO production and erythropoiesis in vivo. Here, we found that signaling through herpesvirus entry mediator (HVEM), a molecule of the TNF receptor superfamily, promoted HIF-1α activity in the kidney and subsequently facilitated renal Epo production and erythropoiesis in vivo under normoxic conditions. This Epo upregulation was mediated by increased production of NO by renal macrophages. Hvem-deficient mice displayed impaired Epo expression and aggravated anemia in response to erythropoietic stress. These data reveal that HVEM signaling functions to promote HIF-1α activity and Epo production, and thus to regulate erythropoiesis. Furthermore, our findings suggest that this molecular mechanism could represent a therapeutic target for Epo-responsive diseases, including anemia. PMID:22080867

  12. Expression of ABCG2 (BCRP in mouse models with enhanced erythropoiesis

    Directory of Open Access Journals (Sweden)

    Gladys Oluyemisi Latunde-Dada

    2014-06-01

    Full Text Available Haem is a structural component of numerous cellular proteins which contributes significantly to iron metabolic processes in mammals but its toxicity demands that cellular levels must be tightly regulated. Breast Cancer Resistance Protein (BCRP/ABCG2, an ATP Binding Cassette G-member protein has been shown to possess porhyrin/haem efflux function. The current study evaluated the expression and regulation of Abcg2 mRNA and protein levels in mouse tissues involved in erythropoiesis. Abcg2 mRNA expression was enhanced in bone marrow hemopoietic progenitor cells from mice that were treated with phenylhydrazine (PHZ. Abcg2 mRNA expression was increased particularly in the extramedullary haematopoietic tissues from all the mice models with enhanced erythropoiesis. Haem oxygenase (ho1 levels tended to increase in the liver of mice with enhanced erythropoiesis and gene expression patterns differed from those observed in the spleen. Efflux of haem biosynthetic metabolites might be dependent on the relative abundance of Abcg2 or ho1 during erythropoiesis. Abcg2 appears to act principally as a safety valve regulating porphyrin levels during the early stages of erythropoiesis and its role in systemic haem metabolism and erythrophagocytosis, in particular, awaits further clarification.

  13. A Systems Approach Identifies Essential FOXO3 Functions at Key Steps of Terminal Erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Raymond Liang

    2015-10-01

    Full Text Available Circulating red blood cells (RBCs are essential for tissue oxygenation and homeostasis. Defective terminal erythropoiesis contributes to decreased generation of RBCs in many disorders. Specifically, ineffective nuclear expulsion (enucleation during terminal maturation is an obstacle to therapeutic RBC production in vitro. To obtain mechanistic insights into terminal erythropoiesis we focused on FOXO3, a transcription factor implicated in erythroid disorders. Using an integrated computational and experimental systems biology approach, we show that FOXO3 is essential for the correct temporal gene expression during terminal erythropoiesis. We demonstrate that the FOXO3-dependent genetic network has critical physiological functions at key steps of terminal erythropoiesis including enucleation and mitochondrial clearance processes. FOXO3 loss deregulated transcription of genes implicated in cell polarity, nucleosome assembly and DNA packaging-related processes and compromised erythroid enucleation. Using high-resolution confocal microscopy and imaging flow cytometry we show that cell polarization is impaired leading to multilobulated Foxo3-/- erythroblasts defective in nuclear expulsion. Ectopic FOXO3 expression rescued Foxo3-/- erythroblast enucleation-related gene transcription, enucleation defects and terminal maturation. Remarkably, FOXO3 ectopic expression increased wild type erythroblast maturation and enucleation suggesting that enhancing FOXO3 activity may improve RBCs production. Altogether these studies uncover FOXO3 as a novel regulator of erythroblast enucleation and terminal maturation suggesting FOXO3 modulation might be therapeutic in disorders with defective erythroid maturation.

  14. Erythropoiesis in mice exposed to continuous whole body irradiation of gamma-rays

    Energy Technology Data Exchange (ETDEWEB)

    Joshima, Hisamasa; Fukutsu, Kumiko; Matsushita, Satoru; Kashima, Masatoshi

    1988-09-01

    The erythropoietic effects of continuous ..gamma..-irradiation with a daily regime of 0.029, 0.083 and 0.374 Gy were studied in mice. Irradiation was performed with /sup 137/Cs ..gamma..-rays for 22 hr/day. The length of irradiation time varied from 3 to 112 days. Erythropoiesis was investigated on the basis of clearance of /sup 59/Fe from the circulation and of incorporation of /sup 59/Fe into circulating erythrocytes and erythropoietic tissue. A chemical method for the separation of heme and nonheme iron-containing fractions was employed to examine the uptake of /sup 59/Fe into both the heme and nonheme iron fractions. Daily exposure to 0.029 and 0.083 Gy caused no significant changes in erythropoiesis. Daily exposure to 0.374 Gy caused some significant changes in erythropoiesis. On day 7 of continuous irradiation, the amount of /sup 59/Fe incorporated into erythrocytes decreased, but the values returned to normal on day 14 and 28 of continuous irradiation, indicating recovery within erythropoietic tissues at earlier time. On day 56, depressed incorporation of /sup 59/Fe into erythrocytes with normal rate of disappearance of /sup 59/Fe from the circulation and increased heme level of /sup 59/Fe in the femoral marrow were observed. Results observed on day 56 may suggest the possibility of ineffective erythropoiesis during the continuous irradiation. On day 112, some mice showed almost the same changes in erythropoiesis as those mice exposed to acute X-rays radiation.

  15. Overexpression of MyrAkt1 in endothelial cells leads to erythropoietin- and BMP4-independent splenic erythropoiesis in mice.

    Directory of Open Access Journals (Sweden)

    Rebekah K O'Donnell

    Full Text Available Under steady state conditions, erythropoiesis occurs in the bone marrow. However, in mice, stress or tissue hypoxia results in increased erythropoiesis in the spleen. There is increasing evidence that the hematopoietic microenvironment, including endothelial cells, plays an important role in regulating erythropoiesis. Here, we show that short-term expression of constitutively active Akt in the endothelium of mice results in non-anemic stress erythropoiesis in the spleen. The initiation of this stress response was independent of erythropoietin and BMP4, and was observed in endothelial myrAkt1 mice reconstituted with wild-type bone marrow. Together, these data suggest that endothelial cell hyperactivation is a potentially novel pathway of inducing red cell production under stress.

  16. Aconitase regulation of erythropoiesis correlates with a novel licensing function in erythropoietin-induced ERK signaling.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Talbot

    Full Text Available BACKGROUND: Erythroid development requires the action of erythropoietin (EPO on committed progenitors to match red cell output to demand. In this process, iron acts as a critical cofactor, with iron deficiency blunting EPO-responsiveness of erythroid progenitors. Aconitase enzymes have recently been identified as possible signal integration elements that couple erythropoiesis with iron availability. In the current study, a regulatory role for aconitase during erythropoiesis was ascertained using a direct inhibitory strategy. METHODOLOGY/PRINCIPAL FINDINGS: In C57BL/6 mice, infusion of an aconitase active-site inhibitor caused a hypoplastic anemia and suppressed responsiveness to hemolytic challenge. In a murine model of polycythemia vera, aconitase inhibition rapidly normalized red cell counts, but did not perturb other lineages. In primary erythroid progenitor cultures, aconitase inhibition impaired proliferation and maturation but had no effect on viability or ATP levels. This inhibition correlated with a blockade in EPO signal transmission specifically via ERK, with preservation of JAK2-STAT5 and Akt activation. Correspondingly, a physical interaction between ERK and mitochondrial aconitase was identified and found to be sensitive to aconitase inhibition. CONCLUSIONS/SIGNIFICANCE: Direct aconitase inhibition interferes with erythropoiesis in vivo and in vitro, confirming a lineage-selective regulatory role involving its enzymatic activity. This inhibition spares metabolic function but impedes EPO-induced ERK signaling and disturbs a newly identified ERK-aconitase physical interaction. We propose a model in which aconitase functions as a licensing factor in ERK-dependent proliferation and differentiation, thereby providing a regulatory input for iron in EPO-dependent erythropoiesis. Directly targeting aconitase may provide an alternative to phlebotomy in the treatment of polycythemia vera.

  17. Participation of signaling cascades in the regulation of erythropoiesis under conditions of cytostatic treatment.

    Science.gov (United States)

    Dygai, A M; Zhdanov, V V; Miroshnichenko, L A; Udut, E V; Zyuz'kov, G N; Simanina, E V; Chaikovskii, A V; Stavrova, L A; Trofimova, E S; Burmina, Ya V

    2015-01-01

    We studied the role of signaling pathways in the regulation of erythropoiesis against the background of myelosuppression caused by administration of 5-fluorouracil. The important role of cyclic AMP in the maturation of erythroid progenitors after cytostatic treatment was demonstrated. The secretory activity of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are involved in the formation of erythropoietic activity of adherent cells of the microenvironment.

  18. Interleukin-2 critically regulates bone marrow erythropoiesis and prevents anemia development.

    Science.gov (United States)

    Chopra, Martin; Langenhorst, Daniela; Beilhack, Andreas; Serfling, Edgar; Patra, Amiya K

    2015-12-01

    Mice deficient in IL-2 signaling develop severe anemia indicating a defect in erythropoiesis. However, why deficiency in IL-2, an essential growth factor for lymphocytes, or in IL-2 signaling components should result in defective erythropoiesis is unclear. Here, we have analyzed the mechanism of IL-2 signaling deficiency induced anemia in mice and show that IL-2 plays an indispensable role in bone marrow (BM) erythropoiesis via maintenance of regulatory T (Treg) cells. In absence of IL-2 signaling, IFN-γ produced by the activated T cells suppressed klf1 expression, resulting in an early block in erythrocyte differentiation. Anemia, in IL-2 or IL-2 signaling deficient mice always developed prior to the manifestation of other autoimmune complications such as colitis, suggesting that anemia in these mice might be a contributing factor in inducing other pathological complications in later stages. Our study shows, how essential cytokines of lymphoid cells could exert critical influence on the development of erythrocytes and thus expanding our understanding of the complex regulation of hematopoiesis in the BM. Besides, our findings might facilitate the use of IL-2 and anti-IFN-γ as a clinical remedy against anemia that arise in cancer patients following radiotherapy or chemotherapy, a context which simulates the situation of IL-2 deficiency. PMID:26404745

  19. Recombinant human erythropoietin-induced erythropoiesis regulates hepcidin expression over iron status in the rat.

    Science.gov (United States)

    Ribeiro, Sandra; Garrido, Patrícia; Fernandes, João; Rocha, Susana; Rocha-Pereira, Petronila; Costa, Elísio; Belo, Luís; Reis, Flávio; Santos-Silva, Alice

    2016-07-01

    The crosstalk between several factors controlling hepcidin synthesis is poorly clarified for different physiological and pathological conditions. Our aim was to study the impact of increasing recombinant human erythropoietin (rHuEPO) doses on erythropoiesis, iron metabolism and hepcidin, using a rat model. Male Wistar rats were divided in 5 groups: control (vehicle) and rHuEPO-treated groups (100, 200, 400 and 600IU/kgbody weight/week), 3 times per week, during 3weeks. Hematological and iron data were evaluated. The expression of several genes involved in iron metabolism was analyzed by qPCR. Liver hepcidin protein was evaluated by Western Blot. The rHuEPO treatment induced erythropoiesis and increased transferrin saturation (TSAT) in a dose dependent manner. Tf receptor 2 (TfR2), hemojuvelin (HJV) and bone morphogenetic protein 6 (BMP6) were up-regulated in rHuEPO200 group. Matriptase-2 was down-regulated in rHuEPO200 group, and up-regulated in the other rHuEPO-treated groups. Hepcidin synthesis was increased in rHuEPO200 group, and repressed in the rHuEPO400 and rHuEPO600 groups. Our study showed that when a high erythropoietic stimulus occurs, hepcidin synthesis is mainly regulated by TSAT; however, when the erythropoiesis rate reaches a specific threshold, extramedullary hematopoiesis is triggered, and the control of hepcidin synthesis is switched to matriptase-2, thus inhibiting hepcidin synthesis. PMID:27282570

  20. p38α controls erythroblast enucleation and Rb signaling in stress erythropoiesis

    Institute of Scientific and Technical Information of China (English)

    Simon M Schultze; Andreas Mairhofer; Dan Li; Jin Cen; Hartmut Beug; Erwin F Wagner; Lijian Hui

    2012-01-01

    Enucleation of erythroblasts during terminal differentiation is unique to mammals.Although erythroid enucleation has been extensively studied,only a few genes,including retinoblastoma protein(Rb),have been identified to regulate nuclear extrusion.It remains largely undefined by which signaling molecules,the extrinsic stimuli,such as erythropoietin(Epo),are transduced to induce enucleation.Here,we show that p38α,a mitogen-activated protein kinase(MAPK),is required for erythroid enucleation.In an ex vivo differentiation system that contains high Epo levels and mimics stress erythropoiesis,p38α is activated during erythroid differentiation.Loss of p38α completely blocks enucleation of primary erythroblasts.Moreover,p38α regulates erythroblast enucleation in a cell-autonomous manner in vivo during fetal and anemic stress erythropoiesis.Markedly,loss of p38α leads to downregulation of p21,and decreased activation of the p21 target Rb,both of which are important regulators of erythroblast enucleation.This study demonstrates that p38α is a key signaling molecule for erythroblast enucleation during stress erythropoiesis.

  1. Gene induction and repression during terminal erythropoiesis are mediated by distinct epigenetic changes.

    Science.gov (United States)

    Wong, Piu; Hattangadi, Shilpa M; Cheng, Albert W; Frampton, Garrett M; Young, Richard A; Lodish, Harvey F

    2011-10-20

    It is unclear how epigenetic changes regulate the induction of erythroid-specific genes during terminal erythropoiesis. Here we use global mRNA sequencing (mRNA-seq) and chromatin immunoprecipitation coupled to high-throughput sequencing (CHIP-seq) to investigate the changes that occur in mRNA levels, RNA polymerase II (Pol II) occupancy, and multiple posttranslational histone modifications when erythroid progenitors differentiate into late erythroblasts. Among genes induced during this developmental transition, there was an increase in the occupancy of Pol II, the activation marks H3K4me2, H3K4me3, H3K9Ac, and H4K16Ac, and the elongation methylation mark H3K79me2. In contrast, genes that were repressed during differentiation showed relative decreases in H3K79me2 levels yet had levels of Pol II binding and active histone marks similar to those in erythroid progenitors. We also found that relative changes in histone modification levels, in particular, H3K79me2 and H4K16ac, were most predictive of gene expression patterns. Our results suggest that in terminal erythropoiesis both promoter and elongation-associated marks contribute to the induction of erythroid genes, whereas gene repression is marked by changes in histone modifications mediating Pol II elongation. Our data map the epigenetic landscape of terminal erythropoiesis and suggest that control of transcription elongation regulates gene expression during terminal erythroid differentiation.

  2. Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.

    Directory of Open Access Journals (Sweden)

    Hsin-Hou Chang

    Full Text Available Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs. Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

  3. Appropriate use of the rules for erythropoiesis stimulating agents in the treatment of anemia in chronic kidney disease%正确掌握红细胞生成刺激剂治疗慢性肾脏病贫血的规范

    Institute of Scientific and Technical Information of China (English)

    孙雪峰

    2010-01-01

    @@ 肾性贫血是慢性肾脏病(chronic kidney disease,CKD)的常见临床表现和重要合并症,CKDⅠ~Ⅴ期的患者均可以合并不同程度的贫血,几乎100%的终末期肾脏疾病的患者都合并不同程度的贫血.肾性贫血的有效治疗对减少CKD患者心血管事件、改善患者脑功能和认知能力,提高生活质量和机体活动能力,降低CKD患者的住院率和死亡率十分重要.

  4. Tracing the progress in erythropoiesis stimulating agents and iron metabolism for the guidance of anemia treatment in chronic ridney disease patients%跟踪红细胞生成刺激剂与铁代谢新进展,指导慢性肾脏病贫血治疗

    Institute of Scientific and Technical Information of China (English)

    郑法雷; 袁群生

    2010-01-01

    @@ 贫血是慢性肾脏病(chronic kidney disease,CKD)尤其是透析患者主要并发症之一.近年研究表明,贫血常常使患者生活质量下降,心血管疾病发病率和死亡率明显增加.肾性贫血的有效治疗,对减少CKD患者心血管事件、改善患者脑功能和机体活动能力,提高生活质量,降低患者住院率和死亡率都十分重要[1,2].

  5. Critical requirement of VEGF-C in transition to fetal erythropoiesis.

    Science.gov (United States)

    Fang, Shentong; Nurmi, Harri; Heinolainen, Krista; Chen, Shuo; Salminen, Essi; Saharinen, Pipsa; Mikkola, Hanna K A; Alitalo, Kari

    2016-08-01

    Vascular endothelial growth factor C (VEGF-C) is a major driver of lymphangiogenesis in embryos and adults. Vegfc gene deletion in mouse embryos results in failure of lymphangiogenesis, fluid accumulation in tissues, and lethality. The VEGF-C receptors VEGFR3 and VEGFR2 are required for embryonic blood vessel formation. The related VEGF is essential for both blood vessel formation and embryonic hematopoiesis, whereas the possible involvement of VEGF-C in hematopoiesis is unknown. Here we unveil a novel hematopoietic function of VEGF-C in fetal erythropoiesis. Deletion of Vegfc in embryonic day 7.5 (E7.5) embryos in the C57BL6 mouse genetic background led to defective fetal erythropoiesis, characterized by anemia and lack of enucleated red blood cells in blood circulation. Macrophages and erythroid cells in the fetal liver (FL) were also decreased after midgestation because of decreased cell proliferation and increased apoptosis. However, the Lin(-)Sca-1(+)c-Kit(+) stem cell compartment in E14.5 FL was not affected by Vegfc deletion. VEGF-C loss did not disrupt the generation of primitive erythroid cells or erythro-myeloid progenitors (EMPs) in the yolk sac, but it decreased the expression of α4-integrin on EMPs and compromised EMP colonization of the FL. The distribution, maturation, and enucleation of primitive erythroblasts were also impaired by Vegfc deletion. In contrast, Vegfc deletion from E10.5 onward did not compromise definitive hematopoiesis in the liver, and Vegfc deletion in adult mice did not cause anemia. These results reveal an unexpected role for VEGF-C, a major lymphangiogenic growth factor, in the transition to FL erythropoiesis. PMID:27343251

  6. 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

  7. Control-relevant erythropoiesis modeling in end-stage renal disease.

    Science.gov (United States)

    Chait, Yossi; Horowitz, Joseph; Nichols, Brendan; Shrestha, Rajiv P; Hollot, C V; Germain, Michael J

    2014-03-01

    Anemia is prevalent in end-stage renal disease (ESRD). The discovery of recombinant human erythropoietin (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hb) measurements. In order to facilitate the design of an AMP using model-based feedback control theory, we present a physiologically relevant erythropoiesis model and demonstrate its applicability using clinical data. PMID:24235247

  8. Stimulative effect of the fungal biocontrol agent Fusarium oxysporum f.sp. Striga on abundance of nitrifying prokaryotes in a maize rhizosphere

    Science.gov (United States)

    Musyoki, Mary; Enowashu, Esther; Zimmermann, Judith; Muema, Esther; Wainright, Henry; Vanlauwe, Bernard; Cadisch, Georg; Rasche, Frank

    2014-05-01

    The integration of resistant crop varieties and Fusarium oxysporum f.sp. strigae (Foxy-2) strains as biological control agent (BCA) has shown to be an effective control of the weed Striga hermonthica which is parasitic to several cereals (e.g., maize) cultivated in Sub-Saharan Africa. Most studies have examined the efficacy of the BCA and its interactions with host crops, while overlooking the interplay among key microorganisms in the soil nitrogen (N) cycle. Hence, we postulated that both Foxy-2 and Striga pose threats to the indigenous plant root-associated microbial communities involved in N cycling through direct or indirect competition for nutrients and that the application of high quality organic residues would compensate these effects. The primary objective of this study was thus to assess the potential impact of Foxy-2 on indigenous nitrifying prokaryotes in maize rhizosphere cultivated on two distinct soils (sandy Ferric Alisol versus clayey Humic Nitisol) obtained from Machanga and Embu, respectively, in central Kenya. These soils were treated with or without Foxy-2 and Striga; and in combination with high quality (i.e. CN ratio; 13, lignins, 8.9 % and polyphenols, 1.7 %) organic residues (i.e., Tithonia diversifolia) as N source. Using quantitative polymerase chain reaction (qPCR), we followed at three pre-defined sampling dates (14, 28 and 42 days after planting) the responses of ammonia-oxidizing archaea (AOA) and bacteria (AOB), total bacteria and archaea in four treatments of a rhizobox experiment: (i) Foxy-2 plus Striga (F+S), (ii) Striga only (C+S), (iii) Foxy-2 plus Striga plus Tithonia diversifolia residues (F+S+T), and (iv) a non-treated control (C). Overall, the treatment effects on soil microbial populations were, in comparison to the clayey Embu soil, more pronounced in the sandy Machanga soil. Contrary to our expectations, we observed a distinct stimulative, but no resource competition effect of Foxy-2 on the abundance of AOA, as well as

  9. 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.

  10. Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens.

    Science.gov (United States)

    Suzuki, Y; Shimizu, H; Nagae, Y; Fukumoto, M; Okonogi, H; Kadokura, M

    1993-01-01

    The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen-induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1-dimethylhydrazine (DMH) 12-24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals--benzo(a)pyrene, 2-naphthylamine--was also observed following pretreatment with cobalt dichloride. PMID:8359151

  11. 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

    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......Mitogen-activated protein kinase/extracellular signal to regulated kinase (MEK) kinase 1 (MEKK1) is a c-Jun N-terminal kinase (JNK) activating kinase known to be implicated in proinflammatory responses and cell motility. Using mice deficient for MEKK1 kinase activity (Mekk1(DeltaKD)) we show a role...... 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...

  12. TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis.

    Science.gov (United States)

    Zamai, L; Secchiero, P; Pierpaoli, S; Bassini, A; Papa, S; Alnemri, E S; Guidotti, L; Vitale, M; Zauli, G

    2000-06-15

    The impact of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal hematopoietic development was investigated using adult peripheral blood CD34(+) hematopoietic progenitor cells, induced to differentiate along the erythroid, megakaryocytic, granulocytic, and monocytic lineages by the addition of specific cytokine cocktails. TRAIL selectively reduced the number of erythroblasts, showing intermediate levels of glycophorin A (glycophorin A(interm)) surface expression, which appeared in liquid cultures supplemented with stem cell factor + interleukin 3 + erythropoietin at days 7-10. However, neither immature (day 4) glycophorin A(dim) erythroid cells nor mature (day 14) glycophorin A(bright) erythroblasts were sensitive to TRAIL-mediated apoptosis. Moreover, pre-exposure to TRAIL significantly decreased the number and size of erythroid colonies in semisolid assays. These adverse effects of TRAIL were selective for erythropoiesis, as TRAIL did not significantly influence the survival of cells differentiating along the megakaryocytic, granulocytic, or monocytic lineages. Furthermore, TRAIL was detected by Western blot analysis in lysates obtained from normal bone marrow mononuclear cells. These findings indicate that TRAIL acts in a lineage- and stage of differentiation-specific manner, as a negative regulator of normal erythropoiesis. (Blood. 2000;95:3716-3724) PMID:10845902

  13. Simplification of an erythropoiesis model for design of anemia management protocols in end stage renal disease.

    Science.gov (United States)

    Nichols, B; Shrestha, R P; Horowitz, J; Hollot, C V; Germain, M J; Gaweda, A E; Chait, Y

    2011-01-01

    Many end stage renal disease (ESRD) patients suffer from anemia due to insufficient endogenous production of erythropoietin (EPO). The discovery of recombinant human EPO (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hgb) measurements. In order to facilitate the design of an AMP based on formal control design methods, we present a physiologically-relevant erythropoiesis model, and show that its nonlinear dynamics can be approximated using a static nonlinearity, a step that greatly simplifies AMP design. We demonstrate applicability of our results using clinical data. PMID:22254256

  14. Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis.

    Science.gov (United States)

    Cheng, Albert W; Shi, Jiahai; Wong, Piu; Luo, Katherine L; Trepman, Paula; Wang, Eric T; Choi, Heejo; Burge, Christopher B; Lodish, Harvey F

    2014-07-24

    The scope and roles of regulated isoform gene expression during erythroid terminal development are poorly understood. We identified hundreds of differentiation-associated isoform changes during terminal erythropoiesis. Sequences surrounding cassette exons of skipped exon events are enriched for motifs bound by the Muscleblind-like (MBNL) family of splicing factors. Knockdown of Mbnl1 in cultured murine fetal liver erythroid progenitors resulted in a strong block in erythroid differentiation and disrupted the developmentally regulated exon skipping of Ndel1 mRNA, which is bound by MBNL1 and critical for erythroid terminal proliferation. These findings reveal an unanticipated scope of the alternative splicing program and the importance of Mbnl1 during erythroid terminal differentiation.

  15. Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir

    OpenAIRE

    Hiasa, Miki; Isoda, Yumiko; Kishimoto, Yasushi; Saitoh, Kenta; Kimura, Yasuaki; Kanai, Motomu; Shibasaki, Masakatsu; Hatakeyama, Dai; Kirino, Yutaka; Kuzuhara, Takashi

    2013-01-01

    Background and Purpose Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. Experimental Approach We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form – oseltamivir carboxylate (OC) or the inactiv...

  16. Alpha4beta1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: integrins in red cell development.

    Science.gov (United States)

    Eshghi, Shawdee; Vogelezang, Mariette G; Hynes, Richard O; Griffith, Linda G; Lodish, Harvey F

    2007-06-01

    Erythropoietin (Epo) is essential for the terminal proliferation and differentiation of erythroid progenitor cells. Fibronectin is an important part of the erythroid niche, but its precise role in erythropoiesis is unknown. By culturing fetal liver erythroid progenitors, we show that fibronectin and Epo regulate erythroid proliferation in temporally distinct steps: an early Epo-dependent phase is followed by a fibronectin-dependent phase. In each phase, Epo and fibronectin promote expansion by preventing apoptosis partly through bcl-xL. We show that alpha(4), alpha(5), and beta(1) are the principal integrins expressed on erythroid progenitors; their down-regulation during erythropoiesis parallels the loss of cell adhesion to fibronectin. Culturing erythroid progenitors on recombinant fibronectin fragments revealed that only substrates that engage alpha(4)beta(1)-integrin support normal proliferation. Collectively, these data suggest a two-phase model for growth factor and extracellular matrix regulation of erythropoiesis, with an early Epo-dependent, integrin-independent phase followed by an Epo-independent, alpha(4)beta(1)-integrin-dependent phase.

  17. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells. PMID:22363217

  18. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  19. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells.

  20. Pro-Inflammatory Cytokine-Mediated Anemia: Regarding Molecular Mechanisms of Erythropoiesis

    Directory of Open Access Journals (Sweden)

    F. Morceau

    2009-01-01

    Full Text Available Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway, without erythropoietin defect. This suggested that pro-inflammatory cytokine-mediated signaling pathways affect erythropoietin activity. They could interfere with erythropoietin-mediated signaling pathways, inducing early apoptosis and perturbing the expression and regulation of specific transcription factors involved in the control of erythroid differentiation. In this review we summarize the effect of tumor necrosis factor (TNFα, TNF-related apoptosis-inducing ligand (TRAIL, and interferon (IFN-γ on erythropoiesis with a particular interest for molecular feature.

  1. Hepcidin-Dependent Regulation of Erythropoiesis during Anemia in a Teleost Fish, Dicentrarchus labrax

    Science.gov (United States)

    Caldas, Carolina; Ramos, Miguel F.; Rodrigues, Pedro N. S.

    2016-01-01

    Anemia is a common disorder, characterized by abnormally low levels of red blood cells or hemoglobin. The mechanisms of anemia development and response have been thoroughly studied in mammals, but little is known in other vertebrates, particularly teleost fish. In this study, different degrees of anemia were induced in healthy European sea bass specimens (Dicentrarchus labrax) and at pre-determined time points hematological parameters, liver iron content and the expression of genes involved in iron homeostasis and hematopoiesis, with particular attention on hepcidins, were evaluated. The experimental anemia prompted a decrease in hamp1 expression in all tested organs, in accordance to an increased need for iron absorption and mobilization, with slight increases in hamp2 in the kidney and intestine. The liver was clearly the major organ involved in iron homeostasis, decreasing its iron content and showing a gene expression profile consistent with an increased iron release and mobilization. Although both the spleen and head kidney are involved in erythropoiesis, the spleen was found to assume a more preponderant role in the recovery of erythrocyte levels. The intestine was also involved in the response to anemia, through the increase of iron transporting genes. Administration of Hamp1 or Hamp2 mature peptides showed that only Hamp1 affects hematological parameters and liver iron content. In conclusion, the molecular mechanisms of response to anemia present in sea bass are similar to the ones described for mammals, with these results indicating that the two hepcidin types from teleosts assume different roles during anemia. PMID:27100629

  2. Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos

    Directory of Open Access Journals (Sweden)

    Keai Sinn Tan

    2015-07-01

    Full Text Available Fetal spleen is a major hematopoietic site prior to initiation of bone marrow hematopoiesis. Morphologic analysis suggested erythropoietic activity in fetal spleen, but it remained unclear how erythropoiesis was regulated. To address this question, we performed flow cytometric analysis and observed that the number of spleen erythroid cells increased 18.6-fold from 16.5 to 19.5 days post-coitum (dpc. Among erythropoietic cytokines, SCF and IGF-1 were primarily expressed in hematopoietic, endothelial and mesenchymal-like fetal spleen cells. Cultures treated with SCF and/or IGF-1R inhibitors showed significantly decreased CD45−c-Kit−CD71+/−Ter119+ erythroid cells and downregulated Gata1, Klf1 and β-major globin expression. Administration of these inhibitors to pregnant mice significantly decreased the number of CD45−c-Kit−CD71+/−Ter119+ cells and downregulated β-major globin gene expression in embryos derived from these mice. We conclude that fetal spleen is a major erythropoietic site where endothelial and mesenchymal-like cells primarily accelerate erythropoietic activity through SCF and IGF-1 secretion.

  3. Engineering superactive granulocyte macrophage colony-stimulating factor transferrin fusion proteins as orally-delivered candidate agents for treating neurodegenerative disease.

