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Sample records for alfa 2b recombinante

  1. Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C

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    Yoan Antonio Sánchez Rodríguez

    2011-03-01

    Full Text Available INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal durante 48 semanas. RESULTADOS: el 88,5 % del total de casos presentó efectos adversos; de ellos el 79,5 % correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 % de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia.

  2. Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

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    Yoan Antonio Sánchez Rodríguez

    2011-03-01

    Full Text Available INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal durante 48 semanas. RESULTADOS: el 88,5 % del total de casos presentó efectos adversos; de ellos el 79,5 % correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 % de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia.INTRODUCTION: chronic hepatitis C has reached the category of pandemic. The hepatitis C virus is the

  3. Experiencia con las reacciones adversas asociadas con el interferón alfa 2b recombinante en hematología Experience with the adverse reactions associated with recombinant alpha 2b interferon in hematology

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    Idalmis Brito Pascual

    2005-08-01

    Full Text Available El interferón alfa 2b es una citoquina con actividad antiviral, antiproliferativa e inmunomoduladora que ha demostrado ser eficaz para el tratamiento de enfermedades virales y neoplásicas. El presente trabajo se realizó con el propósito de describir la frecuencia de las reacciones adversas asociada con la administración de Heberon alfa R (interferón alfa 2b recombinante en enfermedades hematológicas. Se analizaron las características de base de los pacientes, así como la frecuencia, intensidad y relación de causalidad de los eventos reportados. Los eventos adversos más frecuentes fueron las manifestaciones del síndrome gripal que incluyó fiebre, escalofrío, astenia, mialgias, anorexia y cefalea. Estas manifestaciones son transitorias y responden al tratamiento con antiinflamatorios no esteroideos. La mayoría de los eventos fueron de intensidad leve a moderada y no requirieron la suspensión del tratamiento. En conclusión, el Heberon alfa R es un fármaco relativamente seguro para el tratamiento de trastornos hematológicosAlpha 2b interferon is a cytokine with antiviral, antiproliferative and immunomodulator activity that has proved to be efficient for the treatment of viral and neoplastic diseases, This paper is aimed at describing the frequency of adverse reactions associated with the administration of alpha R Heberon (recombinant alpha 2b interferon in hematological diseases. The basic characteristics of the patients, as well as the frequency, intensity and causality relation of the reported events were analyzed. The most common adverse effects were the manifestations of the gripal syndrome that included fever, chills, astenia, myalgia, anorexia and headache. These manifestations are transitory and respond to the treatment with non-steroideal antiinflammatory drugs. Most of the events were from mild to moderate intensity and did not require the suspension of the treatment. To conclude, alpha R Heberon is a relatively safe drug

  4. Terapia combinada de criocirugía e interferón alfa-2b humano recombinante en el condiloma acuminado

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    Alfonso Trujillo , Israel

    2015-01-01

    Las continuas recidivas de lcondiloma acuminado hace necesario la búsqueda constante de alternativas terapéuticas. Para evaluar la eficacia terapéutica y seguridad del interferón alfa-2b asociado a criocirugía en el condiloma acuminado fue realizado un ensayo clínico abierto en 170 pacientes del hospital “Hermanos Ameijeiras” que fueron aleatorizados a recibir durante 6 semanas (grupo A) 3 x 106 UI de interferón subcutáneo, 3 veces por semana y aplicación quincenal de criocirugía o (grupo B) ...

  5. Peginterferon Alfa-2b (PEG-Intron)

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    ... 2b injection pen, follow these steps: Take the carton containing the injection pen out of the refrigerator ... temperature. Check the expiration date printed on the carton, and do not use the carton if the ...

  6. Treatment of human papillomavirus with peg-interferon alfa-2b and ribavirin

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    M.H.P. Pavan

    Full Text Available We reported one case of human immunodeficiency virus and hepatitis C virus co-infected patient who presented a significant improvement of human papillomavirus (HPV lesions during the treatment of chronic hepatitis using peg-interferon alfa-2b and ribavirin.

  7. Treatment persistence in and cost of therapy for patients with chronic hepatitis C: Peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin.

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    Brixner, Diana I; Ye, Xin; Chu, Teng-Chiao; Blumentals, William A; Hassanein, Tarek I

    2009-12-15

    Treatment persistence and cost of therapy for patients with chronic hepatitis C (CHC) treated with peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin were evaluated. This retrospective database analysis used eligibility, pharmacy, and medical claims data from a large U.S. health plan for patients with CHC treated with peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin from January 2002 through June 2006. For the purposes of this analysis, the study population included all hepatitis C virus (HCV) genotypes. Comparable groups for assessment of outcomes were constructed using propensity score matching to reduce the effect of known sources of bias. Outcome variables included treatment persistence and annualized overall and HCV-attributable health care costs. A total of 1783 matched pairs were analyzed. Compared with patients receiving peginterferon alfa-2a plus ribavirin, patients receiving peginterferon alfa-2b plus ribavirin were 18% less likely to be persistent with therapy at week 48 (p = 0.013). During the first six months of follow-up, mean all-cause costs (p = 0.0368) and HCV-attributable costs (p costs (p = 0.0060) and HCV-attributable costs (p = 0.0167) over the entire follow-up period were significantly lower for patients treated with peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin. Analysis of information from a health care claims database suggests that treating CHC with peginterferon alfa-2a plus ribavirin may improve treatment persistence and help reduce the health care costs imposed by CHC compared with treatment with peginterferon alfa-2b plus ribavirin.

  8. Interferon alfa-2b in the management of recurrent conjunctival papillomatosis.

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    Singh, Manpreet; Gautam, Natasha; Gupta, Adit; Kaur, Manpreet

    2016-10-01

    A 2-year-old boy presented with a recurrent strawberry-like reddish mass arising from the left caruncular region for 8 months. An incisional biopsy was performed elsewhere 2 months earlier, followed by an increase in size of mass, significant epiphora, and intermittent bleeding. On examination, exuberant exophytic gelatinous mass with multifocal origin was observed arising from inferior forniceal conjunctiva and caruncle. Clinical differential of multifocal conjunctival papilloma was kept, and topical interferon alfa-2b (INFα-2b) was started. No clinical reduction in mass or symptomatology was observed over 6 weeks. Excision biopsy with cryotherapy and subconjunctival injection of INFα-2b was performed over all foci. Conjunctival papilloma was confirmed on histopathology, and topical INFα-2b was continued in postoperative period for 3 months. At 14 months of follow-up, no recurrence, epiphora, or bleeding was noticed. We advocate a possible role of local INF therapy in managing and preventing recurrences of conjunctival papillomatosis.

  9. IFN Alfa-2B and BCG Therapy Is An Effective Method In Superficial Bladder Carcinoma

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    Ahmet Ozdemir

    2012-04-01

    Full Text Available Aim: The initial therapy for superficial bladder carcinoma is the transurethral resection of the tumor. In spite of successful resections, there are 60-79% recurrence and 15% progression rates. Additional therapies are suggested for the treatment of superficial bladder carcinoma. We compared the efficacy of interferon alfa-2b monotherapy with interferon alfa-2b plus Bacillus Calmette Guerin (BCG combination therapy with urine interleukin (IL 2, 6 and 10 levels of patients with superficial bladder carcinoma. Material and Method: The patients who underwent TUR-BT for superficial bladder tumor (pathological staging Ta-T1 between 2004 and 2007 at our hospital included in this prospective study. Intravesical immunotherapy was administered once a week for 6 weeks and there after a month for 6 months, starting 4 weeks after TUR-BT. IL levels were measured. Results: IL-2, IL-6 and IL- 10 levels in urine samples were taken at 2nd and 4th hours of intravesical therapy. A statistically significant difference was observed between mean urine IL-2 levels of patients treated with IFN%u03B1-2b monotherapy and IFN%u03B1- 2b plus BCG combination both at 2nd and 4th hours. (p=0.05 In IFN%u03B1-2b plus BCG combination group, there was a statistical significant difference between stages regarding IL-2 and IL-6 levels (p=0.05. Among patients with G3 tumors, IL-2 levels were higher at 2 and 4 hours (p=0.05 but there was no significant difference in IL-6 and IL-10 levels in this group of patients regardless of intravesical therapy received (p=0.05. Discussion: IFN%u03B1-2b and BCG combination therapy is a reliable and effective therapy in the management of superficial bladder tumors.

  10. Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia.

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    Holcombe, David J; Lee, Graham A

    2006-10-01

    To evaluate topical interferon alfa-2b (IFN-alpha2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). Prospective, noncomparative, interventional consecutive case series. Ten patients with recalcitrant OSSN were treated with topical IFN-alpha2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow-up of six months. Eight of 10 patients achieved clinical resolution from topical IFN-alpha2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). Topical IFN-alpha2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision.

  11. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera

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    Zagrijtschuk, Oleh; Buxhofer-Ausch, Veronika; Thaler, Josef; Schloegl, Ernst; Gastl, Guenther A.; Wolf, Dominik; Kralovics, Robert; Gisslinger, Bettina; Strecker, Karin; Egle, Alexander; Melchardt, Thomas; Burgstaller, Sonja; Willenbacher, Ella; Schalling, Martin; Them, Nicole C.; Kadlecova, Pavla; Klade, Christoph; Greil, Richard

    2015-01-01

    In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) α-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 µg was tested without the appearance of dose-limiting toxicities. All drug-related adverse events were known toxicities associated with IFN-α. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa-2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial. The study was disclosed at www.clinicaltrials.gov as #NCT01193699 before including the first patient. PMID:26261238

  12. Interferon alfa-2b in the management of recurrent conjunctival papillomatosis

    Directory of Open Access Journals (Sweden)

    Manpreet Singh

    2016-01-01

    Full Text Available A 2-year-old boy presented with a recurrent strawberry-like reddish mass arising from the left caruncular region for 8 months. An incisional biopsy was performed elsewhere 2 months earlier, followed by an increase in size of mass, significant epiphora, and intermittent bleeding. On examination, exuberant exophytic gelatinous mass with multifocal origin was observed arising from inferior forniceal conjunctiva and caruncle. Clinical differential of multifocal conjunctival papilloma was kept, and topical interferon alfa-2b (INFα-2b was started. No clinical reduction in mass or symptomatology was observed over 6 weeks. Excision biopsy with cryotherapy and subconjunctival injection of INFα-2b was performed over all foci. Conjunctival papilloma was confirmed on histopathology, and topical INFα-2b was continued in postoperative period for 3 months. At 14 months of follow-up, no recurrence, epiphora, or bleeding was noticed. We advocate a possible role of local INF therapy in managing and preventing recurrences of conjunctival papillomatosis.

  13. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection.

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    Ascione, Antonio; De Luca, Massimo; Tartaglione, Maria Teresa; Lampasi, Filippo; Di Costanzo, Giovan Giuseppe; Lanza, Alfonso Galeota; Picciotto, Francesco Paolo; Marino-Marsilia, Giuseppina; Fontanella, Luca; Leandro, Gioacchino

    2010-01-01

    Patients with chronic hepatitis C virus (HCV) infection are frequently treated with a combination of pegylated interferon (peginterferon) and ribavirin. This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b, each in combination with ribavirin. A total of 320 consecutive, treatment-naive, HCV RNA-positive patients with chronic hepatitis were randomly assigned to once-weekly peginterferon alfa-2a (180 microg, group A) or peginterferon alfa-2b (1.5 microg/kg, group B) plus ribavirin 1000 mg/day (body weight or=75 kg) for 48 weeks (genotype 1 or 4) or 24 weeks (genotype 2 or 3). The primary end point was sustained virological response (SVR) by intention-to-treat. More patients in group A than group B achieved an SVR (110/160 [68.8%] vs 87/160 [54.4%]; P = .008). Higher SVR rates were obtained in group A than group B among patients with genotype 1/4 (51/93 [54.8%] vs 37/93 [39.8%]; P = .04), with genotype 2/3 (59/67 [88.1%] vs 50/67 [74.6%]; P = .046), without cirrhosis (96/127 [75.6%] vs 75/134 [55.9%]; P = .005), and with baseline levels HCV RNA >500,000 IU/mL (58/84 [69%] vs 43/93 [46.2%]; P = .002). SVR rates in groups A and B were not statistically different among patients with baseline HCV RNA alfa-2a plus ribavirin produced a significantly higher SVR rate than peginterferon alfa-2b plus ribavirin. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels

    DEFF Research Database (Denmark)

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo

    2015-01-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre......-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP......-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median...

  15. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

    Science.gov (United States)

    Solal-Celigny, P; Lepage, E; Brousse, N; Reyes, F; Haioun, C; Leporrier, M; Peuchmaur, M; Bosly, A; Parlier, Y; Brice, P

    1993-11-25

    Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin's lymphoma. In 1986, we designed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin's lymphoma. The trial involved 242 patients with advanced low-grade follicular non-Hodgkin's lymphoma selected on the basis of clinical, radiographic, and biologic criteria. All patients were treated with a regimen consisting of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP), given monthly for six cycles and then every two months for one year. After randomization, 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months. The remaining 119 patients received chemotherapy alone. As compared with the patients treated with CHVP only, the patients treated with CHVP plus interferon alfa had a higher overall rate of response (85 percent vs. 69 percent, P = 0.006), a longer median event-free survival (34 months vs. 19 months, P < 0.001), and a higher rate of survival at 3 years (86 percent vs. 69 percent, P = 0.02). Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone. There were no treatment-related deaths. Interferon alfa had to be stopped because of toxic effects (fatigue and hepatitis) in 13 patients (11 percent). The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response, event-free survival, and overall survival in patients with advanced follicular non-Hodgkin's lymphoma, without serious toxicity, although some patients were unable to tolerate the side effects.

  16. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Hauser, Goran

    2010-01-01

    ) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently...... extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared peginterferon alpha-2a plus ribavirin versus peginterferon...... alfa-2b plus ribavirin. Overall, peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa-2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04-1.19; P = 0.004 [eight trials]). Subgroup analyses...

  17. Health-related quality of life in patients with high-risk melanoma randomised in the Nordic phase 3 trial with adjuvant intermediate-dose interferon alfa-2b

    DEFF Research Database (Denmark)

    Brandberg, Y; Aamdal, S; Bastholt, Lars

    2012-01-01

    To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN).......To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN)....

  18. Resolution of primary acquired melanosis with atypia after treatment with topical mitomycin C and interferon alfa-2b

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    Fariba Ghassemi

    2015-01-01

    Full Text Available Purpose: To report a case of primary acquired melanosis (PAM successfully treated with combined topical mitomycin C and interferon-α2b. Case Report: A 75-year-old man presented with an extensive unilateral pigmented lesion involving 360° of the bulbar conjunctiva, extending to the fornices and palpebral conjunctiva. Map biopsy confirmed PAM with local atypia. Treatment was initiated with mitomycin C 0.04% eye drops for two courses. Although the lesion markedly responded to the treatment, residual lesions justified further therapy. To avoid ocular surface toxicity induced by excessive mitomycin C exposure, interferon-α2b eye drops were started and continued for 6 months. The pigmented lesion almost completely disappeared and no significant complication or recurrence was observed for 24 months. Conclusion: Combination therapy using mitomycin C and interferon-α2b for PAM with atypia may be recommended as an effective treatment modality, avoiding the ocular surface toxicity due to excessive mitomycin C exposure.

  19. Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.

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    Valla, D C; Chevallier, M; Marcellin, P; Payen, J L; Trepo, C; Fonck, M; Bourliere, M; Boucher, E; Miguet, J P; Parlier, D; Lemonnier, C; Opolon, P

    1999-06-01

    To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-alpha2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P <.02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, alpha-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 +/- 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis.

  20. CLINICAL AND IMMUNOLOGICAL EFFICACY OF THE RECOMBINANT INTERFERON alfa-2b OF ACUTE EPSTEIN-BARR VIRAL MONONUCLEOSIS IN PRESCHOOL CHILDREN

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    V. N. Timchenko

    2016-01-01

    Full Text Available Conducted clinical and immunological examination of 51 children with acute Epstein-Barr viral mononucleosis (EBV in age from 1 year to 7 years. All children diagnosed with a moderate degree of the disease. In the treatment of 25 people (comparison group used the standard treatment (pathogenetic, symptomatic, treatment 26 people (main group included the use as antiviral and immunotropic means of the preparation of human recombinant interferon Alfa-2b in the form of rectal suppositories — VIFERON®. The immunological survey was conducted in dynamics: at the height of the disease and in the convalescence period. The blood was determined indicators of cellular immunity (leukocytes, lymphocytes, CD3+, CD4+, CD8+, CD56+, HLAII+, CD95+, CD1 6+, CD25+, the concentration of IFN-a, IFN-y, IL-4 levels in spontaneous and induced production, in the serum. At milestones children of the main group noted rapid regression of clinical symptoms, normalization of body temperature, reducing intoxication, positive dynamics lymphoproliferative syndrome, a significant reduction in bed-days, no layering respiratory viral infections. Interferon had also expressed a positive impact on the changed parameters of cellular immunity and cytokine links. At the same time, 80% of patients after basic treatment is established the predominance of Th2 type immune response, indicating a high risk of developing chronic course of EBV-mononucleosis.

  1. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

    NARCIS (Netherlands)

    Bielack, Stefan S.; Smeland, Sigbjørn; Whelan, Jeremy S.; Marina, Neyssa; Jovic, Gordana; Hook, Jane M.; Krailo, Mark D.; Gebhardt, Mark; Pápai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R. Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette; Letson, G. Douglas; Teot, Lisa A.; Goorin, Allen; Baumhoer, Daniel; Kager, Leo; Werner, Mathias; Lau, Ching C.; Sundby Hall, Kirsten; Gelderblom, Hans; Meyers, Paul; Gorlick, Richard; Windhager, Reinhard; Helmke, Knut; Eriksson, Mikael; Hoogerbrugge, Peter M.; Schomberg, Paula; Tunn, Per-Ulf; Kühne, Thomas; Jürgens, Heribert; van den Berg, Henk; Böhling, Tom; Picton, Susan; Renard, Marleen; Reichardt, Peter; Gerss, Joachim; Butterfass-Bahloul, Trude; Morris, Carol; Hogendoorn, Pancras C. W.; Seddon, Beatrice; Calaminus, Gabriele; Michelagnoli, Maria; Dhooge, Catharina; Sydes, Matthew R.; Bernstein, Mark

    2015-01-01

    Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-alpha-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age

  2. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept.

    Science.gov (United States)

    Pardo-Yules, Benjamin; Gallego-Durán, Rocío; Eslam, Mohammed; García-Collado, Carlos; Grande, Lourdes; Paradas, Carmen; Morillo, Ramón; Dorantes, Benito; Romero-Gómez, Manuel

    2011-12-01

    fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.

  3. Relato do primeiro paciente brasileiro com a forma infantil da doença de Pompe tratado com alfa-glicosidase recombinante humana Report of the first Brazilian infantile Pompe disease patient to be treated with recombinant human acid alpha-glucosidase

    Directory of Open Access Journals (Sweden)

    Sandra J. Pereira

    2008-06-01

    Full Text Available Objetivo: Relatar o primeiro caso de forma infantil da doença de Pompe tratado no Brasil. Descrição: Trata-se de doença de depósito lisossomal que se caracteriza por defeitos da enzima alfa-glicosidase ácida, com acúmulo intracelular de glicogênio, principalmente nos músculos. São descritas a forma infantil e tardia. Desde 2006, está disponível tratamento com enzima recombinante humana. Descreve-se o primeiro caso de forma infantil da doença tratado no Brasil. Trata-se de menina com 2,5 meses de idade e progressão rápida da doença, com perda dos movimentos dos membros, miocardiopatia hipertrófica e insuficiência respiratória aos 7 meses de idade. Após 10 meses de tratamento, apresentou boa resposta clínica, com remissão da insuficiência respiratória, recuperação parcial dos movimentos dos membros e melhora importante do quadro cardiológico. Comentários: Apesar de pouco freqüente, a forma infantil da doença de Pompe é letal. A disponibilidade de tratamento eficaz aumenta a necessidade de conhecimento e diagnóstico precoce da doença.Objective: To describe the first case of infantile Pompe disease to be treated in Brazil. Description: Pompe disease is a glycogen storage disease related to defects in the acid alpha-glucosidase enzyme, leading to an intracellular accumulation of glycogen, mainly in muscles. Two forms are described: infantile and juvenile. Since 2006, treatment with recombinant human acid alpha-glucosidase has been available. This article describes the first case of infantile Pompe disease treated in Brazil. A girl presented at 2.5 months of age with rapid disease progression, exhibiting severe hypotonia, loss of movements in both upper and lower limbs and hypertrophic cardiomyopathy, progressing to respiratory failure by the age of 7 months. After 10 months of treatment, she exhibited a good clinical response, with remission of the respiratory failure, partial recovery of arm and leg movements and

  4. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

    OpenAIRE

    Bielack, Stefan S.; Smeland, Sigbj?rn; Whelan, Jeremy S.; Marina, Neyssa; Jovic, Gordana; Hook, Jane M.; Krailo, Mark D.; Gebhardt, Mark; P?pai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R. Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette

    2015-01-01

    Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, ...

  5. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A. [ISRCTN75125874

    Directory of Open Access Journals (Sweden)

    Ridolfi Ruggero

    2006-02-01

    Full Text Available Abstract Background High-dose interferon alfa-2b (IFNalfa-2b, according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. Methods Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm, or IFNalfa-2b 20 MU/m2/d IV 5 days/week × 4 weeks followed by 10 MU/m2 subcutaneously (SC three times per week × 48 weeks (High Dose Interferon, HDI, arm. Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. Results The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9% (p = 0.0074, yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week (p = 0.003. Conclusion Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited.

  6. Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC of hepatitis C patients during the first 10 weeks of treatment

    Directory of Open Access Journals (Sweden)

    Edenberg Howard J

    2008-11-01

    Full Text Available Abstract Background and Aims This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron™ and ribavirin (administered by weight in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys™ and ribavirin were administered. Methods RNA was isolated from peripheral blood monocytes (PBMC from twenty treatment-naïve patients just before treatment (day 1 and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. Results The expression of many genes differed significantly (p ≤ 0.001 and changed at least 1.5-fold at days 3 (290 probes and 10 (255 probes, but the number dropped at days 6 (165 and 13 (142. Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1, TRAIL, IL1Rα and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1 was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. Conclusion The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our

  7. Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.

    Science.gov (United States)

    Taylor, Milton W; Tsukahara, Takuma; McClintick, Jeanette N; Edenberg, Howard J; Kwo, Paul

    2008-11-05

    This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron) and ribavirin (administered by weight) in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys) and ribavirin were administered. RNA was isolated from peripheral blood monocytes (PBMC) from twenty treatment-naïve patients just before treatment (day 1) and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. The expression of many genes differed significantly (p changed at least 1.5-fold) at days 3 (290 probes) and 10 (255 probes), but the number dropped at days 6 (165) and 13 (142). Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1), TRAIL, IL1Ralpha and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1) was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR) was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our data suggest that more than once a week dosing might be desirable early during

  8. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept Talidomida, peginterferón alfa-2b y ribavirina en el tratamiento de pacientes no respondedores con hepatitis crónica C genotipo 1: estudio piloto

    Directory of Open Access Journals (Sweden)

    Benjamín Pardo-Yules

    2011-12-01

    Full Text Available Background: fewer than half of patients infected with hepatitis C virus (HCV achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC patients, who had failed to respond to the (Peg-IFN/RBV, with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study. Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV. Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia añadiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en

  9. Peginterferon Alfa-2b Injection (Sylatron)

    Science.gov (United States)

    ... Naprosyn), ondansetron (Zofran), paroxetine (Paxil, Pexeva), phenytoin (Dilantin), piroxicam (Feldene), propafenone (Rhythmol), risperidone (Risperdal), rosiglitazone (Avandia), sulfamethoxazole ( ...

  10. Vacunas de bacterias recombinantes vivas

    OpenAIRE

    Blanco León, Marina

    2016-01-01

    La vacunación es uno de los logros más importantes en la historia de la medicina, que ha ido evolucionando a lo largo de los años permitiendo una reducción significativa de la mortalidad infantil, una disminución de la incidencia de enfermedades e incluso la erradicación de algunas de ellas en países enteros. Las vacunas de nueva generación surgen para reducir o eliminar las carencias de las vacunas “tradicionales”. Técnicas biotecnológicas basadas en el ADN recombinante han dado lugar, entre...

  11. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial.

    Science.gov (United States)

    Bielack, Stefan S; Smeland, Sigbjørn; Whelan, Jeremy S; Marina, Neyssa; Jovic, Gordana; Hook, Jane M; Krailo, Mark D; Gebhardt, Mark; Pápai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette; Letson, G Douglas; Teot, Lisa A; Goorin, Allen; Baumhoer, Daniel; Kager, Leo; Werner, Mathias; Lau, Ching C; Sundby Hall, Kirsten; Gelderblom, Hans; Meyers, Paul; Gorlick, Richard; Windhager, Reinhard; Helmke, Knut; Eriksson, Mikael; Hoogerbrugge, Peter M; Schomberg, Paula; Tunn, Per-Ulf; Kühne, Thomas; Jürgens, Heribert; van den Berg, Henk; Böhling, Tom; Picton, Susan; Renard, Marleen; Reichardt, Peter; Gerss, Joachim; Butterfass-Bahloul, Trude; Morris, Carol; Hogendoorn, Pancras C W; Seddon, Beatrice; Calaminus, Gabriele; Michelagnoli, Maria; Dhooge, Catharina; Sydes, Matthew R; Bernstein, Mark

    2015-07-10

    EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and

  12. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

    Science.gov (United States)

    Bielack, Stefan S.; Smeland, Sigbjørn; Whelan, Jeremy S.; Marina, Neyssa; Jovic, Gordana; Hook, Jane M.; Krailo, Mark D.; Gebhardt, Mark; Pápai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R. Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette; Letson, G. Douglas; Teot, Lisa A.; Goorin, Allen; Baumhoer, Daniel; Kager, Leo; Werner, Mathias; Lau, Ching C.; Sundby Hall, Kirsten; Gelderblom, Hans; Meyers, Paul; Gorlick, Richard; Windhager, Reinhard; Helmke, Knut; Eriksson, Mikael; Hoogerbrugge, Peter M.; Schomberg, Paula; Tunn, Per-Ulf; Kühne, Thomas; Jürgens, Heribert; van den Berg, Henk; Böhling, Tom; Picton, Susan; Renard, Marleen; Reichardt, Peter; Gerss, Joachim; Butterfass-Bahloul, Trude; Morris, Carol; Hogendoorn, Pancras C.W.; Seddon, Beatrice; Calaminus, Gabriele; Michelagnoli, Maria; Dhooge, Catharina; Sydes, Matthew R.; Bernstein, Mark

    2015-01-01

    Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped

  13. Levaduras vínicas recombinantes

    OpenAIRE

    González García, Ramón; González Ramos, Daniel

    2008-01-01

    Levaduras vínicas recombinantes. Método de obtención de cepas que secretan una mayor concentración de manoproteínas al medio, cepa de la levadura Saccharomyces cerevisiae depositada en la Colección Española de Cultivos Tipo (CECT), con el número CECT 13012, y usos de dichas cepas.

  14. Drotrecogin alfa Eli Lilly

    NARCIS (Netherlands)

    de Jonge, E.

    2002-01-01

    Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been

  15. ALFA Detector Control System

    CERN Document Server

    Oleiro Seabra, Luis Filipe; The ATLAS collaboration

    2015-01-01

    ALFA (Absolute Luminosity For ATLAS) is one of the sub-detectors of ATLAS (A Toroidal LHC Apparatus). The ALFA system is composed by four stations installed in the LHC tunnel 240 m away from the ATLAS interaction point. Each station has a vacuum and ventilation system, movement control and all the required electronics for signal processing. The Detector Control System (DCS) provides control and monitoring of several components and ensures the safe operation of the detector contributing to good Data Quality. This paper describes the ALFA DCS system including a detector overview, operation aspects and hardware control through a SCADA system, WinCC OA.

  16. ALFA Detector Control System

    CERN Document Server

    Oleiro Seabra, Luis Filipe; The ATLAS collaboration

    2015-01-01

    ALFA (Absolute Luminosity For ATLAS) is one of the sub-detectors of ATLAS/LHC. The ALFA system is composed by two stations installed in the LHC tunnel 240 m away from each side of the ATLAS interaction point. Each station has a vacuum and ventilation system, movement control and all the required electronic for signal processing. The Detector Control System (DCS) provides control and monitoring of several components and ensures the safe operation of the detector contributing to good Data Quality. This paper describes the ALFA DCS system including a detector overview, operation aspects and hardware control through a SCADA system, WinCC OA.

  17. THE ROLE OF INTERFERON ALPHA-2b IN REDUCING OF VIRAL LOAD IN HPV INFECTED WOMEN

    Directory of Open Access Journals (Sweden)

    Кристина Владимировна Марочко

    2017-05-01

    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  18. ALFA beam halo

    CERN Document Server

    Komarek, Tomas

    2014-01-01

    This note serves as a final report about CERN Summer Student Programme 2014 project. The beam halo is an undesired phenomenon for physics analyses on particle accelerators. It surrounds the beam core and constitutes an important part of background for signal measurements on some detectors, eg. in the forward region. In this study, the data from the ALFA detector were used, specifically from the run 191373 ($\\beta^*=90\\unit{m}$) and the run 213268 ($\\beta^*=1\\unit{km}$). Using the ROOT framework, a software for beam halo events selection was created and beam halo properties were examined. In the run 213268, excessive beam halo is suspected to be the reason for multiple beam scrapings that occurred. A kinematic reconstruction of beam halo particles is attempted in order to understand beam halo properties in the interaction point. Some further simulations are employed to find constraints for beam halo particles in order to survive in the accelerator for a longer time/many revolutions. This work represents a st...

  19. GRIN2B encephalopathy

    DEFF Research Database (Denmark)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah

    2017-01-01

    treatment response in the respective patients still remains to be demonstrated. CONCLUSIONS: In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment...

  20. "Alfa" i "Võmpel" bez maski / Andrei Sharov

    Index Scriptorium Estoniae

    Sharov, Andrei

    2004-01-01

    Venemaa FSB keskuse, mille koosseisu kuuluvad ka eriüksused Alfa ja Võmpel, töötajad osalevad terroristide neutraliseerimise ja pantvangide vabastamise erioperatsioonides. Intervjuu keskuse staabi uue juhiga

  1. Estudio de inmunogenicidad para dos vacunas recombinantes contra hepatitis B

    Directory of Open Access Journals (Sweden)

    O. Juliao

    1991-12-01

    Full Text Available Este estudio compara la inmunogenicidad (seroconversión, seroprotección e Hiperrespuesta, producida por dos vacunas recombinantes contra la hepatitis B (Engerix-B de Bélgica y Cubana, en dos esquemas (012 y 016 meses, empleando los métodos de cuantificación para Anti-HBsAg (Abbott y Organón, los cuales fueron también comparados. En el estudio participaron 257 voluntarios,  divididos al azar en 4 grupos (dos vacunas, dos esquemas. Resultados: los dos métodos de Abbon y Organon, no presentan diferencias estadísticas significativas. La vacuna cubana muestra una mayor respuesta inmunogénica para dos dosis de vacuna y para el esquema 012. No hay diferencia entre los esquemas 012 y 016 y en el esquema 016 no se ven diferencias estadísticamente significativas con la vacuna Engerix-B. En esta Última el esquema 016 muestra mejores resultados que el 012.

  2. Producción de proteínas recombinantes de Plasmodium falciparum en Escherichia coli

    OpenAIRE

    Ángela Patricia Guerra; Eliana Patricia Calvo; Moisés Wasserman; Jacqueline Chaparro-Olaya

    2016-01-01

    Introducción. La producción de proteínas recombinantes es fundamental para el estudio funcional de las proteínas de Plasmodium falciparum. Sin embargo, las proteínas recombinantes de P. falciparum están entre las más difíciles de expresar y, cuando lo hacen, usualmente se agregan dentro de cuerpos de inclusión insolubles. Objetivo. Evaluar la producción de cuatro proteínas de P. falciparum usando como sistema de expresión dos cepas de Escherichia coli genéticamente modificadas para favorec...

  3. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection

    DEFF Research Database (Denmark)

    Hézode, Christophe; Hirschfield, Gideon M; Ghesquiere, Wayne

    2015-01-01

    OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infec...

  4. Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment

    Directory of Open Access Journals (Sweden)

    Agostinetto Rita

    2009-05-01

    Full Text Available Abstract Background Gonadotrophins are routinely administered in assisted reproductive technology (ART treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa and recombinant human luteinizing hormone (r-hLH; lutropin alfa can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike. Methods This study investigated whether follitropin alfa (GONAL-f (R, as lyophilized powder for reconstitution or solution from the GONAL-f (R (filled-by-mass [FbM] Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively. Results Follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups. Conclusion Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to

  5. Implementation of Trigger Tiles for ALFA Simulation

    CERN Document Server

    Rehaag, Thomas Joseph

    2017-01-01

    The Absolute Luminosity For ATLAS (ALFA) experiment was designed to accurately measure the luminosity of the intersecting proton beams at the ATLAS interaction point [1]. However, the ALFA experiment has shifted its primary purpose from luminosity measurement to elastic and inelastic proton collisions. This change was the result of difficulty in fitting parameters in the region governed by Coulomb scattering. The operational principle for luminosity measurement with ALFA relied on detecting elastic proton collisions, so the detector is suited to its role in proton collision measurements. The ALFA detector consists of several sensitive components, including the main detector (MD), overlap detectors (ODs) and trigger tiles. A diagram of the ALFA detector is shown in Figure 1. The main detector is composed of layers of 0.5 × 0.5 mm2 cross section scintillating fibres with an active area of 0.48 × 0.48 mm2, which are directed diagonally across the detector with 64 fibres in each layer. The 20 total layers ar...

  6. Producción de proteínas recombinantes en Bacillus megaterium: estado del arte

    OpenAIRE

    Keyla Tortoló-Cabañas; Antonio Bell-García

    2015-01-01

    Se recoge una actualización del estado del arte del uso de Bacillus megaterium como hospedero para la expresión de proteínas recombinantes, las características de este microorganismo, así como las consideraciones generales y algunos aspectos a tener en cuenta.

  7. Interferon alfa with or without ribavirin for chronic hepatitis C

    DEFF Research Database (Denmark)

    Kjaergard, L L; Krogsgaard, K; Gluud, C

    2001-01-01

    To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C.......To assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C....

  8. OPPORTUNITIES OF DORNASE ALFA IN PEDIATRICS

    Directory of Open Access Journals (Sweden)

    O.I. Simonova

    2011-01-01

    Full Text Available Early treatment with Pulmozyme (dornase alfa and its prolonged use in combination with basis therapy results in decrease of exacerbation rate, prolongation of remission of bronchopulmonary process with normal ventilation functions of lungs and gives patients with cystic fibrosis an opportunity to live an active life. The drug is effective as a conservative treatment of chronic sinusitis polyposis; it’s frequent complication of cystic fibrosis. Dornase alfa has 3 clinical effects: strong mucolytic, anti-inflammatory and antibacterial effect. That is the reason for the treatment of other chronic bronchopulmonary diseases with this drug. Efficacy of dornase alpha depends on rough maintenance of the terms of drug use.Key words: children, dornase alfa, cystic fibrosis, chronic bronchopulmonary diseases, chronic rhinosinusitis, nasal polyposis, nebulizer therapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (4: 145–152

  9. Secondary hyperpigmentation during interferon alfa treatment for chronic hepatitis C virus infection.

    Science.gov (United States)

    Tsilika, Katerina; Tran, Albert; Trucchi, Régine; Pop, Sinziana; Anty, Rodolphe; Cardot-Leccia, Nathalie; Lacour, Jean-Philippe; Ortonne, Jean-Paul; Passeron, Thierry

    2013-06-01

    Interferon alfa remains the central treatment for chronic hepatitis C virus (HCV) infection. Cases of cutaneous and mucous hyperpigmentations during interferon alfa treatment have been reported, but they are considered rare adverse effects. To study the clinical presentation and frequency of hyperpigmentation in patients receiving interferon alfa treatment for chronic HCV infection. Prospective, descriptive clinical trial. Monocentric study performed in the Departments of Hepatology and Dermatology of the University Hospital of Nice, Nice, France. Consecutive patients treated with pegylated interferon alfa-2b and ribavirin for chronic HCV infection. Demographic data and medical history were noted. A systematic clinical and dermoscopic examination of skin, nails, and mucous membranes was performed, and skin biopsies were performed if needed. Of 77 patients who were included, 16 (21%) presented with hyperpigmentation. Hyperpigmentation of the oral mucous membrane, acquired longitudinal melononychia, and hyperpigmentation of the face were each observed in 7 patients (9%). All patients with hyperpigmentation of the skin had skin type III or IV and worked outside without sun protection. The intensity of pigmentation was reported to decrease progressively when interferon treatment was discontinued. Most patients with hyperpigmentation of the oral mucosa also had melanonychia. However, patients with hyperpigmentation of the skin did not have mucosal or nail involvement, suggesting 2 distinct mechanisms. Secondary hyperpigmentation during interferon alfa treatment occurs as an adverse event in 21% of patients, especially in those with dark skin types who have unprotected sun exposure. Physicians should be aware of the adverse effects of interferon treatment and advise patients in the use of sun protection, especially patients with darker skin types.