    Science.gov (United States)

    Heinzelman, Pete; Priebe, Molly C

    2015-01-01

    Intravenously injected granulocyte macrophage colony-stimulating factor (GM-CSF) has shown efficacy in Alzheimer's Disease (AD) and Parkinson's Disease (PD) animal studies and is undergoing clinical evaluation. The likely need for dosing of GM-CSF to patients over months or years motivates pursuit of avenues for delivering GM-CSF to circulation via oral administration. Flow cytometric screening of 37 yeast-displayed GM-CSF saturation mutant libraries revealed residues P12, H15, R23, R24, and K72 as key determinants of GM-CSF's CD116 and CD131 GM-CSF receptor (GM-CSFR) subunit binding affinity. Screening combinatorial GM-CSF libraries mutated at positions P12, H15, and R23 yielded variants with increased affinities toward both CD116 and CD131. Genetic fusion of GM-CSF to human transferrin (Trf), a strategy that enables oral delivery of other biopharmaceuticals in animals, yielded bioactive wild type and variant cytokines upon secretion from cultured Human Embryonic Kidney cells. Surface plasmon resonance (SPR) measurements showed that all evaluated variants possess decreases in CD116 and CD131 binding KD values of up to 2.5-fold relative to wild type. Improved affinity led to increased in vitro bioactivity; the most bioactive variant, P12D/H15L/R23L, had a leukocyte proliferation assay EC50 value 3.5-fold lower than the wild type GM-CSF/Trf fusion. These outcomes are important first steps toward our goal of developing GM-CSF/Trf fusions as orally available AD and PD therapeutics. PMID:25737095

  4. Use of antimicrobial agents and granulocyte colony stimulating factors for febrile neutropenia in cancer patients in a tertiary care hospital in India

    Directory of Open Access Journals (Sweden)

    V Roy

    2010-01-01

    Full Text Available Background: Use of antimicrobials (AM and granulocyte colony stimulating factors (G-CSF affect the outcome and cost of treatment of febrile neutropenia (FN. There are no studies describing the AM utilization pattern or the use of G-CSF and cost incurred on them in cancer patients with FN from India. Materials and Methods: A study was conducted in a tertiary care, teaching hospital in New Delhi, India, with the objectives of describing the utilization pattern of AM and G-CSF in cancer patients with FN. The efficacy and costs of AM and G-CSF prescribed were also assessed. Results: A total of 211 patients with FN were enrolled in the study. A majority of 207 (98.1% were in the low-risk category. The average number of AM used per patient was 2.45 ± 0.02 and the AM exposure density was 1.19. All patients were administered five different combinations of AM regimens and G-CSF, irrespective of the risk category. No difference in the time to defervesence or in the recovery of ANC counts were observed with the different AM regimens. The average drug cost per febrile neutropenia episode (FNE was Rs 4694.45 ± 296.35 (113.95 ± 7.19$. G-CSF accounted for 76.14 - 97.58% of the total costs. Conclusion: Large variations in the pattern of AM prescribed with routine use of G-CSF, irrespective of the risk status, was observed. Guidelines for the rational and cost-effective use of AM and G-CSF in patients with FN needed to be prepared. This was especially important as treatment was given free of cost to all patients admitted in the government health facility.

  5. 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.

  6. Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia.

    Science.gov (United States)

    Weiss, Mitchell J; Zhou, Suiping; Feng, Liang; Gell, David A; Mackay, Joel P; Shi, Yigong; Gow, Andrew J

    2005-01-01

    Hemoglobin (Hb) synthesis is coordinated by homeostatic mechanisms to limit the accumulation of free alpha or beta subunits, which are cytotoxic. Alpha hemoglobin-stabilizing protein (AHSP) is an abundant erythroid protein that specifically binds free alphaHb, stabilizes its structure, and limits its ability to participate in chemical reactions that generate reactive oxygen species. Gene ablation studies in mice demonstrate that AHSP is required for normal erythropoiesis. AHSP-null erythrocytes are short-lived, contain Hb precipitates, and exhibit signs of oxidative damage. Loss of AHSP exacerbates beta-thalassemia in mice, indicating that altered AHSP expression or function could modify thalassemia phenotypes in humans, a topic that is beginning to be explored in clinical studies. We used biochemical, spectroscopic, and crystallographic methods to examine how AHSP stabilizes alphaHb. AHSP binds the G and H helices of alphaHb on a surface that largely overlaps with the alpha1-beta1 interface of HbA. This result explains previous findings that betaHb can competitively displace AHSP from alphaHb to form HbA tetramer. Remarkably, binding of AHSP to oxygenated alphaHb induces dramatic conformational changes and converts the heme-bound iron to an oxidized hemichrome state in which all six coordinate positions are occupied. This structure limits the reactivity of heme iron, providing a mechanism by which AHSP stabilizes alphaHb. These findings suggest a biochemical pathway through which AHSP might participate in normal Hb synthesis and modulate the severity of thalassemias. Moreover, understanding how AHSP stabilizes alphaHb provides a theoretical basis for new strategies to inhibit the damaging effects of free alphaHb that accumulates in beta-thalassemia.

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

    Science.gov (United States)

    Miller, Michelle Erin; Rosten, Patty; Lemieux, Madeleine E; Lai, Courteney; Humphries, R Keith

    2016-01-01

    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(ROSA)26Sor(tm1(Cre/ERT)Nat)/J or B6.Cg-Tg(Mx1-Cre)1Cgn/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. PMID:26986211

  8. 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

  9. The c-Myb target gene neuromedin U functions as a novel cofactor during the early stages of erythropoiesis

    OpenAIRE

    Gambone, Julia E; Dusaban, Stephanie S.; Loperena, Roxana; Nakata, Yuji; Shetzline, Susan E.

    2011-01-01

    The requirement of c-Myb during erythropoiesis spurred an interest in identifying c-Myb target genes that are important for erythroid development. Here, we determined that the neuropeptide neuromedin U (NmU) is a c-Myb target gene. Silencing NmU, c-myb, or NmU's cognate receptor NMUR1 expression in human CD34+ cells impaired burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) formation compared with control. Exogenous addition of NmU peptide to NmU or c-myb siRNA-tr...

  10. From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications.

    Science.gov (United States)

    Hattangadi, Shilpa M; Wong, Piu; Zhang, Lingbo; Flygare, Johan; Lodish, Harvey F

    2011-12-01

    This article reviews the regulation of production of RBCs at several levels. We focus on the regulated expansion of burst-forming unit-erythroid erythroid progenitors by glucocorticoids and other factors that occur during chronic anemia, inflammation, and other conditions of stress. We also highlight the rapid production of RBCs by the coordinated regulation of terminal proliferation and differentiation of committed erythroid colony-forming unit-erythroid progenitors by external signals, such as erythropoietin and adhesion to a fibronectin matrix. We discuss the complex intracellular networks of coordinated gene regulation by transcription factors, chromatin modifiers, and miRNAs that regulate the different stages of erythropoiesis.

  11. 42 CFR 494.80 - Condition: Patient assessment.

    Science.gov (United States)

    2010-10-01

    ... poor nutritional status, unmanaged anemia, and inadequate dialysis. .... (4) Evaluation of factors associated with anemia, such as hematocrit, hemoglobin, iron stores, and potential treatment plans for anemia, including administration of erythropoiesis-stimulating agent(s)....

  12. JAK2 exon 12 mutant mice display isolated erythrocytosis and changes in iron metabolism favoring increased erythropoiesis.

    Science.gov (United States)

    Grisouard, Jean; Li, Sai; Kubovcakova, Lucia; Rao, Tata Nageswara; Meyer, Sara C; Lundberg, Pontus; Hao-Shen, Hui; Romanet, Vincent; Murakami, Masato; Radimerski, Thomas; Dirnhofer, Stephan; Skoda, Radek C

    2016-08-11

    Mutations in JAK2 exon 12 are frequently found in patients with polycythemia vera (PV) that do not carry a JAK2-V617F mutation. The majority of these patients display isolated erythrocytosis. We generated a mouse model that expresses JAK2-N542-E543del, the most frequent JAK2 exon 12 mutation found in PV patients. Mice expressing the human JAK2-N542-E543del (Ex12) showed a strong increase in red blood cell parameters but normal neutrophil and platelet counts, and reduced overall survival. Erythropoiesis was increased in the bone marrow and spleen, with normal megakaryopoiesis and absence of myelofibrosis in histopathology. Erythroid progenitors and precursors were increased in hematopoietic tissues, but the numbers of megakaryocytic precursors were unchanged. Phosphorylation Stat3 and Erk1/2 proteins were increased, and a trend toward increased phospho-Stat5 and phospho-Stat1 was noted. However, Stat1 knock out in Ex12 mice induced no changes in platelet or red cell parameters, indicating that Stat1 does not play a central role in mediating the effects of Ex12 signaling on megakaryopoiesis or erythropoiesis. Ex12 mice showed decreased expression of hepcidin and increased expression of transferrin receptor-1 and erythroferrone, suggesting that the strong erythroid phenotype in Ex12 mutant mice is favored by changes in iron metabolism that optimize iron availability to allow maximal production of red cells. PMID:27288519

  13. pRB and E2F4 play distinct cell-intrinsic roles in fetal erythropoiesis.

    Science.gov (United States)

    Zhang, Jing; Lee, Eunice Y; Liu, Yangang; Berman, Seth D; Lodish, Harvey F; Lees, Jacqueline A

    2010-01-15

    The retinoblastoma tumor suppressor protein pRB functions, at least in part, by directly binding to and modulating the activity of the E2F transcription factors. Previous studies have shown that both E2F4 and pRB play important roles in fetal erythropoiesis. Given that these two proteins interact directly we investigated the overlap of E2F4 and pRB function in this process by analyzing E2f4(-/-), conditional Rb knockout (Rb(1lox/1lox)), and compound E2f4(-/-);Rb(1lox/1lox) embryos. At E15.5 E2f4(-/-) and Rb(1lox/1lox) fetal erythroid cells display distinct abnormalities in their differentiation profiles. When cultured in vitro, both E2f4(-/-) and Rb(1lox/1lox) erythroid cells show defects in cell cycle progression. Surprisingly, analysis of cell cycle profiling suggests that E2F4 and pRB control cell cycle exit through different mechanisms. Moreover, only pRB, but not E2F4, promotes cell survival in erythroid cells. We observed an additive rather than a synergistic impact upon the erythroid defects in the compound E2f4(-/-);Rb(1lox/1lox) embryos. We further found that fetal liver macrophage development is largely normal regardless of genotype. Taken together, our results show that E2F4 and pRB play independent cell-intrinsic roles in fetal erythropoiesis.

  14. 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.

  15. Global analysis of induced transcription factors and cofactors identifies Tfdp2 as an essential coregulator during terminal erythropoiesis.

    Science.gov (United States)

    Chen, Cynthia; Lodish, Harvey F

    2014-06-01

    Key transcriptional regulators of terminal erythropoiesis, such as GATA-binding factor 1 (GATA1) and T-cell acute lymphocytic leukemia protein 1 (TAL1), have been well characterized, but transcription factors and cofactors and their expression modulations have not yet been explored on a global scale. Here, we use global gene expression analysis to identify 28 transcription factors and 19 transcriptional cofactors induced during terminal erythroid differentiation whose promoters are enriched for binding by GATA1 and TAL1. Utilizing protein-protein interaction databases to identify cofactors for each transcription factor, we pinpoint several co-induced pairs, of which E2f2 and its cofactor transcription factor Dp-2 (Tfdp2) were the most highly induced. TFDP2 is a critical cofactor required for proper cell cycle control and gene expression. GATA1 and TAL1 are bound to the regulatory regions of Tfdp2 and upregulate its expression and knockdown of Tfdp2 results in significantly reduced rates of proliferation as well as reduced upregulation of many erythroid-important genes. Loss of Tfdp2 also globally inhibits the normal downregulation of many E2F2 target genes, including those that regulate the cell cycle, causing cells to accumulate in S phase and resulting in increased erythrocyte size. Our findings highlight the importance of TFDP2 in coupling the erythroid cell cycle with terminal differentiation and validate this study as a resource for future work on elucidating the role of diverse transcription factors and coregulators in erythropoiesis.

  16. 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

  17. IN-VIVO EFFECTS OF INTERLEUKIN-11 AND STEM-CELL FACTOR IN COMBINATION WITH ERYTHROPOIETIN IN THE REGULATION OF ERYTHROPOIESIS

    NARCIS (Netherlands)

    DEHAAN, G; DONTJE, B; ENGEL, C; LOEFFLER, M; NIJHOF, W

    1995-01-01

    In this study we evaluated the in vivo effects of interleukin-11 (IL-11) and stem cell factor (SCF), in combination with erythropoietin (EPO) on murine erythropoiesis. Mice were treated for 7d with IL-11, SCF and EPO, each at three dose levels, In total, 27 different dose combinations were tested, I

  18. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression

    NARCIS (Netherlands)

    R. Pop (Ramona); J.R. Shearstone (Jeffrey); Q. Shen (Qichang); Y. Liu (Ying); K. Hallstrom (Kelly); M. Koulnis (Miroslav); J.H. Gribnau (Joost); M. Socolovsky (Merav)

    2010-01-01

    textabstractHematopoietic progenitors undergo differentiation while navigating several cell division cycles, but it is unknown whether these two processes are coupled. We addressed this question by studying erythropoiesis in mouse fetal liver in vivo. We found that the initial upregulation of cell s

  19. 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.

  20. Facteurs prédictifs de la réponse à la CERA chez les hémodialysés chroniques naïfs de traitement par agent stimulant l’érythropoïèse

    Science.gov (United States)

    Ezziani, Mariam; Najdi, Adil; Mikou, Souad; Hanin, Hakim; Arrayhani, Mohammed; Houssaini, Tarik Sqalli

    2015-01-01

    La correction et la stabilité du taux d'hémoglobine est un objectif majeur du traitement de l'anémie chez les hémodialysés chroniques. Toutefois, la cible d'hémoglobine > 11g/dl fixée par les recommandations demeure difficile à atteindre dans notre contexte. Le but de cette étude est d’évaluer la réponse au traitement par CERA (continuous erythropoietin receptor activator) chez une population d'hémodialysés chroniques naïfs de tout traitement par agent stimulant de l’érythropoïèse et étudier les différents facteurs associés à une mauvaise réponse au traitement. Il s'agit une étude prospective mono centrique faite au sein d'une population d’ hémodialysés chroniques. Ont été inclus les patients en hémodialyse depuis plus de 12 mois, naïfs de tout traitement par agent stimulant de l’érythropoïèse (ASE) et ayant un taux d'hémoglobine(Hb) 11g/dl. Sur 87 patients en hémodialyse périodique, 22 (25,3%) sont naïfs de tout traitement par ASE. Il s'agit de 13 hommes et 9 femmes avec un âge moyen de 46 ± 19 ans et une ancienneté en hémodialyse de 67 ± 59 mois. Le taux initial d'hémoglobine est de 7,8 ± 1,3 g/dl. Au bout de 4 mois de traitement régulier par la CERA, le taux final d'Hb est de 10,9 ± 2,1g/dl et 63,6% des patients ont atteint la cible d'Hb > 11g/dl. La dose moyenne de CERA à la fin de l’étude est de 0,89 ± 0,35 µg/kg/15j. L'analyse des facteurs prédictifs montre que la réponse finale dépend du taux d'Hb initial (p = 0,002). En effet, quand le taux d'Hb initial est > 8 g/dl, le taux de réponse est de 88% vs 46% lorsque le taux d'Hb 11 g/dl sans dépasser 13 g/dl [9, 10]. Cependant, le maintien d'un taux d'hémoglobine stable nécessite du temps, des ressources humaines et financières et exige des adaptations thérapeutiques fréquentes [11]. Le méthoxy polyéthylène glycol-époétine bêta, activateur continu du récepteur de l’érythropoïétine (C.E.R.A), est un nouvel ASE qui permet la

  1. Cardiovascular actions of drugs classed as stimulants.

    OpenAIRE

    Killian, Lindsey M

    2014-01-01

    The World Anti-Doping Agency prohibits and monitors the use of stimulants in sport. The effects of stimulants on enhancing performance in sport is uncertain. Stimulants have central and peripheral effects that can enhance mental or physical function. They are used therapeutically to treat a range of conditions most notable ADHD, depression and nasal decongestion. The present study looked at the peripheral sympathomimetic effects of stimulants on the cardiovascular system. The agents that were...

  2. Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle

    DEFF Research Database (Denmark)

    Robach, Paul; Cairo, Gaetano; Gelfi, Cecilia;

    2007-01-01

    Iron is essential for oxygen transport because it is incorporated in the heme of the oxygen-binding proteins hemoglobin and myoglobin. An interaction between iron homeostasis and oxygen regulation is further suggested during hypoxia, in which hemoglobin and myoglobin syntheses have been reported...... to increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells...... with increased ferroportin mRNA levels, suggesting enhanced iron export. Thus, in HA, the elevated iron requirement associated with enhanced erythropoiesis presumably elicits iron mobilization and myoglobin down-modulation, suggesting an altered muscle oxygen homeostasis....

  3. Erythropoietin or darbepoetin for patients with cancer

    OpenAIRE

    Tonia, Thomy; Mettler, Annette; Robert, Nadège; Schwarzer, Guido; Seidenfeld, Jerome; Weingart, Olaf; Hyde, Chris; Engert, Andreas; Bohlius, Julia

    2012-01-01

    Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoiesis stimulating agents (ESAs) and red blood cell transfusions.

  4. Infection-stimulated Anemia Results Primarily from Interferon Gamma-dependent, Signal Transducer and Activator of Transcription 1-independent Red Cell Loss

    Institute of Scientific and Technical Information of China (English)

    Zheng Wang; Dong-Xia Zhang; Qi Zhao

    2015-01-01

    Background:Although the onset of anemia during infectious disease is commonly correlated with production of inflammatory cytokines,the mechanisms by which cytokines induce anemia are poorly defined.This study focused on the mechanism research.Methods:Different types of mice were infected perorally with Toxoplasma gondii strain ME49.At the indicated times,samples from each mouse were harvested,processed,and analyzed individually.Blood samples were analyzed using a Coulter Counter and red blood cell (RBC) survival was measured by biotinylation.Levels of tumor necrosis factor-α (TNF-α),inducible nitric oxide synthase (iNOS),and inducible protein 10 (IP-10) mRNA in liver tissue were measured by real-time polymerase chain reaction.Results:T.gondii-infected mice exhibited anemia due to a decrease in both erythropoiesis and survival time of RBC in the circulation (P < 0.02).In addition,infection-stimulated anemia was associated with fecal occult,supporting previous literature that hemorrhage is a consequence of T.gondii infection in mice.Infection-induced anemia was abolished in interferon gamma (IFNγ) and IFNγ receptor deficient mice (P < 0.05) but was still evident in mice lacking TNF-α,iNOS,phagocyte NADPH oxidase or IP-10 (P < 0.02).Neither signal transducer and activator of transcription 1 (STAT1) deficient mice nor 129S6 controls exhibited decreased erythropoiesis,but rather suffered from an anemia resulting solely from increased loss of circulating RBC.Conclusions:Infection-stimulated decrease in erythropoiesis and losses of RBC have distinct mechanistic bases.These results show that during T.gondii infection,IFNγ is responsible for an anemia that results from both a decrease in erythropoiesis and a STAT1 independent loss of circulating RBC.

  5. Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis.

    Science.gov (United States)

    Ludwig, Leif S; Cho, Hyunjii; Wakabayashi, Aoi; Eng, Jennifer C; Ulirsch, Jacob C; Fleming, Mark D; Lodish, Harvey F; Sankaran, Vijay G

    2015-05-01

    Genome-wide association studies (GWAS) hold tremendous promise to improve our understanding of human biology. Recent GWAS have revealed over 75 loci associated with erythroid traits, including the 4q27 locus that is associated with red blood cell size (mean corpuscular volume). The close linkage disequilibrium block at this locus harbors the CCNA2 gene that encodes cyclin A2. CCNA2 mRNA is highly expressed in human and murine erythroid progenitor cells and regulated by the essential erythroid transcription factor GATA1. To understand the role of cyclin A2 in erythropoiesis, we have reduced expression of this gene using short hairpin RNAs in a primary murine erythroid culture system. We demonstrate that cyclin A2 levels affect erythroid cell size by regulating the passage through cytokinesis during the final cell division of terminal erythropoiesis. Our study provides new insight into cell cycle regulation during terminal erythropoiesis and more generally illustrates the value of functional GWAS follow-up to gain mechanistic insight into hematopoiesis.

  6. Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis

    Science.gov (United States)

    Ludwig, Leif S.; Cho, Hyunjii; Wakabayashi, Aoi; Eng, Jennifer C.; Ulirsch, Jacob C.; Fleming, Mark D.; Lodish, Harvey F.; Sankaran, Vijay G.

    2015-01-01

    Genome-wide association studies (GWAS) hold tremendous promise to improve our understanding of human biology. Recent GWAS have revealed over 75 loci associated with erythroid traits, including the 4q27 locus that is associated with red blood cell size (mean corpuscular volume, MCV). The close linkage disequilibrium block at this locus harbors the CCNA2 gene that encodes cyclin A2. CCNA2 mRNA is highly expressed in human and murine erythroid progenitor cells and regulated by the essential erythroid transcription factor GATA1. To understand the role of cyclin A2 in erythropoiesis, we have reduced expression of this gene using short hairpin RNAs in a primary murine erythroid culture system. We demonstrate that cyclin A2 levels affect erythroid cell size by regulating the passage through cytokinesis during the final cell division of terminal erythropoiesis. Our study provides new insight into cell cycle regulation during terminal erythropoiesis and more generally illustrates the value of functional GWAS follow-up to gain mechanistic insight into hematopoiesis. PMID:25615569

  7. Rapid body mass loss affects erythropoiesis and hemolysis but does not impair aerobic performance in combat athletes.

    Science.gov (United States)

    Reljic, D; Feist, J; Jost, J; Kieser, M; Friedmann-Bette, B

    2016-05-01

    Rapid body mass loss (RBML) before competition was found to decrease hemoglobin mass (Hbmass ) in elite boxers. This study aimed to investigate the underlying mechanisms of this observation. Fourteen well-trained combat athletes who reduced body mass before competitions (weight loss group, WLG) and 14 combat athletes who did not practice RBML (control group, CON) were tested during an ordinary training period (t-1), 1-2 days before an official competition (after 5-7 days RBML in WLG, t-2), and after a post-competition period (t-3). In WLG, body mass (-5.5%, range: 2.9-6.8 kg) and Hbmass (-4.1%) were significantly (P < 0.001) reduced after RBML and were still decreased by 1.6% (P < 0.05) and 2.6% (P < 0.001) at t-3 compared with t-1. After RBML, erythropoietin, reticulocytes, haptoglobin, triiodothyronine (FT3 ), and free androgen index (FAI) were decreased compared with t-1 and t-3. An increase occurred in ferritin and bilirubin. Peak treadmill-running performance and VO2peak did not change significantly, but performance at 4-mmol lactate threshold was higher after RBML (P < 0.05). In CON, no significant changes were found in any parameter. Apparently, the significant decrease in Hbmass after RBML in combat athletes was caused by impaired erythropoiesis and increased hemolysis without significant impact on aerobic performance capacity.

  8. 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.

  9. Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi

    Science.gov (United States)

    Trópia de Abreu, Raquel; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Coura-Vital, Wendel; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

    2011-01-01

    Background The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). Methodology/Principal Findings The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Conclusions Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL. PMID:21572995

  10. Antibiotic Agents

    Science.gov (United States)

    ... either as public health or as non-public health antimicrobial agents. What is the difference between bacteriostats, sanitizers, disinfectants ... bacteria, however, there is considerable controversy surrounding their health benefits. The ... producing agents (Table of Antibacterials) have been used for many ...

  11. 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.

  12. The Effects of Hypobaric Hypoxia on Erythropoiesis, Maximal Oxygen Uptake and Energy Cost of Exercise Under Normoxia in Elite Biathletes

    Directory of Open Access Journals (Sweden)

    Milosz Czuba

    2014-12-01

    Full Text Available The aim of the present study was to evaluate the effects of 3 weeks altitude training according to the HiHiLo (live high-base train high-interval train low procedure as described by Chapman et al. (1998, on erythropoiesis, maximal oxygen uptake and energy cost of exercise under normoxia in elite biathletes. Fifteen male elite biathletes randomly divided into an experimental (H group (n = 7; age 27.1 ± 4.6 years; maximal oxygen uptake (VO2max 66.9 ± 3.3 ml·kg–1·min–1; body height (BH 1.81 ± 0.06 m; body mass (BM 73.1 ± 5.4kg, and a control (C group (n = 8; age 23.2 ± 0.9 years; VO2max 68.2 ± 4.1 ml·kg–1·min–1; BH 1.75 ± 0.03 m; BM 63.1 ± 1.5 kg took part in the study. The H group stayed for 3 weeks at an altitude of 2015 m and performed endurance training on skis four times per week at 3000 m. Additionally, the training protocol included three high-intensity interval sessions at an altitude of 1000 m. The C group followed the same training protocol with skirollers in normoxia at an altitude of 600 m. The HiHiLo protocol applied in our study did not change VO2max or maximal workload (WRmax significantly during the incremental treadmill test in group H. However, the energy cost for selected submaximal workloads in group H was significantly (p < 0.01 reduced compared to group C (-5.7%, -4.4%, -6% vs. -3.5%, -2.1%, -2.4%. Also a significant (p < 0.001 increase in serum EPO levels during the first two weeks of HiHiLo training at 2015 m was observed, associated with a significant (p < 0.05 increase in hemoglobin mass, number of erythrocytes, hematocrit value and percent of reticulocytes compared with initial values (by 6.4%, 5%, 4.6% and 16,6%, respectively. In group C, changes in these variables were not observed. These positive changes observed in our study led to a conclusion that the HiHiLo training method could improve endurance in normoxia, since most of the biathlon competitions are performed at submaximal intensities.

  13. Agent, autonomous

    OpenAIRE

    Luciani, Annie

    2007-01-01

    The expression autonomous agents, widely used in virtual reality, computer graphics, artificial intelligence and artificial life, corresponds to the simulation of autonomous creatures, virtual (i.e. totally computed by a program), or embodied in a physical envelope, as done in autonomous robots.

  14. Heme transport and erythropoiesis

    OpenAIRE

    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...

  15. [Pharmacology of bone anabolic agents].

    Science.gov (United States)

    Matsumoto, Toshio

    2015-10-01

    Bone is constantly remodeled to maintain its volume, structural integrity and strength Currently available bone anabolic agent is teriparatide. Teriparatide increases bone mass and strength via both remodeling-dependent and -independent mechanisms, although remodeling-dependent mechanism overweighs the other. Canonical Wnt signal plays an important role in enhancing osteoblast differentiation and bone formation, and its osteocyte-derived inhibitor, sclerostin, regulates bone formation via the regulation of Wnt signaling. Anti-sclerostin antibody stimulates Wnt signaling and enhances bone formation. Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment. The new modality of anabolic agents via remodeling-independent stimulation of bone formation may open up a new avenue for the treatment of osteoporosis.

  16. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  17. 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. PMID:26070756

  18. MORBIDITY AGENTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Shrivastava Neelesh

    2011-09-01

    Full Text Available This paper discuss on clinical representation of morbid jealousy which often termed delusional jealousy or ‘Othello Syndrome’ is a psychiatric condition where a lover believes against all reason and their beloved is being sexually unfaithful. Patients will be preoccupied with their partner’s perceived lack of sexual fidelity and will often behave in an unacceptable or extreme way as they endeavor to prove their ideas. Misuse of any psychomotor is an important association cause morbidity jealousy agents, like CNS stimulants that release the catecholamine, particularly dopamine, from pre synaptic terminals substance should be treated as a priority. Where higher levels of violence are reported Sildenafil may be useful as a diagnostic as well as therapeutic test in such cases .Many studies have shown an association between high alcohol consumption and developing morbid jealousy. Amphetamine-induced psychosis has been extensively studied because of its close resemblance to schizophrenia.

  19. An agent framework for dynamic agent retraining: Agent academy

    OpenAIRE

    Mitkas, P.; A. Symeonidis; Kechagias, D.; Athanasiadis, I.N.; Laleci, G.; KURT, G.; Kabak, Y.; Acar, A.; Dogac, A.

    2004-01-01

    Agent Academy (AA) aims to develop a multi-agent society that can train new agents for specific or general tasks, while constantly retraining existing agents in a recursive mode. The system is based on collecting information both from the environment and the behaviors of the acting agents and their related successes/failures to generate a body of data, stored in the Agent Use Repository, which is mined by the Data Miner module, in order to generate useful knowledge about the application domai...

  20. Acute and chronic elevation of erythropoietin in the brain improves exercise performance in mice without inducing erythropoiesis

    OpenAIRE

    Schuler, Beat; Vogel, Johannes; Grenacher, Beat; Jacobs, Robert A.; Arras, Margarete; Gassmann, Max

    2012-01-01

    Application of recombinant human erythropoietin (rhEpo) improves exercise capacity by stimulating red blood cell production that, in turn, enhances oxygen delivery and utilization. Apart from this, when applied at high doses, rhEpo crosses the blood-brain barrier, triggering protective neuronal effects. Here we show a fundamental new role by which the presence of Epo in the brain augments exercise performance without altering red blood cell production. Two different animal models, the transge...

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

    OpenAIRE

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

    2016-01-01

    Introduction 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 de...

  2. Ovarian stimulation in patients with breast cancer.

    Science.gov (United States)

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  3. Mechanism of anaemia in rheumatoid arthritis: demonstration of raised interleukin 1 beta concentrations in anaemic patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukaemia (HEL) cells in vitro.

    OpenAIRE

    Maury, C P; Andersson, L C; Teppo, A M; Partanen, S. (Sari); Juvonen, E

    1988-01-01

    The pathogenesis of the anaemia associated with rheumatoid disease is unclear. It has previously been shown that the degree of the anaemia correlates with the severity of the inflammatory disease and that serum from patients with arthritis inhibits erythropoiesis. This study was designed to examine whether interleukin 1 could be a mediator of the anaemia in rheumatoid arthritis. Radioimmunoassay of interleukin 1 beta in serum showed that patients with rheumatoid arthritis and associated anaem...

  4. Feldspar, Infrared Stimulated Luminescence

    DEFF Research Database (Denmark)

    Jain, Mayank

    2014-01-01

    This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars.......This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars....

  5. Transcranial Electric Field Stimulation

    OpenAIRE

    Arfaee, Arash

    2015-01-01

    Nervous stimulation with electric methods not only has a long history in the treatment of many conditions but also in the last two decades has been used increasingly as a powerful functional brain mapping tool alongside other imaging techniques. This technology has been used to record the stimulation-evoked activity of the stimulated location. This research describes work surrounding a novel technique for brain and nervous stimulation using the electric field as the medium; particularly tra...

  6. Agent Chameleons: Virtual Agents Real Intelligence

    OpenAIRE

    O'Hare, Gregory; Duffy, Brian; Schoen-Phelan, Bianca; Martin, Alan; Bradley, John

    2003-01-01

    Agent Chameleons provides virtual agents powered by real intelligence, delivering next generation autonomic entities that can seamlessly migrate, mutate and evolve on their journey between and within physical and digital information spaces.

  7. Intrinsic defects in erythroid cells from familial hemophagocytic lymphohistiocytosis type 5 patients identify a role for STXBP2/Munc18-2 in erythropoiesis and phospholipid scrambling.

    Science.gov (United States)

    Kostova, Elena B; Beuger, Boukje M; Veldthuis, Martijn; van der Werff Ten Bosch, Jutte; Kühnle, Ingrid; van den Akker, Emile; van den Berg, Timo K; van Zwieten, Rob; van Bruggen, Robin

    2015-12-01

    Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is a rare genetic disorder caused by mutations in STXBP2/Munc18-2. Munc18-2 plays a role in the degranulation machinery of natural killer cells and cytotoxic T lymphocytes. Mutations in STXBP2/Munc18-2 lead to impaired killing of target cells by natural killer cells and cytotoxic T lymphocytes, which in turn results in elevated levels of the inflammatory cytokine interferon γ, macrophage activation, and hemophagocytosis. Even though patients with FHL-5 present with anemia and hemolysis, no link between the disease and the erythroid lineage has been established. Here we report that red blood cells express Munc18-2 and that erythroid cells from patients with FHL-5 exhibit intrinsic defects caused by STXBP2/Munc18-2 mutations. Red blood cells from patients with FHL-5 expose less phosphatidylserine on their surface upon Ca(2+) ionophore ionomycin treatment. Furthermore, cultured erythroblasts from patients with FHL-5 display defective erythropoiesis characterized by decreased CD235a expression and aberrant cell morphology. PMID:26320718

  8. Interacting agents in finance

    NARCIS (Netherlands)

    C. Hommes

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response t

  9. Performance-enhancing drugs: understanding the risks.

    Science.gov (United States)

    Hatton, Caroline K; Green, Gary A; Ambrose, Peter J

    2014-11-01

    To help clinicians understand the risks associated with performance-enhancing drugs, this overview covers prohibited lists of substances and methods, therapeutic use exemptions, the legitimate indications and adverse effects, including for megadose and polypharmacy doping of stimulants, anabolic steroids, erythropoiesis-stimulating agents, and growth hormone and ways in which physicians or patients risk committing anti-doping rule violations inadvertently. PMID:25442165

  10. Deep Brain Stimulation

    OpenAIRE

    Perlmutter, Joel. S.; Mink, Jonathan W.

    2006-01-01

    Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting t...

  11. Stimulant Use Disorders.

    Science.gov (United States)

    Park, Taryn M; Haning, William F

    2016-07-01

    Compared with other illicit substances, stimulants are not commonly used by adolescents; however, they represent a serious concern regarding substance use among youths. This article uses methamphetamine as a model for stimulant use in adolescents; cocaine and prescription stimulants are also mentioned. Methamphetamine use among adolescents and young adults is a serious health concern with potentially long-term physical, cognitive, and psychiatric consequences. Brain development and the effects of misusing stimulants align such that usage in adolescents can more dangerous than during adulthood. It seems helpful to keep in mind the differences between adolescents and young adults when implementing interventions. PMID:27338967

  12. Bi-functional prodrugs of 5-aminolevulinic acid and butyric acid increase erythropoiesis in anemic mice in an erythropoietin-independent manner.

    Science.gov (United States)

    Rephaeli, Ada; Tarasenko, Nataly; Fibach, Eitan; Rozic, Gabriela; Lubin, Ido; Lipovetsky, Julia; Furman, Svetlana; Malik, Zvi; Nudelman, Abraham

    2016-08-25

    Anemia is a major cause of morbidity and mortality worldwide resulting from a wide variety of pathological conditions. In severe cases it is treated by blood transfusions or injection of erythroid stimulating agents, e.g., erythropoietin (Epo), which can be associated with serious adverse effects. Therefore, there is a need to develop new treatment modalities. We recently reported that treatment of erythroleukemic cells with the novel the bi-functional prodrugs of 5-aminolevulinic acid (ALA) and butyric acid (BA), AN233 and AN908, enhanced hemoglobin (Hb) synthesis to a substantially higher level than did ALA and BA individually or their mixture. Herein, we describe that these prodrugs when given orally to mice induced histone deacetylase inhibition in the kidneys, bone marrow and spleen, thus, indicating good penetrability to the tissues. In mice where anemia was chemically induced, treatment with the prodrugs increased the Hb, the number of red blood cells (RBCs) and the percentage of reticulocytes to normal levels. The prodrugs had no adverse effects even after repeated treatment at 100-200mg/kg for 50days. The lack of increased levels of Epo in the blood of mice that were treated with the prodrugs suggests that AN233 and AN908 affected the Hb and RBC levels in an Epo-independent manner. Taken together with our previous studies, we propose that the prodrugs increase globin expression by BA inhibition of histone deacetylase and elevation heme synthesis by ALA. These results support an Epo-independent approach for treating anemia with these prodrugs. PMID:27283485

  13. 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.

  14. 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. PMID:27418093

  15. Stimulated Resonant Radiation

    CERN Document Server

    Clerici, M; Rubino, E; Moss, D; Couairon, A; Légaré, F; Morandotti, R; Faccio, D

    2014-01-01

    Resonant radiation (RR) is emitted by solitons propagating in a waveguide or by filamenting pulses in bulk media. Recent studies have highlighted the possibility to stimulate RR also in weaker pulses that co-propogate with a pump pulse. We numerically and experimentally demonstrate that RR radiation can be stimulated employing a THz seed co-propagating in diamond with an intense 800 nm pulse. This way we predict and observe the stimulated emission of RR at 425 nm, thus bridging a spectral gap of more than six octaves and allowing the detection of THz pulses by means of a silicon-based device.

  16. AgentChess : An Agent Chess Approach

    OpenAIRE

    Fransson, Henric

    2003-01-01

    The game of chess has many times been discussed and used for test purpose by science departments of Artificial Intelligence (AI). Although the technique of agent and as well multi-agent systems is quite old, the use of these offspring of AI within chess is limited. This report describes the project performed applying the use of agents to a chess program. To measure the performance of the logic has tests between the developed program main parts been performed. Further tests against a tradition...

  17. ACTH stimulation test

    Science.gov (United States)

    ... Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 102. Chernecky CC, Berger BJ. ACTH stimulation test - diagnostic. In: ... . 13th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  18. Geothermal Well Stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, D. A.; Morris, C. W.; Sinclair, A. R.; Hanold, R. J.; Vetter, O. J.

    1981-03-01

    The stimulation of geothermal wells presents some new and challenging problems. Formation temperatures in the 300-600 F range can be expected. The behavior of stimulation fluids, frac proppants, and equipment at these temperatures in a hostile brine environment must be carefully evaluated before performance expectations can be determined. In order to avoid possible damage to the producing horizon of the formation, high temperature chemical compatibility between the in situ materials and the stimulation materials must be verified. Perhaps most significant of all, in geothermal wells the required techniques must be capable of bringing about the production of very large amounts of fluid. This necessity for high flow rates represents a significant departure from conventional petroleum well stimulation and demands the creation of very high near-wellbore permeability and/or fractures with very high flow conductivity.

  19. Riot Control Agents

    Science.gov (United States)

    ... a person has been exposed to riot control agents. Long-term health effects of exposure to riot control agents Prolonged ... person is removed from exposure to riot control agents, long-term health effects are unlikely to occur. How you can ...

  20. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

    2008-01-01

    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in this f

  1. Agents modeling agents in information economies

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, J.M.; Durfee, E.H. [Univ. of Michigan, Ann Arbor, MI (United States)

    1996-12-31

    Our goal is to design and build agents that act intelligently when placed in an agent-based information economy, where agents buy and sell services (e.g. thesaurus, search, task planning services, etc.). The economy we are working in is the University of Michigan Digital Library (UMDL), a large scale multidisciplinary effort to build an infrastructure for the delivery of library services. In contrast with a typical economy, an information economy deals in goods and services that are often derived from unique sources (authors, analysts, etc.), so that many goods and services are not interchangeable. Also, the cost of replicating and transporting goods is usually negligible, and the quality of goods and services is difficult to measure objectively: even two sources with essentially the same information might appeal to different audiences. Thus, each agent has its own assessment of the quality of goods and services delivered.

  2. THE INTEGRATED AGENT IN MULTI-AGENT SYSTEMS

    OpenAIRE

    Maleković, Mirko; Čubrilo, Mirko

    2000-01-01

    [n this paper, we characterize the integrated agent in multi-agent systems. The following result is proved: if a multi-agent system is reflexive (symmetric, transitive, Euclidean) then the integrated agent of the multi-agent system is reflexive (symmetric, transitive, Euclidean), respectively. We also prove that the analogous result does not hold for multi-agent system's serial ness. A knowledge relationship between the integrated agent and agents in a multiagent system is presented.

  3. 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

  4. Chemical crowd control agents.

    Science.gov (United States)

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  5. Decontamination Data - Blister Agents

    Data.gov (United States)

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions This dataset is associated with the following...

  6. Copeptin under glucagon stimulation.

    Science.gov (United States)

    Lewandowski, Krzysztof C; Lewiński, Andrzej; Skowrońska-Jóźwiak, Elżbieta; Stasiak, Magdalena; Horzelski, Wojciech; Brabant, Georg

    2016-05-01

    Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p < 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the time-dependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis. PMID:26578365

  7. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    A new technetium-based scintiscanning agent has been prepared comprising a water soluble sup(99m)Tc-methanehydroxydiphosphonate in combination with a reducing agent selected from stannous, ferrous, chromous and titanous salts. As an additional stabilizer salts and esters of gentisic or ascorbic acids have been used. (E.G.)

  8. Agent Development Toolkits

    CERN Document Server

    Singh, Aarti; Sharma, A K

    2011-01-01

    Development of agents as well as their wide usage requires good underlying infrastructure. Literature indicates scarcity of agent development tools in initial years of research which limited the exploitation of this beneficial technology. However, today a wide variety of tools are available, for developing robust infrastructure. This technical note provides a deep overview of such tools and contrasts features provided by them.

  9. Asimovian Adaptive Agents

    CERN Document Server

    Gordon, D F

    2011-01-01

    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  10. How do agents represent?

    Science.gov (United States)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

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

    NARCIS (Netherlands)

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

    2014-01-01

    Background. 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 dis

  12. Evaluation of Motivational Effects Induced by Intracranial Self-Stimulation Behavior

    OpenAIRE

    Sagara,Hidenori; Sendo, Toshiaki; Gomita,Yutaka

    2010-01-01

    In the runway model of intracranial self-stimulation (ICSS) experimentation, the experimental animal is timed in running a fixed distance to depress a lever that releases electrical stimulation to an electrode implanted along its medial forebrain bundle. This ICSS has both a reward and a motivational component. Using the runway method and priming stimulation, we designed an experimental method for directly measuring motivation. An assessment of pharmacological agents that are known to influen...

  13. Stimulated Black Hole Evaporation

    CERN Document Server

    Spaans, Marco

    2016-01-01

    Black holes are extreme expressions of gravity. Their existence is predicted by Einstein's theory of general relativity and is supported by observations. Black holes obey quantum mechanics and evaporate spontaneously. Here it is shown that a mass rate $R_f\\sim 3\\times 10^{-8} (M_0/M)^{1/2}$ $M_0$ yr$^{-1}$ onto the horizon of a black hole with mass $M$ (in units of solar mass $M_0$) stimulates a black hole into rapid evaporation. Specifically, $\\sim 3 M_0$ black holes can emit a large fraction of their mass, and explode, in $M/R_f \\sim 3\\times 10^7 (M/M_0)^{3/2}$ yr. These stimulated black holes radiate a spectral line power $P \\sim 2\\times 10^{39} (M_0/M)^{1/2}$ erg s$^{-1}$, at a wavelength $\\lambda \\sim 3\\times 10^5 (M/M_0)$ cm. This prediction can be observationally verified.

  14. Cognitive stimulation in brainstorming.

    Science.gov (United States)

    Dugosh, K L; Paulus, P B; Roland, E J; Yang, H C

    2000-11-01

    Research on group brainstorming has demonstrated that it is less effective for generating large numbers of ideas than individual brainstorming, yet various scholars have presumed that group idea sharing should enhance cognitive stimulation and idea production. Three experiments examined the potential of cognitive stimulation in brainstorming. Experiments 1 and 2 used a paradigm in which individuals were exposed to ideas on audiotape as they were brainstorming, and Experiment 3 used the electronic brainstorming paradigm. Evidence was obtained for enhanced idea generation both during and after idea exposure. The attentional set of the participant and the content of the exposure manipulation (number of ideas, presence of irrelevant information) influenced this effect. These results are consistent with a cognitive perspective on group brainstorming.

  15. Sacral nerve stimulation.

    Science.gov (United States)

    Matzel, K E; Stadelmaier, U; Besendörfer, M

    2004-01-01

    The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure) and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

  16. Blood Contrast Agents Enhance Intrinsic Signals in the Retina: Evidence for an Underlying Blood Volume Component

    OpenAIRE

    Schallek, Jesse; Ts'o, Daniel

    2011-01-01

    Systemic injections of blood contrast agents nigrosin and indocyanine green increased stimulus-evoked reflectance signals in the retina. The enhancement of signal strength is consistent with neurovascular coupling in response to visual stimulation.

  17. Motivation and Stimulation

    OpenAIRE

    Macešková, Markéta

    2015-01-01

    The subject of this thesis is the analysis and evaluation of the work environment ( job satisfaction ) in connection with motivation and stimulation in the selected company. The intention of the thesis is to analyze the company, to point out the importance of optimal motivation in connection with an appropriate working environment to identify potential weaknesses and propose solutions for efficient use of the human potential. In the theoretical level, based on studied professional literature,...

  18. Raft River well stimulation experiments: geothermal reservoir well stimulation program

    Energy Technology Data Exchange (ETDEWEB)

    1980-08-01

    The Geothermal Reservoir Well Stimulation Program (GRWSP) performed two field experiments at the Raft River KGRA in 1979. Wells RRGP-4 and RRGP-5 were selected for the hydraulic fracture stimulation treatments. The well selection process, fracture treatment design, field execution, stimulation results, and pre- and post-job evaluations are presented.

  19. Biological warfare agents

    Directory of Open Access Journals (Sweden)

    Duraipandian Thavaselvam

    2010-01-01

    Full Text Available The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  20. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  1. Users, Bystanders and Agents

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina

    2015-01-01

    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...... the construction of the agent’s identity, and (3) how HAI, as a mediated interaction, is framed by an asymmetric participation framework. The paper concludes by suggesting various participation roles, which may inform development of ECAs....

  2. Nanomaterial-enabled neural stimulation

    OpenAIRE

    Yongchen eWang; Liang eGuo

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a h...

  3. Nanomaterial-Enabled Neural Stimulation

    OpenAIRE

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a h...

  4. Physiological aspects of paired stimulation

    NARCIS (Netherlands)

    Meijler, F.L.; Durrer, D.

    1965-01-01

    In this paper some physiological and clinical aspects of paired stimulation are discussed. I) The augmenting effect of paired stimulation on rnyocardial contractility is due to potentiation (increase in speed of restitution) and fusion of two contractions. 2) While using paired stimulation the oxyg

  5. Agent Standards Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation of the work herein proposed is the development of standards for software autonomous agents. These standards are essential to achieve software...

  6. Programming Service Oriented Agents

    OpenAIRE

    Hirsch, Benjamin; Konnerth, Thomas; Burkhardt, Michael; Albayrak, Sahin

    2010-01-01

    This paper introduces a programming language for service-oriented agents. JADL++ combines the ease of use of scripting-languages with a state-of-the-art service oriented approach which allows the seamless integration of web-services. Furthermore, the language includes OWL-based ontologies for semantic descriptions of data and services, thus allowing agents to make intelligent decisions about service calls.

  7. Spinal Cord Stimulation

    DEFF Research Database (Denmark)

    Meier, Kaare

    2014-01-01

    Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain that is refractory to other treatment. Originally described by Shealy et al. in 1967(1), it is used to treat a range of conditions such as complex regional pain syndrome (CRPS I)(2), angina pectoris(3), radicular...... pain after failed back surgery syndrome (FBSS)(4), pain due to peripheral nerve injury, stump pain(5), peripheral vascular disease(6) and diabetic neuropathy(7,8); whereas phantom pain(9), postherpetic neuralgia(10), chronic visceral pain(11), and pain after partial spinal cord injury(12) remain more...

  8. Myeloid cell kinetics in mice treated with recombinant interleukin-3, granulocyte colony-stimulating factor (CSF), or granulocyte-macrophage CSF in vivo

    International Nuclear Information System (INIS)

    Myeloid cell kinetics in mice treated with pure hematopoietic growth factors have been investigated using tritiated thymidine labeling and autoradiography. Mice were injected subcutaneously with 125 micrograms/kg granulocyte colony-stimulating factor (G-CSF) (in some cases 5 micrograms/kg), or 10 micrograms/kg of granulocyte-macrophage CSF (GM-CSF), or interleukin-3 (IL-3) every 12 hours for 84 hours. 3HTdR labeling was performed in vivo after 3 days of treatment. G-CSF increased the peripheral neutrophil count 14-fold and increased the proportion and proliferation rate of neutrophilic cells in the marrow, suppressing erythropoiesis at the same time. Newly produced mature cells were released into the circulation within 24 hours of labeling, compared with a normal appearance time of about 96 hours. By contrast, GM-CSF and IL-3 had little effect on either marrow cell kinetics or on the rate of release of mature cells, although GM-CSF did stimulate a 50% increase in peripheral neutrophils. Monocyte production was also increased about eightfold by G-CSF and 1.5-fold by GM-CSF, but their peak release was only slightly accelerated. While the peripheral half-lives of the neutrophilic granulocytes were normal, those of the monocytes were dramatically reduced, perhaps due to sequestration in the tissues for functional purposes. The stimulated monocyte production in the case of G-CSF required an additional five cell cycles, a level that might have repercussions on the progenitor compartments

  9. Biological Warfare Agents

    Directory of Open Access Journals (Sweden)

    Dev Vrat Kamboj

    2006-10-01

    Full Text Available There is a long historic record of use of biological warfare (BW agents by warring countriesagainst their enemies. However, the frequency of their use has increased since the beginningof the twentieth century. World war I witnessed the use of anthrax agent against human beingsand animals by Germans, followed by large-scale field trials by Japanese against war prisonersand Chinese population during world war II. Ironically, research and development in biologicalwarfare agents increased tremendously after the Geneva Protocol, signed in 1925, because ofits drawbacks which were overcome by Biological and Toxin Weapons Convention (BTWC in1972. Biological warfare programme took back seat after the 1972 convention but biologicalagents regained their importance after the bioterrorist attacks of anthrax powder in 2001. In thelight of these attacks, many of which turned out to be hoax, general awareness is required aboutbiological warfare agents that can be used against them. This review has been written highlightingimportant biological warfare agents, diseases caused by them, possible therapies and otherprotection measures.

  10. Transcranial brain stimulation: closing the loop between brain and stimulation

    DEFF Research Database (Denmark)

    Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

    2016-01-01

    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...... transcranial brain stimulation. Priming interventions or paired associative stimulation can be used to ‘standardize’ the brain-state and hereby, homogenize the group response to stimulation. Neuroanatomical and neurochemical profiling based on magnetic resonance imaging and spectroscopy can capture trait......-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...

  11. Clastogenicity Potential Screening of Pleurotus pulmonarius and Pleurotus ostreatus Metabolites as Potential Anticancer and Antileukaemic Agents Using Micronucleus Assay

    Directory of Open Access Journals (Sweden)

    E.O. Akanni

    2010-11-01

    Full Text Available Development of anticancer agents that will selectively destroy cancer cells without injury to normal cells has led to the discovery of novel immunotherapeutic agents such as Pleurotus pulmonarius and Pleurotus ostreatus metabolites. This study is to screen the agents of dreadful side effects of causing mutation after a prolonged use. Clastogenicity potential of the novel anti-cancer and antileukaemic agents Pleurotus pulmonarius and Pleurotus ostreatus metabolites was evaluated in this study. Wister rats were grouped into four with the test groups inoculated intraperitoneally at doses 64 and 16 mg/kg as 12.8 and 3.2% of the LD50 into the high and low dose rat groups respectively with each metabolite in a separate experiment. The treated rats were sacrificed after 24, 48 and 72 h post treatment. Cyclophosphamide (clastogen was inoculated into the positive control group at doses 112 and 28 mg/kg w hile saline was used for the negative control group. In all the treatment groups, only the rats in the positive control group formed micronuclei in their bone marrow cells. There was only an increase in the formation of normochromatic and polychromatic erythrocytes in rat groups inoculated with Pleurotus ostreatus metabolites. There is no statistically significant difference (p>0.05 between the 3 post treatment sacrificing periods. Similar result was also obtained for Pleurotus pulmonarius group. The chromosomal damaging potential screening reveals that the Pleurotus ostreatus and Pleurotus pulmonarius metabolites are not clastogenic (genotoxic that is, unlikely to cause cancer producing mutations, but rather enhanced erythropoiesis. They could therefore be useful anticancer agents when the potential is fully explored.

  12. Agent Oriented Programming进展%Advances in Agent Oriented Programming

    Institute of Scientific and Technical Information of China (English)

    王一川; 石纯一

    2002-01-01

    Agent-oriented programming (AOP) is a framework to develop agents, and it aims to link the gap betweentheory and practical in agent research. The core of an AOP framework is its language and semantics. In this paper,we propose the necessary properties which agents should have, and then give a summary and analysis about differentAOP languages based on these properties.

  13. Developing Enculturated Agents

    DEFF Research Database (Denmark)

    Rehm, Matthias

    2010-01-01

    on our cultural profiles that provide us with heuristics of behavior and interpretation. Thus, integrating cultural aspects of communicative behaviors in virtual agents and thus enculturating such systems seems to be inevitable. But culture is a multi-defined domain and thus a number of pitfalls arise......Embodied Conversational Agents (ECAs) are complex multimodal systems with rich verbal and nonverbal repertoires. There human-like appearance raises severe expectations regarding natural communicative behaviors on the side of the user. But what is regarded as “natural” is to a large degree dependent...... that have to be avoided in the endeavor. This chapter presents some of the pitfalls for enculturating interactive systems and presents strategies on how to avoid these pitfalls in relation to the standard development process of Embodied Conversational Agents....

  14. 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

  15. 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons.

    OpenAIRE

    DESIMONE, J.; Heller, P; Hall, L; Zwiers, D

    1982-01-01

    In an attempt to stimulate Hb F synthesis in baboons by means other than erythropoietic stress, we considered the possibility that an agent that inhibits methylation of CpG sequences in DNA may be effective. 5-Azacytidine, a cytosine analogue that cannot be methylated, is such an agent. Animals whose packed red cell volume was maintained at approximately 20% by bleeding were given 10 daily intravenous injections of the drug (6 mg/kg) in 12 days. Hb F levels in these animals started to increas...

  16. El agente encubierto

    OpenAIRE

    Anaya Marcos, María del Carmen

    2015-01-01

    [ES] El trabajo versa sobre la figura del agente encubierto. Debemos enmarcar tal medida de investigación dentro del ámbito de la criminalidad organizada. Actualmente, estamos asistiendo a una proliferación de la delincuencia organizada. La sociedad ha evolucionado, y con ella la delincuencia. Fruto de tal evolución fue necesario incluir en nuestra Ley de Enjuiciamiento Criminal medidas extraordinarias de investigación, y una de ellas es el agente encubierto. Se trata de una medida muy polémi...

  17. Stimulated Thomson scattering

    International Nuclear Information System (INIS)

    The theory of stimulated Thomson scattering is investigated both quantum mechanically and classically. Two monochromatic electromagnetic waves of like polarization travelling in opposite directions are allowed to interact for a time tau with the electrons in a collisionless plasma. The electromagnetic waves have frequencies well above the plasma frequency, and their difference frequency is allowed to range upward from the plasma frequency. With the difference frequency well above the plasma frequency, the rate at which energy is transferred from one wave to the other is calculated quantum mechanically, classically from a fluid theory, and classically from an independent electron theory. The rate is calculated in both the homogeneously broadened limit, and in the inhomogeneously broadened limit

  18. Collective stimulated Brillouin scatter

    CERN Document Server

    Korotkevich, Alexander O; Rose, Harvey A

    2011-01-01

    We develop a statistical theory of stimulated Brillouin backscatter (BSBS) of a spatially and temporally partially incoherent laser beam for laser fusion relevant plasma. We find a new collective regime of BSBS which has a much larger threshold than the classical threshold of a coherent beam in long-scale-length laser fusion plasma. We identify two contributions to BSBS convective instability increment. The first is collective with intensity threshold independent of the laser correlation time and controlled by diffraction. The second is independent of diffraction, it grows with increase of the correlation time and does not have an intensity threshold. The instability threshold is inside the typical parameter region of National Ignition Facility (NIF). We also find that the bandwidth of KrF-laser-based fusion systems would be large enough to allow additional suppression of BSBS.

  19. Engagement Sensitive Visual Stimulation.

    Science.gov (United States)

    Kumar, Deepesh; Dutta, Anirban; Das, Abhijit; Lahiri, Uttama

    2016-06-13

    Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one's performance. PMID:27478569

  20. Stimulated Cavity-Optomechanics

    CERN Document Server

    Bahl, Gaurav; Tomes, Matthew; Carmon, Tal

    2011-01-01

    Stimulated Brillouin interaction between sound and light, known to be the strongest optical nonlinearity common to all amorphous and crystalline dielectrics, has been widely studied in fibers and bulk materials but rarely in optical microresonators. The possibility of experimentally extending this principle to excite mechanical resonances in photonic microsystems, for sensing and frequency reference applications, has remained largely unexplored. The challenge lies in the fact that microresonators inherently have large free spectral range, while the phase matching considerations for the Brillouin process require optical modes of nearby frequencies but with different wavevectors. We rely on high-order transverse optical modes to relax this limitation. Here we report on the experimental excitation of mechanical resonances ranging from 49 to 1400 MHz by using forward Brillouin scattering. These natural mechanical resonances are excited in ~100 um silica microspheres, and are of a surface-acoustic whispering-galle...

  1. Femtosecond Stimulated Raman Spectroscopy.

    Science.gov (United States)

    Dietze, Daniel R; Mathies, Richard A

    2016-05-01

    Femtosecond stimulated Raman spectroscopy (FSRS) is an ultrafast nonlinear optical technique that provides vibrational structural information with high temporal (sub-50 fs) precision and high spectral (10 cm(-1) ) resolution. Since the first full demonstration of its capabilities ≈15 years ago, FSRS has evolved into a mature technique, giving deep insights into chemical and biochemical reaction dynamics that would be inaccessible with any other technique. It is now being routinely applied to virtually all possible photochemical reactions and systems spanning from single molecules in solution to thin films, bulk crystals and macromolecular proteins. This review starts with an historic overview and discusses the theoretical and experimental concepts behind this technology. Emphasis is put on the current state-of-the-art experimental realization and several variations of FSRS that have been developed. The unique capabilities of FSRS are illustrated through a comprehensive presentation of experiments to date followed by prospects. PMID:26919612

  2. Stimulated coherent transition radiation

    International Nuclear Information System (INIS)

    Coherent radiation emitted from a relativistic electron bunch consists of wavelengths longer than or comparable to the bunch length. The intensity of this radiation out-numbers that of its incoherent counterpart, which extends to wavelengths shorter than the bunch length, by a factor equal to the number of electrons in the bunch. In typical accelerators, this factor is about 8 to 11 orders of magnitude. The spectrum of the coherent radiation is determined by the Fourier transform of the electron bunch distribution and, therefore, contains information of the bunch distribution. Coherent transition radiation emitted from subpicosecond electron bunches at the Stanford SUNSHINE facility is observed in the far-infrared regime through a room-temperature pyroelectric bolometer and characterized through the electron bunch-length study. To measure the bunch length, a new frequency-resolved subpicosecond bunch-length measuring system is developed. This system uses a far-infrared Michelson interferometer to measure the spectrum of coherent transition radiation through optical autocorrelation with resolution far better than existing time-resolved methods. Hence, the radiation spectrum and the bunch length are deduced from the autocorrelation measurement. To study the stimulation of coherent transition radiation, a special cavity named BRAICER is invented. Far-infrared light pulses of coherent transition radiation emitted from electron bunches are delayed and circulated in the cavity to coincide with subsequent incoming electron bunches. This coincidence of light pulses with electron bunches enables the light to do work on electrons, and thus stimulates more radiated energy. The possibilities of extending the bunch-length measuring system to measure the three-dimensional bunch distribution and making the BRAICER cavity a broadband, high-intensity, coherent, far-infrared light source are also discussed

  3. Programming multi-agent systems

    NARCIS (Netherlands)

    Dastani, Mehdi

    2015-01-01

    With the significant advances in the area of autonomous agents and multi-agent systems in the last decade, promising technologies for the development and engineering of multi-agent systems have emerged. The result is a variety of agent-oriented programming languages, development frameworks, executio

  4. Software Agent Techniques in Design

    DEFF Research Database (Denmark)

    Hartvig, Susanne C

    1998-01-01

    This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments.......This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments....

  5. Trading Agents for Roaming Users

    OpenAIRE

    Boman, Magnus; Bylund, Markus; Espinoza, Fredrik; Danielson, Mats; Lyback, David

    2002-01-01

    Some roaming users need services to manipulate autonomous processes. Trading agents running on agent trade servers are used as a case in point. We present a solution that provides the agent owners with means to upkeeping their desktop environment, and maintaining their agent trade server processes, via a briefcase service.

  6. Hydromechanical stimulation of bioluminescent plankton.

    Science.gov (United States)

    Blaser, Stefan; Kurisu, Futoshi; Satoh, Hiroyasu; Mino, Takashi

    2002-01-01

    The response of the bioluminescent dinoflagellate Pyrocystis fusiformis was investigated for different hydraulic conditions ('hydromechanical stimulation'). Pipe flow and oscillating shear produced luminescence, whereas changes in hydrostatic pressure were not stimulating. More intense fluid motion led to higher intensity, mainly due to a higher probability of cell response. The organism was also able to emit light in a glucose-salt mixture. The experiments suggest that the cells are effectively stimulated if the flow conditions change in time.

  7. Agents of Change

    DEFF Research Database (Denmark)

    Hansen, Jens Aage; Lehmann, Martin

    2004-01-01

    at large, it emphasises universities as key change agents and providers in new learning, including tools such as project based and problem oriented learning (PBL) as well as information and communication technology (ICT); as providers of competent and motivated graduates to fill key positions in society...