  10. Tratamiento con eritropoyetina humana recombinante Human recombinant erythropoietin therapy

    Directory of Open Access Journals (Sweden)

    Hugo Donato

    2006-02-01

    Full Text Available La eritropoyetina recombinante (rHuEPO se ha transformado en la citoquina más utilizada terapéuticamente en el mundo. Luego del éxito obtenido en pacientes con insuficiencia renal terminal, se pudo establecer la utilidad de la terapia con rHuEPO para mejorar otras anemias, incluso en pacientes pediátricos y neonatos. El tratamiento o la prevención de la anemia del prematuro mediante el uso de rHuEPO llevó a una significativa reducción en cantidad de transfusiones y en exposición a dadores. Aún debe establecerse una clara definición sobre cuáles niños prematuros deben recibir tratamiento rutinariamente. Otras indicaciones en período neonatal incluyen anemias hiporregenerativas y hemolíticas. La eficacia de la rHuEPO en niños mayores, con excepción de la insuficiencia renal crónica, no ha sido tan exhaustivamente evaluada como en adultos. Mientras que durante los últimos años se han realizado gran cantidad de estudios en adultos con anemia asociada al cáncer o a infección por HIV, permitiendo establecer conclusiones claras sobre su eficacia, sólo escasa cantidad de estudios con pequeño número de pacientes han sido realizados en niños. Hasta la fecha, los resultados sugieren que la terapia con rHuEPO en niños es tan útil como en adultos, pero la realización de estudios aleatorizados prospectivos incluyendo gran número de pacientes es esencial para alcanzar conclusiones definitivas. Los resultados de estudios dirigidos a evaluar la eficacia de la rHuEpo para mantener una dosis adecuada de ribavirina en pacientes en tratamiento por hepatitis C son alentadores. La utilización potencial de los efectos no hemopoyéticos de la rHuEPO en neonatos es un terreno novedoso y apasionante. El rol de la Epo como citoprotector para sistema nervioso central y mucosa intestinal está bajo investigación exhaustiva.Recombinant human erythropoietin (rHuEpo has become the most widely used cytokine in the world. Following the success of

  11. Functionality and performance of the ALFA_CTPIN module

    CERN Document Server

    Iwanski, Wieslaw; Korcyl, Krzysztof; Oechsle, Jan

    2017-01-01

    The ALFA_CTPIN module has been designed in response to increased internal processing time of the Central Trigger Processor (CTP) of the ATLAS experiment which resulted in reducing time left to the ALFA detector to deliver its own triggers to the CTP within specified latency. Accelerated extraction of ALFA triggers from encoded signals and the possibility to perform local triggers processing by this module allowed ALFA to contribute to global triggering of the ATLAS detector. A huge number of implemented scalers and flexibility in defining triggers processing criteria make also from this module a very attractive tool for in-depth analysis of properties of the LHC beam.

  12. Vectores recombinantes basados en el virus Vaccinia modificado de Ankara (MVA) como vacunas contra la leishmaniasis

    OpenAIRE

    Pérez Jiménez, Eva; Larraga, Vicente; Esteban, Mariano

    2005-01-01

    Vectores recombinantes basados en el virus vaccinia modificado de Ankara (MVA) como vacunas contra la leishmaniasis. Los vectores de la invención contienen secuencias codificantes de la proteína LACK, preferentemente insertadas en el locus de hemaglutinina del virus y bajo el control de un promotor que permite su expresión a lo largo del ciclo de infección del virus. Son vectores seguros, estables, que dan lugar a una potente respuesta inmune que confiere protección frente a la leishmaniasis,...

  13. Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone chronic hepatitis B. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Mellerup, M T; Krogsgaard, K; Mathurin, P

    2000-01-01

    Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon....

  14. JSC “ALFA-BANK” marketing policy. problems and perspectives

    OpenAIRE

    Kirillov, A.; Kuznetcova, E.; Martirosian, M.

    2013-01-01

    The article is devoted to the results of JSC “Alfa-Bank” consumers’ segmentation and the following complex marketing research. The article suggests the ways of the bank’s marketing policy improvement.

  15. Treatment of anemia with darbepoetin alfa in systolic heart failure

    DEFF Research Database (Denmark)

    Swedberg, Karl; Young, James B; Anand, Inder S

    2013-01-01

    Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia.......Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia....

  16. Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue

    Directory of Open Access Journals (Sweden)

    Liliana Morales

    2017-01-01

    Resultados. Los anticuerpos producidos fueron útiles en ensayos de Western blot e inmunofluorescencia y se reportó por primera vez un anticuerpo policlonal anti-NS3 que permitió la inmunoprecipitación de la proteína viral y la detecta con Western blot sin necesidad de inducir sobreexpresión de NS3 o de usar extractos de células marcados metabólicamente con radioisótopos. Conclusión. Las proteínas recombinantes expresadas y los anticuerpos producidos constituyen herramientas valiosas para estudiar procesos infecciosos del DENV que involucren a la proteína NS3 y evaluar pruebas dirigidas a interferir las funciones de esta proteína.

  17. Uso de fator VII recombinante ativado para tratamento e profilaxia de grandes sangramentos

    OpenAIRE

    Vince,Flávio Augusto Henriques; Brandão,Maria José Nascimento

    2009-01-01

    INTRODUÇÃO: O fator VII recombinante ativado (rFVIIa) é uma proteína produzida por engenharia genética, cuja estrutura é muito semelhante à do fator VII intrínseco ativado (FVII). Sua ação se baseia no conhecimento do mecanismo de coagulação in vivo agindo na ativação direta do fator X resultando em formação independente de trombina no local da lesão e contribuindo dessa forma para formação de coágulo estável de fibrina sem a ação dos fatores VIII e IX. MÉTODOS: Foi realizada ampla revisão da...

  18. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

    Directory of Open Access Journals (Sweden)

    Ma Weimin

    2011-01-01

    Full Text Available Abstract In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α, the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR and in 28 non-responder(NR to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

  19. HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b

    Directory of Open Access Journals (Sweden)

    Hui Ma

    2016-01-01

    Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%. The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.

  20. Managing anemia with epoetin alfa in patients with rectal cancer

    International Nuclear Information System (INIS)

    Velenik, V.; Oblak, I.; Kodre, V.

    2005-01-01

    Background. Anemia is one of the most challenging problems in clinical oncology due to its high prevalence among the patients with malignant diseases. The purposes of our study were: (1) to assess the potential of epoetin alfa therapy to prevent the decline in Hb concentrations that typically accompanies chemotherapy/ radiotherapy (ChT/RT) of the patients with rectal cancer; (2) to test the hypothesis that the use of epoetin alfa significantly reduces the transfusion requirements in the patients with rectal cancer treated with ChT/RT after surgery, and (3) to evaluate the safety profile of the administration of epoetin alfa in the clinical setting. Methods. Sixty patients who underwent surgery for rectal cancer were prospectively enrolled. Group A consisted of 39 patients with Hb concentrations ≤13 g/dl at the start of ChT/RT following surgery, and group B of 17 patients with Hb concentrations ≥13 g/dl at the start of ChT/RT following surgery, but whose Hb concentrations fell below 13 g/dl during the ChT/RT protocol. The starting dose of epoetin alfa in both groups was 10,000 IU subcutaneously (sc) three times a week (tiw). The following major parameters were evaluated: (1) change in Hb concentrations relative to the baseline as measured at 4-week intervals, (2) allogenic blood transfusion requirements in relation to Hb concentrations, and (3) incidence and severity of adverse events and their potential relationship to epoetin alfa administration. Results. The study protocol was completed in 56/60 patients. In group A, a statistically significant increase in Hb concentration (p<0.001) was observed after the first 4 weeks of epoetin alfa treatment compared to the baseline values, with the mean increase of Hb concentration of 1.97 g/dl ± 0.91 g/dl and Hb concentrations remained significantly increased through the whole study (p=0.0017). In group B, a continuous decrease in Hb concentrations was observed during the first weeks of therapy, reaching the level of

  1. Extended dosing of darbepoetin alfa in peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Bridges Ian

    2011-03-01

    Full Text Available Abstract Background Anemia is common among peritoneal dialysis (PD patients, and most patients require erythropoiesis-stimulating agents (ESA to maintain their hemoglobin concentrations within current guideline recommendations. Darbepoetin alfa is an ESA with a 3-fold longer half-life and greater in vivo biological activity than recombinant human erythropoietin, allowing less frequent dosing that may simplify anemia management in these patients, providing benefits to patients, care givers and health care providers. Clinical studies have confirmed the efficacy and safety of darbepoetin alfa administered at extended dosing intervals. However, there are limited data on the management of anemia with ESAs in PD patients in routine clinical practice. The aim of this multicenter observational study in European and Australian dialysis patients was to evaluate darbepoetin alfa administered once every 2 weeks (Q2W in routine clinical practice for 12 months. Methods PD patients ≥18 years old and converting to treatment with darbepoetin alfa Q2W were eligible for enrollment regardless of previous or current ESA use. Patients enrolled in the study were treated according to local usual clinical practice. Data were collected up to 6 months prior to and 12 months after conversion to darbepoetin alfa Q2W. The primary endpoint was hemoglobin concentration 12 months after conversion to darbepoetin alfa Q2W. Results Of the 741 eligible PD patients (mean age, 61 years; male, 57%, 640 (86% completed the study. Mean hemoglobin concentration (g/dL was 11.69 (95% CI, 11.53-11.86 6 months before the conversion, 12.25 (95% CI, 12.13-12.38 at conversion, and 11.88 (95% CI, 11.74-12.02 12 months after conversion to darbepoetin alfa Q2W. The weekly equivalent ESA dose (μg/wk was a geometric mean of 25.24 (95% CI, 23.46-27.15 6 months before conversion, 20.90 (95% CI, 19.13-22.83 immediately before conversion, 18.89 (95% CI, 18.13-19.68 at conversion and 19.04 (95% CI, 17

  2. Epoetin alfa ja namaluva nefrotoksicnosta inducirana so cisplatin kaj staorci

    Directory of Open Access Journals (Sweden)

    Dimce Zafirov

    2006-06-01

    Full Text Available Klinickata efikasnost na cisplatin kako antitumorski lek e nesomnena, no dozno-limitiracki faktor za negova upotreba pretstavuva izrazitata nefrotoksicnost. Najnovite istrazuvawa pokazuvaat deka epoetin alfa moze da ima znacajna uloga ne samo vo terapiski celi za korekcija na razni vidovi na anemii, tuku istiot moze da bide efikasen i kako nevroprotektiv, hepatoprotektiv, kardioprotektiv i osobeno znacajno kako nefroprotektiv kaj nefrotoksicnost inducirana od preparati na baza na platina. Glavna cel na ovaa studija bese da se utvrdi efektot na epoetin alfa vo prevencijata na nefrotoksicnost eksperimentalno inducirana so dolgotrajna administracija na cisplatin vo doza od 2 mg/kg/t.t./nedela vo tek na 8 nedeli, kaj Wistar staorci. Dobienite rezultati od ovaa studija pokazuvaat deka epoetin alfa signifikantno gi ublazuva funkcionalnite bubrezni poremetuvawa inducirani so dolgotrajna administracija na cisplatin, ja podobruva opstata sostojba i go namaluva mortalitetot kaj ispituvanite zivotni.

  3. Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients

    DEFF Research Database (Denmark)

    Mann, J; Kessler, M; Villa, Giulio Palludan

    2007-01-01

    AIM: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa...

  4. Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients

    DEFF Research Database (Denmark)

    Mann, J; Kessler, M; Villa, Giulio Palludan

    2007-01-01

    in a large cohort of dialysis patients. METHODS: Data were combined from eight similarly designed 24-week phase 3b European studies, in which patients receiving EPO alfa or beta once-weekly were converted to Q2W darbepoetin alfa. Darbepoetin alfa dosage was titrated to maintain hemoglobin (Hb) between 10...

  5. Resolution and t-spectrum for the ALFA detector

    CERN Document Server

    Guergouri, Hichem

    2016-01-01

    My report as Summer Student is in two parts. In the first part I report about my attendance to the run of the ALFA detector to test different collimation schemas and find a new way to get rid of the background. The second part is about the measurement of the resolution of the ALFA detector and comparing the real data with the Monte-Carlo (MC) simulations. First of all I tried to be more familiar with ROOT, worked on understanding the code used to access to the data in the trees inside the Ntuples, plotting histograms,… This was done using old Ntuples which contain MC data.

  6. New Synthesis of .alfa.,.omega.-Diiodoalkynes and Capped Iodobutadiynes

    Czech Academy of Sciences Publication Activity Database

    Hlavatý, Jaromír; Kavan, Ladislav; Štícha, M.

    - (2002), s. 705-706 ISSN 1472-7781 R&D Projects: GA ČR GA203/00/0634 Institutional research plan: CEZ:AV0Z4040901 Keywords : .alfa.,. omega .-diiodoalkynes * capped iodobutadiynes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.181, year: 2002

  7. Carbonaceous Polymers and Nanotubes from .alfa., .omega.-Dialkali Hexatriynides

    Czech Academy of Sciences Publication Activity Database

    Hlavatý, Jaromír; Kavan, Ladislav; Okabe, K.; Oya, A.

    2002-01-01

    Roč. 40, č. 7 (2002), s. 1147-1150 ISSN 0008-6223 R&D Projects: GA ČR GA203/00/0634 Institutional research plan: CEZ:AV0Z4040901 Keywords : carbon nanotubes * chemically modified carbon * .alfa.,. omega .-dialkali hexatriynides Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.048, year: 2002

  8. Physics prospects with the ALFA and AFP detectors

    CERN Document Server

    Hamal, Petr; The ATLAS collaboration

    2013-01-01

    The ATLAS ALFA and AFP detectors - the experimental challenge of measuring forward protons at the LHC. We will describe the experimental challenge presented by the measurement of the forward protons at the LHC. The ATLAS ALFA and AFP projects involve the deployment of detectors capable of detecting protons that emerge intact from the interaction with very small scattering angles. In the case of the ALFA detector, located at ±240m from the ATLAS interaction point, this measurement has to be performed using special high \\beta* beam optics. The detector chosen for the task is a nearly edgeless scintillating fibre tracker capable of making measurements at very low t – below 10-3 GeV2 – in the Nuclear Coulomb interference region. In order to reach these very small t-values we need to deploy the detector very near to the beam line utilizing Roman Pots. The main purpose of the ALFA detector is to measure the total p-p cross-section, a fundamental quantity in hadronic physics of importance to particle and to cos...

  9. The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

    Science.gov (United States)

    Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

    2017-08-01

    Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

  10. Resposta imune a antígenos recombinantes de Leishmania e imuno-modulação na leishmaniose tegumentar

    OpenAIRE

    Passos, Sara Timóteo

    2006-01-01

    A leishmaniose de modo geral vem sendo amplamente estudada e diversas questões relacionadas aos aspectos imunológicos têm sido abordadas como caracterização e modulação da resposta imune. A linha de pesquisa abordada nesta tese visa caracterizar a resposta imune a antígenos recombinantes de Leishmania em pacientes com leishmaniose visceral e leishmaniose tegumentar e, avaliar aspectos relacionados à modulação da resposta imune na leishmaniose tegumentar. No primeiro artig...

  11. Caracterização estrutural da forma recombinante da proteína Pb27 de Paracoccidioides brasiliensis

    OpenAIRE

    Juliana Barbosa Coitinho

    2009-01-01

    COITINHO, J. B. Caracterização estrutural da forma recombinante da proteína Pb27 de Paracoccidioides brasiliensis. 2009. Dissertação (Mestrado) - Departamento de Bioquímica e Imunologia. Universidade Federal de Minas Gerais. Belo Horizonte, 2009. Paracoccidioidomicose (PCM) é uma das mais importantes micoses sistêmicas do Brasil. O agente etiológico da doença é o fungo termo dimórfico Paracoccidioides brasiliensis. A infecção causa lesões nos pulmões e pode disseminar para outros órgãos e tec...

  12. Estreptoquinasa recombinante en pacientes con infarto agudo del miocardio. Cardiocentro de Camaguey, 2008

    Directory of Open Access Journals (Sweden)

    Héctor Mariño Cano

    2015-12-01

    Full Text Available Se realizó un estudio descriptivo longitudinal, con el objetivo de valorar la eficacia de la utilización de la Estreptoquinasa Recombinante en pacientes con Infarto Agudo de Miocardio (IMA en el Cardiocentro del Hospital Provincial Docente “Manuel Ascunce Doménech” en la provincia de Camagüey, en el período comprendido de enero a diciembre del 2008. El universo estuvo constituido por 200 pacientes, a los que se les diagnosticó Infarto Agudo de Miocardio y la muestra quedó formada por 80 pacientes que recibieron tratamiento trombolítico, las historias clínicas de los pacientes fueron la principal fuente de obtención de la información, utilizando  las  siguientes  variables: resultados criterio de perfusión, evolución clínica, criterio de reacciones adversas y la influencia que ejerce el tiempo puerta-aguja,  así como los cuidados de enfermería. Al terminar se observó que  el criterio de repercusión de mayor incidencia fue el eléctrico; la mayor cantidad de pacientes tuvieron buena evolución clínica; la hipotensión fue la reacción adversa más frecuente; el tiempo de puerta-aguja  que más incidió  fue el menor, de 3h; a todos los pacientes diagnosticados con infarto, que recibieron tratamiento trombolítico, se les  brindaron  cuidados de enfermería.

  13. Procedimiento para la obtención de levaduras vínicas superproductoras de manoproteínas mediante tecnologías no recombinantes

    OpenAIRE

    González García, Ramón; González Ramos, Daniel; Tabera, Laura; Barcenilla Moraleda, José María

    2008-01-01

    Procedimiento para la obtención de levaduras vínicas superproductoras de manoproteínas mediante tecnologías no recombinantes. Procedimiento para obtener cepas de levaduras superproductoras de manoproteínas mediante la selección de mutantes resistentes a la toxina K9, cepas obtenibles por dicho procedimiento y usos.

  14. Reversing factor Xa inhibitors – clinical utility of andexanet alfa

    Directory of Open Access Journals (Sweden)

    Kaatz S

    2017-09-01

    Full Text Available Scott Kaatz,1 Hardik Bhansali,1 Joseph Gibbs,2 Robert Lavender,3 Charles E Mahan,4 David G Paje5 1Division of Hospital Medicine, 2Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, 3Division of General Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 4University of New Mexico, Presbyterian Healthcare Services, Albuquerque, NM, 5Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA Abstract: Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs. Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications. Andexanet alfa is a FXa decoy designed to reverse all anticoagulants that act through this part of the coagulation cascade including anti-FXa DOACs, such as apixaban, edoxaban and rivaroxaban, and indirect FXa inhibitors such as low-molecular-weight heparins. This narrative reviews the development of andexanet alfa and explores its basic science, pharmacokinetics/pharmacodynamics, animal models, and human studies. Keywords: factor Xa, DOAC, andexanet alfa, reversal, rivaroxaban, apixaban

  15. Physics prospects with the ALFA and AFP detectors

    CERN Document Server

    Hamal, P; The ATLAS collaboration

    2013-01-01

    We will describe the experimental challenge presented by the measurement of the forward protons at the LHC. The ATLAS ALFA and AFP projects involve the deployment of detectors capable of detecting protons that emerge intact from the interaction with very small scattering angles. In the case of the ALFA detector, located at $\\pm${240}~m from the ATLAS interaction point, this measurement has to be performed using special high $\\beta^*$ beam optics. The detector chosen for the task is a nearly edgeless scintillating fibre tracker capable of making measurements at very low $t$ - below $10^{-3} \\text{GeV}^2$ - in the Nuclear Coulomb interference region. In order to reach these very small $t$ values we need to deploy the detector very near to the beam line utilizing Roman Pots. The main purpose of the ALFA detector is to measure the total p-p cross-section, a fundamental quantity in hadronic physics of importance to particle and to cosmic ray physicists and to provide absolute measurement of luminosity which includ...

  16. PODAAC-SEAAM-L2B00

    Data.gov (United States)

    National Aeronautics and Space Administration — The SeaWinds on ADEOS-II Level 2B product provides ocean wind vectors in 25 km wind vector cell (WVC) swaths with AMSR corrections in single-orbit files. The AMSR...

  17. A Model of B2B Exchanges

    OpenAIRE

    Gabor Fath; Miklos Sarvary

    2001-01-01

    B2B exchanges are revolutionizing the way businesses will buy and sell a variety of intermediary products and services. It is estimated that most of the roughly $7 trillion worth of business transactions are likely to go through these new institutions within the next decade. This paper tries to understand the economics governing the transactions within B2B exchanges and analyze their likely evolution over time. In doing so, we start by providing the rigorous definitions to a number of critica...

  18. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease

    DEFF Research Database (Denmark)

    Pfeffer, Marc A; Burdmann, Emmanuel A; Chen, Chao-Yin

    2009-01-01

    BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately...... tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin...... assigned to darbepoetin alfa and 496 patients assigned to placebo (Pchronic kidney disease...

  19. Establecimiento de un material de referencia de trabajo para interleucina-2 recombinante

    Directory of Open Access Journals (Sweden)

    Maribel Vega

    2005-08-01

    Full Text Available Resumen La interleucina-2 es una glicoproteína humana de 133 aminoácidos que resulta vital para obtener una respuesta inmunológica efectiva. En el Centro de Ingeniería Genética y Biotecnología ha podido obtenerse por vía recombinante a partir de una cepa de Escherichia coli. Para el control de la calidad de cada lote producido se hizo necesaria la elaboración de un material de referencia de trabajo. En esta publicación se describen los pasos seguidos en la obtención del lote candidato y la preparación del material de referencia como tal. Se demostró que el patrón de trabajo preparado es homogéneo para el uso en las técnicas analíticas de control de calidad de la interleucina-2 y se predijo una pérdida de actividad inferior al 5 % anual mediante un estudio de estabilidad acelerada. Se obtuvieron valores adecuados para la pureza del material de referencia, evaluada por electroforesis y para la actividad biológica, que se estableció con trazabilidad al material de referencia internacional para este producto.Establishment of a working reference material for recombinant interleukin-2 Interleukin-2 is a human glycoprotein with 133 aminoacids that is crucial for attaining an effective immunological reaction. In the Center of Genetic Engineering and Biotechnology this protein has been obtained as a recombinant product from Eschericia coli bacteria. For the quality control of every batch produced, it was necessary to establish a working reference material. In this paper we describe the steps taken to obtain a candidate batch and the preparation of the working material as such. It was proved that the working pattern obtained.is homogenous for its use in the analytical techniques of quality control of interleukin-2. A loss of activity lower than an annual 5 % was predicted by an accelerated stability study. Adequate values were attained for the purity of the reference material, evaluated by electrophoresis, and for the biological

  20. A somatotropina recombinante bovina (bST) e a dinâmica folicular em bovinos leiteiros /

    OpenAIRE

    Aleixo, Marcos André

    2004-01-01

    O trabalho teve por objetivo determinar a influência da somatotropina recombinante bovina (bST) sobre a reprodução de fêmeas bovinas da raça Holandesa Preta e Branca tratadas, avaliando-se um ciclo estral completo. Foi verificado a dinâmica folicular, observando-se o diâmetro dos ovários, número de ondas foliculares durante o ciclo estral, duração de cada onda folicular, número e diâmetro dos folículos recrutados. Foram utilizadas doze fêmeas sendo seis do grupo controle e seis do grupo trata...

  1. Oraal semi-chronisch toxiciteitsonderzoek van alfa-HCH bij de rat

    NARCIS (Netherlands)

    Kuiper HA; den Tonkelaar EM; van Leeuwen FXR; Franken MAM; Dormans JAMA

    1986-01-01

    Zowel voor lindaan (gamma-HCH) als zijn isomeren alfa- en beta-HCH die in levensmiddelen kunnen voorkomen is nu de semi-chronische toxiciteit onderzocht. Uit het onderzoek met alfa-HCH blijkt dat hierbij de lever het belangrijkste doelwitorgaan is, met name de toename van het levergewicht, inductie

  2. Pyoderma gangrenosum in a patient with cryoglobulinemia and hepatitis C successfully treated with interferon alfa.

    Science.gov (United States)

    Smith, J B; Shenefelt, P D; Soto, O; Valeriano, J

    1996-05-01

    We describe a patient with long-standing pyoderma gangrenosum unresponsive to therapy. The patient had concomitant cryoglobulinemia and hepatitis C. When the hepatitis C was treated with interferon alfa-2a his pyoderma gangrenosum resolved. Whether this was from the interferon alfa or spontaneous resolution is not known.

  3. Alternative method for quantification of alfa-amylase activity

    Directory of Open Access Journals (Sweden)

    DF. Farias

    Full Text Available A modification of the sensitive agar diffusion method was developed for macro-scale determination of alfa-amylase. The proposed modifications lower costs with the utilisation of starch as substrate and agar as supporting medium. Thus, a standard curve was built using alfa-amylase solution from Aspergillus oryzae, with concentrations ranging from 2.4 to 7,500 U.mL-1. Clear radial diffusion zones were measured after 4 hours of incubation at 20 °C. A linear relationship between the logarithm of enzyme activities and the area of clear zones was obtained. The method was validated by testing α-amylase from barley at the concentrations of 2.4; 60; 300 and 1,500 U.mL-1. The proposed method turned out to be simpler, faster, less expensive and able to determine on a macro-scale α-amylase over a wide range (2.4 to 7,500 U.mL-1 in scientific investigation as well as in teaching laboratory activities.

  4. Vectores recombinantes basados en el virus modificado de Ankara (MVA) com vacunas preventivas y terapeúticas contra la hepatitis C

    OpenAIRE

    Esteban, Mariano; Gómez, Carmen E.; Perdiguero, Beatriz

    2014-01-01

    [ES] Los virus recombinantes de la invención contienen secuencias que se encuentran insertadas en el mismo sitio de inserción del MVA y que permiten la expresión simultáneamente de varios antígenos del VHC, concretamente las proteínas maduras estructurales (Core, E1, E2 y p7) y no estructurales (NS2, NS3, NS4A, NS4B, NS5A más los 201 aminoácidos de la región N-terminal de NS5B). Con ello se consiguen virus recombinantes estables, que permiten el desencadenamiento de una respuesta inmune contr...

  5. Vectores recombinantes basados en el virus modificado de ankara (MVA) como vacunas preventivas y terapéuticas contra el SIDA

    OpenAIRE

    Heeney, Jonathan L.; Mooij, Petra; Nájera García, José Luis; Jiménez, Victoria; Esteban, Mariano; Gómez, Carmen E.

    2005-01-01

    Vectores Recombinantes basados en el Virus Modificado de Ankara (MVA) como Vacunas Preventivas y Terapéuticas contra el SIDA. Losvirus recombinantes de la invención contienen secuencias que se encuentran insertadas en el mismo sitio de inserción del MVA y permiten la expresión simultánea de varios antígenos, una proteína Env del VIH-I consistente en una proteína gpl20 carente de secuencias correspondientes a la proteína gp41, y una proteína quiméricade fusión de Gag, Pol y Nef. Son virus esta...

  6. WTS-2 b: Too close for comfort?

    Directory of Open Access Journals (Sweden)

    Kovács G.

    2013-04-01

    Full Text Available We report the discovery of WTS-2 b, a typical hot Jupiter in an unusually close 1.02-day orbit to a K-dwarf star. This is the second planet to be discovered in the infrared light curves of the WFCAM Transit Survey (WTS and is only one-and-a-half times the separation from its host star at which is would be destroyed by Roche lobe overflow. The predicted remaining lifetime of the planet is just 38 Myrs, assuming a tidal dissipation quality factor of Q'* = 106. The magnitude of Q'* is largely unconstrained by observations, thus WTS-2 b provides a useful calibration point for theories describing how frictional processes within a host star affect the tidal orbital evolution of its companion giant planets. It is expected that stars with large convective envelopes are more efficient at dissipating the orbital energy of the planet, and WTS-2 b provides an observational constraint in the sparsely populated K-dwarf regime. In addition, despite its relatively faint magnitude, the favourable size ratio of the WTS-2 star-planet system and the predicted hot equilibrium temperature of the planet will make it possible to characterise the planet's atmosphere via secondary eclipse measurements using existing ground-based instrumentation.

  7. F-22 Increment 3.2B Modernization (F-22 Inc 3.2B Mod)

    Science.gov (United States)

    2015-12-01

    predecessor F - 22 software programs. Notes Delivery Order (DO) 0004 was issued under the overarching F - 22 Raptor , Enhancement, Development, and...Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-474 F - 22 Increment 3.2B Modernization ( F - 22 Inc 3.2B Mod) As of FY 2017 President’s Budget...Defense Acquisition Management Information Retrieval (DAMIR) March 23, 2016 16:11:54 UNCLASSIFIED F - 22 Inc 3.2B Mod December 2015 SAR March 23, 2016

  8. A challenging alfa-fetoprotein in a cirrhotic patient.

    Science.gov (United States)

    Gallo, P; Gentilucci, U Vespasiani; Taffon, C; Galati, G; De Vincentis, A; Muda, A Onetti; Picardi, A

    2014-03-01

    A 57-year-old Italian man was admitted to our Hospital for investigation of a progressively raising alfa-fetoprotein (AFP) on the background of chronic hepatitis B infection. At abdominal imaging,liver morphology was suspected for advanced fibrosis but without any focal lesion. Clinical and ultrasonographic examinations were negative for testicular masses. When the patient was screened for gastroesophageal varices, upper intestinal endoscopy did not show signs of portal hypertension, while it revealed a gastric lesion which was histologically characterized as hepatoid adenocarcinoma of the stomach (HAS), with strong immunohistochemical positivity for AFP. The patient underwent subtotal gastrectomy and AFP fell within the normal range. This is a very rare case in which AFP-producing gastric cancer (AFPPGC), in the form of HAS, presented in a patient with chronic liver disease. Physicians should be particularly aware of AFPPGC when following patients with liver disorders due to the common use of AFP in this setting.

  9. Clonamiento, expresión y seroreactividad del antígeno recombinante flagelina de Bartonella bacilliformis

    Directory of Open Access Journals (Sweden)

    Karen Gallegos V

    2005-03-01

    Full Text Available Objetivos. Clonar el gen de la flagelina A (flaA de Bartonella bacilliformis, expresar y evaluar preliminarmente la seroreactividad de la proteína recombinante a sueros de pacientes con Bartonelosis por B. bacilliformis. Materiales y Métodos. Se diseñó una pareja de oligonucleótidos iniciadores -BbFlaA1 y BbFlaA2- para la amplificación del gen completo de la flagelina flaA de B. bacilliformis. El producto de amplificación obtenido se clonó en pGEM y luego se subclonó en el vector de expresión pGEX4T-1. Se indujo la expresión de la proteína de fusión rBbFlaA-GST con isopropil tio-β -D-galactosido (IPTG. La proteνna de fusiσn producida fue digerida con trombina para liberarla de GST. Finalmente, una prueba de ELISA fue estandarizada para detectar los anticuerpos IgG contra la proteína de fusión rBbFlaA-GST y rBbflaA libre de GST. Se evaluaron sueros de pacientes con diagnóstico de Bartonelosis por B. Bacilliformis (n= 30, sueros de individuos sanos (n= 20 y sueros de pacientes con otras enfermedades de posible reactividad cruzada; entre ellas, Brucelosis (n= 3, leptospirosis (n= 3 y salmonelosis (n=7. Resultados. Se determinó que para la expresión óptima en E. coli BL21 de la proteína de fusión rBbFlaA se requiere que el cultivo crezca en caldo LB/ampicilina a 30 °C suplementado con 2% de glucosa a partir de un preinóculo de 100 µL (crecido por toda la noche, hasta que alcance una densidad óptica de 1 OD600 y se induzca por dos horas con 2,5 mM de IPTG. Finalmente, el 57,6 % (17 de 30 sueros de pacientes con diagnóstico confirmado de bartonelosis reaccionaron con la proteína recombinante BbFlaA en el formato de ELISA. Conclusiones. Se logró expresar exitosamente en E. coli la proteína recombinante BbFlaA de B. bacilliformis, determinándose un protocolo de expresión y de purificación de rBbFlaA para la producción de esta proteína. Así también, el antígeno rBbFlaA es reconocido por anticuerpos de sueros de

  10. What Happened with Spectrometer Magnet 2B

    Energy Technology Data Exchange (ETDEWEB)

    Green, Michael A

    2010-05-27

    The spectrometer solenoid is supposed to be the first magnets installed in MICE [1]-[4]. This report described what happened during the test of the MICE spectrometer solenoid 2B. First, the report describes the temperatures in the magnet, the cooler top plate and the shield during the run where the magnet quenched at 258 A. During this quench, a lead between the bottom of the HTS leads and the diode bank burned out causing the magnet to quench. Second, three methods for measuring the net heat flow into the cold mass are described. Third, there is a discussion of possible resistive heating in the HTS leads between liquid helium temperature and the copper plate, which is at about 50 K. Fourth, there is a discussion of the measured first stage heat loads in the magnet, when there is no current in the magnet. The first stage heat load calculations are based on knowing the first stage temperatures of the three two-stage pulse tube coolers and the single stage GM cooler. Fifth, the estimated heat load to the first stage when the magnet has current in it is discussed. Sixth, there is a comparison of the stage 1 heat loads in magnet 1A [5], magnet 2A [6], and magnet 2B [7]. Finally there is a discussion of recommended changes for improving the spectrometer solenoids so that the coolers can keep them cold.

  11. Alfa tahab TeliaSonerat Türgis üle pakkuda / Tõnis Arnover

    Index Scriptorium Estoniae

    Arnover, Tõnis, 1952-

    2005-01-01

    TeliaSoneraga, kellele kuulub 37 protsenti Türgi operaatorfirma Turkcell aktsiatest, konkureerib täiendava 27 protsendise aktsiapaki ostmises Venemaa operaatorfirmaga Alfa Telecom. Lisa: Kaasosanike huvid põrkuvad. Diagramm: Konkurendid Vene MegaFonis

  12. Towards a Total Cross Section Measurement with the ALFA Detector at ATLAS

    CERN Document Server

    Trzebiński, Maciej

    2013-01-01

    The main goals of the Absolute Luminosity For ATLAS (ALFA) detector is to provide an absolute luminosity and total cross section measurement. The measurement method used, the detector alignment and the quality of the collected data are discussed.

  13. Simulation of the ATLAS ALFA detector in comparison with testbeam data

    CERN Document Server

    Pfeiffer, Felix-Fabian; Stenzel, H

    2010-01-01

    ALFA (Absolute Luminosity for ATLAS) is a scintillating fiber detector for the determination of the absolute luminosity. ALFA con- sists of eight Roman Pots, four on each side of ATLAS at a distance of 240 m. Each detector is made of scintillating fibers with quadratic cross section, glued in UV geometry on ten double sided layers. The detectors are mounted in moveable Roman Pots and can approach the LHC beam up to 1.5 mm, to determine the luminosity from the differential t spectrum of elastically scattered protons using the optical theorem. This is done in special LHC calibration runs with large β ∗ , special focusing and low instant luminosity. The results of ALFA are needed for the calibration of ATLAS luminosity monitors like LUCID. This diploma thesis deals with the simulation of ALFA and the most recent testbeam campaign. A special focus is put on the comparison of results from simulation and testbeam.

  14. ONLINE ACQUISITIONS IN B2B MODEL

    Directory of Open Access Journals (Sweden)

    Constantin SASU

    2016-12-01

    Full Text Available Within the present paper, we propose to review some of the main aspects documented by the academic research so far with regard to the online purchasing behaviour in the B2B online environment (more specifically, in the case of the small and medium-sized companies. Preliminary conclusions reveal that, at least in the case studies, the dominant feature is that the geographic delimitation creates a potential obstacle when it comes to applying a general principle governing the small and medium-sized enterprises. Despite this, we consider that some theoretical elements can be acknowledged, elements from which future research can start to develop theories and hypothesis aimed at better explaining the phenomenon. Furthermore, the fact that the studies are rarely involving the same sector, makes it impossible to generalise the process.

  15. Producción de la proteína recombinante JAK2 de ratón

    Directory of Open Access Journals (Sweden)

    Ruth E. Garzón

    2000-03-01

    Full Text Available El presente trabajo describe la producción de la proteina recombinante JAK2, empleando un sistema de vectores de expresión baculovirales. La infección de células Sf9, derivadas del tejido de ovario de Spodoptera frugiperda, permitió establecer las condiciones óptimas de dilución del virus en 10 pllml de medio y de tiempo de recolección en 72 horas postinfección. Se recolectaron y ultrafiltraron extractos correspondientes a la infección de 5 x 10' células, aproximadamente, y se sometieron a cromatografia de intercambio iónico (DEAE-Sephacel, lográndose purificar parcialmente la proteina JAK2 por medio de un gradiente continuo de fuerza iónica (NaCI 10-500 mM. La presencia de JAK2 se verificó por Western blot, empleando un anticuerpo policlonal producido en conejo contra los residuos 758-776 de JAK2 de ratón. Los resultados indicaron que la proteína obtenida por este sistema de expresión se sintetiza en forma fosforiladalactivada.

  16. Expresión y sororreactividad de la lipoproteína recombinante de 43-kda de Bartonella bacilliformis

    Directory of Open Access Journals (Sweden)

    Carlos Padilla R

    2006-07-01

    Full Text Available Objetivo: La lipoproteína de 43-kDa de Bartonella bacilliformis fue obtenida en su forma recombinante (rBbLppB y purificada para evaluar su serorreactividad mediante ELISA. Materiales y métodos: Los niveles de anticuerpos IgG e IgM humanos en los sueros de pacientes con Bartonelosis confirmada y sueros de otras enfermedades (salmonelosis, Brucelosis y leptospirosis frente a rBbLppB fueron evaluados por ELISA, se utilizó sueros de personas sanas como controles. Resultados: La sensibilidad y la especificidad del ELISA IgG fueron 70,4% y 90% respectivamente. Asimismo, la sensibilidad y especificidad de ELISA IgM fueron 85,2% y 90% respectivamente. Conclusiones: Estos resultados demuestran que el ELISA usando rBbLppB tiene una buena sensibilidad y especificidad y puede ser considerada como un buen antígeno para el diagnóstico de Bartonelosis causada por B. bacilliformis.