  8. Programming Agents with Emotions

    NARCIS (Netherlands)

    Dastani, Mehdi; Floor, Chr.; Meyer, John-Jules Charles

    2014-01-01

    In this paper we show how a cognitive agent programming language can be endowed with ways to program emotions. In particular we show how the programming language 2APL can be augmented so that it can work together with the computational emotion model ALMA to deal with appraisal, emotion/mood generati

  9. The need for agents

    DEFF Research Database (Denmark)

    Abolfazlian, Ali Reza Kian

    1996-01-01

    I denne artikel arbejder vi med begrebet Intelligent Software Agents (ISAs), som autonomous, social, reactive, proactive og subservient computer systemer. Baseret på socialt psykologiske argumenter viser jeg endvidere, hvordan både den menneskelige natur og det teknologiske stadium, som mennesket...

  10. SECOND BUYING AGENT

    CERN Multimedia

    SPL - SERVICES ACHATS

    2000-01-01

    Last year the buying agent LOGITRADE started operations on the CERN site, processing purchasing requests for well-defined families of products up to a certain value. It was planned from the outset that a second buying agent would be brought in to handle the remaining product families. So, according to that plan, the company CHARLES KENDALL will be commencing operations at CERN on 8 May 2000 in Building 73, 1st floor, offices 31 and 35 (phone and fax numbers to be announced).Each buying agent will have its own specific list of product families and will handle purchasing requests up to 10'000 CHF.Whenever possible they will provide the requested supplies at a price (including the cost of their own services) which must be equivalent to or lower than the price mentioned on the purchasing request, changing the supplier if necessary. If a lower price cannot be obtained, agents will provide the necessary administrative support free of charge.To ensure that all orders are processed in the best possible conditions, us...

  11. Optically stimulated differential impedance spectroscopy

    Science.gov (United States)

    Maxey, Lonnie C; Parks, II, James E; Lewis, Sr., Samuel A; Partridge, Jr., William P

    2014-02-18

    Methods and apparatuses for evaluating a material are described. Embodiments typically involve use of an impedance measurement sensor to measure the impedance of a sample of the material under at least two different states of illumination. The states of illumination may include (a) substantially no optical stimulation, (b) substantial optical stimulation, (c) optical stimulation at a first wavelength of light, (d) optical stimulation at a second wavelength of light, (e) a first level of light intensity, and (f) a second level of light intensity. Typically a difference in impedance between the impedance of the sample at the two states of illumination is measured to determine a characteristic of the material.

  12. Build Autonomic Agents with ABLE

    Institute of Scientific and Technical Information of China (English)

    吴吉义

    2007-01-01

    The IBM Agent Building and Learning Environment(ABLE) provides a lightweight Java~(TM) agent frame- work,a comprehensive JavaBeansTM library of intelligent software components,a set of development and test tools, and an agent platform.After the introduction to ABLE,classes and interfaces in the ABLE agent framework were put forward.At last an autonomic agent that is an ABLE-based architecture for incrementally building autonomic systems was discussed.

  13. EOR by stimulated microflora

    Energy Technology Data Exchange (ETDEWEB)

    Svarovskaya, L.I.; Altunina, L.K.; Rozhenkova, Z.A.; Bulavin, V.D. [Institute of Petroleum Chemistry, Tomsk (Russian Federation)

    1995-12-31

    A combined microbiological and physico-chemical method for EOR has been developed for flooded West Siberia oil fields with formation temperature of 45{degrees}-95{degrees}C (318-365K). Formation water includes rich and various biocenoses numbering up to 2 x 10{sup 7} cells per ml. Representatives of genera, i.e, Pseudomonas, Bacillus, Actinomyces, Micrococcus, Mycobacterium, Sarcina, etc. were found to be the most widely distributed microorganisms. The method is based on injection of systems exhibiting high oil displacing capacity and at the same time being an additional nitrous nutrient for endemic populations of microorganisms. Their injection into formation water favors biomass growth by 4-6 orders and promotes syntheses of biosurfactants, biopolymers, acids, etc., and gaseous products. The features of residual oil displacement have been studied on laboratory models using a combined microbiological and physico-chemical method. A curve for the yield of residual oil is presented by two peaks. The first peak is stipulated by the washing action of oil displacement system, and the second one by the effect of metabolites produced at stimulation of biogenic processes. Oil displacement index increases by 15%-30%.

  14. 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

  15. Subliminal Stimulation: Hoax or Reality?

    Science.gov (United States)

    Trank, Douglas M.

    Subliminal stimulation is defined as that which is perceived by an individual below the threshold of awareness or cognizance. This article traces the history of research in subliminal stimulation to illustrate that under certain circumstances and conditions, this behavioral phenomenon does occur. Although subliminal stimuli do affect human…

  16. Stimulating Language: Insights from TMS

    Science.gov (United States)

    Devlin, Joseph T.; Watkins, Kate E.

    2007-01-01

    Fifteen years ago, Pascual-Leone and colleagues used transcranial magnetic stimulation (TMS) to investigate speech production in pre-surgical epilepsy patients and in doing so, introduced a novel tool into language research. TMS can be used to non-invasively stimulate a specific cortical region and transiently disrupt information processing. These…

  17. Perioperative allergy: uncommon agents.

    Science.gov (United States)

    Caimmi, S; Caimmi, D; Cardinale, F; Indinnimeo, L; Crisafulli, G; Peroni, D G; Marseglia, G L

    2011-01-01

    Anesthesia may often be considered as a high-risk procedure and anaphylaxis remains a major cause of concern for anesthetists who routinely administer many potentially allergenic agents. Neuromuscular blocking agents, latex and antibiotics are the substances involved in most of the reported reactions. Besides these three agents, a wide variety of substances may cause an anaphylactic reaction during anesthesia. Basically all the administered drugs or substances may be potential causes of anaphylaxis. Among them, those reported the most in literature include hypnotics, opioids, local anesthetics, colloids, dye, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Iodinated Contrast Media (ICM), antiseptics, aprotinin, ethylene oxyde and formaldehyde, and protamine and heparins. No premedication can effectively prevent an allergic reaction and a systematic preoperative screening is not justified for all patients; nevertheless, an allergy specialist should evaluate those patients with a history of anesthesia-related allergy. Patients must be fully informed of investigation results, and advised to provide a detailed report prior to future anesthesia. PMID:22014927

  18. Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils

    OpenAIRE

    1991-01-01

    Human peripheral blood eosinophils released eosinophil survival- enhancing activity when stimulated with the calcium ionophore, ionomycin. The release of activity was detected as early as 3 h after stimulation and was inhibited by an immunomodulating agent, cyclosporin A. The survival-enhancing activity was completely abolished by treatment with anti-interleukin 3 (IL-3) and anti- granulocyte/macrophage colony-stimulating factor (GM-CSF) monoclonal antibodies. Moreover, IL-3 and GM-CSF were m...

  19. SAM : Semantic Agent Model for SWRL rule-based agents

    OpenAIRE

    Subercaze, Julien; Maret, Pierre

    2010-01-01

    International audience SemanticWeb technologies are part of multi-agent engineering, especially regarding knowledge base support. Recent advances in the field of logic for the semantic web enable a new range of applications. Among them, programming agents based on semantic rules is a promising field. In this paper we present a semantic agent model that allows SWRL programming of agents. Our approach, based on the extended finite state machine concept, results in a three layers architecture...

  20. Nanomaterial-enabled neural stimulation

    Directory of Open Access Journals (Sweden)

    Yongchen eWang

    2016-03-01

    Full Text Available Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed.

  1. Nanomaterial-Enabled Neural Stimulation.

    Science.gov (United States)

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed.

  2. Nanomaterial-Enabled Neural Stimulation.

    Science.gov (United States)

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed. PMID:27013938

  3. The Power Trading Agent Competition

    OpenAIRE

    Ketter, W.; Collins, J.; REDDY, P; Flath, C.

    2011-01-01

    This is the specification for the Power Trading Agent Competition for 2011 (Power TAC 2011). Agents are simulations of electrical power brokers, who must compete with each other for both power production and consumption, and manage their portfolios.

  4. Agents Play Mix-game

    CERN Document Server

    Gou, C

    2005-01-01

    In mix-game which is an extension of minority game, there are two groups of agents; group1 plays the majority game, but the group2 plays the minority game. This paper studies the change of the average winnings of agents and volatilities vs. the change of mixture of agents in mix-game model. It finds that the correlations between the average winnings of agents and the mean of local volatilities are different with different combinations of agent memory length when the proportion of agents in group 1 increases. This study result suggests that memory length of agents in group1 be smaller than that of agent in group2 when mix-game model is used to simulate the financial markets.

  5. The Power Trading Agent Competition

    NARCIS (Netherlands)

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph)

    2011-01-01

    textabstractThis is the specification for the Power Trading Agent Competition for 2011 (Power TAC 2011). Agents are simulations of electrical power brokers, who must compete with each other for both power production and consumption, and manage their portfolios.

  6. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset peripheral neuropathy is related to their exposure to Agent Orange or other herbicides during service when the disease ...

  7. An Implantable Neural Stimulator for Intraspinal MicroStimulation

    OpenAIRE

    Troyk, Philip R.; Mushahwar, Vivian K.; Stein, Richard B.; Suh, Sungjae; Everaert, Dirk; Holinski, Brad; Hu, Zhe; DeMichele, Glenn; Kerns, Douglas; Kayvani, Kevin

    2012-01-01

    This paper reports on a wireless stimulator device for use in animal experiments as part of an ongoing investigation into intraspinal stimulation (ISMS) for restoration of walking in humans with spinal cord injury. The principle behind using ISMS is the activation of residual motor-control neural networks within the spinal cord ventral horn below the level of lesion following a spinal cord injury. The attractiveness to this technique is that a small number of electrodes can be used to induce ...

  8. Electrical stimulation in exercise training

    Science.gov (United States)

    Kroll, Walter

    1994-01-01

    Electrical stimulation has a long history of use in medicine dating back to 46 A.D. when the Roman physician Largus found the electrical discharge of torpedo fishes useful in the treatment of pain produced by headache and gout. A rival Greek physician, Dioscorides, discounted the value of the torpedo fish for headache relief but did recommend its use in the treatment of hemorrhoids. In 1745, the Leyden jar and various sized electrostatic generators were used to treat angina pectoris, epilepsy, hemiplegia, kidney stones, and sciatica. Benjamin Franklin used an electrical device to treat successfully a young woman suffering from convulsive fits. In the late 1800's battery powered hydroelectric baths were used to treat chronic inflammation of the uterus while electrified athletic supporters were advertised for the treatment of male problems. Fortunately, such an amusing early history of the simple beginnings of electrical stimulation did not prevent eventual development of a variety of useful therapeutic and rehabilitative applications of electrical stimulation. Over the centuries electrical stimulation has survived as a modality in the treatment of various medical disorders with its primary application being in the rehabilitation area. Recently, a surge of new interest in electrical stimulation has been kindled by the work of a Russian sport scientist who reported remarkable muscle strength and endurance improvements in elite athletes. Yakov Kots reported his research on electric stimulation and strength improvements in 1977 at a Canadian-Soviet Exchange Symposium held at Concordia University in Montreal. Since then an explosion of new studies has been seen in both sport science and in medicine. Based upon the reported works of Kots and the present surge of new investigations, one could be misled as to the origin of electrical stimulation as a technique to increase muscle strength. As a matter of fact, electric stimulation has been used as a technique to improve

  9. Mediating Performance Through Virtual Agents

    OpenAIRE

    Giannachi, Gabriella; Gillies, Marco; Kaye, Nick; Swapp, David

    2009-01-01

    This paper presents the process of creation of virtual agents used in a virtual reality performance. The performance aimed to investigate how drama and performance could inform the creation of virtual agents and also how virtual reality could raise questions for drama and performance. The virtual agents were based on the performance of 2 actors. This paper describes the process of preparing the actors, capturing their performances and transferring them to the virtual agents. A second set of a...

  10. Cultural Differentiation of Negotiating Agents

    NARCIS (Netherlands)

    Hofstede, G.J.; Jonker, C.M.; Verwaart, D.

    2012-01-01

    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  11. Cultural differentiation of negotiating agents

    NARCIS (Netherlands)

    Hofstede, G.J.; Jonker, C.M.; Verwaart, T.

    2010-01-01

    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  12. Assigning agents to a line

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    2014-01-01

    We consider the problem of assigning agents to slots on a line, where only one agent can be served at a slot and each agent prefers to be served as close as possible to his target. Our focus is on aggregate gap minimizing methods, i.e., those that minimize the total gap between targets and assigned...

  13. Divalent cation ionophores stimulate resorption and inhibit DNA synthesis in cultured fetal rat bone

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzo, J.A.; Raisz, L.G.

    1981-06-01

    Two divalent cation ionophores, A23187 and Ionomycin, which are selective for calcium, stimulated the resorption of fetal rat long bones in organ culture at 0.1 to 1 micromolar but not at higher concentrations. Both agents inhibited DNA synthesis at concentrations that stimulated resorption. These results might explain the differences in ionophore effects on bone previously reported, and they imply that cell replication is not required for osteoclast formation in fetal rat long bone cultures.

  14. Chemical warfare agents

    Directory of Open Access Journals (Sweden)

    Vijayaraghavan R

    2010-01-01

    Full Text Available Among the Weapons of Mass Destruction, chemical warfare (CW is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided.

  15. Secure Mobile Trade Agent

    Directory of Open Access Journals (Sweden)

    Musbah M. Aqe

    2007-01-01

    Full Text Available E-commerce on the internet has the ability to produce millions of transactions and a great number of merchants whose supply merchandise over the internet. As a result, it is difficult for entities to roam over every site on the internet and choose the best merchandise to trade. So, in this paper we introduced a mobile trade agent that visit the sites to gather and evaluate the information from merchant servers and decide to trade goods on behalf of the user. We observed that the combination of public key cryptosystem with distributed object technology make this proposed scheme more secure and efficient than the already existed schemes.

  16. Functional EpoR pathway utilization is not detected in primary tumor cells isolated from human breast, non-small cell lung, colorectal, and ovarian tumor tissues.

    Directory of Open Access Journals (Sweden)

    Scott D Patterson

    Full Text Available Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1 were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot. Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues.

  17. Agentes de información Information Agents

    Directory of Open Access Journals (Sweden)

    Alfonso López Yepes

    2005-12-01

    Full Text Available Este artículo realiza un repaso sobre las tipologías de agentes de información y describe aspectos como movilidad, racionalidad y adaptatividad, y el ajuste final de estos conceptos a entornos distribuidos como Internet, donde este tipo de agentes tienen un amplio grado de aplicación. Asimismo, se propone una arquitectura de agentes para un sistema multiagente de recuperación de información donde se aplica un paradigma documental basado en el concepto de ciclo documental.This article summarizes the main information agent types reflecting on issues such as mobility, rationality, adaptability and the final adjustment of this concepts to distributed environments such as the Internet, where this kind of agents has wide range application. Likewise, an information agent architecture is proposed to create a multi-agent information retrieval system in which a documentary paradigm based on the documentary cycle is developed.

  18. 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.......5 nM angiotensin II and 10 nM norepinephrine. Angiotensins I and III were less potent than angiotensin II. For each agent, the dose-dependent increase in oxygen uptake coincided with a dose-dependent increase in perfusion pressure. The effects of both vasopressin and angiotensin to increase oxygen...

  19. Enteral feeding without pancreatic stimulation

    DEFF Research Database (Denmark)

    Kaushik, Neeraj; Pietraszewski, Marie; Holst, Jens Juul;

    2005-01-01

    OBJECTIVE: All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result...... in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. METHODS: The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double...... in plasma glucagon-like peptide-1 and peptide YY concentrations. CONCLUSIONS: Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism....

  20. Demultiplexer circuit for neural stimulation

    Science.gov (United States)

    Wessendorf, Kurt O; Okandan, Murat; Pearson, Sean

    2012-10-09

    A demultiplexer circuit is disclosed which can be used with a conventional neural stimulator to extend the number of electrodes which can be activated. The demultiplexer circuit, which is formed on a semiconductor substrate containing a power supply that provides all the dc electrical power for operation of the circuit, includes digital latches that receive and store addressing information from the neural stimulator one bit at a time. This addressing information is used to program one or more 1:2.sup.N demultiplexers in the demultiplexer circuit which then route neural stimulation signals from the neural stimulator to an electrode array which is connected to the outputs of the 1:2.sup.N demultiplexer. The demultiplexer circuit allows the number of individual electrodes in the electrode array to be increased by a factor of 2.sup.N with N generally being in a range of 2-4.

  1. Evoked response to taste stimulations.

    Science.gov (United States)

    Wada, Masashi

    2005-01-01

    For the recording of gustatory evoked responses, the tip of a stimulator is pressed vertically on one side of the tongue until the trigger pulses are generated by a switch attached to the bottom of the stimulator. According to our results, no detectable response was observed in the absence of taste. The positive waves were distinguishable by using the technique of superimposition before averaging, and the positive wave was made clearer by averaging.

  2. Transcranial electrical stimulation: An introduction

    CERN Document Server

    Tarazona, Carlos G; Chávez, Laura; Andrade, Sebastián

    2015-01-01

    The main objective of the electrical stimulation of the brain is to generate action potentials from the application of electromagnetic fields. Among the available techniques, transcranial electrical stimulation (TES) represents a popular method of administration that has the advantage of being non-invasive and economically more affordable. This article aims to briefly introduce the reader into the understanding of TES in terms of the physics involved as well as for some of the relevant results of studies applying this technique.

  3. Lipid-lowering agents.

    Science.gov (United States)

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented.

  4. Advances in antithrombotic agents.

    Science.gov (United States)

    Chakrabarti, Ranjan; Das, Saibal Kumar

    2007-07-01

    Thrombosis is the condition where an imbalance in the homeostatic mechanism results in unwanted intravascular thrombus formation. Imbalances in this highly regulated process of coagulation and anticoagulation can lead to a variety of pathophysiological conditions leading to stroke, pulmonary heart attack and other serious conditions. In the western world, thromboembolic diseases are the leading cause of morbidity and mortality. Remarkable progress has occurred over the last decade in the development of antithrombotic drugs, which can be classified into 3 major categories - Anticoagulants, Antiplatelets and thrombolytics. Increased understanding of the pathobiology of thrombotic and vascular disorders has helped researchers to target novel pathways involving the coagulation, thrombolytic, fibrinolytic and integrin systems. Traditionally aspirin and unfractionated heparin was used for myocardial infarction. Newer antiplatelet agents such as, clopidogrel, GP IIb/IIIa inhibitors, low molecular weight heparin, direct thrombin inhibitors and several improved thrombolytic agents have been introduced for clinical use. This review will discuss different important drugs, which have been launched in recent years and also some new targets pursued by different companies. PMID:17630943

  5. Holograms as Teaching Agents

    Science.gov (United States)

    Walker, Robin A.

    2013-02-01

    Hungarian physicist Dennis Gabor won the Pulitzer Prize for his 1947 introduction of basic holographic principles, but it was not until the invention of the laser in 1960 that research scientists, physicians, technologists and the general public began to seriously consider the interdisciplinary potentiality of holography. Questions around whether and when Three-Dimensional (3-D) images and systems would impact American entertainment and the arts would be answered before educators, instructional designers and students would discover how much Three-Dimensional Hologram Technology (3DHT) would affect teaching practices and learning environments. In the following International Symposium on Display Holograms (ISDH) poster presentation, the author features a traditional board game as well as a reflection hologram to illustrate conventional and evolving Three-Dimensional representations and technology for education. Using elements from the American children's toy Operation® (Hasbro, 2005) as well as a reflection hologram of a human brain (Ko, 1998), this poster design highlights the pedagogical effects of 3-D images, games and systems on learning science. As teaching agents, holograms can be considered substitutes for real objects, (human beings, organs, and animated characters) as well as agents (pedagogical, avatars, reflective) in various learning environments using many systems (direct, emergent, augmented reality) and electronic tools (cellphones, computers, tablets, television). In order to understand the particular importance of utilizing holography in school, clinical and public settings, the author identifies advantages and benefits of using 3-D images and technology as instructional tools.

  6. Agent-oriented Software Engineering

    Institute of Scientific and Technical Information of China (English)

    GUAN Xu; CHENG Ming; LIU Bao

    2001-01-01

    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to design and build complex systems. Yet. todate, little effort had been devoted to discuss the advantages of agent-oriented approach as a mainstreamsoftware engineering paradigm. Here both of this issues and the relation between object-oriented and agent-oriented will be argued. we describe an agent-oriented methodology and provide a quote for designing anauction system.

  7. Therapeutic Potential of HDPs as Immunomodulatory Agents

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Hancock, Robert E.W.

    2010-01-01

    strategies for intervention tailored around the appropriate (selective) stimulation of the host’s immune system, and particularly rapid acting innate immunity, as an alternative to direct targeting of microbial pathogens. One recent player in such an immunomodulatory strategy is the naturally occurring host...... defence peptides (HDP) and their synthetic innate defence regulator (IDR) analogues. In this chapter, we will discuss the potential therapeutic use of HDPs and IDRs as immunomodulatory agents....... decline in the rate of discovery of new antimicrobial intervention strategies in parallel with an increasing incidence of multidrug-resistant pathogens; if these circumstances do not change we will continue to approach the end of the antibiotic era. Facing this dark future, scientists are considering new...

  8. Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

    Science.gov (United States)

    Andrews, Russell J.

    2003-01-01

    Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

  9. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration.

    Science.gov (United States)

    Takebe, Naoko; Ahmed, Mansoor M; Vikram, Bhadrasain; Bernhard, Eric J; Zwiebel, James; Norman Coleman, C; Kunos, Charles A

    2016-10-01

    A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives.

  10. Product and Agent

    DEFF Research Database (Denmark)

    Montecino, Alex; Valero, Paola

    2015-01-01

    In this paper we will explore how the “mathematics teacher” becomes a subject and, at the same time, is subjected as part of diverse dispositive of power. We argue that the mathematics teacher becomes both a product and a social agent, which has been set, within current societies, from the ideas...... of globalization, social progress, and competitive logic. For our approximation, we use the concepts societies of control, dispositive, and discourses from a Foucault–Deleuze toolbox. Our purpose is to cast light on the social and cultural constitution of the ways of thinking about the mathematics teacher. Hence......, our critical examination offers understandings about how mathematics teachers are part of the larger cultural politics of schooling and education....

  11. Mushrooms as therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sushila Rathee

    2012-04-01

    Full Text Available Mushrooms have been known for their nutritional and culinary values and used as medicines and tonics by humans for ages. In modern terms, they can be considered as functional foods which can provide health benefits beyond the traditional nutrients. There are monographs that cover the medicinal and healing properties of some individual traditional mushrooms. There has been a recent upsurge of interest in mushrooms not only as a health food which is rich in protein but also as a source of biologically active compounds of medicinal value which include complementary medicine/dietary supplements for anticancer, antiviral, hepatoprotective, immunopotentiating and hypocholesterolemic agents. However the mechanisms of the various health benefits of mushrooms to humans still require intensive investigation, especially given the emergence of new evidence of their health benefits. In the present paper the medicinal potential of mushrooms is being discussed.

  12. Newer Hemostatic Agents.

    Science.gov (United States)

    Franchini, Massimo; Favaloro, Emmanuel J; Lippi, Giuseppe

    2015-10-01

    The mainstay of treatment of inherited coagulation disorders is based on the infusion of the deficient clotting factor, when available. Significant advances have been made over the past two decades in the production and availability of factor replacement products. In spite of such progression, several issue are still unsolved, the most important being the need for frequent factor concentrate infusions and the development of inhibitory alloantibodies. To overcome these important limitations, several newer hemostatic agents with an extended half-life are at an advanced stage of clinical development. After a brief overview of hemostasis, this narrative review summarizes the current knowledge on the most promising novel products for hemostasis. The current status of gene therapy for hemophilia, the only therapeutic option to definitively cure this inherited bleeding disorder, is also concisely discussed. PMID:25893779

  13. Microencapsulation of chemotherapeutic agents

    International Nuclear Information System (INIS)

    Mixing various amounts of chemotherapeutic agents such as cisplatinum, 5-fluorouracil, mitomycin-C, and adriamycin with polymers such as poly-d, 1-lactide, ethylhydroxyethylcellulose, and polycaprolactone, several kinds of microcapsules were made. Among them, microcapsule made from ethylhydroxyethylcellulose showed best yield. Under light microscopy, the capsules were observed as particles with refractive properties. For the basic toxicity test, intraarterial administration of cisplatinum was done in 6 adult mongrel dogs. Follow-up angiography was accomplished in 2 wk intervals for 6 wks. Despite no significant difference in the histopathological examination between the embolized and normal kidneys, follow-up angiogram showed atrophy of renal cortex and diminished numbers of arterial branches in the embolized kidneys. In order to identify the structural properties of microcapsules, and to determine the drug content and the rate of release, further experiment is thought to be necessary. (Author)

  14. Hepatocytes as Immunological Agents.

    Science.gov (United States)

    Crispe, Ian N

    2016-01-01

    Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314

  15. UTBot: A Virtual Agent Platform for Teaching Agent System Design

    Directory of Open Access Journals (Sweden)

    In-Cheol Kim

    2007-02-01

    Full Text Available We introduce UTBot, a virtual agent platform for teaching agent system design. UTBot implements a client for the Unreal Tournament game server and Gamebots system. It provides students with the basic functionality required to start developing their own intelligent virtual agents to play autonomously UT games. UTBot includes a generic agent architecture, CAA (Context-sensitive Agent Architecture, a domain-specific world model, a visualization tool, several basic strategies (represented by internal modes and internal behaviors, and skills (represented by external behaviors. The CAA architecture can support complex long-term behaviors as well as reactive short-term behaviors. It also realizes high context-sensitivity of behaviors. We also discuss our experience using UTBot as a pedagogical tool for teaching agent system design in undergraduate Artificial Intelligence course.

  16. Electrical stimulation and motor recovery.

    Science.gov (United States)

    Young, Wise

    2015-01-01

    In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical

  17. Deep brain stimulation: new techniques.

    Science.gov (United States)

    Hariz, Marwan

    2014-01-01

    The technology of the hardware used in deep brain stimulation (DBS), and the mode of delivering the stimulation have not significantly evolved since the start of the modern era of DBS 25 years ago. However, new technology is now being developed along several avenues. New features of the implantable pulse generator (IPG) allow fractionation of the electric current into variable proportions between different contacts of the multi-polar lead. Another design consists in leads that allow selective current steering from directionally placed electrode contacts that would deliver the stimulation in a specific direction or even create a directional shaped electric field that would conform to the anatomy of the brain target aimed at, avoiding adjacent structures, and thus avoiding side effects. Closed loop adaptive stimulation technologies are being developed, allowing a tracking of the pathological local field potential of the brain target, and delivering automatically the stimulation to suppress the pathological activity as soon as it is detected and for as long as needed. This feature may contribute to a DBS therapy "on demand", instead of continuously. Finally, advances in imaging technology are providing "new" brain targets, and increasingly allowing DBS to be performed accurately while avoiding the risks of microelectrode recording. PMID:24262179

  18. Stability of Evolving Agent Populations

    CERN Document Server

    Briscoe, G

    2007-01-01

    Stability is perhaps the most desired feature in the systems that we design. It is important for us to be able to predict the response of a Multi-Agent System (MAS) to various environmental conditions prior to its actual deployment. The Chli-DeWilde agent stability measure views a MAS as a discrete time Markov chain with a potentially unknown transition probabilities. A MAS is considered to be stable when its state, a stochastic process, has converged to an equilibrium distribution. We investigate an extension of their agent stability definition to include MASs with evolutionary dynamics, focusing on evolving agent populations. Additionally, using our extended agent stability measure, we construct an entropy-based definition for the degree of instability. An example system, the Digital Ecosystem, is considered in detail to investigate the stability of an evolving agent population through simulations. The results are consistent with the original Chli-DeWilde measure.

  19. Agent-based enterprise integration

    Energy Technology Data Exchange (ETDEWEB)

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  20. Odor Classification using Agent Technology

    Directory of Open Access Journals (Sweden)

    Sigeru OMATU

    2014-03-01

    Full Text Available In order to measure and classify odors, Quartz Crystal Microbalance (QCM can be used. In the present study, seven QCM sensors and three different odors are used. The system has been developed as a virtual organization of agents using an agent platform called PANGEA (Platform for Automatic coNstruction of orGanizations of intElligent Agents. This is a platform for developing open multi-agent systems, specifically those including organizational aspects. The main reason for the use of agents is the scalability of the platform, i.e. the way in which it models the services. The system models functionalities as services inside the agents, or as Service Oriented Approach (SOA architecture compliant services using Web Services. This way the adaptation of the odor classification systems with new algorithms, tools and classification techniques is allowed.

  1. Agent 与Multi-Agent System 技术研究%The Research on Agent and Multi-Agent System

    Institute of Scientific and Technical Information of China (English)

    党建武; 韩泉叶; 崔文华

    2002-01-01

    分析了Multi-Agent System 涉及的相关问题,在普通的Multi-Agent System的组织结构的基础上提出了管理服务机构,中介服务机构和主控流动服务机构的Multi-Agent System,并对不同组织结构的Agent之间的协同进行了讨论.

  2. Mobile Agents for Digital Signage

    OpenAIRE

    SATOH, Ichiro

    2010-01-01

    International audience This paper presents an agent-based framework for building and operating context-aware multimedia content on digital signage in public/private spaces. It enables active and multimedia content to be composed from mobile agents, which can travel from computer to computer and provide multimedia content for advertising or user-assistant services to users. The framework automatically deploys their agents at computers near to their current positions to provide advertising o...

  3. An agent for ecological deliberation

    OpenAIRE

    Debenham, John; Sierra, Carles

    2010-01-01

    An agent architecture supports the two forms of deliberation used by human agents. Cartesian, constructivist rationalism leads to game theory, decision theory and logical models. Ecological rationalism leads to deliberative actions that are derived from agents’ prior interactions and are not designed; i.e., they are strictly emergent. This paper aims to address the scant attention paid by the agent community to the predominant form of deliberation used by mankind.

  4. Radioactive scanning agents with stabilizer

    International Nuclear Information System (INIS)

    Stable compositions useful as technetium 99-based scintigraphic agents comprise gentisyl alcohol or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

  5. Research on Negotiating Agent Development

    Institute of Scientific and Technical Information of China (English)

    WEI Ding-guo; PENG Hong

    2004-01-01

    The paper presents a flexible and effective method of development of negotiating agents.A strategy specification, which is specified by a state chart and defeasible rules, can be dynamically inserted into an agent shell incorporating a state chart interpreter and a defeasible logic inference engine, in order to yield a desirable agent.The set of desirable criteria and rules is required to be justified with different context of the application.

  6. Agent factory: towards social robots

    OpenAIRE

    O'Hare, G. M. P.; Duffy, Brian R.; Collier, Rem; Rooney, Colm, (Thesis); O'Donoghue, Ruadhan

    1999-01-01

    This paper advocates the application of multi-agent techniques in the realisation of social robotic behaviour. We present the Social Robot Architecture, which integrates the key elements of agent-hood and robotics in a coherent and systematic manner. This architecture seamlessly integrates, real world robots, multi-agent development tools, and VRML visualisation tools into a coherent whole. Using these elements, we deliver a development environment, which facilitates rapid prototyping of soci...