  17. Obtención y evaluación preliminar de un virus canarypox recombinante como candidato a vacuna antirrábica Development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate

    OpenAIRE

    Flavia Zanetti; Liliana Rudak; Matías Micucci; Daniela Conte Grand; Andrea Luque; Susana Russo; Oscar Taboga; Oscar Pérez; Gabriela Calamante

    2012-01-01

    En la Argentina, la rabia está circunscripta a algunas provincias del norte. La disponibilidad de nuevas vacunas que eliminen la manipulación del virus rábico y que permitan el control de la enfermedad es de importancia estratégica nacional y regional. Las vacunas basadas en poxvirus recombinantes se han utilizado con éxito como vacunas antirrábicas a nivel mundial. SI bien estos sistemas no están disponibles comercialmente, la plataforma de obtención de virus canarypox (CNPV) recombinantes y...

  18. Proteínas recombinantes útiles para el diagnóstico, prevención y estudios patogénicos de la leptospirosis : Estudio de mecanismos patogénicos involucrados

    OpenAIRE

    Prêtre, Gabriela

    2011-01-01

    Objetivo general El propósito general de este trabajo es: 1. Generar herramientas moleculares que sean útiles contra la leptospirosis, ya sea para su diagnóstico, prevención o un mejor conocimiento de su patogénesis. 2. Estudiar mecanismos patogénicos involucrados en la leptospirosis. Objetivos específicos 1. Clonado, expresión y purificación de proteínas recombinantes. 2. Producción de antisuero contra las proteínas recombinantes....

  19. The development and validation of a sensitive, dual-flow cell, SPR-based biosensor immunoassay for the detection, semi-quantitation, and characterization of antibodies to darbepoetin alfa and epoetin alfa in human serum.

    Science.gov (United States)

    Mytych, Daniel T; La, Stephon; Barger, Troy; Ferbas, John; Swanson, Steven J

    2009-02-20

    A surface plasmon resonance (SPR)-based biosensor immunoassay was developed and validated using the Biacore 3000 instrument to detect, semi-quantitate, and characterize serum antibodies against darbepoetin alfa (Aranesp) and epoetin alfa (EPOGEN). In this sensitive, dual-flow cell assay, epoetin alfa and darbepoetin alfa are covalently immobilized onto consecutive flow cells of a carboxymethyl dextran-coated sensor chip. Diluted human serum samples are injected sequentially over both surfaces. The binding of serum antibodies to the immobilized proteins are detected and recorded in real time based on the principles of SPR. Furthermore, antibody binding is confirmed with a secondary anti-human immunoglobulin antibody. Positive samples are further characterized to determine the relative concentration of the antibodies using an affinity-purified, rabbit anti-epoetin alfa antibody as a reference control. The assay can detect 80ng/ml and 100ng/ml of antibody to epoetin alfa and darbepoetin alfa, respectively. The dynamic range of the assay is from 0.078microg/ml to 10microg/ml using a rabbit antibody with demonstrated accuracy and intra- and inter-assay precision. Approximately 80 serum samples can be analyzed on each sensor chip while maintaining a stable baseline and consistent immunological reactivity. The analysis of serum samples from subjects administered with epoetin alfa or darbepoetin alfa provided evidence that the assay can detect varying concentrations of antibodies of different off rates, isotypes, and IgG subclasses.

  20. Forward Detectors in ATLAS: ALFA, ZDC and LUCID

    CERN Document Server

    Fabbri, L; The ATLAS collaboration

    2009-01-01

    In order to determine the experimental cross sections for the observed physics processes, an estimation of the absolute luminosity is needed. In fact a careful study of “well known” processes will be one of the first steps of the LHC experiments as it can provide possible signatures of new physics which consist in deviations with respect to the Standard Model (SM) predictions. The methodologies for luminosity monitoring and total cross section estimation at the LHC will be reviewed in this talk along with the dedicated detectors of the ATLAS experiment. ATLAS will make extensive usage of the detectors in the forward region each one with a different task: LUCID (LUminosity measurement using Cherenkov Integrating Detector) is a system of 40 (2 x 20) Cherenkov tubes, surrounding the beam pipe at about 17 m from the interaction region. It will be able to monitor the collision-by-collision luminosity by detecting and counting the number of charged particles coming from the impact point. ALFA (Absolute Luminosi...

  1. ERITROPOETINA: SÍNTESE E LIBERAÇÃO FISIOLÓGICA E O USO DE SUA FORMA RECOMBINANTE NO ESPORTE

    OpenAIRE

    Anderson Martelli

    2013-01-01

    A busca pelo desempenho ótimo tem sido uma constante no esporte de alto rendimento. Para tanto, muitos atletas acabam utilizando drogas e métodos ilícitos. Dentre as substâncias utilizadas nesta prática temos a eritropoetina (EPO), um hormônio endógeno secretado pelos rins que influencia a maturação dos eritrócitos. Suas formas recombinantes vêm sendo usadas indiscriminadamente por atletas em esportes de resistência, por aumentarem a concentração de hemácias, gerando maior aporte ...

  2. Efeito da flunixina meglumina, somatotropina recombinante bovina e sincronização de receptoras sobre a taxa de prenhez de embriões bovinos produzidos in vitro.

    OpenAIRE

    Humberto Fernandes Veloso Neto

    2013-01-01

    A variabilidade do sucesso das transferências de embriões produzidos in vitro ainda é um dos entraves para sua expansão, onde alguns dos problemas são relacionados à mortalidade embrionária precoce. O objetivo com estes trabalhos foi avaliar a aplicação da flunixina meglumina e da somatotropina recombinante bovina e observar o efeito de algumas variáveis como grau de desenvolvimento do embrião, sincronia do embrião com a receptora e classificação do corpo lúteo da receptora no momento da tran...

  3. Efeitos cardiotóxicos do veneno total e da proteína dermonecrótica recombinante da aranha Loxosceles intermedia

    OpenAIRE

    Camila Dias Lopes

    2009-01-01

    Picadas de aranhas do gênero Loxosceles causam numerosos acidentes em humanos no mundo todo. No Brasil, constitui a terceira maior causa de acidentes envolvendo animais venenosos. Injeção, em modelos animais, do veneno de Loxosceles intermedia ou da toxina dermonecrótica recombinante (LiD1r) produzem alterações cutâneas e sintomas sistêmicos similares àqueles encontrados em humanos. O intuito deste trabalho foi caracterizar os efeitos cardíacos, em camundongos, induzidos pelo veneno de L. int...

  4. PODAAC-QSX12-L2B00

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset has been superseded by Version 3: http://podaac.jpl.nasa.gov/dataset/QSCAT_LEVEL_2B_OWV_COMP_12 . This QuikSCAT Level 2B dataset contains...

  5. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  6. Effects of MAPP Compatibilization and Acetylation Treatment Followed by Hydrothermal Aging on Polypropylene Alfa Fiber Composites

    Directory of Open Access Journals (Sweden)

    Noura Hamour

    2015-01-01

    Full Text Available This work investigates the effect of hydrothermal aging on the properties of polypropylene/alfa fiber composites. Hydrothermal aging was induced in an environmental testing chamber at 65°C and 75% relative humidity (RH over a 1000 h period. At the beginning (t=0 h, the results showed that Young’s moduli of the untreated alfa fibers and the acetylation-treated fibers increased by 21% and 36%, respectively, compared with the virgin polypropylene (PP. Additionally, Young’s moduli decreased by 7% for the compatibilized composites composed of maleic anhydride grafted polypropylene (MAPP. After 1000 h of aging, Young’s moduli decreased by 36% for untreated alfa fibers and 29% for the acetylation-treated alfa fibers and the compatibilized composites. Significant degradation was observed in the untreated alfa fiber samples. The Fourier transformed infrared (FTIR allows us to distinguish the characteristic absorption bands of the main chemical functions present in the composite material before and after aging. The thermal properties showed that the thermal stability and the degree of crystallinity of the composites decreased after hydrothermal aging; this result was corroborated by the dynamical mechanical analysis (DMA results.

  7. 7 CFR 301.80-2b - Exempted articles. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit and...

  8. 7 CFR 301.85-2b - Exempted articles. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  9. TRUST IN B2B E-MARKETPLACES

    Directory of Open Access Journals (Sweden)

    SEBASTIAN KOT

    2011-01-01

    Full Text Available The paper presents background of B2B exchanges and review of their forms and functionalities. The benefits and fails reasons are noticed. European enterprises interest in B2B trade is next aspect of consideration. Finally, the trust barriers of B2B exchanges are presented.

  10. Component Based System Framework for Dynamic B2B Interaction

    NARCIS (Netherlands)

    Hu jinmin, Jinmin; Grefen, P.W.P.J.

    Business-to-Business (B2B) collaboration is becoming a pivotal way to bring today's enterprises to success in the dynamically changing e-business environment. Though many business-to-business protocols are developed to support B2B interaction, none are generally accepted. A B2B system should support

  11. Mechanochemical synthesis and characterization of pure Co2B ...

    Indian Academy of Sciences (India)

    Co2B nanoparticles have been com- monly employed as effective catalysts both for the hydro- genation and hydrogen production processes [7–17]. A study on the hydrogenation activity of Co2B particles in the CTAB/. 1-hexanol/water reversed micellar system was performed by. Ma et al [7]. Co2B was first tried as a catalyst ...

  12. Genetics Home Reference: CHMP2B-related frontotemporal dementia

    Science.gov (United States)

    ... Conditions CHMP2B-related frontotemporal dementia CHMP2B-related frontotemporal dementia Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description CHMP2B -related frontotemporal dementia is a progressive brain disorder that affects personality, ...

  13. Aplicación del análisis de riesgo a la producción de proteínas recombinantes expresadas en Escherichia coli

    Directory of Open Access Journals (Sweden)

    José García

    2012-04-01

    Full Text Available En este trabajo se aplicó el análisis de riesgo, empleando la metodología de análisis de modos y efectos de fallas a los procesos de fermentación que utilizan la bacteria Esherichia coli como hospedero, para obtener proteínas recombinantes con fines terapéuticos, vacunales o diagnósticos. Se realizó el análisis del tipo y probabilidad de ocurrencia de las fallas en el proceso fermentativo, la evaluación del impacto en la calidad del mismo y la probabilidad de detección de dichas fallas. Se evaluó la severidad, probabilidad de ocurrencia y probabilidad de detección y se calculó el número de probabilidades de riesgo. Además, se emplearon técnicas utilizadas para el aseguramiento de la calidad como: tormenta de ideas y diagrama causa-efecto. Se concluye que las causas potenciales que tienen mayor influencia en las fallas de un proceso fermentativo de E. coli recombinante son: la inadecuada manipulación durante la inoculación, la presencia de fagos y el personal no calificado. Se proponen acciones a tomar para minimizar el riesgo.

  14. Methadone N-Demethylation by the Common CYP2B6 Allelic Variant CYP2B6.6

    Science.gov (United States)

    Gadel, Sarah; Crafford, Amanda; Regina, Karen

    2013-01-01

    The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability. Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), catalyzed predominantly by CYP2B6. Retrospective studies suggest that the common allele variant CYP2B6*6 may influence methadone plasma concentrations. The catalytic activity of CYP2B6.6, encoded by CYP2B6*6, is highly substrate-dependent. This investigation compared methadone N-demethylation by CYP2B6.6 with that by wild-type CYP2B6.1. Methadone enantiomer and racemate N-demethylation by recombinant-expressed CYP2B6.6 and CYP2B6.1 was determined. At substrate concentrations (0.25–2 µM) approximating plasma concentrations occurring clinically, rates of methadone enantiomer N-demethylation by CYP2B6.6, incubated individually or as the racemate, were one-third to one-fourth those by CYP2B6.1. For methadone individual enantiomers and metabolism by CYP2B6.6 compared with CYP2B6.1, Vmax was diminished, Ks was greater and the in vitro intrinsic clearance was diminished 5- to 6-fold. The intrinsic clearance for R- and S-EDDP formation from racemic methadone was diminished approximately 6-fold and 3-fold for R- and S-methadone, respectively. Both CYP2B6.6 and CYP2B6.1 showed similar stereoselectivity (S>R-methadone). Human liver microsomes with diminished CYP2B6 content due to a CYP2B6*6 allele had lower rates of methadone N-demethylation. Results show that methadone N-demethylation catalyzed by CYP2B6.6, the CYP2B6 variant encoded by the CYP2B6*6 polymorphism, is catalytically deficient compared with wild-type CYP2B6.1. Diminished methadone N-demethylation by CYP2B6.6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6*6 polymorphism. PMID:23298862

  15. Possibilities of uranium recovering as by product of copper lixiviation solution in Salobo 3-Alfa-Carajas

    International Nuclear Information System (INIS)

    Hohn, H.; Ferraioli, R.N.M.

    1983-05-01

    Geochemical and geophysics regional surveys performed by Nuclebras in 'Carajas, Para' State, show several favourable areas for uranium prospecting, including the 'Salobo 3-Alfa' copper mine. Some studies for increasing the Knowledge of uranium quantity and proportion and for accompanying the pilot plant installation, aiming the uranium extraction during the cycel of ore treatment in 'Salobo 3-Alfa' mine are described [pt

  16. Analysis list: Gtf2b [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gtf2b Blood,Cardiovascular,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/m...m9/target/Gtf2b.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2b.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Gtf2b.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Blo...od.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Cardiovascular.t...sv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Liver.tsv http://dbarchive.biosciencedbc.jp/kyu

  17. Impact of illegal trade on the quality of epoetin alfa in Thailand.

    Science.gov (United States)

    Fotiou, Fotis; Aravind, Suresh; Wang, Ping-Ping; Nerapusee, Osot

    2009-02-01

    Reports from the World Health Organization have suggested that counterfeit medicines pose a serious problem in developing countries. An investigation of anti-erythropoietin antibody-mediated pure red cell aplasia in Thailand found evidence of drug smuggling, which may have serious safety implications. This study assessed the authenticity and quality of epoetin alfa samples in Thailand. Samples of epoetin alfa-prefilled syringes were collected from the pharmacies at 2 major hospitals (62 samples), 8 retail pharmacies (41 samples), and Thai authorities (30 samples confiscated from smugglers at 2 airports, and 6 samples from a condominium used by smugglers). These samples were tested against the European Union Pharmacopeia specifications for aggregate content in epoetins of packaging components (eg, batch number, expiration date, appearance, letter size), and company's confidential features (eg, nature of the ink, type and quality of the paper, other covered features) were also investigated. The main outcome measures were protein aggregate content, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting; and isoform distribution, assessed by isoelectric focusing and Western blotting. Epoetin alfa samples obtained from the company's cold-chain and authorized distribution channels met all quality standards, as did all epoetin alfa samples obtained from the hospital pharmacies. However, evidence showed that some samples were being smuggled or sold illegally through certain unauthorized retail pharmacies. The epoetin alfa samples obtained from both airports and the condominium were stored improperly at room temperature. Aggregate levels exceeded the specification of packaging were found to be authentic. This investigation found evidence that some epoetin alfa samples were smuggled into Thailand without proper cold chain, contained high levels of protein aggregates, and were sold illegally through certain retail pharmacies. The Thai

  18. Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha.

    Science.gov (United States)

    Lotrich, Francis E; Ferrell, Robert E; Rabinovitz, Mordechai; Pollock, Bruce G

    2010-07-01

    Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon alfa-based treatments. Evidence also indicates a central nervous system role for tumor necrosis factor alpha (TNF-alpha), whose expression may be increased by interferon alfa. A polymorphism in the promoter region of TNF-alpha has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-alpha polymorphism would influence susceptibility to psychiatric symptoms during interferon alfa therapy. One hundred five patients with hepatitis C, initially without active major depression (major depressive disorder), were treated with interferon alfa and then prospectively monitored using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Beck Depression Inventory II, the Anger Irritability and Assault Questionnaire, and circulating TNF-alpha levels. The A-308G polymorphism (rs1800629) was determined using the 5'-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time. Beck Depression Inventory II score increased during interferon alfa therapy (F = 6.2; P depression incidence (chi = 0.0; P = 0.99) or increased Beck Depression Inventory II (F = 1.2; P = 0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; P = 0.59). During treatment with an exogenous cytokine, vulnerability to worsening labile anger-distinct from major depression-is associated with genetic variability in TNF-alpha. This has implications both for patients being treated with interferon alfa and our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.

  19. Estabilización de holo-alfa-lactoalbúmina en presencia de polioles

    OpenAIRE

    Albis, Alberto; Lozano, José; Romero, Carmen

    2010-01-01

    En este trabajo se presenta un estudio sistemático sobre el efecto de las soluciones acuosas de eritritol, xilitol, sorbitol e inositol con diferentes concentraciones, sobre la estabilidad térmica de la holo- alfa-lactoalbúmina bovina con pH 6,5 usando espectroscopia UV-VIS. Los resultados obtenidos muestran que los polioles usados estabilizan la holo-alfa-lactoalbúmina en un grado significativamente menor al reportado para otras proteínas. Se sugiere que este menor efecto de estabilización o...

  20. ESTABILIZACIÓN DE HOLO-alfa-LACTOALBÚMINA EN PRESENCIA DE POLIOLES

    Directory of Open Access Journals (Sweden)

    Alberto Albis

    2010-02-01

    Full Text Available En este trabajo se presenta un estudio sistemático sobre el efecto de las soluciones acuosas de eritritol, xilitol, sorbitol e inositol con diferentes concentraciones, sobre la estabilidad térmica de la holo- alfa-lactoalbúmina bovina con pH 6,5 usando espectroscopia UV-VIS. Los resultados obtenidos muestran que los polioles usados estabilizan la holo-alfa-lactoalbúmina en un grado significativamente menor al reportado para otras proteínas. Se sugiere que este menor efecto de estabilización ocurre debido a que esta proteína presenta un estado desnaturalizado parcialmente desdoblado.

  1. Oxygenation of a rodent adenocarcinoma is improved by darbepoetin alfa

    International Nuclear Information System (INIS)

    Kirkpatrick, J.P.; Snyder, S.A.; Zhao, Y.; Peltz, C.; Brizel, D.M.; Dewhirst, M.W.; Blackwell, K.L.

    2003-01-01

    Full text: Tumor hypoxia, particularly in anemia, increases the risk of distant metastases and decreases survival. However, the benefits of stimulating erythropoiesis to supraphysiological levels are unclear. This study examines the effect of darbepoetin alfa (DEPA) on tumor oxygenation and the response to therapeutic radiation (XRT) in rats with initially normal hematocrit. R3230 adenocarcinoma was transplanted into the flank of female Fisher 344 rats. Starting on Day 4 post transplant, the rats received DEPA 3 μg/kg or normal saline sc tiw. At 3 weeks post transplant, pO2 was measured and the tumor excised, or the tumor was irradiated. pO2 was determined using an optical microprobe. In histologic studies, rats were injected with pimonidazole prior to sacrifice, and the tumors excised and stained with an antibody to pimonidazole (PIMO). Extent/intensity of staining was assessed by 3 observers and averaged to yield an IHC score. Rats ± DEPA with tumors 7 -12mm diameter were randomised to receive 32 Gy in 4 bid doses or sham irradiation. Tumor diameters in the 4 groups (±DEPA x ±XRT, total n=41) were measured by calipers. Failure was defined by the tumor reaching 15mm in diameter and used to generate Kaplan-Meier curves. Hematocrit at transplant averaged 45% (n=104) versus 67% in the DEPA-treated rats (n=18, p<0.0001) and 44% in the control animals (n=21.) Median pO2 in the DEPA-treated rats vs. controls did not differ significantly (17 vs. 13 mm Hg, p=0.10.) However, the fraction of tumor pO2 measurements <10mm Hg in the DEPA-treated rats was lower (21% vs. 37%, p=0.046.) IHC score was also less in the DEPA group (p=0.03.) XRT significantly improved failure-free survival (p<0.0001.) While the addition of DEPA to either the XRT or control groups did not significantly increase survival, the trend in both cases favored the DEPA-treated groups. In this tumor, treatment with DEPA improves oxygenation. However, no significant enhancement in radioesponsiveness by DEPA

  2. PTK2b function during fertilization of the mouse oocyte

    International Nuclear Information System (INIS)

    Luo, Jinping; McGinnis, Lynda K.; Carlton, Carol; Beggs, Hilary E.; Kinsey, William H.

    2014-01-01

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development

  3. PTK2b function during fertilization of the mouse oocyte

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Jinping [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); McGinnis, Lynda K. [Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Carlton, Carol [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Beggs, Hilary E. [Department of Ophthalmology, University of California, San Francisco, CA (United States); Kinsey, William H., E-mail: wkinsey@kumc.edu [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2014-08-01

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.

  4. Haplotypes frequencies of CYP2B6 in Malaysia

    Directory of Open Access Journals (Sweden)

    N Musa

    2012-01-01

    Full Text Available Background: Drugs with complex pharmacology are used in the management of drug use disorder (DUD and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral. Aims: Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia. Settings and Design: The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals. Materials and Methods: For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6FNx0110, CYP2B6FNx012, CYP2B6FNx0117, CYP2B6FNx0111, CYP2B6FNx018, CYP2B6FNx0114, CYP2B6FNx019, CYP2B6FNx014, CYP2B6FNx016, CYP2B6FNx0127, and CYP2B6FNx0120 were determined using multiplex nested allele-specific PCR. Statistical Analysis: Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test. Results: CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6FNx016 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another ′reduced activity′, CYP2B6FNx012 allele, was found at much lower percentages in the groups. Conclusions: The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.

  5. Analysis list: GTF2B [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available GTF2B Blood,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/GT...F2B.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/GTF2B.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/GTF2B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/GTF2B.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/GTF2B.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  6. Harnessing marketing automation for B2B content marketing

    OpenAIRE

    Järvinen, Joel; Taiminen, Heini

    2016-01-01

    The growing importance of the Internet to B2B customer purchasing decisions has motivated B2B sellers to create digital content that leads potential buyers to interact with their company. This trend has engendered a new paradigm referred to as ‘content marketing.’ This study investigates the organizational processes for developing valuable and timely content to meet customer needs and for integrating content marketing with B2B selling processes. The results of this single case study demonstra...

  7. Respuesta de IFN-y e Il-4 en ratones inoculados con una proteína G recombinante del virus de la rabia

    Directory of Open Access Journals (Sweden)

    Edith Rojas-Anaya

    2015-01-01

    Full Text Available El objetivo de este estudio fue comparar el comportamiento de IFN-  e IL-4 en ratones inoculados con proteína G recombinante del virus de la rabia, que se expresa en maíz transgénico o baculovirus. Para este pr opósito, grupos de ratones se inocularon de la siguiente manera: Grupo 1, vacuna contra el virus de la rabia inactivado vía im; Grupo 2, proteína G recombinante deri vada de plantas por vía oral; Grupo 3, proteína G expresada en baculovirus vía im; Grupo 4, proteína G expresada en baculovirus por vía oral; Grupo 5, maíz no tran sformado por vía oral. Los niveles de IFN-  e IL-4 y los anticuerpos específicos se evaluaron cada 15 días. El desafío se realizó a los 60 días post inoculación (pi. Los grupos 1 y 3 promovieron un a mejor respuesta humoral. Por otro lado, los resultados demostraron que los mismos grupos mostraron los mejores niveles de IFN -  en el día 10 pi; mientras que la IL-4 se detectó en el día 15 pi. Para el estudio de supervivencia, el 83 % de los ratones inmunizados con vacuna inactivada, maíz y los inoculados im con extractos de baculovirus sob revivieron la infección viral. La proteína G de la rabia recombinante expresada en baculovirus promovió IFN-  y los anticuerpos de una manera similar a la vacuna de rabia inactivada. A pesar de esto los ratones alime ntados con maíz transgénico sobrevivieron al desafío en el mismo porcentaje que el grupo 3.

  8. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

    Isaacs, A M; Johannsen, P; Holm, I

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient. ...... features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease....

  9. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Lamm, D.; Brausi, M.; O'Donnell, M.A.; Witjes, J.A.

    2014-01-01

    OBJECTIVES: In this article, we review the various options for and the potential role of interferon alfa (IFN-alpha) in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: PubMed was searched for journal articles on IFN-alpha use in treating bladder cancer. The references listed in

  10. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

    NARCIS (Netherlands)

    Pfeffer, Marc A.; Burdmann, Emmanuel A.; Chen, Chao-Yin; Cooper, Mark E.; de Zeeuw, Dick; Eckardt, Kai-Uwe; Feyzi, Jan M.; Ivanovich, Peter; Kewalramani, Reshma; Levey, Andrew S.; Lewis, Eldrin F.; McGill, Janet B.; McMurray, John J. V.; Parfrey, Patrick; Parving, Hans-Henrik; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Toto, Robert

    2009-01-01

    BACKGROUND Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately

  11. Valorization of Tunisian alfa fibres and sumac tannins for the elaboration of biodegradable insulating panels

    Science.gov (United States)

    Saad, Houda; Charrier, Bertrand; Ayed, Naceur; Charrier-El-Bouhtoury, Fatima

    2017-10-01

    Alfa leaves are important renewable raw materials in Tunisia where they are used basically in handcrafts and paper industry. Sumac is also an abundant species in Tunisia known for its high tannin content and is basically used in traditional medicine. To valorize these natural resources, we studied, for the first time, the possibility of making insulating panels based on alfa fibres and sumac tannins based adhesive. Firstly, alfa leaves were treated with an alkali solution as it is one of the standard procedures commonly used in the paper industry to extract cellulosic fibres. Mercerization effects were studied by characterizing fibres thermal properties and fibres surface morphology. Secondly, the sumac tannin based resin was formulated and characterized. Finally, the insulating panel was elaborated and characterized by determining its thermal conductivity. The thermal gravimetric analysis results show improvement in the thermal stability of fibres after alkali treatment. Environmental Scanning Electron Microscopy showed changes on treated alfa surface which could promote the fibre-matrix adhesion. The reactivity of sumac tannins to formaldehyde test (Stiasny number) showed the possible use of sumac tannins in wood adhesive formulation. Thermomechanical analysis and strength analysis of sumac tannin/hexamin based resin highlighted acceptable bonding properties. The thermal conductivity measurement showed an average value equal to 0.110 W/m K. Contribution to the topical issue "Materials for Energy harvesting, conversion and storage II (ICOME 2016)", edited by Jean-Michel Nunzi, Rachid Bennacer and Mohammed El Ganaoui

  12. Use of drotrecogin alfa (activated) in older patients with severe sepsis.

    Science.gov (United States)

    Alexander, Sherri L; Ernst, Frank R

    2006-04-01

    Drotrecogin alfa (activated) has been approved by the United States Food and Drug Administration for treatment of patients at high risk of death from severe sepsis. Severe sepsis is common, and its occurrence increases dramatically with age. Clinical use data, however, suggest that drotrecogin alfa (activated) may be underused in older patients, possibly due to concern over the drug's anticoagulant effects and perceived high cost. In addition, clinicians often treat older patients less aggressively than younger patients. We reviewed a subgroup analysis of patients aged 75 years and older from a large clinical trial evaluating efficacy and safety of drotrecogin alfa (activated), as well as cost-effectiveness data from real-world clinical use of the drug in older patients. We also explored ethical dilemmas of treating older patients with sepsis. Drotrecogin alfa (activated) is safe, effective, and cost-effective in older patients with severe sepsis and should be considered for elderly intensive care patients who are high risk of death and who have no contraindications to treatment.

  13. Arecibo Pulsar Survey Using ALFA. III. Precursor Survey and Population Synthesis

    NARCIS (Netherlands)

    Swiggum, J.K.; Lorimer, D.R.; McLaughlin, M.A.; Bates, S.D.; Champion, D.J.; Ransom, S.M.; Lazarus, P.; Brazier, A.; Hessels, J.W.T.; Nice, D.J.; Ellis, J.; Senty, T.R.; Allen, B.; Bhat, N.D.R.; Bogdanov, S.; Camilo, F.; Chatterjee, S.; Cordes, J.M.; Crawford, F.; Deneva, J.S.; Freire, P.C.C.; Jenet, F.A.; Karako-Argaman, C.; Kaspi, V.M.; Knispel, B.; Lee, K.J.; van Leeuwen, J.; Lynch, R.; Lyne, A.G.; Scholz, P.; Siemens, X.; Stairs, I.H.; Stappers, B.W.; Stovall, K.; Venkataraman, A.; Zhu, W.W.

    2014-01-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° lsim ℓ lsim 77° and 168° lsim ℓ lsim 214°) close to the Galactic plane (|b| lsim 5°) for pulsars. The PALFA survey is sensitive to sources

  14. Spotlight on taliglucerase alfa in the treatment of pediatric patients with type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Gupta P

    2017-06-01

    Full Text Available Punita Gupta,1 Gregory M Pastores2 1Division of Genetics, Department of Pediatrics, St. Joseph’s Children’s Hospital, Paterson, New Jersey, USA; 2National Center for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland Abstract: Gaucher disease (GD is a heritable storage disorder caused by functional defects of the lysosomal acid β-glucosidase and the accumulation of glucosylceramide within macrophages, resulting in multiple organ dysfunction. There are three commercially available enzyme replacement therapy (ERT products for the treatment of GD type 1 (GD1: imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems; imiglucerase requires postproduction deglycosylation to expose terminal α-mannose residues, which are required for mannose receptor-mediated uptake by target macrophages. These steps are critical to the success of ERT for the treatment of visceral and hematologic manifestations of GD. Taliglucerase alfa is the first US Food and Drug Administration-approved plant-cell-expressed recombinant human protein, using carrot root cell cultures. Furthermore, it does not require postproduction glycosidic modifications. It is indicated for treatment of adults with GD1 in the US, Israel, Australia, Canada, Chile, Brazil, and other countries, and it is additionally approved for the treatment of pediatric patients in the US, Australia, and Canada and for the treatment of hematologic manifestations in pediatric patients with Type 3 GD in Canada and other countries. Our review focuses on the role of taliglucerase alfa in the pediatric population. A literature search through PubMed (from 1995 up till November 2016 of English language articles was performed with the following terms: Gaucher disease, lysosomal storage disease, taliglucerase. Secondary and tertiary references were obtained by reviewing

  15. B2B or Not to Be: Does B2B E-Commerce Increase Labour Productivity?

    OpenAIRE

    Bertschek, Irene; Fryges, Helmut; Kaiser, Ulrich

    2004-01-01

    We implement an endogeneous switching-regression model for labour productivity and firms' decision to use business-to-business (B2B) e-commerce. Our approach allows B2B usage to affect any parameter of the labour productivity equation and to properly take account of strategic complementarities between the input factors and B2B usage. Empirical evidence from 1,394 German firms shows that firms using B2B e-commerce have a significantly higher output elasticity with respect to ICT-investment and...

  16. Association analysis of polymorphism in KIAA1717, HUMMLC2B ...

    African Journals Online (AJOL)

    Single nucleotide polymorphisms (SNPs) in KIAA1717, HUMMLC2B, DECR1, and FTO genes have been found to be associated with some pork meat quality traits. ... with meat color (CIE L), backfat thickness, drip loss, water-holding capacity, and pH24hr; a SNP in HUMMLC2B was associated with chemical composition ...

  17. Mechanochemical synthesis and characterization of pure Co2B ...

    Indian Academy of Sciences (India)

    Cobalt boride (Co 2 B) is a significant transition metal boride having a wide range of usage area due to its high oxidation, abrasion and corrosion resistance as well as its superior electrochemical, magnetic and anisotropicproperties. In this study, pure Co2B nanocrystals were synthesized with Co, B 2 O 3 and Mg as starting ...

  18. Expression and purification of recombinant Shiga toxin 2B from ...

    African Journals Online (AJOL)

    IMAC) column, followed by second step using HaloLink resin. The native Stx2B was obtained after column cleavage of halo-tag using HaloTEV protease. Maximum protein expression of Stx2B economically was obtained using 1 mM IPTG for 4 h at ...

  19. PODAAC-QSX25-L2B02

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset has been superseded by Version 3: http://podaac.jpl.nasa.gov/dataset/QSCAT_LEVEL_2B_OWV_COMP_12 . This QuikSCAT Level 2B dataset contains the Version 2...

  20. PODAAC-RSX12-L2B11

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.1 science-quality ocean surface wind vectors. The Level 2B wind vectors are binned on a 12.5 km Wind...

  1. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

    Isaacs, A M; Johannsen, P; Holm, I

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient...

  2. Papel del factor de crecimiento epidérmico recombinante humano “Heberprot-P” en un paciente con Lepra Multibacilar

    Directory of Open Access Journals (Sweden)

    Wilver Velázquez Chacón

    2014-08-01

    Full Text Available Se presenta el caso de un paciente masculino de 59 años de edad, tratado por vías convencionales a causa de lesiones ulcerativas de miembros inferiores, de más de siete años de evolución, sin diagnóstico y tratamiento. La evolución ulterior permitió reconocer la aparición subsecuente de lepra multibacilar. La basiloscopía fue positiva, indicando el diagnóstico de las lesiones ulcerativas, que se trataron con el uso de factor de crecimiento epidérmico recombinante humano en su formulación Heberprot-P, permitiendo la granulación de las lesiones en toda su extensión en un plazo corto, de 16 días, sin que se presentaran eventos adversos graves. Su resultado final fue satisfactorio

  3. Vírus influenza recombinantes como vetores vacinais: desenvolvimento e aplicação no modelo de doença de chagas

    OpenAIRE

    Rafael Polidoro Alves Barbosa

    2014-01-01

    As vacinas são consideradas uma das aplicações médicas mais bem sucedidas e eficazes na prevenção de doenças infecciosas. Há estimativas que até 3 milhões de vidas são salvas através de vacinação por ano, além de cem milhões de pessoas que deixam de ficar doentes reduzindo o impacto econômico e social causado por diversas doenças. Dentre as tecnologias mais viáveis para o desenvolvimento de novas vacinas se encontram os vírus recombinantes. Em 2010, nosso grupo demonstrou a viabilidade da con...

  4. Obtención de anticuerpos monoclonales de ratón contra proteasa de cisteína 5 recombinante de Entamoeba histolytica

    Directory of Open Access Journals (Sweden)

    Juanita Trejos S.

    2012-08-01

    Full Text Available Objetivo. Obtener anticuerpos monoclonales de ratón contra la proteasas de cisteína 5 (EhCP5 de Entamoeba histolytica. Materiales y métodos. Se inmunizaron ratones BALB/c por vía intraperitoneal con adyuvante de Freund completo e incompleto con la proteína recombinante EhCP5 obtenida a partir del cultivo de E.coli DH5α trasfectada con el vector recombinante pJC45 que expresa dicha proteína. Se seleccionó el animal con mejor respuesta de anticuerpos. Al cual se le extrajo su bazo como fuente de linfocitos B, los cuales se fusionaron utilizando PEG con células de mieloma de ratón SP2-0/Ag14. Se procedió a selección de los hibridomas y a la evaluación de los sobrenadantes de las colonias que crecieron a los 7 días mediante ELISA. Los hibridomas con valores más altos de anticuerpos específicos contra la proteína EhCP5r se seleccionaron, y los clones obtenidos por diluciones limitantes fueron expandidos. Resultados. A partir de un clon secretor estable se purifico el anticuerpo monoclonal anti EhCP5r del isotipo IgG1 por cromatografía de afinidad con proteína G. Los clones fueron expandidos in vivo e in vitro. Con el anticuerpo purificado se diseñaron tres sistemas de captura para evaluar la aplicabilidad del anticuerpo monoclonal anti EhCP5r como método inmunodiagnóstico. Conclusiones. Se logro la producción de un anticuerpo monoclonal específico contra EhCP5r que permite diferenciar Entamoeba histolytica de Entamoeba dispar.

  5. Superconductivity in the intermetallic borocarbides YPd2B2C, YPt2B2C and LaPt2B2C

    Science.gov (United States)

    Durajski, A. P.; Paliwoda, M. K.; Szczȩśniak, R.

    2016-11-01

    We report a detailed study of the thermodynamic properties of the conventional phonon-mediated superconductors YPd2B2C, YPt2B2C and LaPt2B2C. Our calculations conducted within the framework of the Migdal-Eliashberg formalism show that the experimental values of the critical temperature cannot be properly reproduced using commonly accepted value of Coulomb pseudopotential. Moreover, we proved that the values of universal ratios of conventional superconductivity appearing in the Bardeen-Copper-Schrieffer (BCS) theory are inconsistent with our results obtained from the investigated borocarbides. The observed differences are connected with the strong/medium-coupling and retardation effects existing in the studied systems.

  6. INFECÇÃO EXPERIMENTAL DE BEZERROS COM RECOMBINANTES DO HERPESVÍRUS BOVINO TIPO 5 COM DELEÇÕES NOS GENES DA GLICOPROTEÍNA E, TIMIDINA QUINASE E AMBOS

    OpenAIRE

    Cyndia Mara Bezerra dos Santos

    2010-01-01

    O herpesvírus bovino tipo 5 (BoHV-5) é o agente de doença neurológica grave em bovinos. A utilização de vacinas recombinantes tem sido preconizada para o controle da infecção pelo BoHV-5. O objetivo do presente trabalho foi investigar a patogenia, em bezerros, de três recombinantes do BoHV-5, com deleções nos genes da glicoproteína E (BoHV-5gEΔ), da enzima timidina quinase (BoHV-5TKΔ) ou ambos (BoHV-5gETKΔ) para uso potencial em vacinas. Para isso, quatro grupos de bezerros com...

  7. Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with Darbepoetin Alfa

    DEFF Research Database (Denmark)

    Skali, Hicham; Parving, Hans-Henrik; Parfrey, Patrick S

    2011-01-01

    More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association....

  8. Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2018-02-22

    Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. PODAAC-RSX12-L2B12

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.2 science-quality ocean surface wind vectors, which are intended as a replacement and continuation of...

  10. B2B Models for DoD Acquisition

    National Research Council Canada - National Science Library

    Kamel, Magdi N

    2008-01-01

    A central vision of B2B e-commerce is that of an electronic marketplace that would bring suppliers together with major buyers of goods and services for the purpose of conducting "frictionless commerce...

  11. PODAAC-QSX12-L2B31

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the latest reprocessed version 3.1 of the Level 2B science-quality ocean surface wind vector retrievals from the QuikSCAT scatterometer. The...

  12. PODAAC-QSX12-L2B40

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the latest reprocessed version 4.0 of the Level 2B science-quality ocean surface wind vector retrievals from the QuikSCAT scatterometer. The...

  13. PODAAC-RSX12-L2B13

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.3 science-quality ocean surface wind vectors, which are intended as a replacement and continuation of...

  14. PODAAC-QSX12-L2B01

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the latest reprocessed version 3 of the Level 2B science-quality ocean surface wind vector retrievals from the QuikSCAT scatterometer. The...

  15. Scope of Internal Marketing in B2B Companies

    OpenAIRE

    Nigam, Niharika

    2007-01-01

    Abstract Previous studies have focused on "internal marketing" from services marketing perspective. There is, therefore, a great dearth of in-depth research on its application to other business types. This research attempts to find the scope of internal marketing in B2B companies. The purpose of this research is to closely examine the elements, their linkage, tools and applications of Internal marketing when applied to B2B settings. Internal marketing, the application of marketing managem...

  16. PTK2b function during fertilization of the mouse oocyte.

    Science.gov (United States)

    Luo, Jinping; McGinnis, Lynda K; Carlton, Carol; Beggs, Hilary E; Kinsey, William H

    2014-08-01

    Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development. Published by Elsevier Inc.

  17. A Study of Diffractive Scattering with the ATLAS and ALFA Experiment

    CERN Document Server

    AUTHOR|(CDS)2097773

    This thesis presents a study of diffractive scattering of high-energy protons. Hadronic diffraction is not well-understood and many alternative approaches exist. The Monte Carlo event generator Pythia 8 follows a Pomeron-based approach, where the invariant mass of the diffractive system and the squared momentum transfer $t$ of the system is set up according to a phenomenological Pomeron flux parameterization, which is parameterized by the super-critical Pomeron trajectory, $\\alpha(t) = 1 + \\varepsilon + \\alpha' t$, where the intercept parameter $\\varepsilon$ and the slope parameter $\\alpha'$ can be tuned by the user. A fast detector response simulation of the ALFA and ATLAS detectors has been developed in the Rivet toolkit for the purposes of this thesis. The developed simulation framework is able to handle the beam transport of diffractively scattered protons as well as impose the kinematic acceptance of the ALFA detector which was found to be approximately $\\xi \\lesssim 0.22$, with a pseudorapidity coverag...

  18. AN IMPORTANT COMPONENT OF BASIC THERAPY IN CYSTIC FIBROSIS (MUCOVYSCIDOSIS IN CHILDREN: DORNASE ALFA

    Directory of Open Access Journals (Sweden)

    O.I. Simonova

    2011-01-01

    Full Text Available Dornase alpha plays an important role in the basic treatment of cystic fibrosis, having three clinical effects: powerful mucolytic, anti-inflammatory and antibacterial. Early drug inclusion and its permanent administration in the basic therapy allows patients with cystic fibrosis to have an active life, with occasional illness recrudescence, long-lasting remissions, stable function of external respiration. The drug is appropriate to prescribe as preventive and curative for chronic bronchitis and chronic polypoid pansinusitis immediately if the diagnosis of «Cystic fibrosis» is established. The effectiveness of dornase alfa depends on strict adherence to the rules of its use. Key words: cystic fibrosis, chronic bronchopulmonary disease, mukostasis, children, chronic pansinusitis, nasal polyps, basic therapy,  dornase alfa, the rules of administration, inhalation therapy. (Pediatric Pharmacology. — 2011; 8 (5: 122–126.

  19. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

    Science.gov (United States)

    Arends, Maarten; Biegstraaten, Marieke; Wanner, Christoph; Sirrs, Sandra; Mehta, Atul; Elliott, Perry M; Oder, Daniel; Watkinson, Oliver T; Bichet, Daniel G; Khan, Aneal; Iwanochko, Mark; Vaz, Frédéric M; van Kuilenburg, André B P; West, Michael L; Hughes, Derralynn A; Hollak, Carla E M

    2018-02-07

    Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: -18 nmol/L, Pbeta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar. Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Synthesis of 9H-Indeno [1, 2-b] Pyrazine and 11H-Indeno [1, 2-b ...

    African Journals Online (AJOL)

    NICO

    Synthesis of 9H-Indeno [1, 2-b] Pyrazine and. 11H-Indeno [1, 2-b] Quinoxaline Derivatives in. One-step Reaction from 2-Bromo-4-chloro-1-indanone. S. Jasouri1,2, J. Khalafy1,*, M. Badali2 and R.H. Prager3. 1Department of Chemistry, Urmia University, Urmia 57154, Iran. 2Daana Pharmaceutical Co., P.O. Box 5181, Tabriz ...

  1. AlfaMC: A fast alpha particle transport Monte Carlo code

    Energy Technology Data Exchange (ETDEWEB)

    Peralta, Luis, E-mail: luis@lip.pt [Faculdade de Ciências da Universidade de Lisboa (Portugal); Laboratório de Instrumentação e Física Experimental de Partículas (Portugal); Louro, Alina [Laboratório de Instrumentação e Física Experimental de Partículas (Portugal)

    2014-02-11

    AlfaMC is a Monte Carlo simulation code for the transport of alpha particles. This code is based on the Continuous Slowing Down Approximation and uses the NIST/ASTAR stopping-power database. The code uses a powerful geometrical package, which allows coding of complex geometries. A flexible histogramming package is used as well, which greatly eases the scoring of results. The code is tailored for microdosimetric applications in which speed is a key factor. Comparison with the SRIM code is made for deposited energy in thin layers and range for air, mylar, aluminum and gold. The general agreement between the two codes is good for beam energies between 1 and 12 MeV. -- Highlights: • AlfaMC is a Monte Carlo program for fast alpha particle transport in matter. • The model is accurate within a few percent in the energy range of 1–12 MeV. • AlfaMC uses a combinatorial geometry package allowing the modeling of complex bodies.

  2. Preparation And Properties Of Bionanocomposite Films Reinforced With Nanocellulose Isolated From Moroccan Alfa Fibres

    Directory of Open Access Journals (Sweden)

    Youssef Benyoussif

    2015-09-01

    Full Text Available Nanocellulose (NC were extracted from the Moroccan Alfa plant (Stipa tenacissima L. and characterised. These Alfa cellulosic nanoparticles were used as reinforcing phase to prepare bionanocomposite films using carboxymethyl cellulose as matrix. These films were obtained by the casting/evaporation method. The crystallinity of NC was analysed by X-ray diffraction, the dimension of NC by atomic force microscopy, molecular interactions due to incorporation of NC in carboxymethyl cellulose (CMC matrix were supported by Fourier transforms infrared (FTIR spectroscopy. The properties of the ensuing bionanocomposite films were investigated using tensile tests, water vapour permeability (WVP study and thermogravimetric analysis. With the progress of purification treatment of cellulose, the crystallinity is improved compared to the untreated fibres; this can be explained by the disappearance of the amorphous areas in cellulose chain of the plant. Consequently, the tensile modulus and tensile strength of CMC film increased by 60 and 47%, respectively, in the bionanocomposite films with 10 wt% of NC, and decrease by 8.6% for WVP with the same content of NC. The NC obtained from the Moroccan Alfa fibres can be used as a reinforcing agent for the preparation of bionanocomposites, and they have a high potential for the development of completely biodegradable food packaging materials.

  3. Lithium insertion in nanostructured TiO(2)(B) architectures.

    Science.gov (United States)

    Dylla, Anthony G; Henkelman, Graeme; Stevenson, Keith J

    2013-05-21

    Electric vehicles and grid storage devices have potentialto become feasible alternatives to current technology, but only if scientists can develop energy storage materials that offer high capacity and high rate capabilities. Chemists have studied anatase, rutile, brookite and TiO2(B) (bronze) in both bulk and nanostructured forms as potential Li-ion battery anodes. In most cases, the specific capacity and rate of lithiation and delithiation increases as the materials are nanostructured. Scientists have explained these enhancements in terms of higher surface areas, shorter Li(+) diffusion paths and different surface energies for nanostructured materials allowing for more facile lithiation and delithiation. Of the most studied polymorphs, nanostructured TiO2(B) has the highest capacity with promising high rate capabilities. TiO2(B) is able to accommodate 1 Li(+) per Ti, giving a capacity of 335 mAh/g for nanotubular and nanoparticulate TiO2(B). The TiO2(B) polymorph, discovered in 1980 by Marchand and co-workers, has been the focus of many recent studies regarding high power and high capacity anode materials with potential applications for electric vehicles and grid storage. This is due to the material's stability over multiple cycles, safer lithiation potential relative to graphite, reasonable capacity, high rate capability, nontoxicity, and low cost (Bruce, P. G.; Scrosati, B.; Tarascon, J.-M. Nanomaterials for Rechargeable Lithium Batteries. Angew. Chem., Int. Ed.2008, 47, 2930-2946). One of the most interesting properties of TiO2(B) is that both bulk and nanostructured forms lithiate and delithiate through a surface redox or pseudocapacitive charging mechanism, giving rise to stable high rate charge/discharge capabilities in the case of nanostructured TiO2(B). When other polymorphs of TiO2 are nanostructured, they still mainly intercalate lithium through a bulk diffusion-controlled mechanism. TiO2(B) has a unique open crystal structure and low energy Li

  4. Electrification Beyond Light Duty: Class 2b-3 Commercial Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Birky, Alicia [Energetics Incorporated; Laughlin, Michael [Energetics Incorporated; Tartaglia, Katie [Energetics Incorporated; Price, Rebecca [Energetics Incorporated; Lim, Brandon [Energetics Incorporated; Lin, Zhenhong [ORNL

    2018-01-01

    The class 2b-3 truck market covers a wide range of commercial truck applications across a half-million vehicle sales annually. This report collected public information and stakeholder input to assess the opportunity for electrification in this market. Although class 2b-3 pickup truck and van bodies are very similar to personal light vehicles, their functional requirements are quite different due to the demands of the commercial market. These demands vary by application and often vary from day to day for a single application. Fleet customers purchase these vehicles to perform a particular job for their business and are concerned about the overall cost of doing that job. Therefore, the vehicles must meet the job requirements cost effectively. Customers also are sensitive to initial cost. Electrification offers the potential to reduce vehicle operating costs and possibly improve vehicle functionality. However, the current market for class 2b-3 electrified trucks is very small, and the trucks are costly. Increased production volumes are key to cost reductions and may be assisted by sharing components with larger or smaller truck classes. Expanding demand is also crucial and stakeholders identified several niche markets with duty cycles that are likely well-suited to electrified class 2b-3 trucks. To expand beyond these niches, class 2b-3 electric solutions must be robust, flexible, and adaptable in order to cover a wide range of vocations, applications, and duty cycles.

  5. Review of benchmark tests on JENDL-2B library

    International Nuclear Information System (INIS)

    Kikuchi, Yasuyuki

    1982-01-01

    JENDL-2B is a mixed library consisting of JENDL-2 for the most important nuclides, i.e., 235 U, 238 U, 239 Pu, 240 Pu, 241 Pu, Cr, Fe and Ni and of JENDL-1 for other nuclides. Complete reevaluation work was made for these eight nuclides. The simultaneous evaluation method was adopted in the evaluation for the five heavy nuclides. The resonance structure was carefully studied for the structural materials in the unresolved resonance region up to several MeV. Benchmark tests have been made on JENDL-2B. Various core center characteristics were tested with one-dimensional model for total of 27 assemblies. Satisfactory results were obtained as a whole. The results of spectrum indices, however, suggested some inconsistent spectrum prediction. Moreover, the reactivity worths were overestimated for most of materials, and apparent C/E discrepancies were observed between the Pu and U cores. Applicability of JENDL-2B was further tested to more sophisticated problems for MOZART and ZPPR-3 assemblies. The reaction rate distributions were better predicted with JENDL-2B than with JENDL-1. The positive sodium void reactivity worth was much overestimated with JENDL-2B due to too large moderation components. The control rod worths were well predicted in MOZART, but were considerably underpredicted in ZPPR-3. (author)

  6. ORM-Based Semantics of B2B Transactions

    Science.gov (United States)

    Balsters, H.; van Blommestein, F.

    After widespread implementation of Enterprise Resource Planning and Personal Information Management, the next wave in the application of ICT is headed towards business to business (B2B) communication. B2B has a number of specific aspects, one of them being negotiation. This aspect has been largely neglected by present implementations of standard EDI- or XML-messaging and by B2B webservice implementations. In this paper a precise model is given of the negotiation process. The requirements of a potential Buyer and the offer of a potential Seller are matched and, if the negotiation is successful, a contract is concluded. The negotiation process model is represented in ORM, extended with dynamic constraints. Our model may be implemented in the databases of the trading partners and in message- or service definitions.

  7. B2B Integration in Global Supply Chains

    DEFF Research Database (Denmark)

    Schubert, Petra; Legner, Christine

    2011-01-01

    The competitiveness of businesses is increasingly dependent on their electronic networks with customers, suppliers, and partners. While the strategic and operational impact of external integration and IOS adoption has been extensively studied, much less attention has been paid to the organizational......). The reference model comprises technical, organizational, and institutional levels to reflect the multiple facets of B2B integration. In this paper we investigate the current state of electronic collaboration in global supply chains focussing on the technical view. Using an in-depth case analysis we identify...... and technical design of electronic relationships. The objective of our longitudinal research project is the development of a framework for understanding and explaining B2B integration. Drawing on existing literature and empirical cases we present a reference model (a classification scheme for B2B Integration...

  8. Somatotropina bovina recombinante (rBST sobre o desempenho e a digestibilidade aparente de novilhas (½ Nelore x ½ Red Angus em confinamento

    Directory of Open Access Journals (Sweden)

    Nascimento Willian Gonçalves do

    2003-01-01

    Full Text Available O objetivo deste trabalho foi avaliar o efeito da somatotropina bovina recombinante (rBST - análogo do BST, obtido comercialmente pela técnica do DNA recombinante, sobre ganho médio diário (GMD, ingestão de matéria seca (IMS, matéria orgânica (IMO, energia metabolizável (IEM e fibra em detergente neutro (IFDN, ingestão de matéria seca em relação ao peso vivo (IMS/PV, conversão alimentar (CA, rendimento de carcaça (RC e digestibilidade aparente da matéria seca (DAMS, matéria orgânica (DAMO, proteína bruta (DAPB, energia bruta (DAEB e fibra em detergente neutro (DAFDN. Foram utilizadas 24 novilhas mestiças (½ Nelore x ½ Red Angus, com aproximadamente 18 meses de idade e peso médio 255 kg. Os animais foram alimentados com uma dieta contendo silagem de milho, como volumoso, e polpa de citrus e farelo de soja, como concentrado, durante 84 dias. Essa dieta foi utilizada para os três tratamentos, que se diferenciaram pela aplicação de 250 mg de rBST, por via subcutânea, na fossa ísqueo-retal, onde: tratamento 1 controle (aplicação de dois mL de solução salina; 2 dose única e 3 uma dose a cada 14 dias. Os animais foram distribuídos em delineamento inteiramente casualizado, com três tratamentos e oito repetições. O GMD foi determinado a cada 14 dias. A ingestão de alimentos e a conversão da MS foram determinadas ao final do experimento. A digestibilidade aparente (DA foi determinada durante um período de sete dias com uso de indicador interno. Não houve diferença entre animais tratados ou não com rBST sobre o GMD, IMS, IPB, IEM, IMO e IFDN, CAMS e RC. No entanto, a DA da MS, MO, PB, EB e FND foi superior para as novilhas que receberam rBST a cada 14 dias.

  9. Incorporação do hormônio do crescimento humano recombinante (rhGH em matriz de polímero biodegradável

    Directory of Open Access Journals (Sweden)

    Ricardo Fernandes Garcia

    Full Text Available ResumoObjetivoIncorporar o hormônio de crescimento recombinante humano em um polímero biodegradável (PLGA.Material e métodoAs matrizes foram confeccionadas através da técnica de evaporação de solventes. Foi feita uma mistura do polímero (poli ácido glicólico lático e do hormônio do crescimento humano recombinante (Saizen® Merck Serono S.A. Aubonne, Suíça. Essa mistura foi vertida em moldes de silicone circulares de 1 cm de diâmetro e aproximadamente 2 mm de espessura, e levada para secagem em uma câmara de evaporação de solvente por 48 horas. Após esse período, as matrizes foram imersas em PBS e passaram por um banho termostatizado (ensaio de degradação hidrolítica, in vitro, à temperatura de 37°C. As amostras foram retiradas do banho no intervalo de 1, 2, 3, 4, 7, 10 e 14 dias. Foram aferidas a perda de massa, a variação do pH e a concentração do hormônio liberado em função do tempo.ResultadoA concentração do hormônio liberado em função do tempo foi aumentando até o terceiro dia. No quarto dia, houve uma queda e, no sétimo, ocorreu um aumento do hormônio liberado, estendendo-se até o décimo dia; no 14° dia, houve queda novamente. O pH teve uma queda brusca de 7,4 para 3,2 no primeiro dia, mantendo uma pequena queda até o 14° dia. A perda de massa foi gradual em relação ao tempo, como já era esperado.ConclusãoO PLGA é um bom biomaterial para confecção de matrizes com hormônio do crescimento. Revelou-se possível incorporar o rhGH nessa matriz, de modo a, então, desenvolver-se um substituto ósseo.

  10. Intelligent Information Integration in B2B Electronic Commerce

    NARCIS (Netherlands)

    Fensel, Dieter; Omelayenko, Borys; Ding, Ying; Klein, Michel; Flett, Alan; Schulten, Ellen; Botquin, Guy; Brown, Mike; Dabiri, Gloria

    2002-01-01

    Internet and web technology penetrates many aspects of our daily life. Its importance as a medium for business transactions will grow exponentially during the next few years. In terms of the involved market volume, the B2B area will hereby be the most interesting area. Also, it will be the place,

  11. Expression and purification of recombinant Shiga toxin 2B from ...

    African Journals Online (AJOL)

    sunny t

    (SDS-PAGE) and StxB2 yield was 450 µg ml-1 confirmed by Bradford assay. Recombinant Stx2B protein was produced in highly pure yield using HaloTag technology. Key words: Escherichia coli O157:H7, StxB gene, expression, HaloTag technology, purification. INTRODUCTION. Enterohemorrhagic Escherichia coli ...

  12. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

    Biemans, Wim G.; Brencic, Maja Makovec; Malshe, Avinash; Makovec Brenciv, M.

    As the body of knowledge on marketing-sales interface expands, there is a greater need to investigate the specific aspects of marketing-sales configurations in B2B firms. Using a qualitative methodology and interview data collected from over 100 sales and marketing professionals from the US, The

  13. Improved Refolding Efficacy of Recombinant Human Interferon α-2b ...

    African Journals Online (AJOL)

    Interferon α-2b via pH Modulation. Aziz Dashbolaghi1, Shohreh Khatami2, Sorush Sardari3, Reza Ahangari Cohan1 and Dariush Norouzian1*. 1Department of Pilot Biotechnology, 2Department of Biochemistry, 3Drug Design and Bioinformatics Unit, Medical Biotechnology. Department, Biotechnology Research Center, ...

  14. Development of New B2B Venture Corporate Brand Identity

    DEFF Research Database (Denmark)

    Törmälä, Minna; Gyrd-Jones, Richard I.

    2017-01-01

    The development and role of brand identity in new B2B ventures is not well explored despite the challenge for such organisations in establishing reputational legitimacy. Previous research defines corporate brand identity as stable and endogenous to the organisation based either on the reputational...

  15. Strategic Insights from Mystery Shopping in B2B Relationships

    DEFF Research Database (Denmark)

    Mattsson, Jan

    2012-01-01

    This paper describes how mystery shopping can be used to gain valuable strategic input in B2B service relationships. We account for a longitudinal case study framed as a natural experiment (duration 18 months) in a Swedish group of consultancy companies offering a wide selection of industrial...

  16. checkCIF/PLATON report Datablock: exp_2b

    Indian Academy of Sciences (India)

    THIS REPORT IS FOR GUIDANCE ONLY. IF USED AS PART OF A REVIEW PROCEDURE. FOR PUBLICATION, IT SHOULD NOT REPLACE THE EXPERTISE OF AN EXPERIENCED. CRYSTALLOGRAPHIC REFEREE. No syntax errors found. CIF dictionary Interpreting this report. Datablock: exp_2b. Bond precision:.

  17. PODAAC-SEA12-L2B00

    Data.gov (United States)

    National Aeronautics and Space Administration — The SeaWinds on ADEOS-II Level 2B product provides ocean wind vectors in 12.5 km wind vector cell (WVC) slice composites in single-orbit files. The local time at the...

  18. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2001-06-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.

  19. Vanillin production by recombinant strains of Escherichia coli Produção de vanilina por linhagens recombinantes de Escherichia coli

    Directory of Open Access Journals (Sweden)

    Attilio Converti

    2003-11-01

    Full Text Available Vanillin production from ferulate was studied using different recombinant strains of Escherichia coli. To prevent the occurrence of aerobic conditions and then possible product oxidation, tests were performed in Erlenmeyer flasks under mild mixing (150 rpm. Among other transformants, E. coli JM109(pBB1 appeared to be the best vanillin producer, being able to convert no less than 95% of starting ferulate to the product within 1h. This yield decreased down to 72% after 72h, likely because of a non-specific oxidase activity responsible for vanillin oxidation to vanillate.A produção de vanilina a partir de ácido ferúlico foi estudada utilizando-se diferentes linhagens recombinantes de Escherichia coli. Para prevenir a ocorrência de condições de aerobiose e a possível oxidação do produto, os ensaios foram realizados em frascos Erlenmeyer sob agitação moderada (150 rpm. E. coli JM109 (pBBI mostrou-se o melhor produtor de vanilina entre os demais agentes transformantes, sendo capaz de converter 95% do ácido ferúlico inicial em produto após 1h, rendimento este que decresceu para 72% após 72h, provavelmente devido à atividade de uma oxidase não-específica responsável pela oxidação de vanilina a ácido vanílico.

  20. Fermentation of sweet whey by recombinant Escherichia coli K011 Fermentação de soro de leite por Escherichia coli KO11 recombinante

    Directory of Open Access Journals (Sweden)

    Amarildo Ricardo Leite

    2000-09-01

    Full Text Available The production of ethanol from sweet whey using the recombinant Escherichia coli KO11, in batch fermentation, was tested. The maximum ethanol yield was reached after 96h, representing only 38% of the theoretical yield. The supplementation of whey with components of LB broth increased the maximum yield to 96% in 72h. The addition of 0.5% yeast extract to whey resulted in maximum yield of 74% at 36h and it increased to over 100% when yeast extract and trace metals solution (Fe++, Mn++ and Zn++ were added.A produção de etanol a partir de soro de leite empregando a cepa Escherichia coli KO11 recombinante, em fermentação de batelada, foi testada. O rendimento máximo de etanol foi obtido em 96h, representando apenas 38% do rendimento teórico. A suplementação do soro com os componentes do caldo LB aumentou o rendimento para 96% em 72h. A adição de 0,5% de extrato de levedura ao soro resultou em um rendimento máximo de 74% em 36h que aumentou para acima de 100% quando se adicionou extrato de levedura e uma solução de metais traço (Fe++, Mn++ e Zn++.

  1. EVALUACIÓN DE LA PRODUCCIÓN DE ETANOL UTILIZANDO CEPAS RECOMBINANTES DE Saccharomyces cerevisiae A PARTIR DE MELAZA DE CAÑA DE AZÚCAR

    Directory of Open Access Journals (Sweden)

    CAROLINA PEÑA

    2009-01-01

    Full Text Available Se evaluó la producción de etanol, el crecimiento celular y el consumo de sustrato de tres cepas de Saccharomyces cerevisiae: CBS8066 (control y dos recombinantes desarrolladas en la Unidad de Biotecnología Vegetal de CIB, GG570-CIBI y GG570-CIBII. Dichas cepas estuvieron bajo el efecto de dos concentraciones de sacarosa (170 y 250g/L y dos sustratos (industrial con melaza caña azúcar y sintético con sacarosa. Durante la fermentación en sustrato industrial se obtuvo mayor producción de etanol a concentración de 250g sacarosa/L. Bajo estas condiciones, la cepa GG570-CIBII produjo en promedio 2,34g etanol/L mas con respecto a la cepa control y en adición, a las 10h, produjo 8,02g/L por encima de la cepa control. Por otro lado, la cepa GG570- CIBI produjo 3,46g etanol/L menos que la cepa control. De esta forma, se encontró que la cepa GG570-CIBII es tolerante a alta concentración de sacarosa, y además, es capaz de producir una concentración mayor de etanol con respecto a la cepa control en melaza caña azúcar con 250g/L sacarosa.

  2. EFECTO DE LA DENSIDAD CELULAR Y LA MULTIPLICIDAD DE INFECCIÓN SOBRE LA PRODUCCIÓN DE BACULOVIRUS RECOMBINANTES EN CULTIVOS DE CÉLULAS DE INSECTO

    Directory of Open Access Journals (Sweden)

    Cuitláhuac Chávez-Peña

    2010-01-01

    célula con CCI de 1 y 2 x106 cél/mL. Se siguieron las cinéticas de crecimiento de las células infectadas, la concentración de proteína total y de la proteína gp64 en el sobrenadante de los cultivos y los títulos virales al momento de la cosecha. Se encontró que una MDI de 0.1 ufp/cél y una concentración celular de 1x106 cél/mL resultaron en el mayor título viral, 3.8 ± 2 x108 ufp/mL. Los mayores títulos virales estuvieron acompañados por un menor crecimiento celular. Los resultados de este trabajo pueden ser utilizados para producir resguardos de baculovirus recombinantes con títulos virales altos y mejorar la eficiencia del proceso.

  3. Efeito da utilização da somatotropina bovina recombinante (bST sobre a produção de leite em búfalas

    Directory of Open Access Journals (Sweden)

    Jorge André Mendes

    2002-01-01

    Full Text Available O objetivo deste trabalho foi estudar o resultado da utilização da somatotropina bovina recombinante (bST atuando na produção de leite em búfalas da raça Murrah. Empregaram-se 28 búfalas multíparas da raça Murrah, divididas em dois grupos homogêneos de 14 animais, recebendo os seguintes tratamentos: Grupo 1 fraction three-quarters Controle (solução salina e Grupo 2 fraction three-quarters 500 mg de bST/cabeça a cada 14 dias, durante 7 meses. Búfalas tratadas com bST exibiram incrementos de 48,52%, 32,80% e 32,80% nas produções total de leite, corrigida, depois, para 4% de gordura e média diária, respectivamente. A somatotropina elevou a produção total de gordura sem alterar a porcentagem dela no leite. A administração de bST não afetou a porcentagem de proteína do leite todavia, a produção total de proteína foi aumentada. Quanto à duração da lactação, o tratamento com bST diferiu do controle, o que demonstra a maior persistência da lactação de búfalas tratadas com bST.

  4. Human UDP-Glucuronosyltransferase 2B4 and 2B7 Are Responsible for Naftopidil Glucuronidation in Vitro

    Directory of Open Access Journals (Sweden)

    Xia-Wen Liu

    2018-01-01

    Full Text Available Naftopidil (NAF is widely used for the treatment of benign prostatic hyperplasia and prevention of prostate cancer in elderly men. These patients receive a combination of drugs, which involves high risk for drug–drug interaction. NAF exhibits superior efficacy but must be administered at a much higher dosage than other therapeutic drugs. We previously showed that extensive glucuronidation of NAF enantiomers caused poor bioavailability. However, the metabolic pathway and mechanism of action of NAF enantiomer remain to be elucidated. The present study was performed to identify the human UDP-glucuronosyltransferases (UGTs responsible for the glucuronidation of NAF enantiomers and to investigate the potential inhibition of UGT activity by NAF. The major metabolic sites examined were liver and kidney, which were compared with intestine. Screening of 12 recombinant UGTs showed that UGT2B7 primarily contributed to the metabolism of both enantiomers. Moreover, enzyme kinetics for R(+-NAF, UGT2B7 (mean Km, 21 μM; mean Vmax, 1043 pmol/min/mg showed significantly higher activity than observed for UGT2B4 and UGT1A9. UGT2B4 (mean Km, 55 μM; mean Vmax, 1976 pmol/min/mg and UGT2B7 (mean Km, 38 μM; mean Vmax, 1331 pmol/min/mg showed significantly higher catalysis of glucuronidation of S(--NAF than UGT1A9. In human liver microsomes, R(+-NAF and S(--NAF also inhibited UGT1A9: mean Ki values for R(+-NAF and S(--NAF were 10.0 μM and 11.5 μM, respectively. These data indicate that UGT2B7 was the principal enzyme mediating glucuronidation of R(+-NAF and S(--NAF. UGT2B4 plays the key role in the stereoselective metabolism of NAF enantiomers. R(+-NAF and S(--NAF may inhibit UGT1A9. Understanding the metabolism of NAF enantiomers, especially their interactions with metabolic enzymes, will help to elucidate potential drug–drug interactions and to optimize the administration of this medicine.

  5. Effect of darbepoetin alfa on physical function in patients undergoing surgery for colorectal cancer

    DEFF Research Database (Denmark)

    Nørager, C B; Jensen, M B; Madsen, M R

    2007-01-01

    OBJECTIVE: To study whether perioperative treatment with darbepoetin alfa (DA) improves physical performance following colorectal cancer surgery. METHODS: Patients admitted for planned colorectal cancer surgery were randomized to receive either weekly placebo or DA 300 or 150 microg depending...... day 7. RESULTS: Of 221 included patients, 151 were evaluable. Baseline characteristics were similar in the 2 groups. Patients receiving DA had a significantly better working capacity on day 7 (p = 0.03) and day 30 (p = 0.03) compared with the placebo group. There were no statistically significant...

  6. Expressão local do fator de necrose tumoral alfa na ruptura prematura de membranas

    OpenAIRE

    Roveran,Valquíria; Silva,Maria Antonieta Longo Galvão; Yamano,Lucia; Rodrigues,Lilian Paiva; Vasquez,Mônica Lopez; Piato,Sebastião

    2009-01-01

    OBJETIVO: comparar a expressão do fator de necrose tumoral alfa (TNF-α) em membranas ovulares com ruptura prematura (RPM) e com ruptura oportuna das mesmas; verificar a associação entre a expressão do TNF-α em membranas ovulares e o grau de corioamnionite das mesmas e correlacionar a expressão do TNF-α e o tempo de ruptura das membranas. MÉTODOS: foram analisadas as membranas ovulares de 31 parturientes com RPM, com idade gestacional acima de 34 semanas, e de 14 parturientes co...

  7. Induction and characterization of an unusual Alfa-D-galactosidase from Talaromyces flavus

    Czech Academy of Sciences Publication Activity Database

    Simerská, Pavla; Monti, D.; Čechová, Ivana; Pelantová, Helena; Macková, M.; Bezouška, Karel; Riva, S.; Křen, Vladimír

    2007-01-01

    Roč. 128, č. 1 (2007), s. 61-71 ISSN 0168-1656 R&D Projects: GA ČR GA203/05/0172; GA MŠk OC D25.002; GA MŠk LC06010; GA MŠk OC D25.001 Grant - others:US(US) NATO LST.CLG.980125 Institutional research plan: CEZ:AV0Z50200510 Source of funding: N - neverejné zdroje Keywords : alfa-d-galactosidase * talaromyces flavus * enzyme purification Subject RIV: EE - Microbiology, Virology Impact factor: 2.565, year: 2007

  8. A redesigned follitropin alfa pen injector for infertility: results of a market research study

    Directory of Open Access Journals (Sweden)

    Abbotts C

    2011-06-01

    Full Text Available Carole Abbotts1, Cristiana Salgado-Braga2, Céline Audibert-Gros31Pharmaceutical Marketing Research Consultancy, London, UK; 2Fertility and Endocrinology Global Business Unit, 3Business Intelligence, Merck Serono SA, Geneva, SwitzerlandBackground: The purpose of this study was to evaluate patient-learning and nurse-teaching experiences when using a redesigned prefilled, ready-to-use follitropin alfa pen injector.Methods: Seventy-three UK women of reproductive age either administering daily treatment with self-injectable gonadotropins or about to start gonadotropin treatment for infertility (aged 24–47 years; 53 self-injection-experienced and 20 self-injection-naïve and 28 nurses from UK infertility clinics were recruited for the study. Following instruction, patients and nurses used the redesigned follitropin alfa pen to inject water into an orange and completed questionnaires to evaluate their experiences with the pen immediately after the simulated injections.Results: Most (88%, n = 64 patients found it easy to learn how to use the pen. Among injection-experienced patients, 66% (n = 35 agreed that the redesigned pen was easier to learn to use compared with their current method and 70% (n = 37 also said they would prefer its use over current devices for all injectable fertility medications. All nurses considered the redesigned pen easy to learn and believed it would be easy to teach patients how to use. Eighty-six percent (n = 24 of the nurses thought it was easy to teach patients to determine the remaining dose to be dialed and injected in a second pen if the initial dose was incomplete. Compared with other injection devices, 96% (n = 27 thought it was "much easier" to "as easy" to teach patients to use the redesigned pen. Based on ease of teaching, 68% (n = 19 of nurses would choose to teach the pen in preference to any other injection method. Almost all (93%, n = 26 nurses considered that having the same pen format for a range of

  9. GSI Helmholz Centre for Heavy Ion Research - ALFA: Next generation concurrent framework for ALICE and FAIR experiments

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    FAIR is a new, unique international accelerator facility for the research with antiprotons and ions. It is being built at the GSI Darmstadt in Hesse, Germany. The commonalities between the ALICE and FAIR experiments and their computing requirements led to the development of a common software framework in an experiment independent way; ALFA (ALICE-FAIR framework). ALFA is designed for high quality parallel data processing and reconstruction on heterogeneous computing systems. It provides a data transport layer and the capability to coordinate multiple data processing components. ALFA is a flexible, elastic system which balances reliability and ease of development with performance by using a message based multi-processing in addition to multi-threading. The framework allows for usage of heterogeneous computing architectures by offloading (portions of code are accelerated on the device) or natively (where the full program is executed on the device ).

  10. Structured Crowdsourcing: A B2B Innovation Roadmap

    DEFF Research Database (Denmark)

    Edgeman, Rick; Engell, Toke; Jensen, Nik Grewy

    Crowdsourcing is an increasingly popular source of both ideas and funding. Crowdsourcing in a B2B context is less well understood and, as such, much of our discussion will highlight business-to-business crowdsourcing. More generally discussion will address crowdsourcing relative to innovation...... from crowd-sourcing efforts. The roadmap emphasizes on early stages in the overall innovation management activity that is related to development and specification of the task to be crowdsourced, the identification of the crowd, the creation of the environment to connect the crowdsourcer, the task...... and the crowd, motivation of the crowd, and actual activities in reaching the crowd. Managing the input from the crowd is regarded as a later stage in the overall innovation management but also as a focal point in the arguments for improving B2B crowdsourcing. In crowd selection processes this paper aims...

  11. Customer satisfaction in B2B cloud services

    OpenAIRE

    Turunen, Helinä

    2013-01-01

    Tutkimuksen tavoitteena on kirjallisuuskatsauksen kautta esitellä B2B-pilvipalveluiden asiakastyytyväisyyteen vaikuttavia seikkoja, ja kuinka näitä seikkoja tulisi ottaa huomioon asiakastyytyväisyyden parantamisessa. Tässä tutkimuksessa verkkopohjaiseen liiketoimintaan liittyvää asiakastyytyväisyyden tutkimusta käytettiin pohjana etsiessä asiakastyytyväisyyteen vaikuttavia seikkoja pilvipalveluissa. Tutkimuksessa vertaillaan asiakastyytyväisyyteen vaikuttavia seikkoja vertailemalla tyytyväisy...

  12. Mass Customized Technical Textiles in the B2B Sector

    Science.gov (United States)

    Gebhardt, R.; Barteld, M.; Grafmüller, L.; Mosig, T.; Weiß, M.

    2017-10-01

    Mass Customization is a great opportunity for textile companies for both staying competitive in high-wage countries and offering inexpensive, customized products. Within the area of Technical Textiles, this study focuses on the B2B sector and shows the status quo, potentials and strengths. Both management and technological issues are addressed. For the former, business models and the value co-creation process are dealt with, for the latter, the focus is on modelling.

  13. Agent-based services for B2B electronic commerce

    Science.gov (United States)

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  14. Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa.