  7. Chemosensory stimulation during sleep - Arousal responses to gustatory stimulation.

    Science.gov (United States)

    Stuck, B A; Moutsis, T T; Bingel, U; Sommer, J U

    2016-05-13

    The processing of nociceptive, visual, vibrotactile, thermal and acoustic stimuli during sleep has been extensively investigated in the past. Recently, interest has focused on the impact of olfactory stimulation on sleep. In contrast to all other sensory systems, olfactory stimulation does not lead to an increased arousal frequency, regardless of hedonicity and concentration. The impact of the second chemosensory system, gustation, on sleep however has not been investigated to date. Twenty-one normosmic and normogeusic volunteers of both genders, aged 19-33 years, participated in the trial. Stimulation was performed with a gustometer using the following aqueous solutions: saccharose 20% (sweet), sodium chloride (NaCl) 7.5% (salty), citrate 5% (sour), and quinine 0.02% (bitter). A tasteless solution was used as negative control. Capsaicin, a strong trigeminal stimulus, served as positive control. Primary outcome was arousal frequency per stimulus in each sleep stage, as assessed with polysomnography. The frequency of arousals decreased in deeper sleep stages (N1: 211 arousals of 333 stimuli=63%, N2: 676/2728=25%, N3: 43/1378=3%, REM: 57/1010=6%). Statistically significant differences in terms of arousal frequency were found in N2 between the negative control and NaCl 100 μl (psleep induces arousals depending on stimulus intensity and sleep stage, which is different to olfactory stimulation and may be related to differences in central processing of the two chemosensory systems. PMID:26921652

  8. 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.

  9. Agent Mediated Electronic Commerce: Designing Trading Agents and Mechanisms

    NARCIS (Netherlands)

    La Poutré, J.A.; Sadeh, N.M.; Janson, S.

    2006-01-01

    This book constitutes the thoroughly refereed post-proceedings of the 7th International Workshop on Agent-Mediated Electronic Commerce, AMEC VII 2005, held in Utrecht, Netherlands in July 2005, as part of AAMAS 2005, and the third Workshop on Trading Agent Design and Analysis, TADA 2005, held in Edi

  10. Plasmids encoding therapeutic agents

    Science.gov (United States)

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  11. Deliberate evolution in multi-agent systems

    NARCIS (Netherlands)

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.

    1998-01-01

    This paper presents an architecture for an agent capable of deliberation about the creation of new agents, and of actually creating a new agent in the multi-agent system, on the basis of this deliberation. After its creation the new agent participates fully in the running multi-agent system. The age

  12. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    Science.gov (United States)

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  13. Aromatic A-ring analogues of orobanchol, new germination stimulants for seeds of parasitic weeds

    NARCIS (Netherlands)

    Malik, H.; Kohlen, W.; Jamil, M.; Rutjes, F.P.J.T.; Zwanenburg, B.

    2011-01-01

    Strigolactones are signaling compounds in plants of increasing importance. In this paper the focus is on their activity as germinating agents for seeds of parasitic weeds. The syntheses of aromatic A-ring analogues of the germination stimulant orobanchol have been described. Starting substrate is th

  14. Optimizing performance by stimulating conflict

    NARCIS (Netherlands)

    E. van de Vliert; C.K.W. de Dreu

    1994-01-01

    To enhance the quality of group decision making, to promote affective acceptance of decisions by all participants involved, or to increase joint outcomes, a principal party or a third party may stimulate social conflict. We argue that when conflict focuses on identity issues, when tension level is h

  15. Multielectrode intrafascicular and extraneural stimulation

    NARCIS (Netherlands)

    Veltink, P.H.; Alste, van J.A.; Boom, H.B.K.

    1989-01-01

    The relationship between nerve stimulation, pulse amplitude and isometric muscle force was measured to investigate recruitment of motor units. Force addition experiments were performed to obtain insight in the intersection of motor unit groups recruited by different electrodes. Intrafascicular and e

  16. Deep brain stimulation in psychiatry

    Directory of Open Access Journals (Sweden)

    Poznić-Ješić Milana

    2014-01-01

    Full Text Available Introduction. Deep brain stimulation is a stereotactic neurosurgical method used in the treatment of Parkinson’s disease and some other movement disorders. The application of deep brain stimulation in the treatment of certain psychiatric disorders has been intensively investigated taking into account the current knowledge of neurobiological basis of mood regulation, cognition, and behaviour. This paper has been aimed at presenting the available data on experience in the application of deep brain stimulation in the treatment of psychiatric disorders. It gives an overview of scientific and professional literature, bearing in mind all the contemporary approaches in the treatment of certain psychiatric disorders. Research results available so far in the treatment of treatment-resistant depression, obsessive-compulsive disorder, Gilles de la Tourette syndrome, addiction and Alzheimer’s dementia, are affirmative concerning the efficacy of the method and low risk of adverse effects. Deep brain stimulation, as a relatively new neurosurgical method in the treatment of psychiatric disorders, is being intensively developed, and it is certainly going to be one of the treatments of choice, primarily of treatment-resistant disorders.

  17. Optimizing performance by conflict stimulation

    NARCIS (Netherlands)

    Van de Vliert, E; De Dreu, C K W

    1994-01-01

    To enhance the quality of group decision making, to promote affective acceptance of decisions by all participants involved, or to increase joint outcomes, a principal party or a third party may stimulate social conflict. We argue that when conflict focuses on identity issues, when tension level is h

  18. Aversive Stimulation -- Criteria for Application.

    Science.gov (United States)

    O'Donnell, Patrick A.; Ohlson, Glenn A.

    Criteria for applying aversive stimulation with severely handicapped children are examined, and practical and ethical issues are considered. Factors seen to influence punishment outcomes include timing, intensity, and schedule of reinforcement. Suggested is the need for further research on the comparative effectiveness of positive and negative…

  19. Ovarian stimulation and embryo quality

    NARCIS (Netherlands)

    Baart, Esther; Macklon, Nick S.; Fauser, Bart J. C. M.

    2009-01-01

    To Study the effects of different ovarian stimulation approaches on oocyte and embryo quality, it is imperative to assess embryo quality with a reliable and objective method. Embryos rated as high quality by standardized morphological assessment are associated with higher implantation and pregnancy

  20. Agent Roles in Human Teams

    OpenAIRE

    Lewis, M.; Sycara, K.; Payne, T.R.

    2003-01-01

    In this paper, we describe results of a series of experiments investigating the effects of agent aiding on human teams. The role an agent played, its task, and the ease with which it communicated with its human teammates all influenced team behavior. Team supporting tasks such as relaying and reminding seemed particularly effective.

  1. Implementing Lego Agents Using Jason

    CERN Document Server

    Jensen, Andreas Schmidt

    2010-01-01

    Since many of the currently available multi-agent frameworks are generally mostly intended for research, it can be difficult to built multi-agent systems using physical robots. In this report I describe a way to combine the multi-agent framework Jason, an extended version of the agent-oriented programming language AgentSpeak, with Lego robots to address this problem. By extending parts of the Jason reasoning cycle I show how Lego robots are able to complete tasks such as following lines on a floor and communicating to be able to avoid obstacles with minimal amount of coding. The final implementation is a functional extension that is able to built multi-agent systems using Lego agents, however there are some issues that have not been addressed. If the agents are highly dependent on percepts from their sensors, they are required to move quite slowly, because there currently is a high delay in the reasoning cycle, when it is combined with a robot. Overall the system is quite robust and can be used to make simple...

  2. Topical agents in burn care

    Directory of Open Access Journals (Sweden)

    Momčilović Dragan

    2002-01-01

    Full Text Available Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injured. It was not until the XX century, after the discovery of antibiotics, when this condition was fulfilled. In 1968, combining silver and sulfadiazine, fox made silver-sulfadiazine, which is a 1% hydro-soluble cream and a superior agent in topical treatment of burns today. Current topical agents None of the topical antimicrobial agents available today, alone or combined, have the characteristics of ideal prophylactic agents, but they eliminate colonization of burn wound, and invasive infections are infrequent. With an excellent spectrum of activity, low toxicity, and ease of application with minimal pain, silver-sulfadiazine is still the most frequently used topical agent. Conclusion The incidence of invasive infections and overall mortality have been significantly reduced after introduction of topical burn wound antimicrobial agents into practice. In most burn patients the drug of choice for prophylaxis is silver sulfadiazine. Other agents may be useful in certain clinical situations.

  3. Pharmacologic Agents for Chronic Diarrhea

    OpenAIRE

    Lee, Kwang Jae

    2015-01-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reductio...

  4. 2012 Survey of clothing agents

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Clothing agents take part in China International Clothing and Accessories Fairs ( CHIC ) year by year. In order to attracting investment, they compared with each other at improving their originality and service levels. At the exhibition brands manufacturers and agents had a face-to-face communication,

  5. Stimulation of phagocytosis by sulforaphane

    International Nuclear Information System (INIS)

    Research highlights: → Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. → This effect does not require Nrf2-dependent induction of phase 2 genes. → Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-μm diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2-/- mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  6. Dialogue Games for Agent Argumentation

    Science.gov (United States)

    McBurney, Peter; Parsons, Simon

    The rise of the Internet and the growth of distributed computing have led to a major paradigm shift in software engineering and computer science. Until recently, the notion of computation has been variously construed as numerical calculation, as information processing, or as intelligent symbol analysis, but increasingly, it is now viewed as distributed cognition and interaction between intelligent entities [60]. This new view has major implications for the conceptualization, design, engineering and control of software systems, most profoundly expressed in the concept of systems of intelligent software agents, or multi-agent systems [99]. Agents are software entities with control over their own execution; the design of such agents, and of multi-agent systems of them, presents major research and software engineering challenges to computer scientists.

  7. Agent Communications using Distributed Metaobjects

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

    There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementation up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.

  8. Mobile agent driven by aspect

    Directory of Open Access Journals (Sweden)

    Youssef Hannad

    2010-11-01

    Full Text Available Domain application of mobile agents is quite large. They are used for network management and the monitoring of complex architecture. Mobile agent is also essential into specific software architecture such that adaptable grid architecture. Even if the concept of mobile agent seems to be obvious, the development is always complex because it needs to understand network features but also security features and negotiation algorithms. We present a work about an application of aspects dedicated to mobile agent development over a local network. At this level, the underlying protocol is called jini and allows managing several essential concepts such that short transaction and permission management. Three subsets of aspects are defined in this work. A part is for the description of agent host and its security level, accessible resource, etc. A second part is about mobile agent and their collaboration. This means how they can operate on an agent host with the respect of the execution context. All the results are illustrated through a distributed monitoring application called DMA. Its main objective is the observation of component servers.

  9. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    OpenAIRE

    Hui Zhou; Yi Lu; Wanzhen Chen; Zhen Wu; Haiqing Zou; Ludovic Krundel; Guanglin Li

    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 ele...

  10. Intelligent Farmer Agent for Multi-Agent Ecological Simulations Optimization

    OpenAIRE

    Filipe Cruz; António Pereira; Pedro Valente; Pedro Duarte; Luis Paulo Reis

    2007-01-01

    This paper presents the development of a bivalve farmer agent interacting with a realistic ecological simulation system. The purpose of the farmer agent is to determine the best combinations of bivalve seeding areas in a large region, maximizing the production without exceeding the total allowed seeding area. A system based on simulated annealing, tabu search, genetic algorithms and reinforcement learning, was developed to minimize the number of iterations required to unravel a semi-optimum s...

  11. MDE and Mobile Agents : another reflexion on the agent migration

    OpenAIRE

    Gherbi, Tahar; Borne, Isabelle; Meslati, Djamel

    2009-01-01

    International audience Model Driven Engineering (MDE) is a software development approach family based on the use of models in the software construction. It allows the exploitation of models to simulate, estimate, understand, communicate and produce code. Mobile agents are a very interesting technology to develop applications for mobile and distributed environments. A mobile agent is essentially a computer program that acts autonomously on behalf of a user and travels through a network of h...

  12. Agent Based Multiviews Requirements Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Based on the current researches of viewpoints oriented requirements engineering and intelligent agent, we present the concept of viewpoint agent and its abstract model based on a meta-language for multiviews requirements engineering. It provided a basis for consistency checking and integration of different viewpoint requirements, at the same time, these checking and integration works can automatically realized in virtue of intelligent agent's autonomy, proactiveness and social ability. Finally, we introduce the practical application of the model by the case study of data flow diagram.

  13. Antibacterial agents in the cinema.

    Science.gov (United States)

    García Sánchez, J E; García Sánchez, E; Merino Marcos, M L

    2006-12-01

    Numerous procedures used as antibacterial therapy are present in many films and include strategies ranging from different antimicrobial drugs to surgery and supporting measures. Films also explore the correct use and misuse of antimicrobial agents. Side effects and other aspects related to antibacterial therapy have also been reflected in some films. This article refers to the presence of antibacterial agents in different popular movies. There are movies in which antibacterial agents form part of the central plot, while in others it is merely an important part of the plot. In still others, its presence is isolated, and in these it plays an ambient or anecdotal role.

  14. Agent-oriented Software Engineering

    Institute of Scientific and Technical Information of China (English)

    MingCheng; XuGuan; BaoLiu

    2004-01-01

    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to designing and building complex systems. Yet, to date, little effort had been devoted to discussing the advantages of agent-oriented approach as a mainstream software engineering paradiam.Here both of this issues and the relation between object-oriented and agentoriented will be argued.We describe an agent-oriented methodology and provide a quote for designing a auction system.

  15. 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.

  16. Electrical stimulation of experimental nonunions

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, R.R.; Luethi, U.; Dueland, R.T.; Perren, S.M.

    Hypertrophic and oligotrophic nonunions were prepared by resection of a portion of the proximal ulna in dogs. In the hypertrophic nonunions, 20 muamps of direct current for eight weeks produced an increase in bone formation compared to the opposite control limb by radiography, photometry, point counting of new bone, and growth rate by sequential fluorochrome labeling and the dynamic uptake of 99mTc-labeled methylene disphosphonate. Oligotrophic nonunions were treated by plating and aspiration grafting in addition to direct-current stimulation. Ony the point counting of new bone showed a significant increase in bone formation with stimulation. Sequential fluorochrome labeling demonstrated that the new bone was laid down on existing bone and not primarily adjacent to the cathode within the fibrous nonunion. This finding supports the cell-mediated rather than physicochemical effect of electrostimulation.

  17. Higher education stimulating creative enterprise

    OpenAIRE

    Ely, Philip; Campbell, Frances

    2011-01-01

    This report summarises the research undertaken by the Business & Community School at the University for the Creative Arts (UCA), analysing ways that higher ediucation (HEIs) can support, and indeed stimulate, the creative economy. The research, in collaboration with the Arts University College Bournemouth (AUCB) and the University of Winchester, serves as a mere snapshot of the numerous ways that Universities engage with the diverse industries under the 'creative' nomenclature and of the ver...

  18. Tactile Stimulation and Consumer Response.

    OpenAIRE

    Hornik, Jacob

    1992-01-01

    Tactile behavior is a basic communication form as well as an expression of interpersonal involvement. This article presents three studies offering evidence for the positive role of casual interpersonal touch on consumer behavior. More specifically, it provides initial support for the view that tactile stimulation in various consumer behavior situations enhances the positive feeling for and evaluation of both the external stimuli and the touching source. Further, customers touched by a request...

  19. Deep brain stimulation: new directions.

    Science.gov (United States)

    Ostergard, T; Miller, J P

    2014-12-01

    The role of deep brain stimulation (DBS) in the treatment of movement disorders is well established, but there has recently been a proliferation of additional indications that have been shown to be amenable to this technology. The combination of innovative approaches to neural interface technology with novel target identification based on previously discovered clinical effects of lesioning procedures has led to a fundamental paradigm for new directions in the application of DBS. The historical use of neurosurgical lesioning procedures in the treatment of psychiatric diseases such as obsessive compulsive disorder provided an initial opportunity to expand the use of DBS. The list is rapidly expanding and now includes major depressive disorder, Tourette's syndrome, addiction disorders, and eating disorders. Keen observations by neurosurgeons using these devices have lead to the incidental discovery of treatments for diseases without previous neurosurgical treatments. These discoveries are breaking new ground in the treatment of disorders of cognition, headache syndromes, disorders of consciousness, and epilepsy. Two features of DBS make it well-suited for treatment of disorders of nervous system function. First, the reversible, non-lesional nature of DBS allows for investigation of new targets without the morbidity of permanent side effects. Second, the programmable nature of DBS allows practitioners to alter stimulation patterns to minimize side effects and potentially improve efficacy through reprogramming. More importantly, proper scientific evaluation of new targets is aided by the ability to turn stimulation on and off with evaluators blinded to the stimulation status. Knowledge of these emerging therapies is important for practitioners, as there are many situations where a single target can effectively treat the symptoms of more than one disease. The intersection of advances in neuromodulation, neurophysiology, neuroimaging, and functional neuroanatomy has

  20. Gastric stimulation for weight loss

    Institute of Scientific and Technical Information of China (English)

    Meir Mizrahi; Ami Ben Ya'acov; Yaron Ilan

    2012-01-01

    The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy are safe treatments for obesity in the short term,but the durability of the weight loss is limited.Although promising obesity drugs are in development,the currently available drugs lack efficacy or have unacceptable side effects.Surgery leads to long-term weight loss,but it is associated with morbidity and mortality.Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders.GES is a promising,minimally invasive,safe,and effective method for treating obesity.External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time.In addition,data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES.This may involve alteration of secretion of hormones associated with hunger or satiety.Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome.Here,we review the current status,potential mechanisms of action,and possible future applications of gastric stimulation for obesity.

  1. Deliberate Evolution in Multi-Agent Systems

    NARCIS (Netherlands)

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.

    2000-01-01

    This paper presents an architecture for an agent capable of deliberation about the creation of new agents, and of actually creating a new agent in the multi-agent system, on the basis of this deliberation. The agent architecture is based on an existing

  2. Optimistic Agents are Asymptotically Optimal

    OpenAIRE

    Sunehag, Peter; Hutter, Marcus

    2012-01-01

    We use optimism to introduce generic asymptotically optimal reinforcement learning agents. They achieve, with an arbitrary finite or compact class of environments, asymptotically optimal behavior. Furthermore, in the finite deterministic case we provide finite error bounds.

  3. Agents containing chlorhexidine in dentistry

    OpenAIRE

    Lebedeva S.N.; Zemlyanichenko М.К.

    2011-01-01

    Aclinical definition of the efficacy of chlorhexidine-containing means for reducing the risk of dental caries and gingivitis with plastic caps. Chlorhexidine is an effective antimicrobial agent for the formation of individual programs for the prevention of dental caries

  4. Computational Environment of Software Agents

    Directory of Open Access Journals (Sweden)

    Martin Tomášek

    2008-05-01

    Full Text Available Presented process calculus for software agent communication and mobility canbe used to express distributed computational environment and mobile code applications ingeneral. Agents are abstraction of the functional part of the system architecture and theyare modeled as process terms. Agent actions model interactions within the distributedenvironment: local/remote communication and mobility. Places are abstraction of thesingle computational environment where the agents are evaluated and where interactionstake place. Distributed environment is modeled as a parallel composition of places whereeach place is evolving asynchronously. Operational semantics defines rules to describebehavior within the distributed environment and provides a guideline for implementations.Via a series of examples we show that mobile code applications can be naturally modeled.

  5. Deep Brain Stimulation Tested for Early Alzheimer's

    Science.gov (United States)

    ... 160137.html Deep Brain Stimulation Tested for Early Alzheimer's Although treatment seems safe, benefit isn't yet ... brain stimulation appears safe for people with early Alzheimer's disease -- and might even slow down memory loss ...

  6. Ficus Deltoidea: A potential source for new oral antidiabetic agent

    International Nuclear Information System (INIS)

    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 (p50 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)

  7. Epidemic Spreading with External Agents

    OpenAIRE

    Banerjee, Siddhartha; Gopalan, Aditya; Das, Abhik Kumar; Shakkottai, Sanjay

    2012-01-01

    We study epidemic spreading processes in large networks, when the spread is assisted by a small number of external agents: infection sources with bounded spreading power, but whose movement is unrestricted vis-\\`a-vis the underlying network topology. For networks which are `spatially constrained', we show that the spread of infection can be significantly speeded up even by a few such external agents infecting randomly. Moreover, for general networks, we derive upper-bounds on the order of the...

  8. Locating Agents in RFID Architectures

    OpenAIRE

    Abdel-Naby, Sameh; Giorgini, Paolo

    2006-01-01

    The use of software agents can create an “intelligent” interface between users’ preferences and the back‐end systems. Agents are now able to interact and communicate with each other, forming a virtual community and feeding back the user with suggestions. Innovative systems related to Asset Tracking, Inventory and Shelving architectures are more often involving advanced communication techniques (e.g., RFID); these systems are responsible for user authentication and objects verification. RFID s...

  9. Agents in E-learning

    OpenAIRE

    S. Mencke; Dumke, R

    2007-01-01

    This paper presents a framework to describe thecrossover domain of e-learning and agent technology.Furthermore it is used to classify existing work and possiblestarting points for the future development of agenttechniques and technologies order to enhance theperformance and the effectiveness of several aspects of elearningsystems. Agents are not a new concept but their usein the field of e-learning constitutes a basis for consequentialadvances.

  10. Handling of injectable antineoplastic agents.

    OpenAIRE

    Knowles, R S; Virden, J E

    1980-01-01

    Although the clinical toxicity of antineoplastic drugs has been well documented there is little or no information on the problems that may arise on the handling and mishandling of such agents. This paper attempts to highlight the importance of taking precautions to prevent adverse effects resulting from contact with cytotoxic drugs during handling and to suggest a practical guide for the handling of such agents.

  11. PENETRATION ENHANCEMENT OF MEDICINAL AGENTS

    OpenAIRE

    Sharma Ganesh N.; Sanadya Jyotsana; Kaushik Avinash; Dwivedi Abha

    2012-01-01

    Many current therapeutic agents like antibiotics, ionizable and peptide drugs are impermeable or do not possess the requisite physicochemical properties for efficient transport through outer tissue barrier to attain therapeutic blood level. For this reason the delivery of such drugs through barriers is currently one of the major interests in pharmaceutical research. Penetration enhancers or promoters are agents that have no therapeutic properties of their own but can transport the sorption of...

  12. Business Intelligence using Software Agents

    OpenAIRE

    Ana-Ramona BOLOGA; Razvan BOLOGA

    2011-01-01

    This paper presents some ideas about business intelligence today and the importance of developing real time business solutions. The authors make an exploration of links between business intelligence and artificial intelligence and focuses specifically on the implementation of software agents-based systems in business intelligence. There are briefly presented some of the few solutions proposed so far that use software agents properties for the benefit of business intelligence. The authors then...

  13. Antimicrobials for bacterial bioterrorism agents.

    Science.gov (United States)

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  14. Bacteriocins as potential anticancer agents

    OpenAIRE

    Sukhraj eKaur; Sumanpreet eKaur

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  15. Bacteriocins as Potential Anticancer Agents

    OpenAIRE

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  16. Natural products as antimitotic agents.

    Science.gov (United States)

    Dall'Acqua, Stefano

    2014-01-01

    Natural products still play an important role in the medicinal chemistry, especially in some therapeutic areas. As example more than 60% of currently-used anticancer agents are derives from natural sources including plants, marine organisms or micro-organism. Thus natural products (NP) are an high-impact source of new "lead compounds" or new potential therapeutic agents despite the large development of biotechnology and combinatorial chemistry in the drug discovery and development. Many examples of anticancer drugs as paclitaxel, combretastatin, bryostatin and discodermolide have shown the importance of NP in the anticancer chemotherapy through many years. Many organisms have been studied as sources of drugs namely plants, micro-organisms and marine organisms and the obtained NP can be considered a group of "privileged chemical structures" evolved in nature to interact with other organisms. For this reason NP are a good starting points for pharmaceutical research and also for library design. Tubulin and microtubules are one of the most studied targets for the search of anticancer compounds. Microtubule targeting agents (MTA) also named antimitotic agents are compounds that are able to perturb mitosis but are also able to arrest cell growing during interphase. The anticancer drugs, taxanes and vinca alkaloids have established tubulin as important target in cancer therapy. More recently the vascular disrupting agents (VDA) combretastatin analogues were studied for their antimitotics properties. This review will consider the anti mitotic NP and their potential impact in the development of new therapeutic agents.

  17. What makes virtual agents believable?

    Science.gov (United States)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

    In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.

  18. Electrical stimulation for epilepsy: stimulation of hippocampal foci.

    Science.gov (United States)

    Velasco, F; Velasco, M; Velasco, A L; Menez, D; Rocha, L

    2001-01-01

    Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

  19. Has Dialysis Payment Reform Led to Initial Racial Disparities in Anemia and Mineral Metabolism Management?

    OpenAIRE

    Turenne, Marc N.; Cope, Elizabeth L.; Porenta, Shannon; Mukhopadhyay, Purna; Fuller, Douglas S.; Pearson, Jeffrey M.; Dahlerus, Claudia; Lantz, Brett; Tentori, Francesca; Robinson, Bruce M.

    2014-01-01

    Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent s...

  20. Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment

    OpenAIRE

    Dewamitta, Sita R; Russell, Megan R.; Nandurkar, Harshal; Walkley, Carl R

    2013-01-01

    Erythropoiesis stimulating agents are widely used for the treatment of anemia. Recently, we reported erythroid expansion with impaired B lymphopoiesis and loss of trabecular bone in C57BL/6 mice following ten days of treatment with low-dose short acting recombinant human erythropoietin. We have assessed erythropoietin against longer-acting darbepoietin-alfa at a comparable erythroid stimulatory dosage regime. Darbepoietin-alfa and erythropoietin induced similar in vivo erythropoietic expansio...

  1. Thresholds of iron markers for iron deficiency erythropoiesis—finding of the Japanese nationwide dialysis registry

    OpenAIRE

    Hamano, Takayuki; Fujii, Naohiko; Hayashi, Terumasa; Yamamoto, Hiroyasu; Iseki, Kunitoshi; Tsubakihara, Yoshiharu

    2015-01-01

    Reportedly, serum ferritin levels are much lower in Japanese hemodialysis (HD) patients than their Western counterparts. Therefore, the cutoff values of ferritin and transferrin saturation (TSAT) for iron deficiency might differ from other countries. We conducted a cross-sectional observational study using the Japanese nationwide registry data. We enrolled 142,339 maintenance HD patients and assessed the association between these markers, hemoglobin (Hb), and erythropoiesis-stimulating agent ...

  2. Managing anemia in lymphoma and multiple myeloma

    OpenAIRE

    Gunnar Birgegård

    2008-01-01

    Gunnar BirgegårdDepartment of Haematology, University Hospital, Uppsala, SwedenAbstract: Anemia is common in cancer, and lymphoproliferative disease is no exception. Erythropoiesis-stimulating agents (ESA) have been used for renal anemia since 1986, and considerably later in cancer anemia. The first studies were published around 1993, but the use of ESA did not become common in cancer anemia until in the late 1990s. Cancer anemia is still under-treated. This review gives an overview...

  3. High-Throughput Screening of Small Molecules Identifies Hepcidin Antagonists

    OpenAIRE

    Fung, Eileen; Sugianto, Priscilla; Hsu, Jason; Damoiseaux, Robert; Ganz, Tomas; Nemeth, Elizabeta

    2013-01-01

    Anemia of inflammation (AI) is common in patients with infection, autoimmune diseases, cancer, and chronic kidney disease. Unless the underlying condition can be reversed, treatment options are limited to erythropoiesis-stimulating agents with or without intravenous iron therapy, modalities that are not always effective and can cause serious adverse effects. Hepcidin, the iron regulatory hormone, has been identified as a pathogenic factor in the development of AI. To explore new therapeutic o...

  4. Predictors of anemia in a multi-ethnic chronic kidney disease population: a case–control study

    OpenAIRE

    Lau, Bing Chang Vincent; Ong, Kheng Yong; Yap, Chun Wei; Vathsala, Anantharaman; How, Priscilla

    2015-01-01

    Anemia is a common complication of chronic kidney disease (CKD). However, risk factors of anemia in CKD patients in Singapore are not well established. Hence, a retrospective, case–control study involving non-dialysis CKD patients was conducted to determine possible predictors of anemia in the local CKD population. Non-dialysis adult CKD patients, not receiving renal replacement therapy or erythropoiesis-stimulating-agents were included. Parameters collected included demographics e.g. age, se...

  5. Anemia of chronic kidney disease: Treat it, but not too aggressively.

    Science.gov (United States)

    Nakhoul, Georges; Simon, James F

    2016-08-01

    Anemia of renal disease is common and is associated with significant morbidity and death. It is mainly caused by a decrease in erythropoietin production in the kidneys and can be partially corrected with erythropoiesis-stimulating agents (ESAs). However, randomized controlled trials have shown that using ESAs to target normal hemoglobin levels can be harmful, and have called into question any benefits of ESA treatment other than avoidance of transfusions. PMID:27505883

  6. Optical stimulator for vision-based sensors

    DEFF Research Database (Denmark)

    Rössler, Dirk; Pedersen, David Arge Klevang; Benn, Mathias;

    2014-01-01

    We have developed an optical stimulator system for vision-based sensors. The stimulator is an efficient tool for stimulating a camera during on-ground testing with scenes representative of spacecraft flights. Such scenes include starry sky, planetary objects, and other spacecraft. The optical...

  7. [A case of recurrent aseptic meningitis induced by ergot agents].

    Science.gov (United States)

    Ogawa, Tomoko; Tagawa, Asako; Hashimoto, Ritsuo; Kato, Hiroyuki

    2015-01-01

    We describe the case of a 29-year-old woman with recurrent aseptic meningitis that was caused by ergot agents. She miscarried at age 27, and the uterus constrictor methylergometrine was prescribed. Three days later, she developed aseptic meningitis and was hospitalized. Two years later, she again developed aseptic meningitis the day after she took ergotamine tartrate. In both events, her symptoms improved rapidly when the medication was stopped. The drug-induced lymphocyte stimulation test for methylergometrine yielded a value of 180%. Drug-induced meningitis is a rare form of recurrent aseptic meningitis. Many studies have reported cases of meningitis caused by non-steroidal anti-inflammatory drugs, but many other drugs can induce aseptic meningitis. To the best of our knowledge, this is the first case of aseptic meningitis induced by ergot agents. PMID:26103816

  8. Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells.