    Science.gov (United States)

    Schiffmann, Raphael; Ries, Markus; Blankenship, Derek; Nicholls, Kathy; Mehta, Atul; Clarke, Joe T R; Steiner, Robert D; Beck, Michael; Barshop, Bruce A; Rhead, William; West, Michael; Martin, Rick; Amato, David; Nair, Nitin; Huertas, Pedro

    2013-12-01

    Globotriaosylceramide concentrations were assessed as potential predictors of change from baseline after 12 months by estimated glomerular filtration rate and left-ventricular mass index using pooled data from three randomized, placebo-controlled agalsidase alfa trials and open-label extensions of patients with Fabry disease. Males (aged 18 years or older) with Fabry disease received agalsidase alfa (0.2 mg/kg every other week for 12 months). A backward-elimination approach evaluated potential predictors (baseline estimated glomerular filtration rate and left-ventricular mass index; age at first dose; baseline and change from baseline at 12 months of globotriaosylceramide (urine, plasma); urine protein excretion; and systolic and diastolic blood pressure). Subgroups included patients randomized to placebo or agalsidase alfa (double-blind phase), then to agalsidase alfa (open-label extensions; placebo→agalsidase alfa or agalsidase alfa→agalsidase alfa, respectively) and stage 2/3 chronic kidney disease patients. Baseline estimated glomerular filtration rate, age at first dose, baseline urine globotriaosylceramide excretion, and baseline and change from baseline urine protein excretion significantly predicted change from baseline estimated glomerular filtration rate in the analysis population (N = 73; all P<0.05), although not in all subgroups. Change from baseline urine and plasma globotriaosylceramide (baseline and change from baseline) concentrations did not predict change from baseline estimated glomerular filtration rate. No predictors of left-ventricular mass index were significant. Changes in globotriaosylceramide concentrations do not appear to be useful biomarkers for prediction of Fabry disease-related changes in estimated glomerular filtration rate or left-ventricular mass index.

  15. Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study.

    Science.gov (United States)

    Polyzos, N P; De Vos, M; Corona, R; Vloeberghs, V; Ortega-Hrepich, C; Stoop, D; Tournaye, H

    2013-05-01

    Will sequential administration of highly purified (hp)-HMG after corifollitropin alfa in a GnRH antagonist protocol benefit women with poor ovarian response according to the Bologna criteria? Corifollitropin alfa followed by hp-HMG in a GnRH antagonist protocol results in very promising pregnancy rates, albeit only in young (effect in young poor ovarian responders fulfilling the Bologna criteria. The data provide the rationale for performing a randomized controlled trial to determine if there is sound evidence for a clinical introduction of this protocol. No conflicts of interest to declare. No specific funding was received for this study.

  16. alfa-Deuterium kinetic isotope effects in reactions of methyllithium. Is better aggregation the cause of lower reactivity?

    DEFF Research Database (Denmark)

    Holm, Torkil

    1996-01-01

    The value of kH/kD for alfa deuterium kinetic isotope effects for the reaction of methyllithium and methylmagnesium iodid with a series of substrates are consistently ca. 10-15 % higher for the lithium reagent. This may indicate a pre-equilibrium......The value of kH/kD for alfa deuterium kinetic isotope effects for the reaction of methyllithium and methylmagnesium iodid with a series of substrates are consistently ca. 10-15 % higher for the lithium reagent. This may indicate a pre-equilibrium...

  17. The ISS 2B PVTCS Ammonia Leak: An Operational History

    Science.gov (United States)

    Vareha, Anthony

    2014-01-01

    In 2006, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B power channel began leaking ammonia at a rate of approximately 1.5lbm/year (out of a starting approximately 53lbm system ammonia mass). Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity during the STS-134 mission. During this mission the system was topped off with ammonia piped over from a separate thermal control system. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. Without these periodic EVAs to refill the 2B coolant system, the channel would eventually leak enough fluid as to risk pump cavitation and system failure, resulting in the loss of the 2B power channel - the most critical of the Space Station's 8 power channels. In mid-2012, the leak rate increased to approximately 5lbm/year. Once discovered, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to a dormant thermal control system not intended to be utilized as anything other than spare components. The purpose of this rerouting of the TCS was to increase system volume and to isolate the photovoltaic radiator, thought to be the likely leak source. This EVA was successfully executed on November 1st, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a totally different radiator than what the system was designed to utilize. Unfortunately, data monitoring over the next several months showed that the isolated radiator was not leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the

  18. Evaluation of the immune response to CRA and FRA recombinant antigens of Trypanosoma cruzi in C57BL/6 mice Avaliação da resposta imune em camundongos C57BL/6 imunizados com os antígenos recombinantes CRA e FRA de Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Valéria Rêgo Alves Pereira

    2003-07-01

    Full Text Available Humoral and cellular immune responses were evaluated in 44 C57BL/6 mice immunized with the Trypanosoma cruzi recombinant antigens CRA and FRA. Both antigens induced cutaneous immediate-type hypersensitivity response. The levels of IgG1, IgG2a, IgG2b and IgG3 were high in CRA immunized mice. IgG3 was the predominant isotype. Although no difference in antibody levels was observed in FRA-immunized mice when compared to control mice, both antigens were able to induce lymphoproliferation in immunized mice. Significant differences were observed between incorporation of [³H]- thymidine by spleen cell stimulated in vitro with CRA or FRA and the control group. These results suggest that CRA and FRA could be involved in mechanisms of resistance to Trypanosoma cruzi infection.As respostas imune humoral e celular foram avaliadas em 44 camundongos C57Bl/6 imunizados com os antígenos recombinantes CRA e FRA de Trypanosoma cruzi. Ambos antígenos induziram reação de hipersensibilidade do tipo imediato. Os níveis de IgG1, IgG2a, IgG2b e IgG3 foram elevados nos camundongos imunizados com CRA. IgG3 foi o isotipo predominante. Nenhuma diferença nos níveis de anticorpos foi observada em camundongos imunizados com FRA em relação aos animais controle. No entanto, ambos antígenos foram capazes de induzir proliferação de linfócitos em camundongos imunizados. Diferenças significativas foram observadas entre a incorporação da timidina - [³H] pelas células esplênicas estimuladas com CRA ou FRA e o grupo controle. Esses resultados sugerem que CRA e FRA poderão estar envolvidos nos mecanismos de resistência à infecção pelo Trypanosoma cruzi.

  19. Egecto de la Somatropina Recombinante Bovina (rBST) sobre la tasa de concepción en vacas Holstein sincronizadas con dispositivos intravaginales con Progesterona y Benzoato de Estradiol e inseminadas a tiempo fijo

    OpenAIRE

    Muñoz Espinoza, Rodrigo Leonardo

    2013-01-01

    El objetivo fue determinar el efecto de la Somatotropina Recombinante Bovina sobre la morfometría ovárica, el porcentaje de concepción y la tasa de mortalidad embrionaria en vacas Holstein de alta producción sincronizadas con dispositivos intravaginales a base de Progesterona (P4) y Benzoato de Estradiol (BE) e inseminadas artificialmente a tiempo fijo. El estudio se realizó entre Febrero-Agosto del 2012 en la hacienda Chullin, ubicada en el cantón Chambo Chimborazo; se utilizaron 50 vacas ...

  20. Vectores recombinantes basados en el virus modificado de ankara (MVA), con deleción en el gen C6L, como vacunas contra el VIH/SIDA y otras enfermedades

    OpenAIRE

    García-Arriaza, J.; Gómez, Carmen E.; Esteban, Mariano

    2011-01-01

    [ES] La presente invención engloba dentro de los campos de la biología molecular y de la biotecnología. Especificamente se refiere a virus recombinantes basados en el virus modificado de Ankara (MVA) que expresan los antigenos gp120 y Gag-Pol-Nef del virus de la inmunodeficienciahumana (VIH-1) de subtipo B (MVA-B), sobre los que see ha delecionado el gen de vaccinia C6L, y que han sido diseñados para utilizarse como vacunas contra el VIH/SIDA y otras enfermedades.

  1. Vectores recombinantes basados en el virus modificado de Ankara (MVA), con deleción en el gen C6L, como vacunas contra el VIH/SIDA y otras enfermedades

    OpenAIRE

    García-Arriaza, J.; Gómez, Carmen E.; Esteban, Mariano

    2011-01-01

    La presente invención se engloba dentro de los campos de la biología molecular y de la biotecnología. Específicamente se refiere a virus recombinantes basados en el virus modificado de Ankara (MVA) que expresan los antígenos gp120 y Gag-Pol-Nef del virus de la inmunodeficiencia humana (VIH-1) de subtipo B (MVA-B), sobre los que se ha delecionado el gen de vaccinia C6L, y que han sido diseñados para utilizarse como vacunas contra el VIH/SIDA y otras enfermedades.

  2. Efeitos da somatotropina bovina recombinante (BST), da raça e da alimentação sobre a produção e a qualidade do leite de cabra na região Nordeste do Brasil

    OpenAIRE

    LUCENA, Jesane Alves de

    2003-01-01

    A somatotropina bovina recombinante (BST) tem sido utilizada como ferramenta para incrementar a produção leiteira em ruminantes, podendo ser aplicada à caprinocultura leiteira do Nordeste. A presente pesquisa foi realizada com o objetivo de verificar o efeito da BST sobre a produção e a qualidade do leite de cabra, de raças exóticas submetidas a diferentes níveis de concentrado, no semi-árido nordestino. O experimento foi conduzido na Embrapa/Caprinos, em Sobral-Ceará. Utili...

  3. Serotonin 2B receptor (5-HT2B R signals through prostacyclin and PPAR-ß/δ in osteoblasts.

    Directory of Open Access Journals (Sweden)

    Yasmine Chabbi-Achengli

    Full Text Available Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed that bone formation is reduced in the absence of the serotonin receptor 5-HT2B, causing impaired osteoblast proliferation, recruitment, and matrix mineralization. In this study, we investigated the signaling pathways responsible for the osteoblast defect in 5-HT2BR(-/- mice. Notably, we investigated the phospholipase A2 pathway and synthesis of eicosanoids in 5-HT2BR(-/- compared to wild type (WT osteoblasts. Compared to control osteoblasts, the lack of 5-HT2B receptors was only associated with a 10-fold over-production of prostacyclin (PGI2. Also, a specific prostacyclin synthase inhibitor (U51605 rescued totally osteoblast aggregation and matrix mineralization in the 5-HT2BR(-/- osteoblasts without having any effect on WT osteoblasts. Prostacyclin is the endogenous ligand of the nuclear peroxisome proliferator activated receptor ß/δ (PPAR-ß/δ, and its inhibition in 5-HT2BR(-/- cells rescued totally the alkaline phosphatase and osteopontin mRNA levels, cell-cell adhesion, and matrix mineralization. We conclude that the absence of 5-HT2B receptors leads to the overproduction of prostacyclin, inducing reduced osteoblast differentiation due to PPAR-ß/δ -dependent target regulation and defective cell-cell adhesion and matrix mineralization. This study thus reveals a previously unrecognized cell autonomous osteoblast defect in the absence of 5-HT2BR and highlights a new pathway linking 5-HT2B receptors and nuclear PPAR- ß/δ via prostacyclin.

  4. Mango resistance to fruit flies. II - resistance of the alfa cultivar

    International Nuclear Information System (INIS)

    Rossetto, C.J.; Bortoletto, N.; Carvalho, C.R.L.; Castro, J.V. de; Pinto, A.C. de Q.; Cortelazzo, A.L.

    2006-01-01

    The percentage of infested mango fruits of five selected mango varieties was evaluated during three years under field conditions. Three varieties with field resistance to fruit flies had less then 10% of fruits infested. Tommy Atkins, the susceptible commercial check, had 42,9% and the susceptible check had 98.9 % of infested fruits. The three field resistant varieties plus the susceptible commercial check, Tommy Atkins, were further tested in laboratory, under caged conditions, with artificial infestation of Anastrepha obliqua. The attempts of oviposition and the number of pupae developed from each fruit were evaluated. Under caged conditions, the cultivar Alfa maintained its field resistance and Espada Stahl and IAC 111 lost the field resistance and were as susceptible as Tommy Atkins. The attempts of oviposition were positively and highly correlated with the number of pupae developed in the fruits. Non preference for oviposition was confirmed as the main mechanism of resistance of mango fruits to fruit flies. In the absence of a more susceptible variety (no choice test) the cultivar Alfa has kept the resistance (author)

  5. Mango resistance to fruit flies. II - resistance of the alfa cultivar

    Energy Technology Data Exchange (ETDEWEB)

    Rossetto, C.J.; Bortoletto, N., E-mail: rossetto@iac.sp.gov.b [Agencia Paulista de Tecnologia dos Agronegocios (APTA), Votuporanga, SP (Brazil). Polo Regional do Noroeste Paulista; Walder, J.M.M.; Mastrangelo, T. de A., E-mail: jmwalder@cena.usp.b [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil); Carvalho, C.R.L.; Castro, J.V. de, E-mail: climonta@iac.sp.gov.b, E-mail: josalba@iac.sp.gov.b [Instituto Agronomico de Campinas, SP (Brazil); Pinto, A.C. de Q. [EMBRAPA, Brasilia, DF (Brazil); Cortelazzo, A.L., E-mail: angelo@unicamp.b [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Biologia

    2006-07-01

    The percentage of infested mango fruits of five selected mango varieties was evaluated during three years under field conditions. Three varieties with field resistance to fruit flies had less then 10% of fruits infested. Tommy Atkins, the susceptible commercial check, had 42,9% and the susceptible check had 98.9 % of infested fruits. The three field resistant varieties plus the susceptible commercial check, Tommy Atkins, were further tested in laboratory, under caged conditions, with artificial infestation of Anastrepha obliqua. The attempts of oviposition and the number of pupae developed from each fruit were evaluated. Under caged conditions, the cultivar Alfa maintained its field resistance and Espada Stahl and IAC 111 lost the field resistance and were as susceptible as Tommy Atkins. The attempts of oviposition were positively and highly correlated with the number of pupae developed in the fruits. Non preference for oviposition was confirmed as the main mechanism of resistance of mango fruits to fruit flies. In the absence of a more susceptible variety (no choice test) the cultivar Alfa has kept the resistance (author)

  6. FTIR spectroscopy and X-ray powder diffraction characterization of microcrystalline cellulose obtained from alfa fibers

    Directory of Open Access Journals (Sweden)

    Trache D.

    2013-07-01

    Full Text Available Many cereal straws have been used as raw materials for the preparation of microcrystalline cellulose (MCC. These raw materials were gradually replaced with wood products; nevertheless about 10% of the world overall pulp production is obtained from non-wood raw material. The main interest in pulp made from straw is that it provides excellent fibres for different industries with special properties, and that it is the major available source of fibrous raw material in some geographical areas. The aim of the present work was to characterize microcrystalline cellulose prepared from alfa fibers using the hydrolysis process. The products obtained are characterized with FTIR spectroscopy and X-ray powder diffraction. As a result, FTIR spectroscopy is an appropriate technique for studying changes occurred by any chemical treatment. The spectrum of alfa grass stems shows the presence of lignin and hemicelluloses. However, the cellulose spectrum indicates that the extraction of lignin and hemicellulose was effective. The X-ray analysis indicates that the microcrystalline cellulose is more crystalline than the source material.

  7. De-squeeze the beams: the TOTEM and ATLAS/ALFA experiments

    CERN Multimedia

    Stefania Pandolfi

    2016-01-01

    A special week-long proton–proton run with larger beam sizes at the interaction point is intended to probe the p-p elastic scattering regime at small angles.   Nicola Turini, deputy spokesperson for TOTEM, in front of one of the experiment’s ‘Roman Pot’ detectors in the LHC tunnel. (Photo: Maximilien Brice/CERN) Usually, the motto of the LHC is “maximum luminosity”. But for a few days per year, the LHC ignores its motto to run at very low luminosity for the forward experiments. This week, the LHC will provide the TOTEM and ATLAS/ALFA experiments with data for a broad physics programme. The TOTEM experiment at Point 5 and the ATLAS/ALFA experiment at Point 1 study the elastic scattering of protons, which are not observable in normal operation runs. In the elastic scattering process, the two protons survive their encounter intact and only change directions by exchanging momentum. To allow this special run, the operators play with the so-c...

  8. A GENERIC MODEL FOR THE B2B ENVIRONMENT

    OpenAIRE

    MARCO AURELIO F ALBERNAZ

    2004-01-01

    O ambiente de Comércio Eletrônico entre empresas apoiado pela Internet, conhecido como B2B, é muito complexo. Para nele operar, é importante a existência de um instrumento que permita visualizar de forma integrada os diversos elementos que interagem entre si nesse ambiente de negócios, facilite a sua compreensão e dê apoio à tomada de decisões e à elaboração de estratégias que agreguem valor às empresas que aí realizam as suas transações. A necessidade desse instrumento deu ...

  9. Applying conceptual design to B2B sales negotiations

    DEFF Research Database (Denmark)

    Illi, Mikko; Ylirisku, Salu

    problem that will be addressed is the building of understanding of a customer’s current needs and requirements, and then trying to devise an appropriate proposal to match these. The work of the sales agents in B2B sales negotiations is highly complex, as they need to understand both the modular machinery......, service, configuration and customisation of the products in their company as well as to develop an apposite understanding of the key values and characteristics of the client organisation. Based on a design-ethnographical study of real sales practice in lift truck business the paper draws parallels between...

  10. Optimización de una técnica de medida de disrupción endocrina por medio de Saccharomyces cerevisiae recombinantes

    Directory of Open Access Journals (Sweden)

    Karen Keel

    2011-05-01

    Full Text Available Los disruptores endocrinos son sustancias químicas, exógenas al organismo, capaces de alterar la homeostasis del sistema endocrino-reproductivo. Un grupo de ellos, los compuestos estrogénicos, pueden ocasionar efectos negativos sobre la capacidad reproductiva de algunos peces, disminución de la fertilidad, la aptitud sexual y la producción de esperma y feminización de los machos. En este trabajo se describe el desempeno analítico de un método para la cuantificación de estrogenicidad en aguas. Se utilizó la técnica Yeast Estrogen Screen (YES con Saccharomyces cerevisiae recombinante, una levadura modificada genéticamente que expresa el receptor de estrógenos humano y un plasmido de expresión con el gen reportero lacZ, bajo el control de elementos de respuesta a estrógenos. Dicho gen codifica para la ƒÀ-galactosidasa, que se secreta al medio y metaboliza un sustrato cromogénico, observandose un cambio de color que se mide a 420 nm. Se utilizaron estándares de 17 ƒÀ-estradiol para realizar una curva de calibración en el rango de concentraciones entre 1.75 ng/l y 7.5 ƒÊg/l. Las curvas sigmoides dosis.respuesta obtenidas se ajustaron mediante la función de Hill y los r2 fueron mayores a 0,95. El limite de detección fue de 55 ng/l. La estrogenicidad para las muestras ensayadas fue no detectable.

  11. Uso da somatotropina bovina recombinante - rbST como alternativa para a produção de leite de cabra na entressafra

    Directory of Open Access Journals (Sweden)

    Barbosa Paula Galvano

    2002-01-01

    Full Text Available O experimento desenvolveu-se no Setor de Caprinocultura da FMVZ - UNESP - Campus de Botucatu, com o objetivo de estudar a influência da somatotropina bovina recombinante (rbST - nome comercial: Boostin 250 mg na produção de leite, nos constituintes do leite, peso e escore de condição corporal de cabras durante o ciclo lactacional. Foram usadas 21 cabras da raça Parda Alpina, com idade entre 1 fraction one-half e 4 anos, distribuídas aleatoriamente entre três tratamentos de sete animais cada: controle (T1 - sem rbST; completo, safra e entressafra (T2 - rbST após 45 dias de lactação; e apenas entressafra (T3 - rbST após 154 dias de lactação. Os animais dos três tratamentos receberam a mesma alimentação, que diferiu apenas na quantidade de concentrado, ajustada de acordo com a produção de leite dos animais. Não se observou aumento na produção de leite dos animais tratados, mas a persistência da lactação foi maior nestes animais. Não se observou diferença entre animais controles e tratados quanto aos constituintes do leite (densidade, gordura, EST, lactose e proteína. O peso e o índice de condição corporal também não apresentaram diferença significativa entre animais tratados e controle.

  12. The Morphology of TiO2 (B) Nanoparticles.

    Science.gov (United States)

    Hua, Xiao; Liu, Zheng; Bruce, Peter G; Grey, Clare P

    2015-10-28

    The morphology of a nanomaterial (geometric shape and dimension) has a significant impact on its physical and chemical properties. It is, therefore, essential to determine the morphology of nanomaterials so as to link shape with performance in specific applications. In practice, structural features with different length scales are encoded in a specific angular range of the X-ray or neutron total scattering pattern of the material. By combining small- and wide-angle scattering (typically X-ray) experiments, the full angular range can be covered, allowing structure to be determined accurately at both the meso- and the nanoscale. In this Article, a comprehensive morphology analysis of lithium-ion battery anode material, TiO2 (B) nanoparticles (described in Ren, Y.; Liu, Z.; Pourpoint, F.; Armstrong, A. R.; Grey, C. P.; Bruce, P. G. Angew. Chem. Int. Ed. 2012, 51, 2164), incorporating structure modeling with small-angle X-ray scattering (SAXS), pair distribution function (PDF), and X-ray powder diffraction (XRPD) techniques, is presented. The particles are oblate-shaped, contracted along the [010] direction, this particular morphology providing a plausible rationale for the excellent electrochemical behavior of these TiO2(B) nanoparticles, while also provides a structural foundation to model the strain-driven distortion induced by lithiation. The work demonstrates the importance of analyzing various structure features at multiple length scales to determine the morphologies of nanomaterials.

  13. Magnetospheric Multiscale Mission (MMS) Phase 2B Navigation Performance

    Science.gov (United States)

    Scaperoth, Paige Thomas; Long, Anne; Carpenter, Russell

    2009-01-01

    The Magnetospheric Multiscale (MMS) formation flying mission, which consists of four spacecraft flying in a tetrahedral formation, has challenging navigation requirements associated with determining and maintaining the relative separations required to meet the science requirements. The baseline navigation concept for MMS is for each spacecraft to independently estimate its position, velocity and clock states using GPS pseudorange data provided by the Goddard Space Flight Center-developed Navigator receiver and maneuver acceleration measurements provided by the spacecraft's attitude control subsystem. State estimation is performed onboard in real-time using the Goddard Enhanced Onboard Navigation System flight software, which is embedded in the Navigator receiver. The current concept of operations for formation maintenance consists of a sequence of two maintenance maneuvers that is performed every 2 weeks. Phase 2b of the MMS mission, in which the spacecraft are in 1.2 x 25 Earth radii orbits with nominal separations at apogee ranging from 30 km to 400 km, has the most challenging navigation requirements because, during this phase, GPS signal acquisition is restricted to less than one day of the 2.8-day orbit. This paper summarizes the results from high-fidelity simulations to determine if the MMS navigation requirements can be met between and immediately following the maintenance maneuver sequence in Phase 2b.

  14. USING UML SCENARIOS IN B2B SYSTEMS

    Directory of Open Access Journals (Sweden)

    A. Jakimi

    2010-05-01

    Full Text Available Scenarios has become a popular technique for requirements elicitation and specification building. Since scenarios capture only partial descriptions of the system behavior, an approach for scenario composition and/or integration is needed to produce more complete specifications. The Unified Modeling Language (UML, which has become a standard notation for object-oriented modeling, provides a suitable framework for scenario acquisition using Use Case diagrams and Sequence or Collaboration diagrams. In this paper, we suggest an algorithmic and tool support for composing and integrating scenarios that are represented in form of sequence diagrams. We suggest four operators (;: sequential operator, ||: concurrent operator, ?: conditional operator and  * :iteration operator to compose a set of scenarios that describe a use case of a given system. In this paper, we suggest also to apply the scenario approach to B2B systems (Business to Business. We propose to develop B2B systems as a three activities process deriving formal specifications and code skeletons from UML scenarios. Activities of this proposed process are generally automatic and are supported by a set of developed algorithms and tools.

  15. Vortex lattice structures in YNi2B2C

    International Nuclear Information System (INIS)

    Yethiraj, M.; Paul, D.M.; Tomy, C.V.; Forgan, E.M.

    1997-01-01

    The authors observe a flux lattice with square symmetry in the superconductor YNi 2 B 2 C when the applied field is parallel to the c-axis of the crystal. A square lattice observed previously in the isostructural magnetic analog ErNi 2 B 2 C was attributed to the interaction between magnetic order in that system and the flux lattice. Since the Y-based compound does not order magnetically, it is clear that the structure of the flux lattice is unrelated to magnetic order. In fact, they show that the flux lines have a square cross-section when the applied field is parallel to the c-axis of the crystal, since the measured penetration depth along the 100 crystal direction is larger than the penetration depth along the 110 by approximately 60%. This is the likely reason for the square symmetry of the lattice. Although they find considerable disorder in the arrangement of the flux lines at 2.5T, no melting of the vortex lattice was observed

  16. Dornase Alfa

    Science.gov (United States)

    ... lung function in patients with cystic fibrosis. It breaks down the thick secretions in the airways, allowing ... symptoms are severe or do not go away. voice changes sore throat hoarseness eye irritation rash If ...

  17. Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure): Clinical and Prognostic Associations.

    Science.gov (United States)

    van der Meer, Peter; Grote Beverborg, Niels; Pfeffer, Marc A; Olson, Kurt; Anand, Inder S; Westenbrink, B Daan; McMurray, John J V; Swedberg, Karl; Young, James B; Solomon, Scott D; van Veldhuisen, Dirk J

    2018-02-01

    A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215. © 2018 American Heart Association, Inc.

  18. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa

    NARCIS (Netherlands)

    Olivennes, F.; Trew, G.; Borini, A.; Broekmans, F.; Arriagada, P.; Warne, D. W.; Howles, C. M.

    2015-01-01

    In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited

  19. Generation of an alfa-L-rhamnosidase Library and its Application for the Selective Derhamnosylation of Natural Products

    Czech Academy of Sciences Publication Activity Database

    Monti, D.; Pišvejcová, Andrea; Křen, Vladimír; Lama, M.; Riva, S.

    2004-01-01

    Roč. 87, č. 6 (2004), s. 763-771 ISSN 0006-3592 R&D Projects: GA MŠk OC D25.002 Grant - others:GANATO(XX) No LSTCLG.980125 Keywords : alfa-l-rhamnosidases * glycosidases * natural glycosides Subject RIV: EE - Microbiology, Virology Impact factor: 2.216, year: 2004

  20. Increased risk of stroke with darbepoetin alfa in anaemic heart failure patients with diabetes and chronic kidney disease

    NARCIS (Netherlands)

    Bello, Natalie A.; Lewis, Eldrin F.; Desai, Akshay S.; Anand, Inder S.; Krum, Henry; McMurray, John J. V.; Olson, Kurt; Solomon, Scott D.; Swedberg, Karl; van Veldhuisen, Dirk J.; Young, James B.; Pfeffer, Marc A.

    2015-01-01

    Aims The use of an erythropoesis-stimulating agent, darbepoetin alfa (DA), to treat anaemia in patients with diabetes mellitus and chronic kidney disease was associated with a heightened risk of stroke and neutral efficacy in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT),

  1. Characterization of IXINITY® (Trenonacog Alfa, a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    Directory of Open Access Journals (Sweden)

    Dougald M. Monroe

    2016-01-01

    Full Text Available The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148 polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant]. Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX both with and without factor VIIIa (FVIIIa and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed 97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa; once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX.

  2. Dificuldades na identificação laboratorial da talassemia alfa Difficulty on laboratory identification of alpha thalassemia

    Directory of Open Access Journals (Sweden)

    Karlla Greick Batista Dias-Penna

    2010-04-01

    Full Text Available Introdução: Talassemia alfa é uma síndrome associada à redução da síntese de cadeias de globina do tipo alfa. A gravidade das manifestações clínicas está relacionada com a quantidade de globinas produzida e a estabilidade das cadeias beta presentes em excesso. A talassemia alfa mínima resulta da deleção de apenas um dos quatro genes a (-α/αα. Clinicamente apresenta anemia leve com microcitose ou ausência de anemia, sendo o diagnóstico realizado por meio de visualização da hemoglobina (Hb H por eletroforese alcalina em acetato de celulose ou por identificação de inclusões celulares de Hb H coradas pelo azul de crezil brilhante. Objetivo: Avaliar portadores de talassemia alfa e seus respectivos progenitores, correlacionando perfil hematológico e presença de Hb H, utilizando procedimentos laboratoriais clássicos em três diferentes amostragens. Discussão e conclusão: Os dados obtidos mostram que a presença de Hb H, indicativo de talassemia alfa, pode não ser confirmada em uma análise posterior. Entre os fatores que podem influenciar no não aparecimento de Hb H em pessoa comprovadamente com talassemia alfa está a deficiência de ferro. A talassemia alfa está associada a defeitos envolvendo os genes codificadores da cadeia alfa, mas também pode estar relacionada com desbalanciamento temporário na expressão dos genes globina, diminuição de alfa ou aumento de beta, o que poderia explicar o aparecimento de tetrâmeros de cadeia beta (Hb H, sugerindo diagnóstico de talassemia alfa mínima.Introduction: Alpha thalassemia is a syndrome with associated with the reduction of alpha globin chain synthesis. The severity of clinical manifestations is related to the amount of globins produced and the stability of beta chains that are present in excess. Alpha thalassemia minor is caused by the deletion of one of the four genes a (-α/αα. Clinically, it presents mild anemia with microcytosis or absence of anemia. The

  3. Using ALFA for high throughput, distributed data transmission in the ALICE O2 system

    Science.gov (United States)

    Wegrzynek, A.; ALICE Collaboration

    2017-10-01

    ALICE (A Large Ion Collider Experiment) is a heavy-ion detector designed to study the physics of strongly interacting matter (the Quark-Gluon Plasma at the CERN LHC (Large Hadron Collider). ALICE has been successfully collecting physics data in Run 2 since spring 2015. In parallel, preparations for a major upgrade of the computing system, called O2 (Online-Offline), scheduled for the Long Shutdown 2 in 2019-2020, are being made. One of the major requirements of the system is the capacity to transport data between so-called FLPs (First Level Processors), equipped with readout cards, and the EPNs (Event Processing Node), performing data aggregation, frame building and partial reconstruction. It is foreseen to have 268 FLPs dispatching data to 1500 EPNs with an average output of 20 Gb/s each. In overall, the O2 processing system will operate at terabits per second of throughput while handling millions of concurrent connections. The ALFA framework will standardize and handle software related tasks such as readout, data transport, frame building, calibration, online reconstruction and more in the upgraded computing system. ALFA supports two data transport libraries: ZeroMQ and nanomsg. This paper discusses the efficiency of ALFA in terms of high throughput data transport. The tests were performed with multiple FLPs pushing data to multiple EPNs. The transfer was done using push-pull communication patterns and two socket configurations: bind, connect. The set of benchmarks was prepared to get the most performant results on each hardware setup. The paper presents the measurement process and final results - data throughput combined with computing resources usage as a function of block size. The high number of nodes and connections in the final set up may cause race conditions that can lead to uneven load balancing and poor scalability. The performed tests allow us to validate whether the traffic is distributed evenly over all receivers. It also measures the behaviour of

  4. Neutron diffraction studies of magnetic ordering in superconducting ErNi2B2C and TmNi2B2C in an applied magnetic field

    DEFF Research Database (Denmark)

    Toft, Katrine Nørgaard

    The field-induced magnetic structures of ErNi2B2C and TmNi2B2C in are especially interesting because the field suppresses the superconducting order parameter and therefore the magnetic properties can be studied while varying the strength ofsuperconductivity. ErNi2B2C: For magnetic fields along al...

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

    Science.gov (United States)

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

    2008-01-01

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

  6. Matchmaking Framework for B2B E-Marketplaces

    Directory of Open Access Journals (Sweden)

    Fekete ZOLTAN ALPAR

    2010-01-01

    Full Text Available In the recent years trading on the Internet become more popular. Online businesses gradually replace more and more from the conventional business. Much commercial information is exchanged on the internet, especially using the e-marketplaces. The demand and supply matching process becomes complex and difficult on last twenty years since the e-marketplaces play an important role in business management. Companies can achieve significant cost reduction by using e-marketplaces in their trade activities and by using matchmaking systems on finding the corresponding supply for their demand and vice versa. In the literature were proposed many approaches for matchmaking. In this paper we present a conceptual framework of matchmaking in B2B e-marketplaces environment.

  7. Relationship Quality as Predictor of B2B Customer Loyalty

    Directory of Open Access Journals (Sweden)

    Shaimaa S. B. Ahmed Doma

    2013-02-01

    Full Text Available Relationship marketing has become extremely important recently due to the fierce competition in today's marketplace. Companies are required to build long-term profitable relationship with customers and to achieve customer loyalty. Also, switching behaviors frequently occur among most of targeted customers. Fewer studies, however, discuss the effects of relationship quality efforts on customer loyalty. Therefore, this study is aimed to investigate the impact of relationship quality on customer loyalty in B2B context in the Egyptian shipping services sector. Building on prior research, we propose relationship quality as a higher construct comprising trust, commitment and satisfaction. An analytical model is developed as a guideline to test the relationships between relationship quality dimensions and customer loyalty.

  8. The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil

    Directory of Open Access Journals (Sweden)

    Artico Simara

    2012-12-01

    Full Text Available Abstract Background More than 50% of patients infected with chronic hepatitis C virus (HCV do not respond to treatment with conventional interferon (IFN combined with ribavirin (RBV. The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR. Methods From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR. Virological Response (VR within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. Results The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031. As predictive factors that contribute to improve SVR, were identified the age (p = 0.005, to be relapsers to previous treatment (p = 0.023 and present liver biopsy examination Metavir F0-F2 (p = 0.004. In assessing the safety profile, 51 patients (23.6% discontinued treatment prematurely. Conclusions This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.

  9. The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil.

    Science.gov (United States)

    Artico, Simara; Amaral, Karine Medeiros; Gonçalves, Candice Beatriz Treter; Picon, Paulo Dornelles

    2012-12-27

    More than 50% of patients infected with chronic hepatitis C virus (HCV) do not respond to treatment with conventional interferon (IFN) combined with ribavirin (RBV). The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b) concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR). From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg) per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR). Virological Response (VR) within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031). As predictive factors that contribute to improve SVR, were identified the age (p = 0.005), to be relapsers to previous treatment (p = 0.023) and present liver biopsy examination Metavir F0-F2 (p = 0.004). In assessing the safety profile, 51 patients (23.6%) discontinued treatment prematurely. This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.

  10. Expresión de los genes implicados en la glicosilación del alfa-distroglicano en el desarrollo embrionario del pollo (gallus gallus).

    OpenAIRE

    Izquierdo, A.; Luis, O. de; Gómez-Esquer, F.; Tarilonte, P.; Fano, O.; Raducu, M.; Cruces, J.; Coloma, A.

    2009-01-01

    El distroglicano es el componente fundamental del complejo de glicoproteínas de unión a distrofina, sirviendo de puente entre el citoesqueleto de actina y la matriz extracelular en células musculares y en neuronas. El distroglicano es una glicoproteína formada por dos subunidades alfa y beta unidas por uniones no covalentes. El déficit de glicosilación del alfa-distroglicano da lugar a un tipo de distrofias musculares congénitas con afectación neuronal y ocular, denominadas alfa-distroglicano...

  11. ALGLUCOSIDASE ALFA — A NEW STAGE IN THE THERAPY OF INFANTILE POMPE DISEASE

    Directory of Open Access Journals (Sweden)

    E. N. Basargina

    2014-01-01

    Full Text Available Pompe disease is a rare severe hereditary disease caused by excessive glycogen storage in organs and target tissues due to the acid α-glucosidase gene mutation. Infantile and adult Pompe disease is characterized by involvement of cardiovascular, respiratory and muscular systems in the pathological process. The only specific method of treating Pompe disease is enzyme replacement therapy (intravenous administration of recombinant human acid glucosidase, the effectiveness whereof depends on the time the therapy started. Since such a therapy was introduced into practice, Pompe disease mortality decreased by 79%. 6 children with infantile Pompe disease were observed and treated at the cardiovascular care unit of the Scientific Center of Children’s Health in 2011‑2014. The article presents a clinical case demonstrating capabilities of diagnosing infantile Pompe disease in Russia and effective application of alglucosidase alfa in 4-month-old child. 

  12. VizieR Online Data Catalog: UV counterparts in HI clouds using ALFA surveys (Donovan+, 2015)

    Science.gov (United States)

    Donovan Meyer, J.; Peek, J. E. G.; Putman, M.; Grcevich, J.

    2017-10-01

    GALFA-HI is a survey of Galactic HI conducted with the ALFA seven-beam feed array on the 305 m Arecibo antenna. The survey has both high spatial (FWHM~4') and velocity (0.18 km/s) resolution over 13000 (7520 in DR1) degrees2 of sky between -650 and 650 km/s. Details of the observations and data reduction can be found in Peek et al. (2011ApJS..194...20P). The ALFALFA HI-line survey, now 40% complete, also uses the Arecibo Observatory and its seven-beam feed array to detect potential dwarf galaxies in the vicinity of the Milky Way. The survey, which covers over 7000 (2800 in α.40) deg2 of sky out to 18000 km/s, has the sensitivity to detect 105 Mȯ clouds with 20 km/s linewidths at a distance of 1 Mpc. (2 data files).

  13. Profile of efraloctocog alfa and its potential in the treatment of hemophilia A

    Directory of Open Access Journals (Sweden)

    George LA

    2015-04-01

    Full Text Available Lindsey A George,1,2 Rodney M Camire1–3 1Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; 2Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; 3Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Hemophilia care has improved dramatically over the past 50 years, evolving from plasma concentrates, to purified plasma proteins, to recombinant clotting factors. These collective developments allowed for home delivery of on-demand and prophylactic treatment, resulting in the reduction of hemophilia morbidity and mortality and improved quality of life. Although efficacious in treating bleeding, conventional factor products' half-lives require frequent venipuncture, which remains a significant burden to patients. Despite the remarkable advances in hemophilia care, no improvements have, until now, been made to the pharmacokinetic properties of factor products. Multiple strategies have more recently been employed to generate novel bioengineered products that, with great hope, represent the next wave of progress in hemophilia care. The use of these products will undoubtedly raise important discussion about choosing conventional factor over new long-acting factor products. Incorporation of these therapies into clinical care is accompanied by unanswered safety questions that will likely be evaluated only in postmarketing surveillance analysis. Further, these products may change current treatment paradigms with unclear cost repercussions and feasibility. This paper will review efraloctocog alfa (FVIII-Fc and its role in the treatment of hemophilia A. Keywords: hemophilia A, factor VIII, Fc fusion, bioengineered products, efraloctocog alfa

  14. Properties of Cold HI Emission Clouds in the Inner-Galaxy ALFA Survey

    Science.gov (United States)

    Hughes, James Marcus; Gibson, Steven J.; Noriega-Crespo, Alberto; Newton, Jonathan; Koo, Bon-Chul; Douglas, Kevin A.; Peek, Joshua Eli Goldston; Park, Geumsook; Kang, Ji-hyun; Korpela, Eric J.; Heiles, Carl E.; Dame, Thomas M.