    Science.gov (United States)

    Campbell, C R; Berman, A E; Weintraub, N L; Tang, Y L

    2016-03-01

    Injured or ischemic cardiac tissue has limited intrinsic capacity for regeneration. While stem cell transplantation is a promising approach to stimulating cardiac repair, its success in humans has thus far been limited. Harnessing the therapeutic benefits of stem cells requires a better understanding of their mechanisms of action and methods to optimize their function. Cardiac stem cells (CSC) represent a particularly effective cellular source for cardiac repair, and pre-conditioning CSC with electrical stimulation (EleS) was demonstrated to further enhance their function, although the mechanisms are unknown. Recent studies suggest that transplanted stem cells primarily exert their effects through communicating with endogenous tissues via the release of exosomes containing cardioprotective molecules such as miRNAs, which upon uptake by recipient cells may stimulate survival, proliferation, and angiogenesis. Exosomes are also effective therapeutic agents in isolation and may provide a feasible alternative to stem cell transplantation. We hypothesize that EleS enhances CSC-mediated cardiac repair through its beneficial effects on production of cardioprotective exosomes. Moreover, we hypothesize that the beneficial effects of biventricular pacing in patients with heart failure may in part result from EleS-induced preconditioning of endogenous CSC to promote cardiac repair. With future research, our hypothesis may provide applications to optimize stem cell therapy and augment current pacing protocols, which may significantly advance the treatment of patients with heart disease. PMID:26880625

  9. Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive hydrogel stimulates migration of dendritic cells in models human papillomavirus-associated (pre)neoplastic epithelial lesions

    OpenAIRE

    Hubert, Pascale; Evrard, Brigitte; Maillard, Catherine; Franzen-Detrooz, E.; Delattre, Luc; Foidart, Jean-Michel; Noël, Agnès; Boniver, Jacques; Delvenne, Philippe

    2004-01-01

    Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were ev...

  10. Hypothalamic thermal stimulation modulates vasopressin release in hyperosmotically stimulated rabbits.

    Science.gov (United States)

    Keil, R; Gerstberger, R; Simon, E

    1994-10-01

    Under thermoneutral conditions conscious rabbits received systemic infusions of NaCl as hypertonic solution (90 mueq.min-1.kg body wt-1), which raised their plasma osmolality from 283 to 312 mosmol/kgH2O. Rabbits receiving isotonic saline served as controls. Hypertonic stimulation induced a 60% reduction of both respiratory frequency and evaporative water loss. Rectal temperature rose by 0.4 degrees C despite enhanced peripheral vasodilation as indicated by increased ear skin temperature. Plasma vasopressin (AVP), aldosterone (ALDO), and corticosterone (COR) were significantly elevated from 6 to 16 pg/ml, 90 to 180 pg/ml, and 17 to 40 ng/ml, respectively. To elucidate the importance of central temperature for AVP and adrenal corticosteroid release, hypothalamic thermal stimulations (20 min) were superimposed during established iso- and hyperosmotic steady-state conditions. Different from isosmotic controls, hyperosmotic animals responded to hypothalamic cooling (37 degrees C) with a significant decrease in plasma AVP from 16 to 13 pg/ml and to hypothalamic warming (41 degrees C) with a significant rise from 16 to 19 pg/ml. A weak temperature effect on COR release was also disclosed, especially of hypothalamic cooling, which significantly lowered plasma COR from 42 to 34 ng/ml. These results provide evidence for positive local temperature coefficients of hypothalamic control of AVP release and suggest a similar property also for the control of COR release by the hypothalamo-adenohypophysial axis. PMID:7943420

  11. Geo-Agents: Design and Implement

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Geo-Agents, a multi-agent system that processes distr ib utedgeospatial information and geospatial service was presented. Firstly, the requirement for distributed geographical information process was discussed, and the architecture of Geo-Agents was introduced. Then in-depth discussions were r aised on agent system implementation, such as the basic agent, agent advertising , message passing, and collaborating. An example was also given to explain the p roblem solving process.

  12. Special issue about advances in Physical Agents

    OpenAIRE

    Cazorla Quevedo, Miguel Ángel; Matellán Olivera, Vicente

    2011-01-01

    Nowadays, there are a lot of Spanish groups which are doing research in areas related with physical agents: they use agent-based technologies concepts, especially industrial applications, robotics and domotics (physical agents) and applications related to the information society, (software agents) highlighting the similarities and synergies among physical and software agents. In this special issue we will show several works from those groups, focusing on the recent advances in Physical Agents.

  13. Erythropoietin stimulating agents in the management of anemia of chronic kidney disease

    OpenAIRE

    Hayat, Amir; Haria, Dhiren; Salifu, Moro O

    2008-01-01

    Anemia is a very common clinical problem in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality in these patients. Erythropoietin is a hormone synthesized in the kidney responsible for red blood cell maturation in the bone marrow. It is deficient in the majority of patients with advanced kidney disease thereby predisposing to anemia. Since the approval of recombinant human erythropoietin (epoetin alfa) by the US FDA in 1989, epoetin alfa and sim...

  14. Erythropoietin stimulating agents in the management of anemia of chronic kidney disease

    OpenAIRE

    Salifu, Moro O

    2008-01-01

    Amir Hayat, Dhiren Haria, Moro O SalifuDivision of Nephrology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USAAbstract: Anemia is a very common clinical problem in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality in these patients. Erythropoietin is a hormone synthesized in the kidney responsible for red blood cell maturation in the bone marrow. It is deficient in the majority of patients with advanced kidney disease ...

  15. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent.

    Science.gov (United States)

    Bendall, Linda J; Bradstock, Kenneth F

    2014-08-01

    G-CSF was among the first cytokines to be identified and rapidly transitioned into clinical medicine. Initially used to promote the production of neutrophils in patients with chemotherapy-induced neutropenia it helped to revolutionize the delivery of cancer therapy. Its ability to mobilize hematopoietic stem cells from the bone marrow into the blood was subsequently exploited, changing the face of hematopoietic stem cell transplantation. Today the knowledge gained in unraveling the mechanisms of stem cell mobilization by G-CSF is being explored as a means to increase chemosensitivity in hematological malignancies. This review provides a brief history of G-CSF and then focuses on recent advances in our understanding of G-CSF-induced stem cell mobilization and the potential clinical application of this knowledge in chemo-sensitization. PMID:25131807

  16. Detection of nerve agent stimulants based on photoluminescent porous silicon interferometer

    OpenAIRE

    Kim, Seongwoong; Cho, Bomin; Sohn, Honglae

    2012-01-01

    Porous silicon (PSi) exhibiting dual optical properties, both Fabry-Pérot fringe and photolumincence, was developed and used as chemical sensors. PSi samples were prepared by an electrochemical etch of p-type silicon under the illumination of 300-W tungsten lamp during the etch process. The surface of PSi was characterized by cold field-emission scanning electron microscope. PSi samples exhibited a strong visible orange photoluminescence at 610 nm with an excitation wavelength of 460 nm as we...

  17. BEBIDAS ENERGIZANTES: ¿HIDRATANTES O ESTIMULANTES? Energy drinks: rehydrating agents or stimulants?

    OpenAIRE

    Miguel Cote-Menéndez; Claudia Ximena Rangel-Garzón; Marlib Yolima Sánchez-Torres; Adalbeis Medina-Lemus

    2011-01-01

    Antecedentes. Las bebidas energizantes tienen amplia distribución, su consumo ha aumentado debido al fácil acceso, sus propiedades estimulantes y a las características de inocuidad que se les atribuyen. El poco conocimiento de sus características lleva a confusión con las bebidas hidratantes usándolas de forma indiscriminada, aunque las bebidas hidratantes buscan prevenir la deshidratación y las energizantes tienen un efecto estimulante. Objetivo. Describir los componentes de las bebidas ener...

  18. Colitis associated with biological agents

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2012-01-01

    In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occasionally,fatal.Other agents include rituximab (an antiCD20 monoclonal antibody),bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.

  19. Stimulated Brillouin Scattering Microscopic Imaging.

    Science.gov (United States)

    Ballmann, Charles W; Thompson, Jonathan V; Traverso, Andrew J; Meng, Zhaokai; Scully, Marlan O; Yakovlev, Vladislav V

    2015-01-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

  20. Stimulated Brillouin Scattering Microscopic Imaging

    Science.gov (United States)

    Ballmann, Charles W.; Thompson, Jonathan V.; Traverso, Andrew J.; Meng, Zhaokai; Scully, Marlan O.; Yakovlev, Vladislav V.

    2015-12-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

  1. Transverse stimulated Raman scattering in KDP

    Energy Technology Data Exchange (ETDEWEB)

    Barker, C.E.; Sacks, R.A.; Wonterghem, B.M. Van; Caird, J.A.; Murray, J.R.; Campbell, J.H.; Kyle, K.; Ehrlich, R.E.; Nielsen, N.D.

    1995-09-12

    Optical components of large-aperture, high irradiance and high fluence lasers can experience significant levels of stimulated scattering along their transverse dimensions. The authors have observed transverse stimulated Raman scattering in large aperture KDP crystals, and have measured the stimulated gain coefficient. With sufficiently high gain, transverse stimulated scattering can lead to energy loss from the main beam and, more importantly, optical damage in the components in which this scattering occurs. Thus transverse stimulated,scattering is of concern in large aperture fusion lasers such as Nova and Beamlet, which is a single-aperture, full-scale scientific prototype of the laser driver for the proposed National Ignition Facility.

  2. Social training of autistic children with interactive intelligent agents.

    Science.gov (United States)

    Barakova, Emilia; Gillessen, Jan; Feijs, Loe

    2009-03-01

    The ability of autistic children to learn by applying logical rules has been used widely in behavioral therapies for social training. We propose to teach social skills to autistic children through games that simultaneously stimulate social behavior and include recognition of elements of social interaction. For this purpose we created a multi-agent platform of interactive blocks, and we created appropriate games that require shared activities leading to a common goal. The games included perceiving and understanding elements of social behavior that non-autistic children can recognize. We argue that the importance of elements of social interaction such as perceiving interaction behaviors and assigning metaphoric meanings has been overlooked, and that they are very important in the social training of autistic children. Two games were compared by testing them with users. The first game focused only on the interaction between the agents and the other combined interaction between the agents and metaphoric meanings that are assigned to them. The results show that most of the children recognized the patterns of interaction as well as the metaphors when they were demonstrated through embodied agents and were included within games having features that engage the interest of this user group. The results also show the potential of the platform and the games to influence the social behavior of the children positively.

  3. Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Fassett Robert G

    2008-08-01

    Full Text Available Abstract Background The main hypothesis of this study is that Oxpentifylline administration will effectively treat erythropoietin- or darbepoietin-resistant anaemia in chronic kidney disease patients. Methods/design Inclusion criteria are adult patients with stage 4 or 5 chronic kidney disease (including dialysis patients with significant anaemia (haemoglobin ≤ 110 g/L for at least 3 months for which there is no clear identifiable cause and that is unresponsive to large doses of either erythropoietin (≥ 200 IU/kg/week or darbepoetin (≥ 1 μg/kg/week. Patients will be randomized 1:1 to receive either placebo (1 tablet daily or oxpentifylline (400 mg daily per os for a period of 4 months. During this 4 month study period, haemoglobin measurements will be performed monthly. The primary outcome measure will be the difference in haemoglobin level between the 2 groups at the end of the 4 month study period, adjusted for baseline values. Secondary outcome measures will include erythropoiesis stimulating agent dosage, Key's index (erythropoiesis stimulating agent dosage divided by haemoglobin concentration, and blood transfusion requirement. Discussion This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their chronic kidney disease patients determine whether oxpentifylline represents a safe and effective strategy for treating erythropoiesis stimulating agent resistance in chronic kidney disease. Trial Registration Australian New Zealand Clinical Trials Registry Number ACTRN12608000199314.

  4. Multichannel magnetic stimulation system design considering mutual couplings among the stimulation coils.

    Science.gov (United States)

    Han, Byung H; Chun, In K; Lee, Sang C; Lee, Soo Y

    2004-05-01

    We introduce some simulation and experiment results of the multichannel magnetic stimulator development that has been carried out as an initial attempt to realize a multichannel functional magnetic stimulator. For efficient functional magnetic stimulations, precise spatial localization of stimulation sites without any movements of the stimulation coils is very important. We have found that the mutual coupling effect among the adjacent stimulation coils in the coil array has to be considered in the determination of the charge voltages in some coil array configurations. Experimental results obtained with a 4-channel magnetic stimulator are presented. PMID:15132507

  5. A multi-agent architecture for geosimulation of moving agents

    Science.gov (United States)

    Vahidnia, Mohammad H.; Alesheikh, Ali A.; Alavipanah, Seyed Kazem

    2015-10-01

    In this paper, a novel architecture is proposed in which an axiomatic derivation system in the form of first-order logic facilitates declarative explanation and spatial reasoning. Simulation of environmental perception and interaction between autonomous agents is designed with a geographic belief-desire-intention and a request-inform-query model. The architecture has a complementary quantitative component that supports collaborative planning based on the concept of equilibrium and game theory. This new architecture presents a departure from current best practices geographic agent-based modelling. Implementation tasks are discussed in some detail, as well as scenarios for fleet management and disaster management.

  6. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Germing, Ulrich; List, Alan; MacBeth, Kyle J

    2014-01-01

    Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians' ability to predict/monitor response and identify patients at risk of relapse.

  7. Bubble stimulation efficiency of dinoflagellate bioluminescence.

    Science.gov (United States)

    Deane, Grant B; Stokes, M Dale; Latz, Michael I

    2016-02-01

    Dinoflagellate bioluminescence, a common source of bioluminescence in coastal waters, is stimulated by flow agitation. Although bubbles are anecdotally known to be stimulatory, the process has never been experimentally investigated. This study quantified the flash response of the bioluminescent dinoflagellate Lingulodinium polyedrum to stimulation by bubbles rising through still seawater. Cells were stimulated by isolated bubbles of 0.3-3 mm radii rising at their terminal velocity, and also by bubble clouds containing bubbles of 0.06-10 mm radii for different air flow rates. Stimulation efficiency, the proportion of cells producing a flash within the volume of water swept out by a rising bubble, decreased with decreasing bubble radius for radii less than approximately 1 mm. Bubbles smaller than a critical radius in the range 0.275-0.325 mm did not stimulate a flash response. The fraction of cells stimulated by bubble clouds was proportional to the volume of air in the bubble cloud, with lower stimulation levels observed for clouds with smaller bubbles. An empirical model for bubble cloud stimulation based on the isolated bubble observations successfully reproduced the observed stimulation by bubble clouds for low air flow rates. High air flow rates stimulated more light emission than expected, presumably because of additional fluid shear stress associated with collective buoyancy effects generated by the high air fraction bubble cloud. These results are relevant to bioluminescence stimulation by bubbles in two-phase flows, such as in ship wakes, breaking waves, and sparged bioreactors.

  8. Interleukin-10 inhibits burst-forming unit-erythroid growth by suppression of endogenous granulocyte-macrophage colony-stimulating factor production from T cells.

    Science.gov (United States)

    Oehler, L; Kollars, M; Bohle, B; Berer, A; Reiter, E; Lechner, K; Geissler, K

    1999-02-01

    Numerous cytokines released from accessory cells have been shown to exert either stimulatory or inhibitory growth signals on burst-forming unit-erythroid (BFU-E) growth. Because of its cytokine synthesis-inhibiting effects on T cells and monocytes, interleukin-10 (IL-10) may be a potential candidate for indirectly affecting erythropoiesis. We investigated the effects of IL-10 on BFU-E growth from normal human peripheral blood mononuclear cells (PBMC) using a clonogenic progenitor cell assay. The addition of recombinant human IL-10 to cultures containing recombinant human erythropoietin suppressed BFU-E growth in a dose-dependent manner (by 55.2%, range 47.3-63.3%, p cultivating highly enriched CD34+ cells. BFU-E growth from PBMC also was markedly suppressed in the presence of a neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody (by 48.7%, range 32.9-61.2% inhibition,p < 0.01), but not by neutralizing antibodies against granulocyte colony-stimulating factor and interleukin-3. This suggests a stimulatory role of endogenously released GM-CSF on BFU-E formation. Also, the addition of exogenous GM-CSF completely restored IL-10-induced suppression of BFU-E growth. To determine the cellular source of GM-CSF production, we analyzed GM-CSF levels in suspension cultures containing PBMC that were either depleted of monocytes or T cells. Monocyte-depleted PBMC showed spontaneous production of increasing amounts of GM-CSF on days 3, 5, and 7, respectively, which could be suppressed by IL-10, whereas GM-CSF levels did not increase in cultures containing T-cell-depleted PBMC. Our data indicate that IL-10 inhibits the growth of erythroid progenitor cells in vitro, most likely by suppression of endogenous GM-CSF production from T cells.

  9. Calcium channel as a potential anticancer agent.

    Science.gov (United States)

    Kriazhev, L

    2009-11-01

    Anticancer treatment in modern clinical practices includes chemotherapy and radiation therapy with or without surgical interventions. Efficiency of both methods varies greatly depending on cancer types and stages. Besides, chemo- and radiotherapy are toxic and damaging that causes serious side effects. This fact prompts the search for alternative methods of antitumor therapy. It is well known that prolonged or high increase of intracellular calcium concentration inevitably leads to the cell death via apoptosis or necrosis. However, stimulation of cell calcium level by chemical agents is hardly achievable because cells have very sophisticated machinery for maintaining intracellular calcium in physiological ranges. This obstacle can be overridden, nevertheless. It was found that calcium channels in so called calcium cells in land snails are directly regulated by extracellular calcium concentration. The higher the concentration the higher the calcium intake is through the channels. Bearing in mind that extracellular/intracellular calcium concentration ratio in human beings is 10,000-12,000 fold the insertion of the channel into cancer cells would lead to fast and uncontrollable by the cells calcium intake and cell death. Proteins composing the channel may be extracted from plasma membrane of calcium cells and sequenced by mass-spectrometry or N-terminal sequencing. Either proteins or corresponding genes could be used for targeted delivery into cancer cells.

  10. Development of secreted proteins as biotherapeutic agents.

    Science.gov (United States)

    Bonin-Debs, Angelika L; Boche, Irene; Gille, Hendrik; Brinkmann, Ulrich

    2004-04-01

    As one of the most important classes of proteins, secreted factors account for about one-tenth of the human genome, 3000 - 4000 in total, including factors of signalling pathways, blood coagulation and immune defence, as well as digestive enzymes and components of the extracellular matrix. Secreted proteins are a rich source of new therapeutics and drug targets, and are currently the focus of major drug discovery programmes throughout the industry. Many of the most important novel drugs developed in biotechnology have resulted from the application of secreted proteins as therapeutics. Secreted proteins often circulate throughout the body and, therefore, have access to most organs and tissues. Because of that, many of the factors are themselves therapeutic agents. This paper gives an overview on the features and functions of human secreted proteins and peptides, as well as strategies by which to discover additional therapeutic proteins from the human 'secretome'. Furthermore, a variety of examples are provided for the therapeutic use of recombinant secreted proteins as 'biologicals', including features and applications of recombinant antibodies, erythropoietin, insulin, interferon, plasminogen activators, growth hormone and colony-stimulating factors. PMID:15102604

  11. Stimulated emission from NV centres in diamond

    CERN Document Server

    Jeske, Jan; McGuinness, Liam P; Reineck, Philip; Johnson, Brett C; McCallum, Jeffrey C; Jelezko, Fedor; Volz, Thomas; Cole, Jared H; Gibson, Brant C; Greentree, Andrew D

    2016-01-01

    Stimulated emission is the process fundamental to laser operation, thereby producing coherent photon output. Despite negatively-charged nitrogen-vacancy (NV$^-$) centres being discussed as a potential laser medium since the 1980's, there have been no definitive observations of stimulated emission from ensembles of NV$^-$ to date. Reasons for this lack of demonstration include the short excited state lifetime and the occurrence of photo-ionisation to the neutral charge state by light around the zero-phonon line. Here we show both theoretical and experimental evidence for stimulated emission from NV$^-$ states using light in the phonon-sidebands. Our system uses a continuous wave pump laser at 532 nm and a pulsed stimulating laser that is swept across the phononic sidebands of the NV$^-$. Optimal stimulated emission is demonstrated in the vicinity of the three-phonon line at 700 nm. Furthermore, we show the transition from stimulated emission to photoionisation as the stimulating laser wavelength is reduced fro...

  12. 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.

  13. Braille line using electrical stimulation

    International Nuclear Information System (INIS)

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards

  14. Braille line using electrical stimulation

    Science.gov (United States)

    Puertas, A.; Purés, P.; Echenique, A. M.; Ensinck, J. P. Graffigna y. G.

    2007-11-01

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards.

  15. Braille line using electrical stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Puertas, A; Pures, P; Echenique, A M; Ensinck, J P Graffigna y G [Gabinete de TecnologIa Medica. Universidad N. de San Juan (Argentina)

    2007-11-15

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards.

  16. Relational agents in clinical psychiatry.

    Science.gov (United States)

    Bickmore, Timothy; Gruber, Amanda

    2010-01-01

    Relational agents are computational artifacts, such as animated, screen-based characters or social robots, that are designed to establish a sense of rapport, trust, and even therapeutic alliance with patients, using ideal therapeutic relationships between human counselors and patients as role models. We describe the development and evaluation of several such agents designed for health counseling and behavioral-change interventions, in which a therapeutic alliance is established with patients in order to enhance the efficacy of the intervention. We also discuss the promise of using such agents as adjuncts to clinical psychiatry, a range of possible applications, and some of the challenges and ethical issues in developing and fielding them in psychiatric interventions.

  17. Multi-Agent Software Engineering

    International Nuclear Information System (INIS)

    This paper proposed an alarm-monitoring system for people based on multi-agent using maps. The system monitors the users physical context using their mobile phone. The agents on the mobile phones are responsible for collecting, processing and sending data to the server. They can determine the parameters of their environment by sensors. The data are processed and sent to the server. On the other side, a set of agents on server can store this data and check the preconditions of the restrictions associated with the user, in order to trigger the appropriate alarms. These alarms are sent not only to the user who is alarmed to avoid the appeared restriction, but also to his supervisor. The proposed system is a general purpose alarm system that can be used in different critical application areas. It has been applied for monitoring the workers of radiation sites. However, these workers can do their activity tasks in the radiation environments safely

  18. Agent Based Individual Traffic Guidance

    DEFF Research Database (Denmark)

    Wanscher, Jørgen

    This thesis investigates the possibilities in applying Operations Research (OR) to autonomous vehicular traffic. The explicit difference to most other research today is that we presume that an agent is present in every vehicle - hence Agent Based Individual Traffic guidance (ABIT). The next...... evolutionary step for the in-vehicle route planners is the introduction of two-way communication. We presume that the agent is capable of exactly this. Based on this presumption we discuss the possibilities and define a taxonomy and use this to discuss the ABIT system. Based on a set of scenarios we conclude...... that the system can be divided into two separate constituents. The immediate dispersion, which is used for small areas and quick response, and the individual alleviation, which considers the longer distance decision support. Both of these require intrinsicate models and cost functions which at the beginning...

  19. Agent review phase one report.

    Energy Technology Data Exchange (ETDEWEB)

    Zubelewicz, Alex Tadeusz; Davis, Christopher Edward; Bauer, Travis LaDell

    2009-12-01

    This report summarizes the findings for phase one of the agent review and discusses the review methods and results. The phase one review identified a short list of agent systems that would prove most useful in the service architecture of an information management, analysis, and retrieval system. Reviewers evaluated open-source and commercial multi-agent systems and scored them based upon viability, uniqueness, ease of development, ease of deployment, and ease of integration with other products. Based on these criteria, reviewers identified the ten most appropriate systems. The report also mentions several systems that reviewers deemed noteworthy for the ideas they implement, even if those systems are not the best choices for information management purposes.

  20. Dual Rationality and Deliberative Agents

    Science.gov (United States)

    Debenham, John; Sierra, Carles

    Human agents deliberate using models based on reason for only a minute proportion of the decisions that they make. In stark contrast, the deliberation of artificial agents is heavily dominated by formal models based on reason such as game theory, decision theory and logic—despite that fact that formal reasoning will not necessarily lead to superior real-world decisions. Further the Nobel Laureate Friedrich Hayek warns us of the ‘fatal conceit’ in controlling deliberative systems using models based on reason as the particular model chosen will then shape the system’s future and either impede, or eventually destroy, the subtle evolutionary processes that are an integral part of human systems and institutions, and are crucial to their evolution and long-term survival. We describe an architecture for artificial agents that is founded on Hayek’s two rationalities and supports the two forms of deliberation used by mankind.

  1. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration.

    Science.gov (United States)

    Takebe, Naoko; Ahmed, Mansoor M; Vikram, Bhadrasain; Bernhard, Eric J; Zwiebel, James; Norman Coleman, C; Kunos, Charles A

    2016-10-01

    A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives. PMID:27619249

  2. Agent communication and artificial institutions

    OpenAIRE

    Fornara, Nicoletta; Viganò, Francesco; Colombetti, Marco

    2011-01-01

    In this paper we propose an application-independent model for the definition of artificial institutions that can be used to define open multi-agent systems. Such a model of institutional reality makes us able also to define an objective and external semantics of a commitment-based Agent Communication Language (ACL). In particular we propose to regard an ACL as a set of conventions to act on a fragment of institutional reality, defined in the context of an artificial institution. Another c...

  3. Autonomous sensor manager agents (ASMA)

    Science.gov (United States)

    Osadciw, Lisa A.

    2004-04-01

    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  4. Neonate intestinal immune response to CpG oligodeoxynucleotide stimulation.

    Directory of Open Access Journals (Sweden)

    Sonia Lacroix-Lamandé

    Full Text Available BACKGROUND: The development of mucosal vaccines is crucial to efficiently control infectious agents for which mucosae are the primary site of entry. Major drawbacks of these protective strategies are the lack of effective mucosal adjuvant. Synthetic oligodeoxynucleotides that contain several unmethylated cytosine-guanine dinucleotide (CpG-ODN motifs are now recognized as promising adjuvants displaying mucosal adjuvant activity through direct activation of TLR9-expressing cells. However, little is known about the efficacy of these molecules in stimulating the intestinal immune system in neonates. METHODOLOGY/PRINCIPAL FINDINGS: First, newborn mice received CpG-ODN orally, and the intestinal cytokine and chemokine response was measured. We observed that oral administration of CpG-ODN induces CXC and CC chemokine responses and a cellular infiltration in the intestine of neonates as detected by immunohistochemistry. We next compared the efficiency of the oral route to intraperitoneal administration in stimulating the intestinal immune responses of both adults and neonates. Neonates were more responsive to TLR9-stimulation than adults whatever the CpG-ODN administration route. Their intestinal epithelial cells (IECs indirectly responded to TLR9 stimulation and contributed to the CXC chemokine response, whereas other TLR9-bearing cells of the lamina-propria produced CC chemokines and Th1-type cytokines. Moreover, we showed that the intestine of adult exhibited a significantly higher level of IL10 at homeostasis than neonates, which might be responsible for the unresponsiveness to TLR9-stimulation, as confirmed by our findings in IL10-deficient mice. CONCLUSIONS/SIGNIFICANCE: This is the first report that deciphers the role played by CpG-ODN in the intestine of neonates. This work clearly demonstrates that an intraperitoneal administration of CpG-ODN is more efficient in neonates than in adults to stimulate an intestinal chemokine response due to their

  5. Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro

    Directory of Open Access Journals (Sweden)

    Jun-ichi Ito

    2000-01-01

    Full Text Available The influence of anti-allergic drugs, epinastine hydrochloride (EP and disodium cromoglycate (DSCG, on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 μg/ml haemocyanin and various concentrations of the agents. Low concentrations (< 1.5 2 10-4 M of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 × 10-4 M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 × 10-4 M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 × 10-4 M of the agents and the expression of molecules were examined by flow cytometer 24 h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro.

  6. Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro.

    Science.gov (United States)

    Ito, J; Asano, K; Tryka, E; Kanai, K; Yamamoto, S; Hisamitsu, T; Suzaki, H

    2000-01-01

    The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 microg/ml haemocyanin and various concentrations of the agents. Low concentrations (DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 x 10(-4) M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the agents and the expression of molecules were examined by flow cytometer 24h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro. PMID:10958379

  7. Vestibular stimulation by magnetic fields

    Science.gov (United States)

    Ward, Bryan K.; Roberts, Dale C.; Della Santina, Charles C.; Carey, John P.; Zee, David S.

    2015-01-01

    Individuals working next to strong static magnetic fields occasionally report disorientation and vertigo. With the increasing strength of magnetic fields used for magnetic resonance imaging (MRI) studies, these reports have become more common. It was recently learned that humans, mice and zebrafish all demonstrate behaviors consistent with constant peripheral vestibular stimulation while inside a strong, static magnetic field. The proposed mechanism for this effect involves a Lorentz force resulting from the interaction of a strong static magnetic field with naturally occurring ionic currents flowing through the inner ear endolymph into vestibular hair cells. The resulting force within the endolymph is strong enough to displace the lateral semicircular canal cupula, inducing vertigo and the horizontal nystagmus seen in normal mice and in humans. This review explores the evidence for interactions of magnetic fields with the vestibular system. PMID:25735662

  8. Acupuncture stimulation and neuroendocrine regulation.

    Science.gov (United States)

    Yu, Jung-Sheng; Zeng, Bai-Yun; Hsieh, Ching-Liang

    2013-01-01

    Acupuncture has been used to treat different conditions for at least 3000 years in China and has gained increasing acceptance worldwide. The acupuncture needle inserted into the muscle layer at the acupoint produces the so-called obtaining qi sensation that causes the excitation of A-δ and C-fibers of the muscle tissue, resulting in afferent signals. The afferent signals pass through the dorsal horn cells of the spinal cord ascending to the brain, such as the hypothalamus, enhancing the release of neuropeptides and hormones, and these afferent signals in the spinal segment may innervate the visceral organ, inducing effect on visceral function. Here, we reviewed the effect of acupuncture stimulation on neuropeptides and hormones, including β-endorphin, serotonin, oxytocin, adrenocorticotropic hormone, gonadotropin-releasing hormone, corticotrophin-releasing hormone, cholecystokinin, and acetylcholine, as well as insulin sensitivity, immunomodulation (anti-inflammation), and autonomic nerve activity. PMID:24215920

  9. Electrode array for neural stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Wessendorf, Kurt O. (Albuquerque, NM); Okandan, Murat (Edgewood, NM); Stein, David J. (Albuquerque, NM); Yang, Pin (Albuquerque, NM); Cesarano, III, Joseph (Albuquerque, NM); Dellinger, Jennifer (Albuquerque, NM)

    2011-08-16

    An electrode array for neural stimulation is disclosed which has particular applications for use in a retinal prosthesis. The electrode array can be formed as a hermetically-sealed two-part ceramic package which includes an electronic circuit such as a demultiplexer circuit encapsulated therein. A relatively large number (up to 1000 or more) of individually-addressable electrodes are provided on a curved surface of a ceramic base portion the electrode array, while a much smaller number of electrical connections are provided on a ceramic lid of the electrode array. The base and lid can be attached using a metal-to-metal seal formed by laser brazing. Electrical connections to the electrode array can be provided by a flexible ribbon cable which can also be used to secure the electrode array in place.