    2017-01-01

    Star formation, a critical process within galaxies, occurs in the coldest, densest interstellar clouds, whose gas and dust content are observed primarily at radio and infrared wavelengths. The formation of molecular hydrogen (H2) from neutral atomic hydrogen (HI) is an essential early step in the condensation of these clouds from the ambient interstellar medium, but it is not yet completely understood, e.g., what is the predominant trigger? Even more troubling, the abundance of H2 may be severely underestimated by standard tracers like CO, implying significant "dark" H2, and the quantity of HI may also be in error if opacity effects are neglected. We have developed an automated method to account for both HI and H2 in cold, diffuse clouds traced by narrow-line HI 21-cm emission in the Arecibo Inner-Galaxy ALFA (I-GALFA) survey. Our algorithm fits narrow (2-5 km/s), isolated HI line profiles to determine their spin temperature, optical depth, and true column density. We then estimate the "visible" H2 column in the same clouds with CfA and Planck CO data and the total gas column from dust emission measured by Planck, IRAS, and other surveys. Together, these provide constraints on the dark H2 abundance, which we examine in relation to other cloud properties and stages of development. Our aim is to build a database of H2-forming regions with significant dark gas to aid future analyses of coalescing interstellar clouds. We acknowledge support from NSF, NASA, Western Kentucky University, and Williams College. I-GALFA is a GALFA-HI survey observed with the 7-beam ALFA receiver on the 305-meter William E. Gordon Telescope. The Arecibo Observatory is a U.S. National Science Foundation facility operated under sequential cooperative agreements with Cornell University and SRI International, the latter in alliance with the Ana G. Mendez-Universidad Metropolitana and the Universities Space Research Association.

  15. A large, multicentre, observational, post-marketing surveillance study of the 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice for assisted reproductive technology.

    Science.gov (United States)

    Bühler, Klaus; Naether, Olaf G J; Bilger, Wilma

    2014-01-14

    Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) both have a role to play in follicular development during the natural menstrual cycle. LH supplementation during controlled ovarian stimulation (COS) for assisted reproductive technology (ART) is used for patients with hypogonadotropic hypogonadism. However, the use of exogenous LH in COS in normogonadotropic women undergoing ART is the subject of debate. The aim of this study was to investigate characteristics of infertile women who received the 2:1 formulation of follitropin alfa and lutropin alfa (indicated for stimulation of follicular development in women with severe LH and FSH deficiency) in German clinical practice. A 3-year, multicentre, open-label, observational/non-interventional, post-marketing surveillance study of women (21-45 years) undergoing ART. Primary endpoint: reason for prescribing the 2:1 formulation of follitropin alfa and lutropin alfa. Secondary variables included: COS duration/dose; oocytes retrieved; fertilization; clinical pregnancy; ovarian hyperstimulation syndrome (OHSS). In total, 2220 cycles were assessed; at least one reason for prescribing the 2:1 formulation was given in 1834/2220 (82.6%) cycles. Most common reasons were: poor ovarian response (POR) (39.4%), low baseline LH (17.8%), and age (13.8%). COS: mean dose of the 2:1 formulation on first day, 183.1/91.5 IU; mean duration, 10.8 days. In 2173/2220 (97.9%) cycles, human chorionic gonadotrophin was administered. Oocyte pick-up (OPU) was attempted in 2108/2220 (95.0%) cycles; mean (standard deviation) 8.0 (5.4) oocytes retrieved/OPU cycle. Fertilization (≥1 oocyte fertilized) rates: in vitro fertilization (IVF), 391/439 (89.1%) cycles; intracytoplasmic sperm injection (ICSI)/IVF + ICSI, 1524/1613 (94.5%) cycles. Clinical pregnancy rate: all cycles, 25.9%; embryo transfer cycles, 31.3%. OHSS: hospitalization for OHSS, 8 (0.36%) cycles, Grade 2, 60 (2.7%), and Grade 3, 1 (0.05%). In German routine clinical

  16. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2012-04-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.         JEL Codes: D23, L86Keywords: Cost, Transaction Costs, Transactions

  17. Getting started with Oracle SOA B2B Integration a hands-on tutorial

    CERN Document Server

    Bhatia, Krishnaprem; Perlovsky, Alan

    2013-01-01

    This hands on tutorial gives you the best possible start you could hope for with Oracle B2B. Learn using real life scenarios and examples to give you a solid footing of B2B.This book is for B2B architects, consultants and developers who would like to design and develop B2B integrations using Oracle B2B. This book assumes no prior knowledge of Oracle B2B and explains all concepts from scratch using illustrations, real world examples and step-by-step instructions. The book covers enough depth and details to be useful for both beginner and advanced B2B users.

  18. Treatment Outcomes and Predictors of Response in Treatment-Naive HCV Patients Treated with Peginterferon Alfa/Ribavirin in Real-World Italian Clinics: Sub-Analysis from the PROPHESYS Cohort.

    Science.gov (United States)

    Ascione, Antonio; Bruno, Savino; Coppola, Carmine; Mangia, Alessandra; Orlandini, Alessandra; Schmitz, Manuela; Deodato, Barbara; Puoti, Massimo

    2014-06-01

    Within Europe, Italy has the highest incidence of HCV. PROPHESYS was a large, non-interventional, multinational cohort study of patients treated with peginterferon alfa-2a or -2b/ribavirin for CHC; 22.4% of patients were from Italian centers. This sub-analysis evaluates real-life practice and treatment outcomes in Italy. The PROPHESYS 2 cohort included 1604 HCV mono-infected, treatment-naive patients. All patients were prescribed peginterferon alfa/ribavirin at the discretion of the treating physician according to country-specific requirements. The majority of G1-3 patients were White/Caucasian and 48.4% had HCV G1 infection. Overall, SVR24 rates of 44.9%, 81.4% and 69.1% were achieved in G1-, 2- and 3-infected patients. In G1 patients, SVR24 rates declined with increasing FIB-4 score; this trend was not observed for G2/3-infected patients. Virologic response by Week 2 and 4 was highly predictive of SVR24 (G1: 91.7%, 84.8%; G2: 91.1%, 89.7%; G3: 92.9%, 86.7%, respectively). Absence of virologic response by Week 12 had the highest negative predictive value across genotypes. In Italian patients, a virologic response by Week 2 or 4 was highly predictive of SVR24 across genotypes. These data demonstrate the importance of monitoring on-treatment response to help guide treatment decisions. FIB-4 score correlated well with SVR24 in G1 patients.

  19. Natural releases from contaminated groundwater, Example Reference Biosphere 2B

    International Nuclear Information System (INIS)

    Simon, I.; Naito, M.; Thorne, M.C.; Walke, R.

    2005-01-01

    Safety assessment is a tool which, by means of an iterative procedure, allows the evaluation of the performance of a disposal system and its potential impact on human health and the environment. Radionuclides from a deep geological disposal facility may not reach the surface environment until many tens of thousands of years after closure of the facility. The BIOMASS Programme on BIOsphere Modelling and ASSessment developed Examples of 'Reference Biospheres' to illustrate the use of the methodology and to demonstrate how biosphere models can be developed and justified as being fit for purpose. The practical examples are also intended to be useful in their own right. The Example Reference Biosphere 2B presented here involves the consideration of alternative types of geosphere-biosphere interfaces and calculation of doses to members of hypothetical exposure groups arising from a wide range of exposure pathways within agricultural and semi-natural environments, but without allowing for evolution of the corresponding biosphere system. The example presented can be used as a generic analysis in some situations although it was developed around a relatively specific conceptual model. It should be a useful practical example, but the above numerical results are not intended to be understood as prescribed biosphere 'conversion factors'

  20. Molecular characterization of an. alpha. sub 2B -adrenergic receptor

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, J.K.; Dewan Zeng; D' Angelo, D.D.; Tucker, A.L.; Zhihong Lu; Barber, C.M.; Lynch, K.R. (Univ. of Virginia Health Sciences Center, Charlottesville (United States))

    1990-02-26

    {alpha}{sub 2}-Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNG{alpha}2) encoding a previously undescribed third subtype of an {alpha}{sub 2}-adrenergic receptor from a rat kidney cDNA library. The library was screened with an oligonucleotide encoding a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of G-protein coupled receptors with exception of the absence of the consensus N-linked glycosylation site at the amino terminus. Membranes prepared from COS-1 cells transfected with pRNG{alpha}2 display high affinity and saturable binding to {sup 3}H-rauwolscine (K{sub d}=2 nM).Competition curve data analysis shows that pRNG{alpha}2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine {ge} cholorpromazine > prazosin {ge} clonidine > norepinephrine {ge} oxymetazoline. pRNG{alpha}2 RNA accumulates in both adult rat kidney and rat neonatal lung (predominant species is 4.0 kb). They conclude that pRNG{alpha}2 likely represents a cDNA for the {alpha}{sub 2B}-adrenergic receptor.

  1. The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonist

    Directory of Open Access Journals (Sweden)

    Seyhan A

    2011-08-01

    Full Text Available Ayse Seyhan, Baris AtaDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montreal, QC, CanadaAbstract: Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone (rFSH molecule containing a hybrid beta subunit, which provides a plasma half-life of ∼65 hours while maintaining its pharmocodynamic activity. A single injection of corifollitropin alfa can replace daily FSH injections for the first week of ovarian stimulation for in vitro fertilization. Stimulation can be continued with daily FSH injections if the need arises. To date, more than 2500 anticipated normoresponder women have participated in clinical trials with corifollitropin alfa. It is noteworthy that one-third of women did not require additional gonadotropin injections and reached human chorionic gonadotropin criterion on day 8. The optimal corifollitropin dose has been calculated to be 100 µg for women with a body weight ≤ 60 kg and 150 µg for women with a body weight >60 kg, respectively. Combination of corifollitropin with daily gonadotropin-releasing hormone antagonist injections starting on stimulation day 5 seems to yield similar or significantly higher numbers of oocytes and good quality embryos, as well as similar ongoing pregnancy rates compared with women stimulated with daily rFSH injections. Stimulation characteristics, embryology, and clinical outcomes seem consistent with repeated corifollitropin-stimulated assisted reproductive technologies cycles. Multiple pregnancy or ovarian hyperstimulation syndrome rates with corifollitropin were not increased over daily FSH regimen. The corifollitropin alfa molecule does not seem to be immunogenic and does not induce neutralizing antibody formation. Drug hypersensitivity and injection-site reactions are not increased. Incidence and nature of adverse events and serious adverse events are similar to daily FSH injections. Current trials do not

  2. Dolor lumbar por estreptoquinasa recombinante: Presentación de un caso Lumbar pain caused by recombinant streptokinase: A case presentation

    Directory of Open Access Journals (Sweden)

    María Julia Cigales Reyes

    2009-08-01

    Full Text Available La Heberkinasa® (estreptoquinasa recombinante, es un trombolítico utilizado en el tratamiento del infarto agudo del miocardio, presentada en forma de liofilizado en bulbos estériles, de conocidos y probados efectos de reperfusión coronaria y reducción del tamaño del infarto, además de otras aplicaciones como en la trombosis venosa profunda, trombosis de acceso vascular permanente de pacientes con insuficiencia renal crónica terminal tratados por hemodiálisis periódicas, disfunción de prótesis valvulares cardíacas por trombos y en el tromboembolismo pulmonar; se asocian reacciones adversas durante el tratamiento, frecuentes y menos frecuentes, dentro de las que se encuentra el dolor lumbar. Se presenta a una paciente con el diagnóstico de un infarto agudo del miocardio, de cara diafragmática, a quien se le aplicó la trombolisis con Heberkinasa y durante esta presentó dolor lumbar agudo, intenso, que cedió con la reducción de goteo de la infusión y esta se pudo continuar sin más problemas.The Heberkinase® (recombinant streptokinase is a thrombolytic agent used in treatment of acute myocardial infarction, presented as sterile bulbs, of known and proved effects of coronary reperfusion and reduction of infarction dimension, besides of other applications e.g. the deep venous thrombosis, permanent vascular access thrombosis in patients presenting with terminal chronic renal insufficiency treated by periodical hemodialysis, dysfunction of cardiac vascular prostheses by thrombi, and in case of pulmonary thromboembolism; there are adverse reactions associated during treatment, frequent and less frequent including those of lumbar pain. Authors present a case of a woman diagnosed with acute myocardial infarction of diaphragmatic side undergoing thrombolysis with Heberkinase, and during it she had intense and acute lumbar pain improving with reduction of dripping infusion without subsequent problems.

  3. Efecto de adición de iones hierro y zinc sobre la producción de etanol de dos cepas recombinantes de Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Carolina Peña Serna

    2010-01-01

    Full Text Available La producción de etanol por fermentación es influenciada por la presencia de iones metálicos como hierro y zinc dado que son cofactores de la enzima alcohol deshidrogenasa. El estudio de este efecto permitiría identificar el comportamiento de los microorganismos fermentadores en sustratos industriales que contienen altas concentraciones de este tipo de iones. Este trabajo evaluó la producción de biomasa, los azúcares residuales y la producción de etanol por fermentación de tres cepas de S. cerevisiae, CBS8066, recombinantes GG570-CIBI y GG570-CIBII, bajo el efecto de la adición de hierro a 0, 50 y 150 M, y zinc a 0 y 50 M. Las cepas presentaron inhibición en la producción de biomasa y etanol bajo efecto de iones de hierro y zinc, siendo dicha inhibición mayor al estar en presencia de zinc o alta concentración de hierro. GG570-CIBI mostró disminución en producción de biomasa de 4 g/L y una caída en producción de etanol de 40% en el tratamiento 150 M hierro-50 M zinc (con respecto al tratamiento basal. GG570-CIBII fue la menos afectada con inhibición en la producción de etanol inferior a 11% a las 20 h de fermentación. Adicionalmente, presentó la mayor producción de etanol cuando hubo adición de 150 M Fe con o sin adición de zinc, siendo dicha producción entre un 9 y 14% superior a la de las cepas CBS8066 y GG570-CIBI respectivamente, bajo las mismas condiciones. Posteriormente, GG570-CIBII será evaluada en sustratos industriales debido a su menor inhibición en la producción de etanol, permitiendo así obtener mejores rendimientos.

  4. Efecto protector de una vacuna recombinante contra la hepatitis B siguiendo tres esquemas de inmunización: Lima - Perú 2004

    Directory of Open Access Journals (Sweden)

    Luis Marocho

    2006-03-01

    Full Text Available Objetivo: Demostrar que el efecto protector contra la hepatitis B en estudiantes del área de ciencias de la salud susceptibles se logra igualmente luego de completar tres esquemas de vacunación, uno convencional y dos acortados en tiempo y dosis. Diseño: Estudio experimental, controlado, abierto y con asignación aleatoria de grupo. Materiales y Métodos: Participaron 89 alumnos del último año de estudios (internado de la Escuela Académico Profesional de Tecnología Médica, Facultad de Medicina, UNMSM, de ambos sexos y menores de 30 años, a quienes se asignó aleatoriamente a tres grupos de receptores de la vacuna, siguiendo uno de tres esquemas de vacunación: el convencional de tres dosis (0, 1 y 6 meses , el acortado de tres dosis (0, 1 y 2 meses y acortado de dos dosis (0 y 1 mes. Se excluyó los vacunados contra hepatitis B y aquellos que fueron positivos a marcadores de antígeno de superficie (HBsAg o anti core total (anti-HBc IgG. Según el cronograma establecido, se administró las dosis de vacuna recombinante contra virus de hepatitis B (REVAC-B en concentraciones de 20 mcg/mL y se tomó muestras de sangre para la titulación de anticuerpos. Resultados: La edad promedio de los 89 alumnos fue 23,5 años, siendo 51,7% (46 del sexo masculino y 48,3% (43 del femenino. A los 30 días de la primera dosis, el 12,4% alcanzó protección, a los 30 días posterior a la segunda dosis, 98,8%, y a los 180 días, hubo 100% de protección. Conclusiones: En el presente estudio se obtuvo igual efecto protector contra la hepatitis B mediante la administración de la vacuna con tres esquemas diferentes: esquema convencional (tres dosis, esquema acortado (dos dosis y esquema acortado (tres dosis. Se plantea la posibilidad de un esquema con dos dosis, el cual tendría un menor costo e igual beneficio.

  5. First Principles Study on Structure Stability and Mechanical Properties of YNi2B2C and LuNi2B2C under Pressure

    Directory of Open Access Journals (Sweden)

    Lili Liu

    2017-06-01

    Full Text Available The pressure effects on the lattice parameters and elastic constants of the tetragonal RNi 2 B 2 C (R=Y, Lu are investigated by means of the first principles. The predicted lattice constants and elastic constants of YNi 2 B 2 C and LuNi 2 B 2 C at 0 GPa agree well with the available data. By the elastic stability criteria under isotropic pressure, it is predicted that YNi 2 B 2 C and LuNi 2 B 2 C with tetragonal structure are not mechanically stable above 93 GPa and 50 GPa, respectively. Pugh’s modulus ratio, Poisson’s ratio, Vickers hardness, elastic anisotropy and Debye temperature of YNi 2 B 2 C in the pressure range of 0–100 GPa and LuNi 2 B 2 C in the pressure range of 0-60 GPa are further investigated. It is shown that the ductility and Debye temperature of tetragonal RNi 2 B 2 C (R=Y, Lu increase with increasing pressure, and LuNi 2 B 2 C is more ductile and lower Debye temperature than YNi 2 B 2 C under different pressures.

  6. Dgroup: DG01750 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tical recombination) (JAN) D02745 ... Interferon alfa-2b (USAN); Interferon alfa-2b (genetica... DG01750 Chemical ... DGroup Interferon alpha ... D00745 ... Interferon alfa-2a (USAN/INN); Interferon alfa-2a (gene

  7. The influence of monovalent cations on trimeric G protein Gi1alfa activity in HEK293 cells stably expressing DOR-Gi1alfa (Cys351-Ile351) fusion protein

    Czech Academy of Sciences Publication Activity Database

    Vošahlíková, Miroslava; Svoboda, Petr

    2011-01-01

    Roč. 60, č. 3 (2011), s. 541-547 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110606; GA MŠk(CZ) LC554; GA ČR(CZ) GD305/08/H037 Institutional research plan: CEZ:AV0Z50110509 Keywords : delta-opioid receptor (DOR) * monovalent ions * G(i)1alfa protein Subject RIV: CE - Biochemistry Impact factor: 1.555, year: 2011

  8. Evaluación serológica de una proteína recombinante a partir de una cepa aislada del virus de la fiebre amarilla en el Perú: un estudio piloto

    Directory of Open Access Journals (Sweden)

    Carlos Yábar V

    2003-10-01

    Full Text Available Objetivo: Evaluar serológicamente una proteína recombinante de 66 kDa (Er66 de una cepa del virus de la fiebre amarilla aislada en el Perú usando anticuerpos inmunoreactivos. Material y métodos: La proteína Er66 fue expresada in vitro en la bacteria Escherichia coli y enfrentada a títulos de 1/100, 1/50 y 1/25 de anticuerpos monoclonales, y a sueros con anticuerpos IgM e IgG inmunoreactivos contra el virus de la fiebre amarilla mediante ensayos de Western blot (WB. Asimismo, se evaluaron proteínas totales de las cepas de referencia del virus dengue (DEN y fiebre amarilla como controles de antigenicidad. Resultados: La proteína recombinante Er66 presentó antigenicidad contra títulos de 1/50 y 1/25 de anticuerpo monoclonal (MAB8701; sin embargo, no se observó inmunoreactividad en sueros positivos para fiebre amarilla y dengue. Los ensayos con extractos crudos de la cepa de fiebre amarilla Asibi 17D (PTFA revelaron que la antigenicidad de las proteínas virales comprendidas entre 60 y 80 kDa fue afectada negativamente a temperaturas desnaturalizantes de 100°C. En cambio, tratamientos con ß-mercaptoetanol sin calor generó un aumento de la antigenicidad de dichas proteínas. Siguiendo este mismo principio, la proteína Er66 fue sometida a tratamientos desnaturalizantes con ß-mercaptoetanol sin incluir calor y fue enfrentada nuevamente a los sueros reactivos. El resultado final reveló que la proteína Er66 generó inmunoreactividad frente a sueros con altos títulos de anticuerpos IgM e IgG para fiebre amarilla mientras que en otras muestras se observó una débil señal. Conclusiones: Los datos obtenidos en este trabajo demuestran que la Er66 pudo ser reconocida por anticuerpos IgM e IgG específicos para fiebre amarilla presentes en sueros de pacientes infectados. Los datos presentados en este artículo sugieren el uso de proteínas recombinantes como posibles candidatas de valor diagnóstico para la FA.

  9. Beyond the exchange--the future of B2B.

    Science.gov (United States)

    Wise, R; Morrison, D

    2000-01-01

    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important.

  10. Hanstholm phase 2B. Offshore wave energy test 1994 - 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-01

    The wave power converter consists of a float 2.5 meter in diameter, connected by a rope to a seabed-mounted piston pump, installed on 25 meter deep water 2,5 km offshore Hanstholm, Denmark. The converter is designed to absorb an average maximum power of 1 kW. Measured data in real sea conditions are compared to results based on computer simulations and previous tank testing. Losses caused by rope elasticity and hysteresis, friction in the pump and back flow through the valves are assessed. The economic perspectives of a large wave power plant are presented, based on a revised prototype incorporating the results and experience gained during the test period. The wave energy conversion test `Hanstholm phase 2B` has showed, that it it technically possible to exploit the offshore wave energy resource. This source of energy could become attractive for commercial enterprise. The wave power converter demonstrated a reliable performance over a period of nine months. It produced energy under all wave conditions and survived storm waves of 9,6 m. A 300 MW wave power plant in the Danish part of the North sea is estimated to produce electricity at a cost between 2,1 - 2,4 DKK/kWh. The electrical transmission to shore contribute to approximately 20% of the cost. New data predict a potential of 23 kW per meter wave front. The energy plan Energy 21 proposed by the Danish Department of Energy, includes a scenario incorporating wave energy in the energy system year 2030. A strategy for the development of wave energy, has been proposed as part of the project OWEC-1 supported by the European Joule R and D programme. A proposal for future Danish initiatives to develop second generation point absorber systems is outlined. (ARW) 29 refs.

  11. Efficient cell culture system for hepatitis C virus genotype 2B

    DEFF Research Database (Denmark)

    2014-01-01

    The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from...... transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analysis.......The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2...

  12. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy was underpowered

    Directory of Open Access Journals (Sweden)

    Ortiz A

    2015-11-01

    Full Text Available Alberto Ortiz,1,2 Maria Dolores Sanchez-Niño1,2 1Department of Nephrology, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autónoma de Madrid, 2Department of Nephrology, Instituto Reina Sofia de Investigación Nefrológica, Madrid, Spain We read with interest the report by Goláň et al on the “Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease”.1 Based on the reported results, the authors conclude that no efficacy or safety differences were found when the approved every-other-week (EOW dosage of agalsidase alfa was increased to weekly administration. However, the key question is whether the study, as designed and performed, could have had a different outcome. View original article by Goláň et al.

  13. Concentração de alfa-tocoferol no soro e colostro materno de adolescentes e adultas

    OpenAIRE

    Dimenstein,Roberto; Pires,Jeane Franco; Garcia,Lígia Rejane Siqueira; Lira,Larissa Queiroz de

    2010-01-01

    OBJETIVOS: avaliar a concentração de alfa-tocoferol no soro e colostro materno de puérperas adolescentes e adultas e verificar a adequação nutricional de vitamina E do colostro oferecido ao lactente. MÉTODOS: participaram do estudo 72 puérperas, sendo 25 adolescentes e 47 adultas. Foram coletados 5 mL de sangue e 2 mL de colostro em condição de jejum para análise dos níveis de alfa-tocoferol. As amostras foram analisadas por cromatografia líquida de alta eficiência. A adequação nutricional do...

  14. [Experience of use of allokin-alfa in the treatment of genitourinary infections complicated by excretory-toxic infertility].

    Science.gov (United States)

    Akimov, O V; Kostromeev, S A; Dyshkovets, A A

    2013-01-01

    The results of the examination and treatment of 67 patients aged 18 to 45 years are presented. Patients suffered from chronic prostatitis, chronic prostatovesiculitis, chronic uretroprostatitis complicated by excretory-toxic infertility. Pathogens, including sexually transmitted infections (STIs), were identified in all patients. The control group received conventional therapy (causative agents, a-adrenoblockers, enzyme therapy). In the study group, patients received allokin alpha in addition to conventional therapy. The use of allokin-alfa promoted more rapid and complete eradication of STI pathogens, and normalization of the spermogram. The results of this study allow to recommend allokin-alfa for the combined treatment of patients with infectious and inflammatory diseases of the genitourinary system, complicated by excretory-toxic infertility.

  15. Efek Pemberian Seduhan Teh Hijau terhadap Gelombang Alfa Otak pada Mahasiswa Tingkat Akhir Fakultas Kedokteran Universitas Islam Bandung

    Directory of Open Access Journals (Sweden)

    Helga Marwa Afifah

    2015-09-01

    Full Text Available Abstrak Teh merupakan bahan alam yang sudah dikenal memiliki banyak manfaat salah satunya sebagai zat relaksan. Sifat relaksan diperoleh dari kandungan senyawa pada teh terutama teh hijau yaitu L-teanin yang memicu peningkatan aktivitas gamma-aminobutyric acid (GABA, produksi serotonin dan dopamin, serta menghambat kerja glutamat. Efek keseluruhan L-teanin pada otak memicu seseorang menjadi rileks, kondisi rileks dapat dinilai dari aktivitas gelombang alfa otak. Tujuan penelitian ini menilai efek pemberian seduhan teh hijau terhadap gelombang alfa otak pada mahasiswa tingkat akhir Fakultas Kedokteran Unisba. Penelitian menggunakan metode eksperimental, melalui dua kali perekaman gelombang alfa otak sebelum dan setelah pemberian seduhan teh hijau yang mengandung 50 mg L-teanin dengan menggunakan brain wave sensors. Hasil penelitian dianalisis melalui Uji Wilcoxon. Penelitian dilakukan di Fakultas Kedokteran Unisba pada bulan April–Mei 2014. Sampel yang digunakan adalah mahasiswa tingkat akhir Fakultas Kedokteran Unisba yaitu sebanyak 30 orang, terdiri atas 13 laki-laki dan 17 perempuan. Hasil penelitian menunjukkan bahwa pada 28 dari 30 orang memperlihatkan peningkatan gelombang alfa otak setelah pemberian seduhan teh hijau dan hanya 2 orang yang memperlihatkan gelombang alfa otak yang lebih rendah. Hasil Uji Wilcoxon menunjukkan nilai signifikansi <0,001. Berdasarkan hasil penelitian, dapat disimpulkan bahwa pemberian seduhan teh hijau memiliki efek meningkatkan gelombang alfa otak pada mahasiswa tingkat akhir Fakultas Kedokteran Unisba. Hal ini dapat disebabkan karena aktivitas L-teanin dalam teh hijau yang dapat memicu aktivitas GABA, serotonin, dan dopamin serta menghambat kerja glutamat sehingga memicu kondisi relaksasi yang dinilai dalam gelombang alfa otak. Kata kunci: Gelombang alfa otak, L-teanin, teh, teh hijau   The Effect of Green Tea to Alpha Brain Waves of Final Students of Faculty of Medicine Universitas Islam Bandung Abstract

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

    Directory of Open Access Journals (Sweden)

    Flávio Augusto Henriques Vince

    2009-09-01

    Full Text Available INTRODUÇÃO: O fator VII recombinante ativado (rFVIIa é uma proteína produzida por engenharia genética, cuja estrutura é muito semelhante à do fator VII intrínseco ativado (FVII. Sua ação se baseia no conhecimento do mecanismo de coagulação in vivo agindo na ativação direta do fator X resultando em formação independente de trombina no local da lesão e contribuindo dessa forma para formação de coágulo estável de fibrina sem a ação dos fatores VIII e IX. MÉTODOS: Foi realizada ampla revisão da literatura com o objetivo de determinar os achados recentes relacionados ao uso de fator VII recombinante ativado em pacientes com sangramento severo. RESULTADOS: Constatou-se que o uso de rFVIIa foi iniciado na década de 80 para profilaxia e tratamento de sangramento em pacientes com antecedente de hemofilia A ou B com inibidores de fator VIII e IX, deficiência de fator VII e trombastenia de Glanzmann refratários à reposição plaquetária. Em 1999 seu uso foi ampliado para outras situações clínicas e dessa forma, começaram a ser publicados diversos trabalhos mostrando a eficácia do rFVIIa como agente pró-hemostático em paciente com outras coagulopatias ou pacientes previamente hígidos com história de sangramento agudo de grande monta. Trauma é a principal causa de mortalidade no mundo sendo sangramento incontrolado o principal desafio no atendimento a estes pacientes. É comum a associação de trauma com coagulopatia, necessitando em algumas situações de terapia específica para o tratamento da mesma. Neste momento a terapia adjuvante com rFVIIa deve ser considerada. Outras causas comuns de sangramento são as operações cardíacas e ginecológicas/ obstétricas e doenças envolvendo o fígado. A coagulopatia nesses casos ocorre por deficiência dos fatores dependentes de vitamina K, sendo o FVII o com menor meia-vida. CONCLUSÃO: O uso de rFVIIa tem sido sugerido como opção terapêutica promissora para esses

  17. Secondary bronchiolitis obliterans organizing pneumonia during treatment of chronic hepatitis C: role of pegylated interferon alfa-2a

    OpenAIRE

    Martins, Ronaldo Soares; Machado, Juliano Antunes; Teixeira, Rosângela

    2012-01-01

    The treatment of chronic hepatitis C has frequent side effects such as cytopenias and neuropsychiatric symptoms. However, pulmonary toxicity associated with interferon is rarely described. This paper describes the clinical case of a 67-year-old female patient with chronic hepatitis C who presented an acute onset of dry cough, dyspnoea, and fever 36 weeks after the use of pegylated interferon alfa-2a and ribavirin. The lung biopsy confirmed the diagnosis of a bronchiolitis obliterans organizin...

  18. [TNF-alfa (-857C/T) polymorphism in open angle glaucoma in Romania -- results of a pilot study].

    Science.gov (United States)

    Simionescu, Ruxandra; Voinea, Liliana; Cornăţeanu, Roxana Sfrenţ

    2013-01-01

    Primary open angle glaucoma is a progressive optic neuropathy with multiple causative factors including genetic immune disregulation. TNF-alfa has pro-apoptotic effects on the retinal ganglion cells, thus being directly involved in the neurodegeneration of the optic nerve head. Our purpose was to investigate the influence on susceptibility and/or clinical and characteristics of TNF-alfa promoter polymorphism -857 C/T in Romanian patients diagnosed with POAG. We assessed 159 Romanian subjects, 61 diagnosed with glaucoma (F/M 39/22) and 98 healthy unrelated matched controls-HC for the polymorphism -857 C/T, genotyped by Real Time PCR (Taqman SNP Genotyping Assay C_2215707_10, Applied Biosystems, USA). The diagnosis and the staging of the disease in the POAG group were assessed using the current guidelines. Association tests for the SNP were performed using SPSS 11.2 (Fisher test) and p values < or = 0.05 were considered significant. The Hardy-Weinberg equilibrium assessed using Chi-square test was respected in both studied groups- POAG and HC (p = 0.000009 and respectively p = 0.04771). There was no association found between the frequencies of alleles between studied groups (CC/CT/TT= 0.81/0.09/0.08 respectively 0.70/0.23/0.06). TNF-alfa promoter polymorphism -857 C/T doesn't seem to influence the susceptibility to POAG and the results should be confirmed on larger cohorts.

  19. Efeito do flunixin meglumine, da somatotropina recombinante bovina e/ou da gonadotrofina coriônica humana na redução da mortalidade embrionária em vacas nelore (Bos taurus indicus)

    OpenAIRE

    Rossetti, Rita Cristina [UNESP

    2010-01-01

    Estratégias farmacológicas são empregadas para reduzir a mortalidade embrionária em fêmeas bovinas. Objetivou se comparar o efeito do Flunixin Meglumine (FM), Somatotropina Recombinante Bovina (bST) e/ou Gonadotrofina Coriônica Humana (hCG) na redução da mortalidade embrionária em vacas Nelore no período compreendido entre o 15º e 19º dias da gestação, baseando se na taxa de concepção aos 40 dias de gestação. A hipótese é que vacas tratadas com FM, bST e/ou hCG, apresentam menor mortalidade e...

  20. Transformação de plantas de tabaco (Nicotiana tabacum L.) com os genes recombinantes 35SHBsAg e 35SHBsAgER do vírus da hepatite B

    OpenAIRE

    Ribeiro, Juliana Martins; Bastos, Débora Costa; Oliveira, Eduardo Alves Gamosa de; Souza, Jackson Antônio Marcondes de; Pinto, Márcio dos Santos Teixeira; Hansen, Ekkehard Ernst Theodor

    2010-01-01

    http://dx.doi.org/10.5007/2175-7925.2010v23n1p1 O antígeno de superfície do vírus da hepatite B (HBsAg) recombinante, purificado de plantas transgênicas, mostrou-se bastante eficiente quando utilizado para a indução da produção de anticorpos anti-HBs para a prevenção da hepatite B. Devido ao importante papel demonstrado pelo antígeno HBsAg para a prevenção da hepatite B, a sequência codificadora do antígeno HBsAg, adicionada ou não da sequência carboxi-terminal para retenção da proteína n...

  1. Obtención y evaluación preliminar de un virus canarypox recombinante como candidato a vacuna antirrábica Development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate

    Directory of Open Access Journals (Sweden)

    Flavia Zanetti

    2012-06-01

    Full Text Available En la Argentina, la rabia está circunscripta a algunas provincias del norte. La disponibilidad de nuevas vacunas que eliminen la manipulación del virus rábico y que permitan el control de la enfermedad es de importancia estratégica nacional y regional. Las vacunas basadas en poxvirus recombinantes se han utilizado con éxito como vacunas antirrábicas a nivel mundial. SI bien estos sistemas no están disponibles comercialmente, la plataforma de obtención de virus canarypox (CNPV recombinantes ya ha sido implementada en nuestro laboratorio. El objetivo de este trabajo fue obtener y evaluar un candidato a vacuna antirrábica basado en CNPV recombinantes que expresan la glicoproteína G (RG del virus rábico (RV. Se construyó un virus recombinante que expresa la secuencia codificante de RG (CNPV-RG. La inoculación de ratones con este virus indujo altos títulos de anticuerpos seroneutralizantes de RV (3,58 y 9,76 Ul/ml después de una o dos inmunizaciones, respectivamente y protegió al 78 % de los animales desafiados intracerebralmente con RV. Además, se determinó que el CNPV-RG posee una potencia relativa de 3,5 Ul/ml. Los resultados obtenidos constituyen la primera etapa en la evaluación del CNPV-RG como candidato a vacuna antirrábica. Se requerirán nuevos ensayos para confirmar su utilidad en especies de interés veterinario.In Argentina, rabies is limited to some northern provinces. Availability of new vaccines abolishing the handling of the rabies virus and allowing disease control has regional and national strategic importance. Vaccines based on recombinant poxviruses have been successfully used as antirabic vaccines worldwide. Although these systems are not commercially available, the platform to obtain recombinant canarypox viruses (CNPV has been previously set up in our laboratory. The aim of this work was the development and evaluation of an antirabic vaccine candidate based on recombinant CNPV expressing the rabies virus (RV

  2. Construção e caracterização de linhagens bacterianas Gram-negativas recombinantes com capacidade aumentada para biorremediar efluentes contaminados com mercúrio e arsênio.

    OpenAIRE

    Carolina Angélica da Silva Parada

    2012-01-01

    Este trabalho descreve a construção de plasmídeos para expressão e ancoragem de proteínas de alta afinidade a íons Hg2+ e As5+. Os genes merR e arsR de C. metallidurans foram inseridos no vetor que contém o sistema para expressão e ancoragem de proteínas heterólogas em bactérias Gram-negativas originando os plasmídeos pCM-Hg e pCM-As. MerR e ArsR foram produzidas sob comando do promotor pan. E. coli recombinantes apresentaram resistência 100% superior a Hg2+ e As5+. C. metallidurans/pCM-As ap...

  3. Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group

    NARCIS (Netherlands)

    Keilholz, Ulrich; Punt, Cornelis J. A.; Gore, Martin; Kruit, Wim; Patel, Poulam; Lienard, Danielle; Thomas, Jose; Proebstle, Thomas M.; Schmittel, Alexander; Schadendorf, Dirk; Velu, Thierry; Negrier, Sylvie; Kleeberg, Ulrich; Lehman, Frederic; Suciu, Stefan; Eggermont, Alexander M. M.