  10. Multisensory stimulation in stroke rehabilitation

    Directory of Open Access Journals (Sweden)

    Barbro Birgitta Johansson

    2012-04-01

    Full Text Available The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, or various kinds of music therapy. Several studies have shown positive effects been reported but to give general recommendation more studies are needed. Patient heterogeneity and the interactions of age, gender, genes and environment are discussed. Randomized controlled longitudinal trials starting earlier post stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation.

  11. Raspberry Pi for secret agents

    CERN Document Server

    Sjogelid, Stefan

    2015-01-01

    This book is an easy-to-follow guide with practical examples in each chapter. Suitable for the novice and expert alike, each topic provides a fast and easy way to get started with exciting applications and also guides you through setting up the Raspberry Pi as a secret agent toolbox.

  12. SEM: A Cultural Change Agent

    Science.gov (United States)

    Barnes, Bradley; Bourke, Brian

    2015-01-01

    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  13. The Power Trading Agent Competition

    NARCIS (Netherlands)

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph); M.M. Weerdt (Mathijs)

    2011-01-01

    textabstractThis is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff

  14. The Power Trading Agent Competition

    NARCIS (Netherlands)

    Ketter, W.; Collins, J.; Reddy, P.; Flath, C.; De Weerdt, M.M.

    2011-01-01

    This is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff contracts,

  15. Antibacterial activities of antineoplastic agents.

    OpenAIRE

    Bodet, C A; Jorgensen, J H; Drutz, D J

    1985-01-01

    Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens. Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities.

  16. Kriitikute lemmikfilm on "Agent Sinikael"

    Index Scriptorium Estoniae

    2003-01-01

    Eesti Filmiajakirjanike Ühing andis kümnendat korda välja auhinda Aasta film 2002. Parimaks filmiks tunnistati mängufilm "Agent Sinikael" : režissöör Marko Raat. Viimane sai preemiaks Neitsi Maali kuju ja 12 000 krooni

  17. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    A wide range of pharmaceuticals for labeling with Tc-99m, developed by the Soreq Radiopharmaceuticals Department, is described. Details of the production and quality control of 13 kits are given, as well as the range of results required for consistently high quality imaging agents

  18. Relational agents: A critical review

    DEFF Research Database (Denmark)

    Campbell, Robert H.; Grimshaw, Mark Nicholas; Green, Gill

    2009-01-01

    Relationships between people who meet in virtual worlds are common and these relationships can be long term, in some cases lasting a life-time. Although relationships formed in virtual worlds have invited a lot of recent interest, surprisingly little work has been done on developing computer agents...

  19. Direct Vasodilators and Sympatholytic Agents.

    Science.gov (United States)

    McComb, Meghan N; Chao, James Y; Ng, Tien M H

    2016-01-01

    Direct vasodilators and sympatholytic agents were some of the first antihypertensive medications discovered and utilized in the past century. However, side effect profiles and the advent of newer antihypertensive drug classes have reduced the use of these agents in recent decades. Outcome data and large randomized trials supporting the efficacy of these medications are limited; however, in general the blood pressure-lowering effect of these agents has repeatedly been shown to be comparable to other more contemporary drug classes. Nevertheless, a landmark hypertension trial found a negative outcome with a doxazosin-based regimen compared to a chlorthalidone-based regimen, leading to the removal of α-1 adrenergic receptor blockers as first-line monotherapy from the hypertension guidelines. In contemporary practice, direct vasodilators and sympatholytic agents, particularly hydralazine and clonidine, are often utilized in refractory hypertension. Hydralazine and minoxidil may also be useful alternatives for patients with renal dysfunction, and both hydralazine and methyldopa are considered first line for the treatment of hypertension in pregnancy. Hydralazine has also found widespread use for the treatment of systolic heart failure in combination with isosorbide dinitrate (ISDN). The data to support use of this combination in African Americans with heart failure are particularly robust. Hydralazine with ISDN may also serve as an alternative for patients with an intolerance to angiotensin antagonists. Given these niche indications, vasodilators and sympatholytics are still useful in clinical practice; therefore, it is prudent to understand the existing data regarding efficacy and the safe use of these medications. PMID:26033778

  20. Identity Management in Agent Systems

    NARCIS (Netherlands)

    Brazier, F.M.T.; Groot, de D.R.A.

    2006-01-01

    If agent-based applications are to be used in large scale, open environments, security is a main issue; digital identity management (DIDM) an essential element. DIDM is needed to be able to determine the rights and obligations of the four main

  1. Foodborne illness and microbial agents

    Science.gov (United States)

    Foodborne illnesses result from the consumption of food containing microbial agents such as bacteria, viruses, parasites or food contaminated by poisonous chemicals or bio-toxins. Pathogen proliferation is due to nutrient composition of foods, which are capable of supporting the growth of microorgan...

  2. Bridging humans via agent networks

    International Nuclear Information System (INIS)

    Recent drastic advance in telecommunication networks enabled the human organization of new class, teleorganization, which differ from any existing organization in that the organization which is easy to create by using telecommunication networks is virtual and remote, that people can join multiple organizations simultaneously, and that the organization can involve people who may not know each other. In order to enjoy the recent advance in telecommunication, the agent networks to help people organize themselves are needed. In this paper, an architecture of agent networks, in which each agent learns the preference or the utility functioin of the owner, and acts on behalf of the owner in maintaining the organization, is proposed. When an agent networks supports a human organization, the conventional human interface is divided into personal and social interfaces. The functionalities of the social interface in teleconferencing and telelearning were investigated. In both cases, the existence of B-ISDN is assumed, and the extension to the business meeting scheduling using personal handy phone (PHS) networks with personal digital assistant (PDA) terminals is expected. These circumstances are described. Mutual selection protocols (MSP) and their dynamic properties are explained. (K.I.)

  3. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Science.gov (United States)

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  4. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Science.gov (United States)

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Funding Leverage by Use of Sba-Guaranteed Trust Certificates (âtcsâ) § 107.1620... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  5. Multi-Agent Transport Planning

    NARCIS (Netherlands)

    Zutt, J.; Witteveen, C.

    2005-01-01

    We discuss a distributed transport planning problem with competitive autonomous actors that carry out time-constrained pick-up delivery orders from customers. The agents have to find conflict-free routes to execute a series of orders they have accepted. Hatzack and Nebel [2] were the first to sugges

  6. Using Agent to Coordinate Web Services

    CERN Document Server

    Liu, C H; Chen, Jason J Y

    2009-01-01

    Traditionally, agent and web service are two separate research areas. We figure that, through agent communication, agent is suitable to coordinate web services. However, there exist agent communication problems due to the lack of uniform, cross-platform vocabulary. Fortunately, ontology defines a vocabulary. We thus propose a new agent communication layer and present the web ontology language (OWL)-based operational ontologies that provides a declarative description. It can be accessed by various engines to facilitate agent communication. Further, in our operational ontologies, we define the mental attitudes of agents that can be shared among other agents. Our architecture enhanced the 3APL agent platform, and it is implemented as an agent communication framework. Finally, we extended the framework to be compatible with the web ontology language for service (OWL-S), and then develop a movie recommendation system with four OWL-S semantic web services on the framework. The benefits of this work are: 1) dynamic ...

  7. Bursting behaviours in cascaded stimulated Brillouin scattering

    Institute of Scientific and Technical Information of China (English)

    Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

    2012-01-01

    Stimulated Brillouin scattering is studied by numerically solving the Vlasov-Maxwell system.A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma.It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light,as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction.The bursting time in the reflectivity is found to be less than half the ion acoustic period.The ion temperature can affect the stimulated Brillouin scattering cascade,which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures.For stimulated Brillouin scattering saturation,higher-harmonic generation and wave-wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter.In addition,stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light.

  8. A Chip for an Implantable Neural Stimulator

    DEFF Research Database (Denmark)

    Gudnason, Gunnar; Bruun, Erik; Haugland, Morten

    2000-01-01

    This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation (FES). The purpose of FES is to restore muscular control in disabled patients. The chip performs all the signal processing required in an implanted neural stimulator. The power and digital data...... transmission to the stimulator passes through a 5 MHz inductive link. From the signals transmitted to the stimulator, the chip is able to generate charge-balanced current pulses with a controllable length up to 256 µs and an amplitude up to 2 mA, for stimulation of nerve fibers. The quiescent current...... consumption of the chip is approx. 650 µA at supply voltages of 6–12 V, and its size is 3.9×3.5 mm2. It has 4 output channels for use in a multipolar cuff electrode....

  9. Anchor Toolkit - a secure mobile agent system

    OpenAIRE

    Mudumbai, Srilekha S.; Johnston, William; Essiari, Abdelilah

    2008-01-01

    Mobile agent technology facilitates intelligent operation in software systems with less human interaction. Major challenge to deployment of mobile agents include secure transmission of agents and preventing unauthorized access to resources between interacting systems, as either hosts, or agents, or both can act maliciously. The Anchor toolkit, designed by LBNL, handles the transmission and secure management of mobile agents in a heterogeneous distributed computing environment. It provide...

  10. Halide test agent replacement study

    Energy Technology Data Exchange (ETDEWEB)

    Banks, E.M.; Freeman, W.P.; Kovach, B.J. [and others

    1995-02-01

    The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

  11. Metallic Taste from Electrical and Chemical Stimulation

    OpenAIRE

    Lawless, Harry T.; Stevens, David A.; Chapman, Kathryn W.; Kurtz, Anne

    2005-01-01

    A series of three experiments investigated the nature of metallic taste reports after stimulation with solutions of metal salts and after stimulation with metals and electric currents. To stimulate with electricity, a device was fabricated consisting of a small battery affixed to a plastic handle with the anode side exposed for placement on the tongue or oral tissues. Intensity of taste from metals and batteries was dependent upon the voltage and was more robust in areas dense in fungiform pa...

  12. Motivation-stimulating Strategies in English Classes

    Institute of Scientific and Technical Information of China (English)

    李宁

    2015-01-01

    Motivation plays a very important role in foreign language learning. So it becomes worthwhile to study the teachers’ motivation-stimulating strategies. This article mainly discusses two strategies of stimulating the students’motivation in English classes:environment-providing strategies and goal-oriented strategies. They are hoped to provide some references for English teachers to stimulate the students’learning motivation in their classes.

  13. Auditory stimulation and cardiac autonomic regulation

    OpenAIRE

    Vitor E Valenti; Guida, Heraldo L.; Frizzo, Ana C F; Cardoso, Ana C. V.; Vanderlei, Luiz Carlos M; Luiz Carlos de Abreu

    2012-01-01

    Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: "auditory stimulation", "autonomic nervous system", "music" and "heart rate variability". The selected studies indicated that there is a strong correlation bet...

  14. What galvanic vestibular stimulation actually activates

    OpenAIRE

    IanSCurthoys

    2012-01-01

    In a recent paper in Frontiers Cohen et al. (2012) asked “What does galvanic vestibular stimulation actually activate?” and concluded that galvanic vestibular stimulation (GVS) causes predominantly otolithic behavioural responses. In this Perspective paper we show that such a conclusion does not follow from the evidence. The evidence from neurophysiology is very clear: galvanic stimulation activates primary otolithic neurons as well as primary semicircular canal neurons (Kim and Curthoys,...

  15. Communication between osteoblasts stimulated by electromagnetic fields

    Institute of Scientific and Technical Information of China (English)

    ZHANG JianBao; ZHANG XiaoJun

    2007-01-01

    Pulsed electromagnetic field can affect the proliferation of osteoblasts, but the mechanism is obscure yet. The communication between osteoblasts, isolated from calvaria bone of newborn SD rats and stimulated with the rectangular electromagnetic field of 15 Hz and 4 mT, was studied. Our results showed that the osteoblasts radiated a kind of light after they were stimulated with the electromagnetic field and it is the light that promotes the proliferation of un-stimulated osteoblasts.

  16. Screening of carbonaceous nanoporous materials for capture of nerve agents.

    Science.gov (United States)

    Kowalczyk, Piotr; Gauden, Piotr A; Terzyk, Artur P; Neimark, Alexander V

    2013-01-01

    A strategy for combined experimental and computational screening of candidate carbonaceous materials for capturing highly volatile nerve agents at ambient temperature using physisorption. Based on theoretical calculations of Henry constants and zero-coverage adsorption enthalpies for sarin and DMMP (its common stimulant) adsorbed in model slit-shaped carbon pores at 298 K, we found the following. Slit-shaped carbon pores with pore width ~0.5 nm are optimal for agent adsorption due to strong confinement of adsorbed molecules. Agent adsorption enthalpy at zero coverage computed for optimal pore width is very high and reaches ~83 kJ mol(-1). Widening of pore width above ~1 nm results in a significant decrease of the Henry constant and zero-coverage adsorption enthalpy (~44 kJ mol(-1)). Polydispersity of studied candidate carbonaceous materials strongly affects adsorption capacity for DMMP under the operating conditions. The optimal carbonaceous adsorbent, pitch-based P7 activated carbon fiber, adsorbed ~100 μg g(-1) DMMP at 0.03 μg m(-3). Commercial Norit activated carbon adsorbed only ~20 μg g(-1) DMMP at 0.03 μg m(-3). Surprisingly, a small shift of the pore size distribution towards wider micropores has a great impact on agent adsorption. Because the adsorption enthalpies computed at zero coverage weakly dependent on pore size, the heat released during agent adsorption is similar for all studied candidate adsorbents (i.e.~55-60 kJ mol(-1)). PMID:23165364

  17. Migration Dynamics in Artificial Agent Societies

    Directory of Open Access Journals (Sweden)

    Harjot Kaur

    2014-02-01

    Full Text Available An Artificial Agent Society can be defined as a collection of agents interacting with each other for some purpose and/or inhabiting a specific locality, possibly in accordance to some common norms/rules. These societies are analogous to human and ecological societies, and are an expanding and emerging field in research about social systems. Social networks, electronic markets and disaster management organizations can be viewed as such artificial (open agent societies and can be best understood as computational societies. Members of such artificial agent societies are heterogeneous intelligent software agents which are operating locally and cooperating and coordinating with each other in order to achieve goals of an agent society. These artificial agent societies have some kind of dynamics existing in them in terms of dynamics of Agent Migration, Role-Assignment, Norm- Emergence, Security and Agent-Interaction. In this paper, we have described the dynamics of agent migration process, starting from the various types of agent migration, causes or reasons for agent migration, consequences of agent migration, and an agent migration framework to model the its behavior for migration of agents between societies.

  18. Artifacts of Functional Electrical Stimulation on Electromyograph

    Institute of Scientific and Technical Information of China (English)

    DUAN Ren-quan; ZHANG Ding-guo

    2014-01-01

    The purpose of this study is to investigate different factors of the artifact in surface electromyography (EMG) signal caused by functional electrical stimulation (FES). The factors investigated include the size of stimulation electrode pads, the amplitude, frequency, and pulse width of the stimulation waveform and the detecting electrode points. We calculate the root mean square (RMS) of EMG signal to analyze the effect of these factors on the M-wave properties. The results indicate that the M-wave mainly depends on the stimulation amplitude and the distribution of detecting electrodes, but not on the other factors. This study can assist the reduction of artifact and the selection of detecting electrode points.

  19. State-dependent amygdala stimulation-induced cardiovascular effects in rats.

    Science.gov (United States)

    Chiou, Ruei-Jen; Kuo, Chung-Chih; Liang, Keng-Chen; Yen, Chen-Tung

    2009-12-31

    Stimulation of the amygdala is known to produce pressor, depressor, or has no effects. The present study was performed to test whether amygdala cardiovascular effects are influenced by consciousness states and by different types of anesthetics. Adult rats were set up for stimulation amygdala and measurement of blood pressure in a chronic preparation. After recovery, same sites of the amygdala were stimulated electrically for several trials with the rat under conscious or anesthetic states induced by pentobarbital, urethane, ketamine, alpha-chloralose and urethane plus alpha-chloralose, respectively. The interval between any two stimulation trials was at least 2 days. The stimulation was an 80-Hz, 0.5-ms, 100-micro A square wave pulse train lasting for 15 s. Cardiovascular responsive sites were found in the central, medial, and basolateral nuclei of the amygdala. In stimulating these responsive sites, significantly different cardiovascular effects were induced under a conscious state and an anesthetized state of the animal, yet no significant differences were found among the various anesthetic agents. We conclude, that the cardiovascular influence of the amygdala is state-dependent in the rat.

  20. Securiosides A and B, novel acylated triterpene bisdesmosides with selective cytotoxic activity against M-CSF-stimulated macrophages.

    Science.gov (United States)

    Kuroda, M; Mimaki, Y; Sashida, Y; Kitahara, M; Yamazaki, M; Yui, S

    2001-02-12

    We report the discovery of securiosides A (1) and B (2), novel acylated triterpene bisdesmosides, isolated from the roots of Securidaca inappendiculata. Securiosides A and B showed potent selective cytotoxic activity against M-CSF-stimulated macrophages and were suggested to have potential as new agents for the treatment of inflammatory diseases such as RA and atherosclerosis. PMID:11212113

  1. The role of pre-operative androgen stimulation in hypospadias surgery

    OpenAIRE

    Kaya, Cevdet; Radmayr, Christian

    2014-01-01

    The hormonal stimulation for the purpose of penile enlargement before the hypospadias repair has been commonly used, but rarely reported. In addition to functional outcome, dihydrotestosterone (DHT) pretreatment has been suggested to improve cosmetic outcome in a preliminary randomized study. Since the randomized and controlled clinical trials on this topic are insufficient, the hormonal agent, the route of administration, dosing schedule, and the timing of treatment has been remained controv...

  2. Biological agents in management of osteoporosis.

    Science.gov (United States)

    Tella, Sri Harsha; Gallagher, J Christopher

    2014-11-01

    Osteoporosis is a skeletal disease associated with an imbalance between formation and resorption, leading to net loss of bone mass, loss of bone microarchitecture, and development of fractures. Bone resorption is primarily due to an activation of osteoclastogenesis and an increase in receptor activator of nuclear factor kappa-B ligand (RANKL) expression, a cytokine involved in the final pathway of the osteoclast cycle.Recent studies of genetic diseases led to the discovery of the wingless-type (Wnt) signaling pathway that plays a major role in bone formation. Further work showed that sclerostin produced by osteocytes and the Dickkopf (DKK1) protein secreted in bone were negative regulators of the Wnt signaling bone formation pathway that act directly by binding to the co-receptors LRP5 and LRP6 of WnT and thereby inhibiting the anabolic Wnt pathway. This understanding of the bone remodeling led to the discovery of new biological drugs that target these pathways and have been evaluated in clinical trials.The current article discusses the role of these newer "biological" agents in management of osteoporosis. Denosumab, a human monoclonal antibody that specifically binds RANKL, blocks the binding of RANK to its ligand markedly reducing bone resorption, increases bone density, and reduces fractures and is approved for osteoporosis. Parathyroid hormone PTH 1-34 (teriparatide) stimulates bone formation through inhibition of sclerostin, DKK1, and frizzled protein; increases BMD; improves microarchitecture; and decreases fractures and is approved for osteoporosis. The anti-sclerostin antibodies (romosozumab, blosozumab) increase bone mass by neutralizing the negative effects of sclerostin on the Wnt signaling pathway. These biologics are being evaluated now in a clinical trial and early data looks promising. Cathepsin K is a proteolytic enzyme that degrades bone matrix and inhibitors such as odanacatib show increasing bone density and perhaps decreased fractures. The

  3. 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.

  4. Thermally stimulated discharge conductivity study of zinc oxide thermoelectrets

    Indian Academy of Sciences (India)

    Vijaya S Sangawar; Manisha C Golchha

    2014-10-01

    The present work deals with transmission electron microscopy (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermally stimulated discharge current (TSDC) study of inorganic metal oxide (ZnO) nanoparticles and its thermoelectrets. The thermoelectrets were prepared by applying different electric polarizing field (P) at constant polarizing temperature (P), for constant polarization time (P). The TSDC study was carried out in the temperature region of 313–473 K. It was observed that the conductivity of ZnO samples increases with the increase in temperature and polarizing field. The dependence of TSDC data on polarizing agents, i.e. field and temperature shows Arrhenius type of behviour and is explained on the basis of variable range hopping mechanism.

  5. CATS-based Agents That Err

    Science.gov (United States)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  6. Role of 5α-reductase inhibitors in androgen-stimulated skin disorders.

    Science.gov (United States)

    Azzouni, Faris; Zeitouni, Nathalie; Mohler, James

    2013-02-01

    5α-reductase (5α-R) isozymes are ubiquitously expressed in human tissues. This enzyme family is composed of 3 members that perform several important biologic functions. 5α-R isozymes play an important role in benign prostate hyperplasia, prostate cancer, and androgen-stimulated skin disorders, which include androgenic alopecia, acne, and hirsutism. Discovery of 5α-R type 2 deficiency in 1974 sparked interest in development of pharmaceutical agents to inhibit 5α-R isozymes, and 2 such inhibitors are currently available for clinical use: finasteride and dutasteride. 5α-R inhibitors are US Food and Drug Administration (FDA)-approved for the treatment of benign prostate hyperplasia. Only finasteride is FDA-approved for treatment of male androgenic alopecia. This article reviews the pathophysiology of androgen-stimulated skin disorders and the key clinical trials using 5α-R inhibitors in the treatment of androgen-stimulated skin disorders. PMID:23377402

  7. Biological effects of mutagenic agents

    International Nuclear Information System (INIS)

    There is an increasing body of evidence that mutagenic agents (biological, chemical and physical) play an important role in the etiology of human diseases. Mutations may occur in the germinal as well as in the somatic cells. Mutations of the germ cells may result on infertility or fertilization of damaged cells, the later leading to abortion or birth of a malformed fetus. Somatic-cells mutations may have various biological effects, depending on the period of the human life at which the mutation occurs. If it occurs during the prenatal life, a teratogenic or carcinogenic effect will be observed. If the somatic cell is damaged during the postnatal life, this will lead to neoplastic transformation. Therefore it is extremely important to know the mutagenic, teratogenic and carcinogenic effects of various biological, chemical and physical agents in order to eliminate them from our environment. (author). 13 refs, 4 figs, 1 tab

  8. [Infectious agents and autoimmune diseases].

    Science.gov (United States)

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  9. Bacteriocins as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Sukhraj eKaur

    2015-11-01

    Full Text Available Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity towards cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  10. Oral agents in multiple sclerosis.

    Science.gov (United States)

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  11. Radioprotection: mechanism and radioprotective agents including honeybee venom

    International Nuclear Information System (INIS)

    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)

  12. 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)

  13. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  14. On the possible role of stimulation duration for after-effects of transcranial alternating current stimulation

    OpenAIRE

    Stefan Rach; Toralf Neuling; Herrmann, Christoph S.

    2015-01-01

    Transcranial alternating current stimulation is a novel method that allows application of sinusoidal currents to modulate brain oscillations and cognitive processes. Studies in humans have demonstrated tACS after-effects following stimulation durations in the range of minutes. However, such after-effects are absent in animal studies using much shorter stimulation protocols in the range of seconds. Thus, stimulation duration might be a critical parameter for after-effects to occur. To test thi...

  15. Crimen organizado y agente encubierto

    OpenAIRE

    Herrero Reus, Ignacio

    2014-01-01

    Uno de los objetivos de la justicia penal actual es la lucha contra la criminalidad organizada, bien por su propia naturaleza de “crimen organizado”, bien porque presenta elementos trasnacionales que impiden su investigación a fondo. Todo ello exige la creación de recursos que permitan la investigación de dichos delitos, recursos como el de infiltración de los agentes policiales, objeto del trabajo.

  16. Antipsychotic agents and QT changes.

    OpenAIRE

    Welch, R.; Chue, P

    2000-01-01

    Recently, antipsychotic medications of the novel or atypical classes have received increased attention because of concerns with respect to potential lengthening of the QT interval, yet the currently available and commonly prescribed conventional antipsychotics are significantly more cardiotoxic, particularly agents in the butyrophenone and phenothiazine classes. Lengthening of the QT interval can be associated with a fatal paroxysmal ventricular arrhythmia known as torsades de pointes. The sp...

  17. Topical agents in burn care

    OpenAIRE

    Momčilović Dragan

    2002-01-01

    Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injure...

  18. Multi-agent autonomous system

    Science.gov (United States)

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

    2010-01-01

    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  19. An Agent Based Classification Model

    CERN Document Server

    Gu, Feng; Greensmith, Julie

    2009-01-01

    The major function of this model is to access the UCI Wisconsin Breast Can- cer data-set[1] and classify the data items into two categories, which are normal and anomalous. This kind of classifi cation can be referred as anomaly detection, which discriminates anomalous behaviour from normal behaviour in computer systems. One popular solution for anomaly detection is Artifi cial Immune Sys- tems (AIS). AIS are adaptive systems inspired by theoretical immunology and observed immune functions, principles and models which are applied to prob- lem solving. The Dendritic Cell Algorithm (DCA)[2] is an AIS algorithm that is developed specifi cally for anomaly detection. It has been successfully applied to intrusion detection in computer security. It is believed that agent-based mod- elling is an ideal approach for implementing AIS, as intelligent agents could be the perfect representations of immune entities in AIS. This model evaluates the feasibility of re-implementing the DCA in an agent-based simulation environ- ...

  20. Pharmacologic Agents for Chronic Diarrhea.

    Science.gov (United States)

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.

  1. Pharmacologic Agents for Chronic Diarrhea.

    Science.gov (United States)

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  2. Preponderant agent, what is that?

    Directory of Open Access Journals (Sweden)

    Clara Luz Álvarez

    2015-05-01

    Full Text Available Purpose – Preponderant agent is a new instrument for preventing and reverting adverse impact in competition due to highly concentrated markets. Therefore, this paper's objective is to present and analyze the preponderant agent concept in Mexico with emphasis on the broadcast sector, the telecommunication regulator decisions and the courts' interpretation. Methodology/approach/design – The objectives were achieved by researching and analyzing the main legal documents, the Congress reports and debates, the regulator's decisions and other relevant regulator's documents, as well as final decisions by the courts in connection with broadcast sector. Findings – Among the findings are that certain topics were not duly addressed by the Mexican regulator, or by the Congress, whereas the courts were more willing to hold decisions in favor of public interest based on constitutional intent and deference to the regulator's decision. Originality/value – This paper will be valuable for persons interested in telecommunications, broadcast and antitrust. Although the preponderant agent concept created in Mexico is not necessarily a “best practice”, it does provide an alternative instrument in antitrust. Moreover, the courts decisions also provide criteria regarding regulatory deference for the regulator.

  3. Evolution of a predictive internal model in an embodied and situated agent.

    Science.gov (United States)

    Gigliotta, Onofrio; Pezzulo, Giovanni; Nolfi, Stefano; Nolfi, Sefano

    2011-12-01

    We show how simulated robots evolved for the ability to display a context-dependent periodic behavior can spontaneously develop an internal model and rely on it to fulfill their task when sensory stimulation is temporarily unavailable. The analysis of some of the best evolved agents indicates that their internal model operates by anticipating sensory stimuli. More precisely, it anticipates functional properties of the next sensory state rather than the exact state that sensors will assume. The characteristics of the states that are anticipated and of the sensorimotor rules that determine how the agents react to the experienced states, however, ensure that they produce very similar behaviour during normal and blind phases in which sensory stimulation is available or is self-generated by the agent, respectively. Agents' internal models also ensure an effective transition during the phases in which agents' internal dynamics is decoupled and re-coupled with the sensorimotor flow. Our results suggest that internal models might have arisen for behavioral reasons and successively exapted for other cognitive functions. Moreover, the obtained results suggest that self-generated internal states should not necessarily match in detail the corresponding sensory states and might rather encode more abstract and motor-oriented information.

  4. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正

    2015-01-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  5. Agent planning in AgScala

    Science.gov (United States)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  6. Dimensions and Issues of Mobile Agent Technology

    Directory of Open Access Journals (Sweden)

    Yashpal Singh

    2012-09-01

    Full Text Available Mobile Agent is a type of software system which acts “intelligently” on one’s behalf with the feature of autonomy, learning ability and most importantly mobility. Now mobile agents are gaining interest in the research community. In this article mobile agents will be addressed as tools for mobile computing. Mobile agents have been used in applications ranging from network management to information management. We present mobile agent concept, characteristics, classification, need, applications and technical constraints in the mobile technology. We also provide a brief case study about how mobile agent is used for information retrieval.

  7. Violet stimulated luminescence: geo- or thermochronometer?

    DEFF Research Database (Denmark)

    Ankjærgaard, Christina; Guralnik, Benny; Porat, N.;

    2015-01-01

    The method of quartz optically stimulated luminescence (OSL) dating is widely used, but generally limited to the past ~0.1 million years (Ma) due to early saturation of the desired signal. Violet stimulated luminescence (VSL) of quartz has previously been shown as a promising alternative, with a...

  8. Pseudomonas putida Stimulates Primordia on Agaricus bitorquis.

    Science.gov (United States)

    Colauto, Nelson B; Fermor, Terry R; Eira, Augusto F; Linde, Giani A

    2016-04-01

    Casing layer is one step of Agaricus bisporus cultivation where there is a competitive environment with a high number of microorganisms and diversity interacting with mycelia. It is suggested that a minimal community of these microorganisms would be necessary to stimulate fructification. However, A. bisporus is not able to produce primordia in sterile casing layers or Petri dishes. Thus, the objective of this study was to characterize bacterial microbiota of casing layers from A. bisporus cultivation, isolate, identify and characterize the bacteria responsible for the stimulation of primordium and their action mechanism using Agaricus bitorquis as a primordium stimulation model. Bacterial and Pseudomonas spp. communities of different casing layers of A. bisporus cultivation were collected and quantified. It was concluded that Pseudomonas spp. corresponds to 75-85% of bacterial population of the casing layers in A. bisporus cultivation and among those 12% are Pseudomonas putida. Four biochemical assays were used to identify P. putida. In vitro primordium stimulation of living P. putida and non-living bacterial suspensions, after chemical or physical treatments, was tested using A. bitorquis as a primordium stimulation model. Primordium stimulation assay was registered by photographs, and micrographs of vertical cut of primordium were registered by scanning electron microscope. Interaction of living P. putida with A. bitorquis mycelia is capable of stimulating primordial instead of non-living bacterial suspensions. Stimulation of A. bitorquis primordia does not imply or is related to mycelial growth inhibition, but a hierarchical relation of primordium succession and development is suggested. PMID:26742772

  9. Violet stimulated luminescence: geo- or thermochronometer?

    NARCIS (Netherlands)

    Ankjaergaard, C.; Guralnik, B.; Porat, N.; Heimann, A.; Jain, M.; Wallinga, J.