    2005-01-01

    Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients

  4. Evaluación de la inmunogenicidad de una vacuna recombinante antivirus hepatitis B en mujeres adultas sanas, Santafé de Bogotá, D.C., julio 1997 - noviembre 1998

    Directory of Open Access Journals (Sweden)

    María T. Herrera Mendoza

    1999-06-01

    Full Text Available Este estudio se realizó con el propósito de evaluar la inmunogenicidad de la vacuna recombinante antivirus de la hepatitis B HEPRECOMB BERNABy el desarrollo de efectos secundarios atribuibles a la vacuna y a la vía de aplicación, empleando y comparando dos dosis distintas en individuos sanos sin evidencia clínica de enfermedad hepática y sin evidencia serológica de contacto previo con VHB (virus hepatitis 6. Igualmente se monitorizó la respuesta humoral in vivo inducida por la aplicación de esta vacuna. Se incluyeron 50 voluntarios del sexo femenino en Santafé de Bogotá, los cuales fueron divididos al azar en dos grupos: El grupo 1, vacunado con tres dosis de 20pg, y el grupo 2, vacunado con tres dosis de 10pg; en ambos grupos se utilizó el esquema O, 1, 6 meses y fueron observados durante 7 meses. Los criterios de inclusión en el estudio fueron la participación voluntaria, edad mayor de 18 años y ausencia de antiHBsAg. El título de anticuerpos fue significativamente mayor para el grupo 2 ( P= 0.03 a los dos y seis meses, aunque al séptimo mes los títulos se igualaron. El trabajo concluyó que lavacuna recombinante antivirus de la hepatitis B HEPRECOMB BERNA 8 con la dosis de 10pg tiene una mayor respuesta a los dos y seis meses de observación, que con la dosis de 20pg, llegando a resultados similares al séptimo mes. Se recomienda realizar estudios con una muestra mayor.

  5. Producción de anticuerpos policlonales IgG contra la proteina iduronato-2-sulfato sulfatasa y desarrollo de un sistema de detección para IDS humana recombinante.

    Directory of Open Access Journals (Sweden)

    Olga Peña

    2005-06-01

    Full Text Available Introducción. La enfermedad de Hunter es un trastorno lisosómico caracterizado por la deficiencia de la enzima iduronato-2-sulfato sulfatasa (IDS (EC 3.1.6.13. Esta enfermedad, al igual que muchos trastornos metabólicos, son patologías intratables mediante la terapéutica convencional; sin embargo, existe la posibilidad de ser tratada alternativamente mediante terapia génica o terapia de reemplazo enzimático. Objetivo. El Instituto de Errores Innatos del Metabolismo (IEIM ha desarrollado un sistema de expresión de sulfatasas para producir IDS humana recombinante (IDShr en Escherichia coli y Pichia pastoris, con resultados favorables. El objetivo principal de este trabajo fue desarrollar un sistema de detección de IDS humana recombinante. Materiales y métodos. Para el efecto, se inmunizaron con IDS comercial de TKT (Cambridge, MA dos conejos de raza Nueva Zelanda blanca y los anticuerpos purificados a partir del suero se utilizaron en el desarrollo de una técnica semicuantitativa por dot-blot. Diferentes muestras de extractos crudos de fermentaciones con P. pastoris y E. coli se procesaron con el fin de poder determinar la presencia de la enzima. Resultados. Se demostró que los anticuerpos eran específicos en el reconocimiento de la IDS sin presentar reactividad cruzada con proteínas contaminantes de los extractos crudos. Conclusión. Por consiguiente, los anticuerpos se podrán usar en el desarrollo de una técnica ELISA tipo sandwich como método de detección y cuantificación de la enzima y en procesos de purificación de la misma mediante cromatografía de afinidad.

  6. Structural stability of the square flux line lattice in YNi2B2C and LuNi2B2C studied with small angle neutron scattering

    DEFF Research Database (Denmark)

    Eskildsen, M.R.; Gammel, P.L.; Barber, B.P.

    1997-01-01

    We have studied the flux line lattice in YNi2B2C and LuNi2B2C, the nonmagnetic end members of the borocarbide superconductors using small angle neutron scattering and transport. For fields, H parallel to c, we find a square symmetric lattice which disorders rapidly above H/H-c2 similar to 0.2, well...

  7. Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance and metabolism

    Science.gov (United States)

    Kharasch, Evan D.; Regina, Karen J.; Blood, Jane; Friedel, Christina

    2015-01-01

    Background Interindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone elimination. The CYP2B6 gene is highly polymorphic, with several variant alleles. CYP2B6.6, the protein encoded by the CYP2B6*6 polymorphism, deficiently catalyzes methadone metabolism in vitro. This investigation determined the influence of CYP2B6*6, and other allelic variants encountered, on methadone concentrations, clearance, and metabolism. Methods Healthy volunteers in genotype cohorts CYP2B6*1/*1 (n=21), CYP2B6*1/*6 (n=20), and CYP2B6*6/*6 (n=17), and also CYP2B6*1/*4 (n=1), CYP2B6*4/*6 (n=3), CYP2B6*5/*5 (n=2) subjects received single doses of intravenous and oral methadone. Plasma and urine methadone and metabolite concentrations were determined by tandem mass spectrometry. Results Average S-methadone apparent oral clearance was 35 and 45% lower in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively, compared with CYP2B6*1/*1, and R-methadone apparent oral clearance was 25 and 30% lower. R- and S-methadone apparent oral clearance was 3- and 4-fold greater in CYP2B6*4 carriers. Intravenous and oral R- and S-methadone metabolism was significantly lower in CYP2B6*6 carriers compared with CYP2B6*1 homozygotes, and greater in CYP2B6*4 carriers. Methadone metabolism and clearance were lower in African-Americans due to the CYP2B6*6 genetic polymorphism. Conclusions CYP2B6 polymorphisms influence methadone plasma concentrations, due to altered methadone metabolism and thus clearance. Genetic influence is greater for oral than intravenous, and S- than R-methadone. CYP2B6 pharmacogenetics explains, in part, interindividual variability in methadone elimination. CYP2B6 genetic effects on methadone metabolism and clearance may identify subjects at risk for methadone toxicity and drug interactions. PMID:26389554

  8. Li2b2-Façade: Simulation of i2b2 Data Warehouse Server and Client for Interaction with Other Systems.

    Science.gov (United States)

    Majeed, Raphael W; Xu, Tingyan; Stöhr, Mark R; Röhrig, Rainer

    2017-01-01

    Since its release in 2004, the i2b2 data warehouse software has become a valuable tool for clinical researchers. Physicians can use its browser-based query frontend intuitively without additional training or reading through documentation. While the i2b2 software describes it's API as "REST", it is neither stateless nor does it follow the common guidelines for RESTful APIs. Thus, interfacing other software with i2b2's custom RPC-style XML-API is a very cumbersome process. To overcome these issues, we developed a lightweight software abstraction layer "lightweight i2b2 façade" (li2b2-façade).

  9. Profile of efraloctocog alfa and its potential in the treatment of hemophilia A.

    Science.gov (United States)

    George, Lindsey A; Camire, Rodney M

    2015-01-01

    Hemophilia care has improved dramatically over the past 50 years, evolving from plasma concentrates, to purified plasma proteins, to recombinant clotting factors. These collective developments allowed for home delivery of on-demand and prophylactic treatment, resulting in the reduction of hemophilia morbidity and mortality and improved quality of life. Although efficacious in treating bleeding, conventional factor products' half-lives require frequent venipuncture, which remains a significant burden to patients. Despite the remarkable advances in hemophilia care, no improvements have, until now, been made to the pharmacokinetic properties of factor products. Multiple strategies have more recently been employed to generate novel bioengineered products that, with great hope, represent the next wave of progress in hemophilia care. The use of these products will undoubtedly raise important discussion about choosing conventional factor over new long-acting factor products. Incorporation of these therapies into clinical care is accompanied by unanswered safety questions that will likely be evaluated only in postmarketing surveillance analysis. Further, these products may change current treatment paradigms with unclear cost repercussions and feasibility. This paper will review efraloctocog alfa (FVIII-Fc) and its role in the treatment of hemophilia A.

  10. LHC Report: special run with de-squeezed beams for ATLAS/ALFA and TOTEM

    CERN Multimedia

    Helmut Burkhardt for the LHC team

    2015-01-01

    The main high-luminosity proton-proton run of the LHC is complemented by one week per year of special proton-proton runs. The special runs are performed with larger beam sizes at the interaction points to allow the forward physics experiments, TOTEM and ATLAS/ALFA, the chance to make precise measurements of protons as they emerge from collisions at small angles.   In standard high-luminosity operation, the beams are squeezed to give small beam sizes at the interaction points to maximise the collision rates. The “squeeze” takes place at top energy and the beam size at the centre of ATLAS (IP1) and CMS (IP5) is reduced from 66 micrometres at the top of the ramp to 18 micrometres before colliding beams are established. Protons that avoid the fate of an inelastic collision but yet still interact – in elastic or diffractive events – are scattered and emerge in the forward direction. The reduction in beam size has a side effect of increasing the an...

  11. Characterization of autoantibodies in autoimmune hemolytic anemia following treatment with interferon alfa

    International Nuclear Information System (INIS)

    Bencomo Hernandez, Antonio; Gutierrez Diaz, Adys; Avila Cabrera, Onel; Rodriguez, Luis Ramon

    2012-01-01

    We studied 13 patients with chronic myeloid leukemia and autoimmune hemolytic anemia induced by interferon alfa. They underwent tests for immune protein detection and characterization of IgG subclasses in RBCs by direct antiglobulin test (PAD) and the microplate technique. Also they were applied ELISA test for quantifying immunoglobulins in the red blood cells. It was detected the presence of IgG and C3 in 53.84 % of cases, IgG alone in 23.07 % and in 15.38 % were identified IgG and IgA autoantibodies. In 11 patients the presence of IgG1 was showed and also in one case the subclass IgG3 autoantibodies was identified. The ELISA detected antibodies at concentrations of 183 IgG molecules per erythrocyte in a patient with negative PAD. In high-grade hemolysis patients, it was found a concentration of autoantibodies between 1 500 and 3 180 molecules of IgG per erythrocyte, while in low-grade hemolysis patients it behaved between 183 and 1 000 molecules. There was a negative correlation between Hb and plasma haptoglobin values with the number of IgG molecules per erythrocyte and a positive correlation between the latter with the reticulocyte count

  12. Development of solar energy education IASEE-Argentina, Arquisur and Alfa-built

    International Nuclear Information System (INIS)

    Schiller, S. de; Evans, J.M.

    1997-01-01

    Three educational experiences are presented in this paper on the development of national and regional networks to incorporate renewable energy in curricular programmes. IASEE-Argentina, established in 1990 as the National Section of IASEE, the International Association for Solar Energy Education, was designated in 1993 as the Education Working Group of ASADES, the Argentine Association of Solar Energy. It holds annual meetings to coincide with the ASADES conference. Arquisur is a regional network established by Architectural Faculties of State Universities within the Mercosur Region, covering Argentina, southern Brazil, Paraguay and Uruguay, to promote exchange and development between the 19 faculties involved. A Working Group set up by Arquisur with members from four countries developed the programme for short post-graduate courses on bioclimatic design and rational energy use in buildings, which has been given in Argentina and Uruguay. Alfa-Built, a project supported by the European Union for promoting academic exchange in the field of energy efficient building is also introduced. This paper presents the development and initial results of these educational experiences. (author)

  13. Testing stable boundary layer parameterizations against the BASE:ALFA measurements

    Science.gov (United States)

    Bonafè, G.; Tampieri, F.; di Giuseppe, F.; Caporaso, L.

    2010-09-01

    The Po valley in the Northern Italy is a large plain in a semi-closed basin surrounded by complex orography; the Alps to the North and Apennines to the South-East, and closed to the east by the Adriatic sea. As a flatland basin shielded by mountains, calm wind is very frequent and strong temperature inversions are often observed near the ground, during the night and in the winter period the occurrence of a extremely stable boundary layer is common. A complete set of surface and atmospheric measurements have been collected during a four month observational program carried out at San Pietro Capofiume meteo station, in the middle of the Po Valley. The long term dataset has been collected in the contest of the project BASE:ALFA with the main aim of creating a data pool of micro-meteorological /soil data to test and validate numerical weather prediction PBL schemes. The measurement periods span summer, winter and spring and allows to analyse a wide range of PBL stability conditions. Different parameterizations of first and second order moments of velocity and temperature are tested against the collected data. A particular focus is given to stable boundary layer and the values of its height obtained from Nieuwstadt 1984 and Zilitinkievich et al 2005 formulas will be provided and compared against radiosounding profile estimates.

  14. Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study.

    Science.gov (United States)

    Schaefer, Franz; Hoppe, Bernd; Jungraithmayr, Therese; Klaus, Günter; Pape, Lars; Farouk, Mourad; Addison, Janet; Manamley, Nick; Vondrak, Karel

    2016-03-01

    Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD). In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded. A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5%) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0%), gastroenteritis (6.0%), and hypertension (4.1%). Six patients (1.9%) died (unrelated to DA). Four patients (1.3%) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4-2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2-11.7 g/dl, respectively. Overall, 48 patients (15.0%) received ≥1 transfusion. No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.

  15. Efficient cell culture system for hepatitis C virus genotype 2B

    DEFF Research Database (Denmark)

    2014-01-01

    The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2...

  16. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

    DEFF Research Database (Denmark)

    Clayton, Emma L.; Mizielinska, Sarah; Edgar, James R.

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The a...

  17. Incidence and prevalence of multiple endocrine neoplasia 2B in Denmark

    DEFF Research Database (Denmark)

    Mathiesen, Jes Sloth; Kroustrup, Jens Peter; Vestergaard, Peter

    2017-01-01

    Extract: Multiple endocrine neoplasia 2B (MEN2B) is an autosomal dominant inherited cancer syndrome associating medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), ganglioneuromatosis of the aerodigestive tract and facial, ophthalmologic and skeletal abnormalities. MEN2B is caused by the M...

  18. Asociación de la actividad alfa-amilasa salivar matutina con índices de psicopatología internalizante en niñas de 8-11 años

    OpenAIRE

    Maldonado-Montero, Enrique Francisco

    2014-01-01

    ANTECEDENTES: Recientemente, se ha observado una reducción estadísticamente significativa en los niveles de actividad de la alfa-amilasa salivar en mujeres adolescentes diagnosticadas de depresión mayor (Cubala & Landowski, 2014). OBJETIVO: El objetivo del presente estudio ha sido analizar la relación entre índices de psicopatología internalizada y niveles matutinos de cortisol, de alfa-amilasa salivar y de sus respectivos ratios (cortisol/alfa-amilasa y alfa-amilasa/cortisol) en 45 niños y 5...

  19. Efeito da somatotropina recombinante bovina (rbst no desempenho de novilhos alimentados com diferentes volumosos Effect of recombinant bovine somatotropin (rbst on the performance of steers fed different forages

    Directory of Open Access Journals (Sweden)

    Jane Maria Bertocco Ezequiel

    1999-01-01

    Full Text Available O efeito da somatotropina recombinante bovina (rBST no desempenho de novilhos alimentados com rações com diferentes volumosos foi avaliado. Quarenta novilhos cruzados e castrados, com 360,2 kg PV médio e 30 meses de idade, foram usados. Os animais foram alimentados com rações contendo diferentes volumosos (silagem de milho, cana-de-açúcar, silagem de milho + cana-de-açúcar e bagaço de cana hidrolisado e receberam aplicação de 320 mg rBST a cada 28 dias e foram pesados a cada 14 dias durante um periodo experimental de 84 dias. Ganho de peso, consumo de matéria seca e proteína bruta por kg de ganho de peso e conversão alimentar, foram avaliados. Não houve diferença no ganho de peso entre os animais que receberam (1,210 kg/cab•dia ou não (1,062 kg/cab•dia rBST, apesar de os animais que receberam rBST terem apresentado maior ganho de peso nos períodos após a segunda e terceira aplicação. Não houve, também, diferença entre as rações contendo silagem de milho (1,100 kg/cab•dia, cana-de-açúcar (1,240 kg/cab•dia, cana+silagem (1,064 kg/cab•dia e bagaço hidrolisado (1,138 kg/cab•dia. A conversão alimentar foi 9,43 e 9,69 kg MS/kg de ganho de peso para os animais que receberam ou não rBST, respectivamente. O consumo de proteína bruta reduziu com a aplicação de rBST e foi mais expressivo na ração contendo cana-de-açúcar. Não houve interação entre a aplicação do hormônio e o tipo de volumoso.Effect of recombinant bovine somatotropin (rBST on the performance of steers fed diets with different forages was evaluated. Forty crossbred steers, with average 360.2 kg LW and 30 months of age, were used. The animals were fed diets containing different forages (corn silage, sugarcane, corn silage + sugarcane and hydrolyzed sugarcane bagasse, and received an application of 320 mg rBST at every 28 days and were weighed at every 14 days during an experimental period of 84 days. The weight gain, dry matter and

  20. CDKN2B methylation is associated with carotid artery calcification in ischemic stroke patients

    OpenAIRE

    Shuyu Zhou; Yumeng Zhang; Li Wang; Zhizhong Zhang; Biyang Cai; Keting Liu; Hao Zhang; Minhui Dai; Lingli Sun; Xiaomeng Xu; Huan Cai; Xinfeng Liu; Guangming Lu; Gelin Xu

    2016-01-01

    Background Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) near chromosome 9p21 have been associated with both atherosclerosis and artery calcification, but the underlying mechanisms remained largely unknown. Considering that CDKN2A/2B is a frequently reported site for DNA methylation, this study aimed to evaluate whether carotid artery calcification (CarAC) is related to methylation levels of CDKN2A/2B in patients with ischemic stroke. Methods DNA methylation levels of CDKN2A/2B were mea...

  1. The brain-specific neural zinc finger transcription factor 2b (NZF-2b/7ZFMyt1 suppresses cocaine self-administration in rats

    Directory of Open Access Journals (Sweden)

    Vijay Chandrasekar

    2010-04-01

    Full Text Available Brain-specific neural-zinc-finger transcription factor-2b (NZF2b/7ZFMyt1 is induced in the mesolimbic dopaminergic region after chronic cocaine exposure and lentiviral-mediated expression of NZF2b/7ZFMyt1 in the nucleus accumbens results in decreased locomotor activity (Chandrasekar and Dreyer, 2009. In this study the role of NZF2b/7ZFMyt1 in active cocaine seeking and of its interaction with histone deacetylase on the altered behavior has been observed. Localized expression of NZF2b/7ZFMyt1 in the nucleus accumbens resulted in attenuated cocaine self-administration, whereas silencing this transcription factor with lentiviruses expressing siRNAs increased the animal′s motivation to self-infuse cocaine. Low doses of sodium butyrate, a potent inhibitor of histone deacetylase, were sufficient to reverse the NZF2b/7ZFMyt1-mediated decrease in cocaine self-administration. NZF2b/7ZFMyt1 expression resulted in strong induction of transcription factors REST1 and NAC1 and of the dopamine D2 receptor, with concomitant inhibition of BDNF and its receptor TrkB. We show that NZF2b/7ZFMyt1 colocalizes with histone deacetylase-2 (HDAC2, probably overcoming the suppression of transcriptional activity caused by Lingo1. These findings show that molecular adaptations mediated by NZF2b/7ZFMyt1 expression possibly lead to decreased responsiveness to the reinforcing properties of cocaine and play a prominent role in affecting the behavioral changes induced by the drug.

  2. Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn Phox2b heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Nelina eRamanantsoa

    2011-09-01

    Full Text Available The Phox2b gene is necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/- pups and their wild-type littermates (Phox2b+/+ to hypoxia (10% O2 or hypercapnia (8% CO2 under thermoneutral (33°C or cold (26°C conditions. We found that Phox2b+/- pups showed less normoxic ventilation (VE in the cold than Phox2b+/+ pups. Phox2b+/- pups also showed lower oxygen consumption (VO2 in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/- pups. Finally, because serotonin (5-HT neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high-pressure liquid chromatography, and found that it was altered in Phox2b+/- pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.

  3. Characterization of the UV-crosslinked heterodimer of histones H2B and H4

    International Nuclear Information System (INIS)

    Johnson, E.R.; Brown, D.M.; DeLange, R.J.

    1986-01-01

    At relatively high salt concentrations (1.2 M), histone 2B (H2B) and histone 4 (H4) can be covalently crosslinked by irradiation with ultraviolet light to yield a mixture of the three possible dimers: H2B-H2B, H4-H4, and H2B-H4. The formation of the H2B-H4 heterodimer was found to be favored at lower histone concentrations (> 90% H2B-H4 at 0.1 mg/ml total histone protein). CNBr cleavage of the H2B-H4 dimer produced three fragments which were separated by reverse phase HPLC. These fragments were identified by amino acid compositional analysis to be H4(85-102), H2B(62-125), and the crosslinked N-terminal regions H2B(1-59)-H4(1-84). Amino acid sequence analysis of the crosslinked fragment indicated that tyrosine-40 of H2B is likely involved in the covalent crosslinkage which joins the histone monomers to form the heterodimer

  4. Downregulation of the Adenosine A2b Receptor by RNA Interference Inhibits Hepatocellular Carcinoma Cell Growth

    OpenAIRE

    Xiang, Hong-Jun; Chai, Fu-Lu; Wang, De-Sheng; Dou, Ke-Feng

    2011-01-01

    To investigate the biological effect of adenosine A2b receptor (A2bR) on the human hepatocellular carcinoma cell line HepG2, three A2bR siRNA constructs were transiently transfected into HepG2 cells. The results showed that A2bR siRNA reduced the levels of A2bR mRNA and protein. In order to further detect the function of A2bR, we established a stable hepatocellular carcinoma cell line (HepG2) expressing siRNA targeting the adenosine A2b receptor. Targeted RNAi significantly inhibited tumor ce...

  5. Quantitative structure-activity relationship study on tetrahydro-beta-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus.

    Science.gov (United States)

    Singh, P; Kumar, R

    2001-12-01

    The antagonist actions of three sub-series of tetrahydro-beta-carbolines at the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus are analyzed in relation to the physicochemical properties of the molecules. Significant correlations are obtained between the 5HT2B receptor antagonist affinity and the hydrophobic, steric, electronic, hydrogen bond acceptor and some indicator variables of substituents. Based on these findings, the mode of actions of these congeneric series and future strategy to synthesize more potential compounds are discussed.

  6. Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation.

    Science.gov (United States)

    Xie, H-J; Yasar, U; Lundgren, S; Griskevicius, L; Terelius, Y; Hassan, M; Rane, A

    2003-01-01

    The role of polymorphic CYP2B6 in cyclophosphamide (CPA) bioactivation was investigated in human liver microsomes. A total of 67 human liver specimens were first genotyped with respect to the CYP2B6*5 and CYP2B6*6 variant alleles. CYP2B6 apoprotein levels in 55 liver microsomal preparations were assessed by immunoblotting. 4-Hydroxy-CPA and hydroxy-bupropion were quantified by using HPLC and LC-MS, respectively. 7-Ethoxy-4-trifluoromethyl coumarin O-deethylase activity was measured fluorometrically. The frequencies of CYP2B6*5 and CYP2B6*6 mutant alleles were 9.0 and 16.4%, respectively. CYP2B6 protein expression was detected in 80% of the samples, with a large variation (0.003-2.234, arbitrary units). There was a high correlation between CYP2B6 apoprotein content and CPA 4-hydroxylation (n=55, r=0.81, P<0.0001). When based on the CYP2B6 apoprotein levels, the *6 carriers had significantly higher CPA 4-hydroxylation (P<0.05). CPA 4-hydroxylation also correlated significantly with other CYP2B6-specific reactions (n=20, P<0.0001). V(max) and K(m) for CPA 4-hydroxylation in recombinant CYP2B6 enzyme were 338 nmol/min/nmol enzyme and 1.4 mM, respectively. CYP2B6 showed much higher in vitro intrinsic clearance than previously observed in recombinant CYP2C19 and CYP2C9 variants in yeast expression system. Our results demonstrate that the polymorphic CYP2B6 is a major enzyme in the bioactivation of CPA. Moreover, we identified a strong impact of CYP2B6*6 on CPA 4-hydroxylation.

  7. Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

    Energy Technology Data Exchange (ETDEWEB)

    Wilderman, P. Ross, E-mail: pwilderman@ucsd.edu [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Jang, Hyun-Hee [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Malenke, Jael R. [Department of Biology, University of Utah, Salt Lake City, UT (United States); Salib, Mariam; Angermeier, Elisabeth; Lamime, Sonia [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Dearing, M. Denise [Department of Biology, University of Utah, Salt Lake City, UT (United States); Halpert, James R. [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States)

    2014-02-01

    Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in Escherichia coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system. - Highlights: • Three CYP2B enzymes from Neotoma lepida were cloned, engineered, and expressed. • A mix of catalytic and binding assays yields unique results for each enzyme. • Mutational analysis indicates CYP{sub 2}B substrate recognition remains to be clarified. • Reported N. lepida gene

  8. LONG TERM MUCOLYTIC THERAPY WITH DORNASE ALFA AT NOVOSIBIRSK CENTER FOR DIAGNOSTICS, TREATMENT, RHEABILITATION AND ADAPTATION OF CHILDREN WITH CYSTIC FIBROSIS

    Directory of Open Access Journals (Sweden)

    N.I. Romanenko

    2006-01-01

    Full Text Available The center for diagnostic, treatment, rehabilitation and social adaptation of patients with cystic fibrosis was established in pulmonology department of the children's clinical hospital № 3 of Novosibirsk in 1994. Since 1995 the database of the center has registered 23 patients. the center has carried out an open prospective study of clinical efficacy and safety of dornase alfa (pulmozyme, «F. hoffmannala roche ltd.», basel in 10 patients with cystic fibrosis. The patients have received mucolytic therapy with dornase alfa for 2 years (2003–2005. They have been administered a daily inhalation of 2.5 ml of the solution (pulmozyme inhalation solution containing 2.5 of dornaza alfa. The study has shown an improvement of pulmonary function and elevation of oxygen saturation. The number of respiratory infections have dropped by 33%, the administration of intravenous antibiotics has shortened by 25%, the nutrition status has trended towards improvement. regardless of it's high price, dornasa alfa has proven its' benefits in the treatment of cystic fibrosis in patients of any age and disease severity.Key words: dornase alfa, children, cystic fibrosis, treatment.

  9. Informe sobre el Proyecto Alfa Biblioteca de Babel: ¿Un atajo para la administración de bibliotecas universitarias? Biblioteca de Babel Alfa Project Report: A shortcut for the academic libraries management?

    OpenAIRE

    Liliana Laura Rega

    2006-01-01

    El Proyecto Alfa Biblioteca de Babel que reúne bibliotecas universitarias de América Latina y Europa comenzó en marzo de 2005 y prevé su conclusión en marzo de 2007. El presente trabajo intenta describir los objetivos y los resultados esperados, e informa las actividades realizadas por la Red Biblioteca de Babel. Finalmente se analizan las propuestas del proyecto en cuanto al rol de las bibliotecas universitarias, y su relación con la innovación en las prácticas pedagógicas.Biblioteca de Babe...

  10. Análise comparativa do controle interno no contas a receber e a pagar nas empresas Beta Ltda e Alfa Ltda = A comparative internal control analysis of receivable and payable accounts in Beta and Alfa Ltd Companies

    Directory of Open Access Journals (Sweden)

    Cleyton de Oliveira Ritta

    2010-07-01

    Full Text Available A necessidade constante de um excelente desempenho empresarial leva à busca da qualidade e confiabilidade da informação para o auxílio na tomada de decisão. Neste contexto, a auditoria contábil tem um papel importante na análise das práticas administrativas adotadas pelas entidades. Desse modo, o objetivo deste artigo é comparar a estruturação dos controles internos no contas a receber e a pagar nas empresas Beta Ltda, a qual não contrata serviços de auditoria externa, e Alfa Ltda, que os contrata. Este estudo caracteriza-se como de caso comparativo de caráter descritivo por meio de questionário e entrevista. Os resultados apontam que a empresa Alfa Ltda tem melhores níveis de controle interno e, consequentemente, está menos exposta a erros e fraudes. Desse modo, entende-se que os seviços de auditoria atuam como um instrumento de auxílio para minimização dos riscos operacionais e servem de alerta aos gestores quanto à eficiência das transações. Contudo, percebe-se que a qualidade dos controles internos nas organizações depende diretamente da utilização de procedimentos de monitoramento.The constant need for excellent business performance triggers the quest for information quality and reliability to help in decision making. Considering this context, accounting auditing plays an important role in the analysis of administrative practices adopted by entities. Thus, the objective of this article is to compare the structure of the internal controls for receivable and payable accounts in Beta Ltd companies, which do not contract external auditing services, and Alfa Ltd, which does. This study is a descriptive comparative case study, carried out through questionnaire and interview. The results have showed that Alfa Ltd has better internal control levels and consequently is less exposed to errors and fraud. This way, auditing services are seen as auxiliary instruments to minimize operational risks and serve to alert

  11. Comparative therapeutic effects of velaglucerase alfa and imiglucerase in a Gaucher disease mouse model.

    Directory of Open Access Journals (Sweden)

    You-Hai Xu

    2010-05-01

    Full Text Available Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid beta-glucosidase (GCase. Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela, in a Gaucher mouse, D409V/null. About 80+% of either enzyme localized to the liver interstitial cells and <5% was recovered in spleens and lungs after bolus i.v. injections. Glucosylceramide (GC levels and storage cell numbers were reduced in a dose (5, 15 or 60 U/kg/wk dependent manner in livers (60-95% and in spleens ( approximately 10-30%. Compared to Vela, Imig (60 U/kg/wk had lesser effects at reducing hepatic GC (p = 0.0199 by 4 wks; this difference disappeared by 8 wks when nearly WT levels were achieved by Imig. Anti-GCase IgG was detected in GCase treated mice at 60 U/kg/wk, and IgE mediated acute hypersensitivity and death occurred after several injections of 60 U/kg/wk (21% with Vela and 34% with Imig. The responses of GC levels and storage cell numbers in Vela- and Imig-treated Gaucher mice at various doses provide a backdrop for clinical applications and decisions.

  12. CHANGES IN TUMOR NECROSIS FACTOR ALFA DURING TREATMENT OF PATIENTS WITH MULTIPLE SCLEROSIS BY TRANSIMMUNIZATION METHOD

    Directory of Open Access Journals (Sweden)

    A. V. Kil'dyushevskiy

    2016-01-01

    Full Text Available Background: Despite the availability of a  large number of treatments for multiple sclerosis with various targets, these treatments are not always effective. According to the literature, experimental studies have shown a  significant decrease in tumor necrosis factor alfa (TNF-α with the use of extracorporeal photochemotherapy. Aim: To assess changes in TNF-α in patients with multiple sclerosis during treatment with transimmunization. Materials and methods: The study recruited 13 adult patients with multiple sclerosis. Serum TNF-α was measured by immunochemiluminescence analysis (IMMULITE 1000, Siemens. The patients were treated by transimmunization, i.e. a  modified photopheresis. Two hours before the procedure, Ammifurin (8-methoxypsoralene was administered to all the patients, then their mononuclear cells were isolated under PBSC protocol with Haemonetics MCS+ cell separator. Thereafter, mononuclear cells were irradiated with ultraviolet for 90  minutes and incubated for 20 hours at 37 °С. The next day the cells were re-infused to the patients. The procedure was performed 2  times per week for 6  months, then once per 4  months. Results: Before transimmunization, mean TNF-α level in adult patients with multiple sclerosis was 9.958±0.812  pg/mL (normal, below 8.1 pg/mL. After transimmunization, its level was 6.992±0.367  pg/mL (р<0.05. Conclusion: Ultraviolet irradiation of peripheral blood monocytes with their subsequent incubation (transimmunization led to a 30% decrease of serum TNF-α in patients with multiple sclerosis. This indicates a suppressive effect of transimmunization on TNF-α. Hence, in patients with multiple sclerosis transimmunization exerts an anti-inflammatory effect.

  13. Intervalos de Confianza para el coeficiente alfa de Cronbach: aportes a la investigación pediátrica

    Directory of Open Access Journals (Sweden)

    Tomás Caycho-Rodríguez

    2017-06-01

    Full Text Available En la actualidad, es cada vez más común encontrar estudios que brinden evidencias de la confiabilidad de las puntuaciones obtenidas, por instrumentos de medida utilizadas en investigaciones en ciencias de la salud. Este es el caso de la valiosa contribución de Aguilar-Navarro et al, quienes adaptaron la Escala de Actitudes hacia la Alimentación Infantil de Iowa (IIFAS en México, reportando la confiabilidad a través del alfa de Cronbach.

  14. Comportamiento de glicinina, beta-conglicinina y alfa-amilasa en semillas de soja deterioradas y no deterioradas

    OpenAIRE

    Salinas,Adriana Rita; Yoldjian,Ana Maria; Dietrich,María Lucrecia; Craviotto,Roque Mario; Bisaro,Vilma

    2002-01-01

    El objetivo del trabajo fue estudiar el comportamiento de glicinina y beta-conglicinina y la actividad de alfa-amilasa en semillas deterioradas y no deterioradas de 10 cultivares de soja [Glycine max (L.) Merr.]. Las semillas se sometieron a dos tratamientos: deterioradas por envejecimiento acelerado y no deterioradas. Se determinó la presencia de las proteínas de reserva a partir de semillas con 0, 3 y 8 días de germinadas por electroforesis en geles de poliacrilamida (SDS-PAGE). La activida...

  15. Factor de necrosis tumoral alfa en pacientes con preeclampsia a término y pretérmino

    Directory of Open Access Journals (Sweden)

    Eduardo Reyna Villasmil

    2012-07-01

    Full Text Available El objetivo de la investigación fue identificar y comparar las concentraciones de factor de necrosis tumoral alfa en pacientes con preeclampsia a término y pre-término. Se seleccionó un total de 50 pacientes. Se incluyeron a 20 pacientes preeclámpticas pre-término (grupo A y 30 preeclámpticas a término (grupo B. Las muestras de sangre para la determinación de factor de necrosis tumoral alfa se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico de preeclampsia. No se encontraron diferencias significativas con relación a la edad materna e Índice de masa corporal al momento de la toma de la muestra. Se observaron diferencias estadísticamente significativas entre los grupos con respecto a la edad gestacional (p < 0,0001. El valor promedio de la presión arterial sistólica en el grupo A fue de 149,4 ± 11,3 mmHg mientras que en las pacientes del grupo B fue de 148,1 ± 12,3 mmHg (p = 0,7071 y el valor promedio de presión arterial diastólica en el grupo A fue de 103,8 ± 8,6 mmHg y en el grupo B fue de 102,7 ± 7,9 mmHg (p = 0,6436. Las concentraciones de factor de necrosis tumoral alfa fueron similares en el grupo de preeclámpticas pre-término (98,2 ± 45,1 pg/mL comparado con el grupo de preeclámpticas a término (96,6 ± 48,7 pg/mL; p = 0,9072. Al realizar la correlación entre los valores de factor de necrosis tumoral alfa con los valores de presión arterial se observó que no existía correlación con la presión arterial sistólica (r = 0,129; p = 0,374 ni con la de presión arterial diastólica (r = 0,158, p = 0,273. Se concluye que las concentraciones sanguíneas del factor de necrosis tumoral alfa resultaron similares en las pacientes preeclámpticas con embarazo pretérmino y a término. La correlación de las concentraciones de factor de necrosis tumoral alfa con los valores de presión arterial sistólica y diastólica resultó no significativa. Palabras clave:Factor de

  16. Synthesis of Ni2B nanoparticles by RF thermal plasma for fuel cell catalyst

    International Nuclear Information System (INIS)

    Cheng, Y; Tanaka, M; Watanabe, T; Choi, S Y; Shin, M S; Lee, K H

    2014-01-01

    The catalyst of Ni 2 B nanoparticles was successfully prepared using nickel and boron as precursors with the quenching gas in radio frequency thermal plasmas. The generating of Ni 2 B needs adequate reaction temperature and boron content in precursors. The quenching gas is beneficial for the synthesis of Ni 2 B in RF thermal plasma. The effect of quenching rate, powder feed rate and boron content in feeding powders on the synthesis of nickel boride nanoparticles was studied in this research. The high mass fraction of 28 % of Ni 2 B nanoparticles can be generated at the fixed initial composition of Ni:B = 2:3. Quenching gas is necessary in the synthesis of Ni 2 B nanoaprticles. In addition, the mass fraction of Ni 2 B increases with the increase of quenching gas flow rate and powder feed rate

  17. Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; de Wit, Heidi; Walter, Alexander M

    2013-01-01

    Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE-dependent exocytosis in mouse chromaffin cells, but the role of a closely related calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in chromaffin cells using Doc2b knock-out mice and high temporal...... resolution measurements of exocytosis. We found that the calcium dependence of vesicle priming and release triggering remained unchanged, ruling out an obligatory role for Doc2b in those processes. However, in the absence of Doc2b, release was shifted from the readily releasable pool to the subsequent...... sustained component. Conversely, upon overexpression of Doc2b, the sustained component was largely inhibited whereas the readily releasable pool was augmented. Electron microscopy revealed an increase in the total number of vesicles upon Doc2b overexpression, ruling out vesicle depletion as the cause...

  18. Some physico-chemical characteristics of a modified histone H2b on acute radiation affection

    International Nuclear Information System (INIS)

    Khrapunov, S.N.; Mel'nik, G.G.; Blyum, Ya.B.; Tsudzevich, B.A.; Kucherenko, N.E.

    1980-01-01

    A study was made of optical characteristics of histone H2b isolated from liver nuclei 12 h following irradiation in a dose of 0.21 C/kg. It was demonstrated that under similar conditions, the control and exposed histones H2b have different steric organization which correlates with radiation-induced modifications of lateral radicals in H2b histone molecules

  19. Insights into CYP2B6-mediated drug–drug interactions

    Directory of Open Access Journals (Sweden)

    William D. Hedrich

    2016-09-01

    Full Text Available Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR and pregnane X receptor (PXR in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.

  20. Informe sobre el Proyecto Alfa Biblioteca de Babel: ¿Un atajo para la administración de bibliotecas universitarias? Biblioteca de Babel Alfa Project Report: A shortcut for the academic libraries management?