    2015-01-01

    The method of quartz optically stimulated luminescence (OSL) dating is widely used, but generally limited to the past ~0.1 million years (Ma) due to early saturation of the desired signal. Violet stimulated luminescence (VSL) of quartz has previously been shown as a promising alternative, with a dos

  10. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

    The first section of the bibliography lists materials on the stimulation of seeds by low dose irradiation, with particular reference to stimulation of germination and yield. The second section contains a small number of selected references on seed irradiation facilities. (author)

  11. Electrocutaneous stimulation system for Braille reading.

    Science.gov (United States)

    Echenique, Ana Maria; Graffigna, Juan Pablo; Mut, Vicente

    2010-01-01

    This work is an assistive technology for people with visual disabilities and aims to facilitate access to written information in order to achieve better social inclusion and integration into work and educational activities. Two methods of electrical stimulation (by current and voltage) of the mechanoreceptors was tested to obtain tactile sensations on the fingertip. Current and voltage stimulation were tested in a Braille cell and line prototype, respectively. These prototypes are evaluated in 33 blind and visually impaired subjects. The result of experimentation with both methods showed that electrical stimulation causes sensations of touch defined in the fingertip. Better results in the Braille characters reading were obtained with current stimulation (85% accuracy). However this form of stimulation causes uncomfortable sensations. The latter feeling was minimized with the method of voltage stimulation, but with low efficiency (50% accuracy) in terms of identification of the characters. We concluded that electrical stimulation is a promising method for the development of a simple and unexpensive Braille reading system for blind people. We observed that voltage stimulation is preferred by the users. However, more experimental tests must be carry out in order to find the optimum values of the stimulus parameters and increase the accuracy the Braille characters reading.

  12. [MRI compatibility of deep brain stimulator].

    Science.gov (United States)

    Zhang, Yujing

    2013-07-01

    Deep brain stimulation (DBS) therapy develops rapidly in clinical application. The structures of deep brain stimulator and magnetic resonance imaging (MRI) equipment are introduced, the interactions are analyzed, and the two compatible problems of radio frequency (RF) heating and imaging artifact are summarized in this paper.

  13. 14th International Conference on Practical Applications of Agents and Multi-Agent Systems : Special Sessions

    CERN Document Server

    Escalona, María; Corchuelo, Rafael; Mathieu, Philippe; Vale, Zita; Campbell, Andrew; Rossi, Silvia; Adam, Emmanuel; Jiménez-López, María; Navarro, Elena; Moreno, María

    2016-01-01

    PAAMS, the International Conference on Practical Applications of Agents and Multi-Agent Systems is an evolution of the International Workshop on Practical Applications of Agents and Multi-Agent Systems. PAAMS is an international yearly tribune to present, to discuss, and to disseminate the latest developments and the most important outcomes related to real-world applications. It provides a unique opportunity to bring multi-disciplinary experts, academics and practitioners together to exchange their experience in the development of Agents and Multi-Agent Systems. This volume presents the papers that have been accepted for the 2016 in the special sessions: Agents Behaviours and Artificial Markets (ABAM); Advances on Demand Response and Renewable Energy Sources in Agent Based Smart Grids (ADRESS); Agents and Mobile Devices (AM); Agent Methodologies for Intelligent Robotics Applications (AMIRA); Learning, Agents and Formal Languages (LAFLang); Multi-Agent Systems and Ambient Intelligence (MASMAI); Web Mining and ...

  14. Mechanistic aspects of radioprotection by todralazine hydrochloride, a hematopoietic stem cell expanding agent

    International Nuclear Information System (INIS)

    Previously, we have reported todralazine hydrochloride, an antihypertensive drug, as a radioprotector and hematopoietic stem cell (HSC) expanding agent. The present study aims at unraveling mechanistic aspects of its radioprotective and HSC expanding potential. Zebrafish Tg (cmyb:GFP) embryos treated with 5 μM todralazine from 24-36 hours post fertilization (hpf), increased the number of HSCs (∼ 2 folds) at aorta gonad mesonephros (AGM) region. Similarly, the expression of HSC marker genes, runx1 (3.3 folds) and cMyb (1.4 folds) were also found to be increased. Further, todralazine also accelerated hematopoietic lineage production, erythropoiesis, as evaluated in chemical induced anemic model in zebrafish. Genome wide expression changes in todralazine treated embryos (from 24-36 hpf) using microarray, revealed up and down regulation of 645 and 429 genes respectively. Pathway analysis using DAVID database strongly suggested up regulation of wnt pathway (p<0.019253), which is known to involve in HSC expansion, in todralazine pre-treated embryos. NOS1, known to have its role in HSC expansion through wnt pathway, has been significantly upregulated (1.54 folds; q PCR) by todralazine treatment (from 24-36 hpf). Todralazine treatment (∼30 minutes; 20 Gy) led to a significant upregulation of antioxidant genes (SOD, catalase), DNA damage response genes (p53, p21, GADD45) and nucleotide excision repair genes (XPC, XPA, XPF, XPD) when compared to irradiated control. Immunohistochemical analysis of DNA damage marker (γH2AX) (30 minutes post irradiation), further supported radiation induced DNA damage and protection by todralazine pre-treatment. Corroborating these results, pre-irradiation treatment of todralazine reduced radiation induced apoptosis (caspase 3 assay). Overall, the results suggest that, todralazine protects zebrafish from radiation induced damages by upregulating antioxidant defense system, DNA damage recognition, DNA repair machinery and by reducing cell

  15. Point Electric Stimulation and Children's Amblyopia

    Institute of Scientific and Technical Information of China (English)

    YAN Xing-ke; CHU Hui-ju; WANG Fu-chun; YANG Bo; GAO Yang; HAN Chou-ping

    2007-01-01

    To observe the therapeutic efficacy of electric stimulation on points for children's amblyopia.Method:Ninety children amblyopia cases with ametropia upon correction were randomized into three groups:point electric stimulation,comprehensive conventional therapy and integrative therapy of the above two.And then visual function changes of kids in the three groups were observed.Results:Among the above three therapies,the recovery rates of point electric stimulation,comprehensive conventional therapy and integrative therapy of the two were 83.9%,82.6%and 94.25 respectively,showing no significant difierence(P>0.05) among the three groups.Conclusion:Point electric stimulation has similar action with comprehensive conventional therapy in the treatment of children's amblyopia,and the combination of the two therapies has better effect,indicating point electric stimulation can speed up recovery of visual function of kids with amblyopia.

  16. Spatially selective photoconductive stimulation of live neurons

    Directory of Open Access Journals (Sweden)

    Jacob eCampbell

    2014-05-01

    Full Text Available Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and microelectrode and optogenetic techniques require specialized equipment and expertise. We report an optimized and improved technique for laser based photoconductive stimulation of live neurons using an inverted confocal microscope that overcomes these limitations. The advantages of this approach include its non-invasive nature and adaptability to temporal and spatial manipulation. We demonstrate that the technique can be manipulated to achieve spatially selective stimulation of live neurons. Coupled with live imaging of fluorescent indicators, this simple and efficient technique should allow for significant advances in neuronal cell biology.

  17. Electronic stimulators for surface neural prosthesis

    Directory of Open Access Journals (Sweden)

    Broderick Barry J.

    2008-01-01

    Full Text Available This paper presents the technological advancements in neural prosthesis devices using Functional Electrical Stimulation (FES. FES refers to the restoration of motor functions lost due to spinal cord injury (SCI, stroke, head injury, or diseases such as Cerebral Palsy or Multiple Sclerosis by eliciting muscular contractions through the use of a neuromuscular electrical stimulator device. The field has developed considerably since its inception, with the miniaturisation of circuity, the development of programmable and adaptable stimulators and the enhancement of sensors used to trigger the application of stimulation to suit a variety of FES applications. This paper discusses general FES system design requirements in the context of existing commercial and research FES devices, focusing on surface stimulators for the upper and lower limbs. These devices have demonstrated feasible standing and stepping in a clinical setting with paraplegic patients, improvements in dropped foot syndrome with hemiplegic patients and aided in the restoration of grasping function in patients with upper limb motor dysfunction.

  18. Optical nerve stimulation for a vestibular prosthesis

    Science.gov (United States)

    Harris, David M.; Bierer, Steven M.; Wells, Jonathon D.; Phillips, James O.

    2009-02-01

    Infrared Nerve Stimulation (INS) offers several advantages over electrical stimulation, including more precise spatial selectivity and improved surgical access. In this study, INS and electrical stimulation were compared in their ability to activate the vestibular branch of the VIIIth nerve, as a potential way to treat balance disorders. The superior and lateral canals of the vestibular system of Guinea pigs were identified and approached with the aid of precise 3-D reconstructions. A monopolar platinum stimulating electrode was positioned near the ampullae of the canals, and biphasic current pulses were used to stimulate vestibular evoked potentials and eye movements. Thresholds and input/output functions were measured for various stimulus conditions. A short pulsed diode laser (Capella, Lockheed Martin-Aculight, Inc., Bothell WA) was placed in the same anatomical position and various stimulus conditions were evaluated in their ability to evoke similar potentials and eye movements.

  19. Regimen of ovarian stimulation affects oocyte and therefore embryo quality.

    Science.gov (United States)

    Bosch, Ernesto; Labarta, Elena; Kolibianakis, Efstratios; Rosen, Mitchell; Meldrum, David

    2016-03-01

    Without any doubt the regimen used to mature multiple capable oocytes for IVF impacts IVF outcomes. Studies have indicated that the inclusion of LH activity, adjuvant agents such as growth hormone (GH), and regimens providing for simultaneous action of both LH and FSH during final oocyte maturation may have beneficial effects on IVF outcomes. Because of the difficulty in improving IVF outcomes in poor responders, the studies on GH are of particular interest. As pointed out in this review, the apparent beneficial effects of GH on oocyte competence may also apply to older women or to normal responders with reduced embryo quality. A much more difficult question is whether and how much ovarian stimulation impacts on oocyte competence. Paradoxically it seems that there are not demonstrated differences between the stimulated and the natural unstimulated cycle, whereas studies in laboratory animals and IVF patients have shown deleterious effects of higher compared with lower doses of gonadotropins. Recent studies suggest that the use of high doses of gonadotropins as an independent factor correlates negatively with the probability of live birth, whereas a high ovarian response per se is associated with better cumulative pregnancy rates, owing to the availability of more euploid and good-quality embryos. Although adjunctive use of androgens has not been discussed here, it is briefly covered in the first review of this series. PMID:26826273

  20. Epidermal growth factor-stimulated protein phosphorylation in rat hepatocytes

    International Nuclear Information System (INIS)

    Epidermal growth factor (EGF) causes a 6-fold increase in the phosphorylation state of a cytosolic protein (pp36, M/sub r/ = 36,000, pI = 5.5) in hepatocytes isolated from fasted, male, Wistar rats. Stimulation of 32P incorporation is observed as early as 1 min following treatment of hepatocytes with EGF and is still present at 30 min after exposure to the growth factor. The phosphate incorporated into pp36 in response to EGF is located predominantly in serine but not tyrosine residues. Phosphorylation of pp36 does not occur in response to insulin or to agents which specifically activate the cAMP-dependent protein kinase (S/sub p/ -cAMPS), protein kinase C (PMA) or Ca2+/calmodulin-dependent protein kinases (A23187) in these cells. Prior treatment of hepatocytes with the cAMP analog, S/sub p/-cAMPS, or ADP-ribosylation of N/sub i/, the inhibitory GTP-binding protein of the adenylate cyclase complex, does not prevent EGF-stimulated phosphorylation of pp36. However, as seen in other cell types, pretreatment of hepatocytes with PMA abolishes all EGF-mediated responses including phosphorylation of pp36. These results suggest that EGP specifically activates an uncharacterized, serine protein kinase in hepatocytes that is distal to the intrinsic EGF receptor tyrosine protein kinase. The rapid activation of this kinase suggests that it may play an important role in the early response of the cell to EGF

  1. A framework for organization-aware agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia; Villadsen, Jørgen

    2016-01-01

    Open systems are characterized by the presence of a diversity of heterogeneous and autonomous agents that act according to private goals. Organizations, such as those used in real-life to structure human activities such as task allocation, coordination and supervision, can regulate the agents...... explicit coordination mechanisms within the agents. The organizational model is independent of that of the agents, and the approach is not tied to a specific organizational model, but uses an organizational metamodel. We show how AORTA helps agents work together in a system with an organization......’ behavior space and describe the expected behavior of the agents. Assuming an open environment, where agents are developed independently of the Organizational structures, agents need to be able to reason about the structure, so that they can deliberate about their actions and act within the expected...

  2. Analysis and Optimization for Mobile Agent Communication

    Institute of Scientific and Technical Information of China (English)

    YANGBo; LIUDayou

    2005-01-01

    Communication performance is one of the most important factors affecting the efficiency of mobile agent system. Only traditional optimization techniques for communication performance are not enough, especially in large-scale intelligent mobile agent system, so more intelligent optimization techniques are needed. In the background, the paper studies communication of mobile agent system from the viewpoint of performance. The paper makes qualitative and quantitative analysis of four important factors that will affect the communication performance of mobile agent system and presents the communication performance optimization model. The model hasthree primary functions. First, the model provides a formalism method to describe the communication task and process of mobile agent. Second, the model provides a means to make quantitative analysis of the performance of mobile agent system. Third, the model can plan out an optimal communication scheme for mobile agent to minimize the cost of whole communication. The model could thus be a building block for the optimization of the communication behavior of mobile agent.

  3. A Framework for Multi-Agent Planning

    NARCIS (Netherlands)

    Bos, A.; Tonino, J.F.M.; De Weerdt, M.M.; Witteveen, C.

    2000-01-01

    We introduce a computational framework, consisting of resources, skills, goals and services to represent the plans of individual agents and to develop models and algorithms for cooperation processes between a collection of agents.

  4. Agent Communication Channel Based on BACnet

    Institute of Scientific and Technical Information of China (English)

    Jiang Wen-bin; Zhou Man-li

    2004-01-01

    We analyze the common shortcoming in the existing agent MTPs (message transport protocols). With employing the File object and related service AtomicWriteFile of BACnet (a data communication protocol building automation and control networks), a new method of agent message transport is proposed and implemented. Every agent platform (AP) has one specified File object and agents in another AP can communicate with agents in the AP by using AtomicWriteFile service. Agent messages can be in a variety of formats. In implementation, BACnet/IP and Ethernet are applied as the BACnet data link layers respectively. The experiment results show that the BACnet can provide perfect support for agent communication like other conventional protocols such as hypertext transfer protocol(HTTP), remote method invocation (RMI) etc. and has broken through the restriction of TCP/IP. By this approach, the agent technology is introduced into the building automation control network system.

  5. Comparison of Communication Models for Mobile Agents

    Directory of Open Access Journals (Sweden)

    Xining Li

    2003-04-01

    Full Text Available An agent is a self-contained process being acting on behalf of a user. A Mobile Agent is an agent roaming the internet to access data and services, and carry out its assigned task remotely. This paper will focus on the communication models for Mobile Agents. Generally speaking, communication models concern with problems of how to name Mobile Agents, how to establish communication relationships, how to trace moving agents, and how to guarantee reliable communication. Some existing MA systems are purely based on RPC-style communication, whereas some adopts asynchronous message passing, or event registration/handling. Different communication concepts suitable for Mobile Agents are well discussed in [1]. However, we will investigate these concepts and existing models from a different point view: how to track down agents and deliver messages in a dynamic, changing world.

  6. Porphyria Cutanea Tarda and Agent Orange

    Science.gov (United States)

    ... ZIP code here Porphyria Cutanea Tarda and Agent Orange VA presumes porphyria cutanea tarda (PCT) is related to Veterans' exposure to Agent Orange or other herbicides during military service when the ...

  7. Soft Tissue Sarcomas and Agent Orange

    Science.gov (United States)

    ... ZIP code here Soft Tissue Sarcomas and Agent Orange VA presumes some soft tissue sarcomas in Veterans are related to their exposure to Agent Orange or other herbicides during military service. The soft ...

  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. Sports Agent Industry Emerges in China

    Institute of Scientific and Technical Information of China (English)

    HeiZiand; YiYou

    2003-01-01

    The agent profession is not new to Chinese. First appearing in the Western Zhou Dynasty, agents were called "Zhi Ren" then and "Ya Ren" from the Tang Dynasty onwards. In the Ming Dynasty, a certain amount of property and a license were required if one wanted to become an agent. In the late Qing Dynasty, Mai Ban (Chinese executives working in foreign firms), also a sort of agents, began to emerge in major cities of China.

  10. Mobile agents for distributed decision support systems

    OpenAIRE

    Blaz Rodič

    2011-01-01

    This article focuses on the performance of Java based mobile agents using format translation via an intermediary XML based format. Our goal was to develop and verify the performance of a lightweight, mobile agent based solution that would allow strong security, portability and access to heterogeneous data resources from a mobile platform to facilitate exchange of data between simulation models and data resources. We have developed two types of agents: a mobile agent that functions as a server...

  11. Security Issues in Mobile Agent Paradigm

    OpenAIRE

    Nitin Jain; Neeraj Singla

    2011-01-01

    A mobile Agent is a Software program that migrates from node tonode of a heterogeneous network. They are goal-oriented i.e. workautonomously towards a goal, capable of suspending their executionon one platform and moving to other where they can resumeexecution using resources of these nodes and they meet and interactwith other agents. Agents may be stationary, always resident at asingle platform or mobile, capable of moving among differentplatforms at different time. The mobile agent paradigm...

  12. Explaining Simulations Through Self Explaining Agents

    OpenAIRE

    Maaike Harbers; John-Jules Meyer; Karel Van den Bosch

    2010-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is more variable and harder to predict than reactive behavior, and therefore it might be harder to explain. However, the approach presented in this paper tries to make advantage of the agents' pro-active...

  13. ENZYMATIC DEINKING AGENTS FOR MIXED OFFICE WASTEPAPER

    Institute of Scientific and Technical Information of China (English)

    HuayuQiu; ChuanfuLiu; XiaokeMa; YingjuanFu

    2004-01-01

    This article focused on deinking agents for enzymatic deinking of MOW (mixed office wastepaper). The deinking performances of many series of surfactants were discussed at the experimental conditions, and finally some surfactants, which had good deinking effect, were selected. Then two-composed deinking agents were discussed. The deinkability of the deinking agents, e.g. deinking agents containing T-123 50% and P-10 50%, T-123 70% and O-15 30%, were better than that of the imported product.

  14. ENZYMATIC DEINKING AGENTS FOR MIXED OFFICE WASTEPAPER

    Institute of Scientific and Technical Information of China (English)

    Huayu Qiu; Chuanfu Liu; Xiaoke Ma; Yingjuan Fu

    2004-01-01

    This article focused on deinking agents for enzymatic deinking of MOW (mixed office wastepaper). The deinking performances of many series of surfactants were discussed at the experimental conditions, and finally, some surfactants, which had good deinking effect, were selected. Then two-composed deinking agents were discussed. The deinkability of the deinking agents, e.g. deinking agents containing T-123 50% and P-10 50%, T-123 70% and O-1530%, were better than that of the imported product.

  15. Virtual Knowledge Communities for Semantic Agents

    OpenAIRE

    Subercaze, Julien; Maret, Pierre

    2011-01-01

    International audience Virtual Knowledge Communities are a well suited paradigm for decentralized knowldege exchanges and they have been applied in several domains. In this paper we investigate the implementation of virtual knowledge communities with se- mantic agents. Using the SAM (Semantic Agent Modeling) approach, we show that agents can exchange community re- lated concepts (in OWL) and behavior (in SWRL). Agents can then learn and adapt new community-related behavior, which is useful...

  16. Topology and Social Behaviour of Agents

    OpenAIRE

    O. Hudak

    2003-01-01

    In a social group its members are caled here agents. Any two agents from the group may interact. The interaction consists of the exchange of information and it costs some energy. There exist subgroups of interacting agents which are nonreducibile. The structure, configuration of interactions between agents in the group, forms a macroscopic structure. The statistical equilibrium due to microreversibility is characterised by the maximum of entropy and by the minimum of energy, costs of informat...

  17. Integration of Agent System with Legacy Software

    Institute of Scientific and Technical Information of China (English)

    SHEN Qi; ZHAO Yan-hong; YIN Zhao-lin

    2003-01-01

    Agent technique is a new method that can analyze, design and realize a distributed open system. It has been used in almost every field. But if act for the real practical words in technique, it must integrate with legacy software, such as database system etc, and control them. This paper introduces the specification of agent software integration, ontology, instances database as implementing agent software integration with CORBA technique and takes XML, ACL as language communicating among agents.

  18. Bisimulation for Single-Agent Plausibility Models

    DEFF Research Database (Denmark)

    Andersen, Mikkel Birkegaard; Bolander, Thomas; van Ditmarsch, H.;

    2013-01-01

    Epistemic plausibility models are Kripke models agents use to reason about the knowledge and beliefs of themselves and each other. Restricting ourselves to the single-agent case, we determine when such models are indistinguishable in the logical language containing conditional belief, i.e., we......-agent epistemic plausibility models on a finite set of propositions. This gives decidability for single-agent epistemic plausibility planning....

  19. Self-Adapting Reactive Autonomous Agents

    Science.gov (United States)

    Andrecut, M.; Ali, M. K.

    This paper describes a new self-adapting control algorithm for reactive autonomous agents. The architecture of the autonomous agents integrates the reactive behavior with reinforcement learning. We show how these components perform on-line adaptation of the autonomous agents to various complex navigation situations by constructing an internal model of the environment. Also, a discussion on cooperation and coordination of teams of agents is presented.

  20. Pathogenic agents in freshwater resources

    Science.gov (United States)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  1. Honey - A Novel Antidiabetic Agent

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa, Siti A. Sulaiman, Mohd S. Ab Wahab

    2012-01-01

    Full Text Available Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT, on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise of these experimental data in diabetic human subjects.

  2. A fully implantable rodent neural stimulator

    Science.gov (United States)

    Perry, D. W. J.; Grayden, D. B.; Shepherd, R. K.; Fallon, J. B.

    2012-02-01

    The ability to electrically stimulate neural and other excitable tissues in behaving experimental animals is invaluable for both the development of neural prostheses and basic neurological research. We developed a fully implantable neural stimulator that is able to deliver two channels of intra-cochlear electrical stimulation in the rat. It is powered via a novel omni-directional inductive link and includes an on-board microcontroller with integrated radio link, programmable current sources and switching circuitry to generate charge-balanced biphasic stimulation. We tested the implant in vivo and were able to elicit both neural and behavioural responses. The implants continued to function for up to five months in vivo. While targeted to cochlear stimulation, with appropriate electrode arrays the stimulator is well suited to stimulating other neurons within the peripheral or central nervous systems. Moreover, it includes significant on-board data acquisition and processing capabilities, which could potentially make it a useful platform for telemetry applications, where there is a need to chronically monitor physiological variables in unrestrained animals.

  3. Modified pulse shapes for effective neural stimulation

    Directory of Open Access Journals (Sweden)

    Lorenz eHofmann

    2011-09-01

    Full Text Available Electrical stimulation of neuronal structures is used as treatment of many neu- rological disorders, e.g. for the treatment of Parkinsons disease via deep brain stimulation. To reduce side effects, to avoid tissue or electrode damage and to increase battery lifetimes, an effective but gentle electrical stimulation is of prime importance. We study different modified pulse shapes for application in deep brain stimulation with respect to their efficiency to initiate neuronal activity. Numeri- cal simulations of two mathematical neuron models are performed to investigate the effectiveness of different modified pulse shapes. According to our results, the considered pulse shapes show a considerably increased efficiency in terms of both activation and entrainment of neural activity. We find that the introduction of a gap of specific and optimized duration in a biphasic pulse and the reversal of the stan- dard pulse phase order yield stimulation protocols that may increase the efficiency and therefore reduce the energy consumption of stimulation. The improvements are achieved only by simple modifications of existing stimulation techniques. The modification of the pulse shapes results in an improvement of up to 50% for both the activation of resting neurons and the entrainment of bursting neurons.

  4. Embedded Automation in Human-Agent Environment

    CERN Document Server

    Tweedale, Jeffrey W

    2012-01-01

    This research book proposes a general conceptual framework for the development of automation in human-agents environments that will allow human- agent teams to work effectively and efficiently. We examine various schemes to implement artificial intelligence techniques in agents.  The text is directed to the scientists, application engineers, professors and students of all disciplines, interested in the agency methodology and applications.

  5. Preferences of Agents in Defeasible Logic

    NARCIS (Netherlands)

    Dastani, M.; Governatori, G.; Rotolo, A.; Torre, L.W.N. van der

    2005-01-01

    Defeasible Logic is extended to programming languages for cognitive agents with preferences and actions for planning. We define rule-based agent theories that contain preferences and actions, together with inference procedures. We discuss patterns of agent types in this setting. Finally, we illustra

  6. Cooperative heuristic multi-agent planning

    NARCIS (Netherlands)

    De Weerdt, M.M.; Tonino, J.F.M.; Witteveen, C.

    2001-01-01

    In this paper we will use the framework to study cooperative heuristic multi-agent planning. During the construction of their plans, the agents use a heuristic function inspired by the FF planner (l3l). At any time in the process of planning the agents may exchange available resources, or they may r

  7. Multi-Agent Planning with Planning Graph

    NARCIS (Netherlands)

    Bui, The Duy; Jamroga, Wojciech

    2003-01-01

    In this paper, we consider planning for multi-agents situations in STRIPS-like domains with planning graph. Three possible relationships between agents' goals are considered in order to evaluate plans: the agents may be collaborative, adversarial or indifferent entities. We propose algorithms to dea

  8. Explaining simulations through self explaining agents

    NARCIS (Netherlands)

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.

    2010-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is mor

  9. Explaining Simulations through Self Explaining Agents

    NARCIS (Netherlands)

    Harbers, M.; Dignum, F.; Bosch, K. van den; Meyer, J.J.C.

    2008-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is mor

  10. Stability of Evolving Multi-Agent Systems

    CERN Document Server

    De Wilde, Philippe; 10.1109/TSMCB.2011.2110642

    2011-01-01

    A Multi-Agent System is a distributed system where the agents or nodes perform complex functions that cannot be written down in analytic form. Multi-Agent Systems are highly connected, and the information they contain is mostly stored in the connections. When agents update their state, they take into account the state of the other agents, and they have access to those states via the connections. There is also external, user-generated input into the Multi-Agent System. As so much information is stored in the connections, agents are often memory-less. This memory-less property, together with the randomness of the external input, has allowed us to model Multi-Agent Systems using Markov chains. In this paper, we look at Multi-Agent Systems that evolve, i.e. the number of agents varies according to the fitness of the individual agents. We extend our Markov chain model, and define stability. This is the start of a methodology to control Multi-Agent Systems. We then build upon this to construct an entropy-based defi...

  11. The Ontogenesis of Agent: Linguistic Expression.

    Science.gov (United States)

    Olswang, Lesley Barrett; Carpenter, Robert L.

    1982-01-01

    Some of the findings of a longitudinal study of three infants between their 11th and 22nd months to document development of linguistic expression of the agent concept indicated that first vocalizations were inconsistently associated with nonverbal agentive behaviors and later mature utterances coded agent-action-recipient events. (MC)

  12. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    Science.gov (United States)

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...

  13. Radioactive scanning agents with hydroquinone stabilizer

    International Nuclear Information System (INIS)

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise hydroquinone in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material which carries the radionuclide to bone, thus providing a skeletal imaging agent

  14. 7 CFR 1430.210 - MILC agents.

    Science.gov (United States)

    2010-01-01

    ... MILC agents. (a) MILC benefits may be disbursed by a dairy marketing cooperative that serves special... operation may authorize an agent of a dairy cooperative or milk handler affiliated with such cooperative to... 7 Agriculture 10 2010-01-01 2010-01-01 false MILC agents. 1430.210 Section 1430.210...

  15. Agents and Lattice-valued Logic

    Institute of Scientific and Technical Information of China (English)

    Germanno Resconi

    2006-01-01

    In fuzzy set theory, instead of the underlying membership set being a two -valued set it is a multi-valued set that generally has the structure of a lattice L with a minimal element O and the maximal element I. Furthermore if ∧, ∨, → and (「) are defined in the set L, then we can use these operations to define, as in the ordinary set theory, operations on fuzzy subsets. In this paper we give a model of the Lattice-Valued Logic with set of agents.Any agents know the logic value of a sentence p. The logic value is compatible with all of the accessible conceptual models or worlds of p inside the agent. Agent can be rational or irrational in the use of the logic operation.Every agent of n agents can have the same set of conceptual models for p and know the same logic for p in this case the agents form a consistent group of agents.When agents have different conceptual models for p,different subgroup of agents know different logic value for p. In this case the n agents are inconsistent in the expression of the logic value for p. The valuation structure of set of agents can be used as a semantic model for the Lattice-valued Logic and fuzzy logic.

  16. Improving Multi-Agent Systems Using Jason

    DEFF Research Database (Denmark)

    Vester, Steen; Boss, Niklas Skamriis; Jensen, Andreas Schmidt;

    2011-01-01

    We describe the approach used to develop the multi-agent system of herders that competed as the Jason-DTU team at the Multi-Agent Programming Contest 2010. We also participated in 2009 with a system developed in the agentoriented programming language Jason which is an extension of AgentSpeak. We ...

  17. Construction and Evaluation of Animated Teachable Agents

    Science.gov (United States)

    Bodenheimer, Bobby; Williams, Betsy; Kramer, Mattie Ruth; Viswanath, Karun; Balachandran, Ramya; Belynne, Kadira; Biswas, Gautam

    2009-01-01

    This article describes the design decisions, technical approach, and evaluation of the animation and interface components for an agent-based system that allows learners to learn by teaching. Students learn by teaching an animated agent using a visual representation. The agent can answer questions about what she has been taught and take quizzes.…

  18. Stigmergy in multi-agent reinforcement learning

    OpenAIRE

    Aras, Raghav; Dutech, Alain; Charpillet, François

    2004-01-01

    http://www.computer.org In this paper, we describe how certain aspects of the biological phenomena of stigmergy can be imported into multi-agent reinforcement learning (MARL), with the purpose of better enabling coordination of agent actions and speeding up learning. In particular, we detail how these stigmergic aspects can be used to define an inter-agent communication framework.

  19. Agent for roentgenocontrast examination of cavities

    International Nuclear Information System (INIS)

    The water-soluble agent, additionaly containing starch, agar, water, is suggested to increase accuracy of injured cavity diagnostics. The method for roentgenocontrast agent preparation on the base of starch-agar gel is described. Advantages of the agent suggested in comparison with those of roentgenologic cavity investigation used are shown

  20. On Programming Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt

    2013-01-01

    Since it is difficult (or even impossible) to assume anything about the agents’ behavior and goals in an open multi-agent system, it is often suggested that an organization is imposed upon the agents, whichhich, by abstracting away from the agents, specifies boundaries and objectives that the age...