    Directory of Open Access Journals (Sweden)

    Liliana Laura Rega

    2006-12-01

    Full Text Available El Proyecto Alfa Biblioteca de Babel que reúne bibliotecas universitarias de América Latina y Europa comenzó en marzo de 2005 y prevé su conclusión en marzo de 2007. El presente trabajo intenta describir los objetivos y los resultados esperados, e informa las actividades realizadas por la Red Biblioteca de Babel. Finalmente se analizan las propuestas del proyecto en cuanto al rol de las bibliotecas universitarias, y su relación con la innovación en las prácticas pedagógicas.Biblioteca de Babel Alfa Project that assembles academic libraries from Latin America and Europe was approved on March, 2005 and its conclusion is foreseen on March, 2007. This article attempts to describe the aims and the expected results, and reports the activities of the Biblioteca de Babel Network. Finally it analizes the proposals of the project about the role of academic libraries and their relationship with innovations in pedagogical practices.

  1. Immunogenicity and antigenicity of the recombinant EMA-1 protein of Theileria equi expressed in the yeast Pichia pastoris Imunogenicidade e antigenicidade da proteína recombinante EMA-1 de Theileria equi expressa em Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Leandro Q. Nizoli

    2009-06-01

    Full Text Available The equine piroplasmosis caused by Theileria equi is one of the most important parasitic diseases of the equine, causing damage to animal health and economic losses. In T. equi, 2 merozoite surface proteins, equi merozoite antigen EMA-1 and EMA-2, have been identified as the most immunodominant antigens. This suggests that these antigens might be used as immunobiological tools. The EMA-1 of Theileria equi was cloned and expressed in the yeast Pichia pastoris. The transformed yeast was grown at high cell density, expressing up to 389 mg.L-1 of recombinant protein. The protein was concentrated and detected in Dot blot. The recombinant product was antigenically similar to the native protein as determined using monoclonal antibodies, and polyclonal antibodies obtained from equines naturally infected with T. equi. The immunogenicity of rEMA-1 protein was demonstrated by IFAT using sera from recombinant-protein-immunized mice using aluminum hydroxide as adjuvant. All animals vaccinated with rEMA-1 developed a high specific antibody response. This results suggest that rEMA-1expressed in P. pastoris might be a strong candidate to be used as an antigen for immune diagnostics as well as a vaccine antigen.A piroplasmose equina causada por Theileria equi é uma das mais importantes doenças parasitárias de equídeos, causando danos a saúde animal e perdas econômicas. Em T. equi, 2 proteínas de superfície de merozoítos, equi merozoite antigen EMA-1 e EMA-2, têm sido identificadas como antígenos imunodominantes. Sugerindo que estes antígenos possam ser usados como produtos imunobiológicos. O gene EMA-1 de T. equi foi clonado e expressado na levedura Pichia pastoris. As leveduras transformadas foram cultivadas a altas densidades celulares expressando 389 mg.L-1 de proteína recombinante. A proteína foi concentrada e detectada em Dot blot. O produto recombinante foi antigenicamente similar à proteína nativa quando determinado usando anticorpo

  2. El ácido alfa lipoico y su poder antioxidante frente al cáncer y las patologías de sensibilización central

    OpenAIRE

    Durand Cavalleri, Marisa

    2013-01-01

    El objetivo del presente trabajo es reunir y contrastar información sobre las propiedades antioxidantes del ácido alfa lipoico (ALA) en la prevención y desarrollo de las patologías relacionadas con el estrés oxidativo. L'objectiu del present treball és reunir i contrastar informació sobre les propietats antioxidants de l'àcid alfa lipoico (ALA) en la prevenció i desenvolupament de les patologies relacionades amb l'estrès oxidatiu.

  3. Uso de la tierra y diversidades alfa, beta y gamma de diplópodos en la cuenca del río Otún, Colombia

    OpenAIRE

    Ruiz-Cobo, Darío Hernán; Grupo Gestión en Agroecosistemas Tropicales Andinos (GATA), Facultad de Ciencias Ambientales, Universidad Tecnológica de Pereira. Vereda La Julita A.A. 97, Pereira; Bueno-Villegas, Julián; Laboratorio de Sistemática Animal, Centro de Investigaciones Biológicas, Universidad Autónoma del Estado de Hidalgo. Km. 4.5 carretera Pachuca - Tulancingo S/N. Colonia Carboneras, Mineral de la Reforma, Hidalgo, 42184; Feijoo-Martínez, Alexander; Grupo Gestión en Agroecosistemas Tropicales Andinos (GATA), Facultad de Ciencias Ambientales, Universidad Tecnológica de Pereira. Vereda La Julita A.A. 97, Pereira

    2010-01-01

    Objetivo: Determinar la relación entre los cambios promovidos por la intervención humana en ecosistemas y grosistemas y la diversidad alfa, beta y gamma de Diplopoda de la cuenca media del río Otún. Materiales y métodos: Se utilizó un diseño sistemático estratificado con la selección de siete ventanas y 16 puntos de muestreo. Se separaron los diplópodos en familias y morfotipos para calcular la diversidad alfa, beta y gamma relacionada con la heterogeneidad de usos del terreno. Resultados: Se...

  4. An improved 2b-RAD approach (I2b-RAD) offering genotyping tested by a rice (Oryza sativa L.) F2 population.

    Science.gov (United States)

    Guo, Yu; Yuan, Hui; Fang, Dongming; Song, Lianbo; Liu, Yan; Liu, Yong; Wu, Lu; Yu, Jianping; Li, Zichao; Xu, Xun; Zhang, Hongliang

    2014-11-05

    2b-RAD (type IIB endonucleases restriction-site associated DNA) approach was invented by Wang in 2012 and proven as a simple and flexible method for genome-wide genotyping. However, there is still plenty of room for improvement for the existent 2b-RAD approach. Firstly, it doesn't include the samples pooling in library preparation as other reduced representation libraries. Secondly, the information of 2b-RAD tags, such as tags numbers and distributions, in most of species are unknown. The purposes of the research are to improve a new 2b-RAD approach which possesses samples pooling, moreover to figure out the characteristic and application potentiality of 2b-RAD tags by bioinformatics analysis. Twelve adapter1 and an adapter2 were designed. A library approach comprising digestion, ligation, pooling, PCR and size selection were established. For saving costs, we used non-phosphorylated adapters and indexed PCR primers. A F2 population of rice (Oryza sativa .L) was genotyped to validate the new approach. On average, 2000332 high quality reads of each sample were obtained with high evenness. Totally 3598 markers containing 3804 SNPs were discovered and the missing rate was 18.9%. A genetic linkage map of 1385 markers was constructed and 92% of the markers' orders in the genetic map were in accordance with the orders in chromosomes. Meanwhile, the bioinformatics simulation in 20 species showed that the BsaXI had the most widespread recognition sites, indicating that 2b-RAD tags had a powerful application potentiality for high density genetic map. Using modified adapters with a fix base in 3'end, 2b-RAD was also fit for QTL studies with low costs. An improved 2b-RAD genotyping approach was established in this research and named as I2b-RAD. The method was a simple, fast, cost-effective and multiplex sequencing library approach. It could be adjusted by selecting different enzymes and adapters to fit for alternative uses including chromosomes assembly, QTL fine mapping and

  5. Somatotropina bovina recombinante (rBST nos aspectos hematológicos e metabólitos do sangue de novilhas (½ Nelore x ½ Red Angus em confinamento

    Directory of Open Access Journals (Sweden)

    Prado Ivanor Nunes do

    2003-01-01

    Full Text Available O objetivo deste trabalho foi avaliar o efeito da somatotropina bovina recombinante (rBST - análogo do BST, obtido comercialmente pela técnica do DNA recombinante, sobre os aspectos hematológicos (hematócrito, eritrócitos, hemoglobina, leucócitos, neutrófilos, eosinófilos, linfócitos e monócitos e metabólitos (glicose, insulina, IGF-I, triglicérides, colesterol total e uréia do sangue de novilhas confinadas. Foram utilizadas 24 novilhas mestiças (½ Nelore x ½ Red Angus, com aproximadamente 18 meses de idade e peso médio 255 kg. Os animais foram alimentados com uma dieta contendo silagem de milho como volumoso e polpa de citrus peletizada e farelo de soja, como concentrado, durante 84 dias. Essa dieta foi utilizada para os três tratamentos, que se diferenciaram pela aplicação de 250 mg de rBST, por via subcutânea, na fossa ísqueo-retal, onde: 1 controle (aplicação de dois mL de solução salina; 2 dose única e 3 uma dose a cada 14 dias. Os animais foram distribuídos em delineamento inteiramente casualizado, com três tratamentos e oito repetições. Coleta de sangue foi realizada no início do experimento e nos dias 28, 56 e 84 do experimento, para as determinações dos aspectos hematológicos e metabólitos. Não houve influência da aplicação de rBST sobre os aspectos hematológicos do sangue no início e final do experimento. Todavia, independentemente do tratamento, o dia de coleta teve um efeito linear positivo sobre os níveis de hematócrito, linear negativo sobre os níveis de glicose e triglicérides e quadrático positivo sobre os níveis de IGF-I e uréia. Ainda, não foi observado efeito do dia de coleta sobre os níveis de insulina e colesterol total.

  6. ITF-2B protein levels are correlated with favorable prognosis in patients with colorectal carcinomas

    Science.gov (United States)

    Brandl, Lydia; Horst, David; de Toni, Enrico; Kirchner, Thomas; Herbst, Andreas; Kolligs, Frank T

    2015-01-01

    The majority of sporadic forms of colorectal carcinomas is characterized by deregulation of Wnt/β-catenin signaling early in colorectal carcinogenesis. As a consequence, ITF-2B protein levels are increased in adenomas of these patients. However, ITF-2B protein levels are strongly reduced with increasing carcinoma stages, suggesting that reduction of ITF-2B protein is required for progression of adenomas to colorectal carcinomas. To find out if ITF-2B protein levels are correlated with the survival of patients with colorectal carcinomas, a tissue microarray containing samples from 213 colorectal carcinomas (T-categories T2 and T3) with corresponding survival information was stained with an ITF-2B antibody. In addition, we analyzed if detection of ITF-2B in microsatellite instable and microsatellite stable carcinomas as well as in colorectal carcinomas with KRAS mutations is correlated with survival. Detection of cytoplasmic ITF-2B protein was associated with better overall and progression free survival of patients with colorectal carcinomas (P=0.033 and 0.024, respectively). Multivariate Cox regression analysis revealed an increased risk to suffer from poor overall survival and recurrent disease if no cytoplasmic ITF-2B was detectable (HR=1.91; P=0.033 and HR=1.75; P=0.033, respectively). Similarly, patients with MSS carcinomas had a better overall survival, if they showed cytoplasmic positivity for ITF-2B (P=0.013). Remarkably, patients with colorectal carcinomas carrying KRAS mutations had a better overall and progression free survival rate if the carcinomas were positive for cytoplasmic ITF-2B (HR=4.71; P=0.002 and HR=2.57; P=0.024, respectively). These data suggest that cytoplasmic protein levels of ITF-2B could be used as a prognostic marker for patients with colorectal carcinomas. PMID:26328254

  7. The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Hillary Johnston-Cox

    Full Text Available High fat diet (HFD-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR, an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance. As the A2bAR is expressed in different tissues, here, we provide the first lead to cellular mechanism by demonstrating that the receptor's influence on tissue insulin sensitivity is mediated via its expression in macrophages. This was shown using a newly generated transgenic mouse model expressing the A2bAR gene in the macrophage lineage on an otherwise A2bAR null background. Reinstatement of macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance and tissue insulin signaling to the level of control mice. The molecular mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine monophosphate in macrophages, reducing the expression and release of inflammatory cytokines, which downregulate insulin receptor-2. Thus, our results illustrate that macrophage A2bAR signaling is needed and sufficient for relaying the protective effect of the A2bAR against HFD-induced tissue inflammation and insulin resistance in mice.

  8. Field production and functional evaluation of chloroplast-derived interferon-alpha2b.

    Science.gov (United States)

    Arlen, Philip A; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M; Oishi, Karen K; Daniell, Henry

    2007-07-01

    Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-alpha2b for the treatment of hepatitis C infection is $26,000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological activity to commercially produced PEG-Introntrade mark when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-alpha2b, transgene containment and biological activity akin to that of commercial preparations of IFN-alpha2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization.

  9. Field production and functional evaluation of chloroplast-derived interferon-α2b

    Science.gov (United States)

    Arlen, Philip A.; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M.; Oishi, Karen K.; Daniell, Henry

    2008-01-01

    Summary Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-α2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-α2b for the treatment of hepatitis C infection is $26 000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-α2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-α2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-α2b had similar in vitro biological activity to commercially produced PEG-Intron™ when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-α2b were also seen in vivo . Chloroplast-derived IFN-α2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-α2b purified from chloroplast transgenic lines (cpIFN-α2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-α2b, transgene containment and biological activity akin to that of commercial preparations of IFN-α2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization. PMID:17490449

  10. Factor de necrosis tumoral alfa en una población infanto-juvenil con sobrepeso

    Directory of Open Access Journals (Sweden)

    Teresita del R. Carrizo

    2013-08-01

    Full Text Available El sobrepeso infantil está asociado a sobrepeso/obesidad en la edad adulta. El tejido adiposo en obesos produce una cantidad incrementada de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF-a, ejerciendo un efecto deletéreo sobre la función vascular. El objetivo de este trabajo fue evaluar niveles de TNF-a en una población infantojuvenil con sobrepeso y su relación con otras variables. Se estudiaron 30 niños con sobrepeso (12 varones de edades entre 8-13 años, se midió circunferencia de cintura (CC e índice de masa corporal (IMC y fueron comparados con 20 controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC = 85 < 95 percentilo para edad y sexo. En ambos grupos se determinó: glucemia en ayunas (método glucosa oxidasa, insulina plasmática (ECLIA, fibrinógeno (Fg, método de Clauss, proteína C reactiva ultrasensible (uPCR, método inmunoturbidimétrico, TNF-a (ELISA, perfil lipídico (métodos enzimáticos, eritrosedimentación y se calculó el índice HOMA. Los datos se expresaron como mediana y rango intercuartil y con el coeficiente de Spearman se investigaron las correlaciones entre variables, considerándose significativo un p < 0.05. Los niveles de TNF-a fueron mayores en los sujetos con sobrepeso [15.4 (13.2-24.0 vs. 12.7 (11.2-14.8 pg/ml; p = 0.028]. También resultaron más elevados los valores de Fg, insulina plasmática, índice HOMA, uPCR y triglicéridos. El TNF-a se correlacionó con la CC (r = 0.654; p = 0.021. Los niveles elevados de TNF-a, uPCR y Fg encontrados confirman un estado proinflamatorio asociado a obesidad abdominal en la población estudiada.

  11. Aspectos pulmonares na deficiência de alfa-1-antitripsina

    Directory of Open Access Journals (Sweden)

    Luiza Érika Schmid Melo Neto

    2004-03-01

    Full Text Available RESUMO: A deficiência de α-1-antitripsina é uma desordem genética de herança autossómica recessiva, tendo como fenótipo mais comum o inibidor de protease tipo ZZ. A doença predomina em indivíduos brancos de origem europeia, e a sua frequência, tanto na Europa, como na América do Norte, é comparável à da fibrose quística (1:2000 a 1:7000. Os indivíduos com esta deficiência podem ser assintomáticos, sendo que a manifestação mais prevalente, também apontada como a maior causa de invalidez e morte nesses pacientes, é a doença pulmonar obstrutiva crónica. Nos indivíduos portadores da doença, o tabagismo constitui o factor de risco mais importante. A doença é muito pouco diagnosticada. Várias estratégias de tratamento têm sido utilizadas.REV PORT PNEUMOL 2004; X (2: 145-154 ABSTRACT: Alpha-1-antitrypsin deficiency is an autosomal hereditary disorder and the large majority of individuals with severe deficiency are protease inhibitor type ZZ. The disease occurs predominantly in white persons of European origin and its frequency in Europe and North America is comparable to that of cystic fibrosis (1 in 2000 to 1 in 7000. Persons with this deficiency may have no clinical manifestations, but the most prevalent clinical disorder associated, also pointed as the most frequent cause of disability and death, is chronic obstructive pulmonary disease. In those individuals, tobacco smoking is the major risk. The condition appears to be widely underdiagnosed, based on studies. Several strategies have been explored in the treatment of this deficiency.REV PORT PNEUMOL 2004; X (2: 145-154 Palavras-chave: alfa-1-antitripsina, doença pulmonar obstrutiva crónica, Key-words: alpha-1-antitripysin, chronic obstructive pulmonary disease

  12. Estimadores de consistencia interna en las investigaciones en salud: el uso del coeficiente alfa

    Directory of Open Access Journals (Sweden)

    Franciele Cascaes da Silva

    Full Text Available La producción académica ha aumentado en el área de la salud, exigiendo cada vez más calidad en las publicaciones de gran impacto. Una de las formas de considerar la calidad es por medio de procedimientos que aumentan la consistencia del análisis de los datos, como la confiabilidad, que dependiendo del tipo de datos, puede ser evaluada por diferentes coeficientes, en especial el coeficiente alfa. Basados en lo anterior, la presente revisión reúne sistemáticamente artículos científicos producidos en los últimos cinco años, que de manera metodológica hicieron uso psicométrico del coeficiente α como un estimador de consistencia interna y de confiabilidad en procesos de construcción, adaptación y validación de instrumentos. La identificación de los estudios fue realizada sistemáticamente en las bases de datos Biomed Central Journals, Google Scholar, Web of Science, Wiley Online Library, Medline via Pubmed, Scielo, Scopus, Journals@Ovid, BMJ y Springer por medio del Portal de Periódicos CAPES, utilizando criterios de inclusión y exclusión. El análisis de los datos fue realizado por medio de triangulación, análisis de contenido y análisis descriptivo. Se obtuvo que la mayoría de los estudios fueron realizados principalmente en Irán (f=3, España (f=2 y Brasil (f=2, estos estudios tuvieron como objetivo testar las propiedades psicométricas de instrumentos, siendo que ocho estudios utilizaron el coeficiente α para evaluar la confiabilidad y nueve para evaluar la consistencia interna. Todos los estudios fueron clasificados como investigaciones metodológicas al analizar sus objetivos. Adicionalmente, cuatro estudios también fueron clasificados como correlacionales y uno como descriptivo-correlacional. Se puede concluir que a pesar de que el coeficiente α es ampliamente utilizado como uno de los principales parámetros para la evaluación de consistencia interna de instrumentos de medición del tipo cuestionario en el

  13. Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy.

    Science.gov (United States)

    Kaehler, Katharina C; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Haalck, Thomas; Heinzerling, Lucie; Kornek, Thomas; Livingstone, Elisabeth; Loquai, Carmen; Maul, Lara Valeska; Lang, Berenice M; Schadendorf, Dirk; Stade, Barbara; Terheyden, Patrick; Utikal, Jochen; Wagner, Tobias; Hauschild, Axel; Garbe, Claus; Augustin, Matthias

    2016-11-01

    Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit.We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health).Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: disease-free health and melanoma recurrence (with or without previous use of IFNα-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects.Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer.On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in

  14. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    Science.gov (United States)

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

  15. A novel Blind Start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease.

    Science.gov (United States)

    Harmatz, Paul; Whitley, Chester B; Wang, Raymond Y; Bauer, Mislen; Song, Wenjie; Haller, Christine; Kakkis, Emil

    2018-02-12

    Drug development for ultra-rare diseases is challenging because small sample sizes and heterogeneous study populations hamper the ability of randomized, placebo-controlled trials with a single primary endpoint to demonstrate valid treatment effects. To overcome these challenges, a novel Blind Start design was utilized in a study of vestronidase alfa in mucopolysaccharidosis VII (Sly syndrome), an ultra-rare lysosomal disease, that demonstrates the strengths of this approach in a challenging drug-development setting. Twelve subjects were randomized to 1 of 4 blinded groups, each crossing over to active treatment in a blinded fashion at different timepoints with efficacy analysis comparing the last assessment before cross over to after 24 weeks of treatment. Study assessments included: Percentage change from baseline in urinary GAG (uGAG); a Multi-Domain Responder Index (MDRI) using prespecified minimal important differences (6-Minute Walk Test, Forced Vital Capacity, shoulder flexion, visual acuity, and Bruininks-Oseretsky Test of Motor Proficiency); fatigue as assessed by the Pediatric Quality of Life Inventory™ Multidimensional Fatigue Scale; and safety. Vestronidase alfa treatment for 24 weeks significantly reduced uGAG excretion (dermatan sulfate: 64.8%, p design improve statistical power that enhances detection of a positive treatment effect in this rare heterogeneous disease and could be utilized for other ultra-rare diseases. Copyright © 2018 Ultragenyx Pharmaceutical Inc. Published by Elsevier Inc. All rights reserved.

  16. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

    Science.gov (United States)

    McMurray, John J.V.; Anand, Inder S.; Diaz, Rafael; Maggioni, Aldo P.; O'Connor, Christopher; Pfeffer, Marc A.; Solomon, Scott D.; Tendera, Michal; van Veldhuisen, Dirk J.; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B.; Amuchastegui, M.; Belziti, C.; Bluguermann, J.; Caccavo, M.; Cartasegna, L.; Colque, R.; Cuneo, C.; Fernandez, A.; Gabito, A.; Goicochea, R.; Gonzalez, M.; Gorosito, V.; Grinfeld, L.; Hominal, M.; Kevorkian, R.; Litvak Bruno, M.; Llanos, J.; Mackinnon, I.; Manuale, O.; Marzetti, E.; Nul, D.; Perna, E.; Riccitelli, M.; Sanchez, A.; Santos, D.; Schygiel, P.; Toblli, J.; Vogel, D.; Aggarwal, A.; Amerena, J.; De Looze, F.; Fletcher, P.; Hare, D.; Ireland, M.; Krum, H.; Lattimore, J.; Marwick, T.; Sindone, A.; Thompson, P.; Waites, J.; Altenberger, J.; Ebner, C.; Lenz, K.; Pacher, R.; Poelzl, G.; Charlier, F.; de Ceuninck, M.; De Keulenaer, G.; Dendale, P.; Maréchal, P.; Mullens, W.; Thoeng, J.; Vanderheyden, M.; Vanhaecke, J.; Weytjens, C.; Wollaert, B.; Albuquerque, D.; Almeida, D.; Aspe y Rosas, J.; Bocchi, E.; Bordignon, S.; Clausell, N.; Kaiser, S.; Leaes, P.; Martins Alves, S.; Montera, M.; Moura, L.; Pereira de Castro, R.; Rassi, S.; Reis, A.; Saraiva, J.; Simões, M.; Souza Neto, J.; Teixeira, M.; Benov, H.; Chompalova, B.; Donova, T.; Georgiev, P.; Gotchev, D.; Goudev, A.; Grigorov, M.; Guenova, D.; Hergeldjieva, V.; Ivanov, D.; Kostova, E.; Manolova, A.; Marchev, S.; Nikolov, F.; Popov, A.; Raev, D.; Tzekova, M.; Czarnecki, W.; Giannetti, N.; Haddad, H.; Heath, J.; Huynh, T.; Lepage, S.; Liu, P.; Lonn, E.; Ma, P.; Manyari, D.; Moe, G.; Parker, J.; Pesant, Y.; Rajda, M.; Ricci, J.; Roth, S.; Sestier, F.; Sluzar, V.; Sussex, B.; Vizel, S.; Antezana, G.; Bugueno, C.; Castro, P.; Conejeros, C.; Manriquez, L.; Martinez, D.; Potthoff, S.; Stockins, B.; Vukasovic, J.; Gregor, P.; Herold, M.; Jerabek, O.; Jirmar, R.; Kuchar, R.; Linhart, A.; Podzemska, B.; Soucek, M.; Spac, J.; Spacek, R.; Vodnansky, P.; Bronnum-Schou, J.; Clemmensen, K.; Egstrup, K.; Jensen, G.; Kjoller-Hansen, L.; Kober, L.; Markenvard, J.; Rokkedal, J.; Skagen, K.; Torp-Pedersen, C.; Tuxen, C.; Videbak, L.; Laks, T.; Vahula, V.; Harjola, V.; Kettunen, R.; Kotila, M.; Bauer, F.; Cohen Solal, A.; Coisne, D.; Davy, J.; De Groote, P.; Dos Santos, P.; Funck, F.; Galinier, M.; Gibelin, P.; Isnard, R.; Neuder, Y.; Roul, G.; Sabatier, R.; Trochu, J.; Anker, S.; Denny, S.; Dreykluft, T.; Flesch, M.; Genth-Zotz, S.; Hambrecht, R.; Hein, J.; Jeserich, M.; John, M.; Kreider-Stempfle, H.; Laufs, U.; Muellerleile, K.; Natour, M.; Sandri, M.; Schäufele, T.; von Hodenberg, E.; Weyland, K.; Winkelmann, B.; Tse, H.; Yan, B.; Barsi, B.; Csikasz, J.; Dezsi, C.; Edes, I.; Forster, T.; Karpati, P.; Kerekes, C.; Kis, E.; Kosa, I.; Lupkovics, G.; Nagy, A.; Preda, I.; Ronaszeki, A.; Tomcsanyi, J.; Zamolyi, K.; Agarwal, D.; Bahl, V.; Bordoloi, A.; Chockalingam, K.; Chopda, M.; Chopra, V.; Dugal, J.; Ghaisas, N.; Ghosh, S.; Grant, P.; Hiremath, S.; Iyengar, S.; Jagadeesa Subramania, B.; Jain, P.; Joshi, A.; Khan, A.; Mullasari, A.; Naik, S.; Oomman, A.; Pai, V.; Pareppally Gopal, R.; Parikh, K.; Patel, T.; Prakash, V.; Sastry, B.; Sathe, S.; Sinha, N.; Srikanthan, V.; Subburamakrishnan, P.; Thacker, H.; Wander, G.; Admon, D.; Katz, A.; Klainman, E.; Lewis, B.; Marmor, A.; Moriel, M.; Mosseri, M.; Shotan, A.; Weinstein, J.; Zimlichman, R.; Agostoni, P.; Albanese, M.; Alunni, G.; Bini, R.; Boccanelli, A.; Bolognese, L.; Campana, C.; Carbonieri, E.; Carpino, C.; Checco, L.; Cosmi, F.; D'Angelo, G.; De Cristofaro, M.; Floresta, A.; Fucili, A.; Galvani, M.; Ivleva, A.; Marra, S.; Musca, G.; Peccerillo, N.; Perrone Filardi, P.; Picchio, E.; Russo, T.; Scelsi, L.; Senni, M.; Tavazzi, L.; Erglis, A.; Jasinkevica, I.; Kakurina, N.; Veze, I.; Volans, E.; Bagdonas, A.; Berukstis, E.; Celutkiene, J.; Dambrauskaite, A.; Jarasuniene, D.; Luksiene, D.; Rudys, A.; Sakalyte, G.; Sliaziene, S.; Aguilar-Romero, R.; Cardona-Muñoz, E.; Castro-Jimenez, J.; Chavez-Herrera, J.; Chuquiure Valenzuela, E.; De la Pena, G.; Herrera, E.; Leiva-Pons, J.; Lopez Alvarado, A.; Mendez Machado, G.; Ramos-Lopez, G.; Basart, D.; Buijs, E.; Cornel, J.; de Leeuw, M.; Dijkgraaf, R.; Dunselman, P.; Freericks, M.; Hamraoui, K.; Lenderlink, T.; Linssen, G.; Lodewick, P.; Lodewijks, C.; Lok, D.; Nierop, P.; Ronner, E.; Somsen, A.; van Dantzig, J.; van der Burgh, P.; van Kempen, L.; van Vlies, B.; Voors, A.; Wardeh, A.; Willems, F.; Dickstein, K.; Gundersen, T.; Hole, T.; Thalamus, J.; Westheim, A.; Dabrowski, M.; Gorski, J.; Korewicki, J.; Kuc, K.; Miekus, P.; Musial, W.; Niegowska, J.; Piotrowski, W.; Podolec, P.; Polonski, L.; Ponikowski, P.; Rynkiewicz, A.; Szelemej, R.; Trusz-Gluza, M.; Ujda, M.; Wojciechowski, D; Wysokinski, A.

    2013-01-01

    Aims This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Methods and results Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L. Conclusion The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity. PMID:23329651

  17. SPECIFIC DISORDERS OF THE RESPIRATORY SYSTEM IN CYSTIC FIBROSIS. CLINICAL EFFICACY OF THERAPY WITH DORNASE ALFA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T.V. Simanova

    2010-01-01

    Full Text Available The article is devoted to specific disorders of the respiratory system in cystic fibrosis. 64 patients with cystic fibrosis (CF aged 2 months to 32 years and residing in the Udmurtian Republic were studied. Epidemiological and genetic specifics of this disease in the mentioned region of the RF were examined. Clinical, X-ray, functional and microbiological studies of the CF patients’ respiratory system were conducted. It was found that genotype delF508 and chronic infection Pseudomonas aeruginosa, Staphylococcus aureus cause severe structural changes to the bronchopulmonary system more often. The obtained data suggest the advisability of identifying the groups of CF patients at the highest risk of severe respiratory system disorders in order to optimise therapeutic efforts. The article provides indicators of clinical efficacy of a dornase alfa therapy in CF children.Key words: cystic fibrosis, genotype, delF508 mutation, respiratory organs, pseudomonas aeruginosa infection, staphylococcal infection, respiratory function, mucolytic function, dornase alfa. (Pediatric Pharmacology. – 2010; 7(6:44-48

  18. Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution.

    Science.gov (United States)

    Gauthier-Landry, Louis; Bélanger, Alain; Barbier, Olivier

    2015-01-01

    In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed. This article is part of a special issue entitled 'Essential role of DHEA'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. AMP and adenosine are both ligands for adenosine 2B receptor signaling.

    Science.gov (United States)

    Holien, Jessica K; Seibt, Benjamin; Roberts, Veena; Salvaris, Evelyn; Parker, Michael W; Cowan, Peter J; Dwyer, Karen M

    2018-01-15

    Adenosine is considered the canonical ligand for the adenosine 2B receptor (A 2B R). A 2B R is upregulated following kidney ischemia augmenting post ischemic blood flow and limiting tubular injury. In this context the beneficial effect of A 2B R signaling has been attributed to an increase in the pericellular concentration of adenosine. However, following renal ischemia both kidney adenosine monophosphate (AMP) and adenosine levels are substantially increased. Using computational modeling and calcium mobilization assays, we investigated whether AMP could also be a ligand for A 2B R. The computational modeling suggested that AMP interacts with more favorable energy to A 2B R compared with adenosine. Furthermore, AMPαS, a non-hydrolyzable form of AMP, increased calcium uptake by Chinese hamster ovary (CHO) cells expressing the human A 2B R, indicating preferential signaling via the G q pathway. Therefore, a putative AMP-A 2B R interaction is supported by the computational modeling data and the biological results suggest this interaction involves preferential G q activation. These data provide further insights into the role of purinergic signaling in the pathophysiology of renal IRI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Neutron diffraction studies of Ho1-xYxNi2B2C compounds

    DEFF Research Database (Denmark)

    Chang, L.J.; Tomy, C.V.; Paul, D.M.K.

    1996-01-01

    Neutron diffraction measurements have been carried out to investigate the nature of magnetic ordering in Ho(1-x)Y(x)Ni(2)B(2)C (x = 0, 0.1 and 0.2) compounds. HoNi(2)B(2)C shows a complex type of magnetic ordering below the superconducting transition, with a commensurate antiferromagnetic ordering...

  1. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes...

  2. SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

    Science.gov (United States)

    Sinai, Laleh; Duffy, Steven; Roder, John C.

    2010-01-01

    The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src…

  3. RSCAT_LEVEL_2B_OWV_COMP_12_V1.1:1

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.1 science-quality ocean surface wind vectors. The Level 2B wind vectors are binned on a 12.5 km Wind...

  4. Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling.

    Science.gov (United States)

    Ikuta, Kayo; Segawa, Hiroko; Sasaki, Shohei; Hanazaki, Ai; Fujii, Toru; Kushi, Aoi; Kawabata, Yuka; Kirino, Ruri; Sasaki, Sumire; Noguchi, Miwa; Kaneko, Ichiro; Tatsumi, Sawako; Ueda, Otoya; Wada, Naoko A; Tateishi, Hiromi; Kakefuda, Mami; Kawase, Yosuke; Ohtomo, Shuichi; Ichida, Yasuhiro; Maeda, Akira; Jishage, Kou-Ichi; Horiba, Naoshi; Miyamoto, Ken-Ichi

    2017-11-11

    Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na + -dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Although the Na + -dependent Pi transport in brush-border membrane vesicle uptake levels was significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.

  5. Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations

    DEFF Research Database (Denmark)

    Urwin, Hazel; Authier, Astrid; Nielsen, Jørgen Erik

    2010-01-01

    Mutations in CHMP2B cause frontotemporal dementia (FTD) in a large Danish pedigree, which is termed FTD linked to chromosome 3 (FTD-3), and also in an unrelated familial FTD patient. CHMP2B is a component of the ESCRT-III complex, which is required for function of the multivesicular body (MVB), a...

  6. 14 CFR 250.2b - Carriers to request volunteers for denied boarding.

    Science.gov (United States)

    2010-01-01

    ... boarding. 250.2b Section 250.2b Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION... boarding. (a) In the event of an oversold flight, every carrier shall request volunteers for denied boarding before using any other boarding priority. A “volunteer” is a person who responds to the carrier's...

  7. Automated Report Generation for Research Data Repositories: From i2b2 to PDF.

    Science.gov (United States)

    Thiemann, Volker S; Xu, Tingyan; Röhrig, Rainer; Majeed, Raphael W

    2017-01-01

    We developed an automated toolchain to generate reports of i2b2 data. It is based on free open source software and runs on a Java Application Server. It is sucessfully used in an ED registry project. The solution is highly configurable and portable to other projects based on i2b2 or compatible factual data sources.

  8. Evidence for multiple polytypes of semiconducting boron carbide (C2B10) from electronic structure

    International Nuclear Information System (INIS)

    Lunca-Popa, Petru; Brand, J I; Balaz, Snjezana; Rosa, Luis G; Boag, N M; Bai Mengjun; Robertson, B W; Dowben, P A

    2005-01-01

    Boron carbides fabricated via plasma enhanced chemical vapour deposition from different isomeric source compounds with the same C 2 B 10 H 12 closo-icosahedral structure result in materials with very different direct (optical) band gaps. This provides compelling evidence for the existence of multiple polytypes of C 2 B 10 boron carbide and is consistent with electron diffraction results

  9. GRIN2B encephalopathy : Novel findings on phenotype, variant clustering, functional consequences and treatment aspects

    NARCIS (Netherlands)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M.; Mefford, Heather C.; Myers, Candace T.; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette G.; Scheffer, Ingrid E.; Brilstra, Eva; van Haelst, Mieke M.; van der Smagt, Jasper J.; Bok, Levinus A; Møller, Rikke S.; Jensen, Uffe Birk; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H.; Abou Jamra, Rami; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E.; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B.; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R.

    2017-01-01

    Background: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research

  10. Identification of Phox2b-regulated genes by expression profiling of cranial motoneuron precursors

    Directory of Open Access Journals (Sweden)

    Reiprich Simone

    2008-06-01

    Full Text Available Abstract Background Branchiomotor neurons comprise an important class of cranial motor neurons that innervate the branchial-arch-derived muscles of the face, jaw and neck. They arise in the ventralmost progenitor domain of the rhombencephalon characterized by expression of the homeodomain transcription factors Nkx2.2 and Phox2b. Phox2b in particular plays a key role in the specification of branchiomotor neurons. In its absence, generic neuronal differentiation is defective in the progenitor domain and no branchiomotor neurons are produced. Conversely, ectopic expression of Phox2b in spinal regions of the neural tube promotes cell cycle exit and neuronal differentiation and, at the same time, induces genes and an axonal phenotype characteristic for branchiomotor neurons. How Phox2b exerts its pleiotropic functions, both as a proneural gene and a neuronal subtype determinant, has remained unknown. Results To gain further insights into the genetic program downstream of Phox2b, we searched for novel Phox2b-regulated genes by cDNA microarray analysis of facial branchiomotor neuron precursors from heterozygous and homozygous Phox2b mutant embryos. We selected for functional studies the genes encoding the axonal growth promoter Gap43, the Wnt antagonist Sfrp1 and the transcriptional regulator Sox13, which were not previously suspected to play roles downstream of Phox2b and whose expression was affected by Phox2b misexpression in the spinal cord. While Gap43 did not produce an obvious phenotype when overexpressed in the neural tube, Sfrp1 induced the interneuron marker Lhx1,5 and Sox13 inhibited neuronal differentiation. We then tested whether Sfrp1 and Sox13, which are down-regulated by Phox2b in the facial neuron precursors, would antagonize some aspects of Phox2b activity. Co-expression of Sfrp1 prevented Phox2b from repressing Lhx1,5 and alleviated the commissural axonal phenotype. When expressed together with Sox13, Phox2b was still able to promote

  11. Nonlinear Elasticity of Borocarbide Superconductor YNi2B2C: A First-Principles Study

    Directory of Open Access Journals (Sweden)

    Lili Liu

    2017-01-01

    Full Text Available First-principles calculations combined with homogeneous deformation methods are used to investigate the second- and third-order elastic constants of YNi2B2C with tetragonal structure. The predicted lattice constants and second-order elastic constants of YNi2B2C agree well with the available data. The effective second-order elastic constants are obtained from the second- and third-order elastic constants for YNi2B2C. Based on the effective second-order elastic constants, Pugh’s modulus ratio, Poisson’s ratio, and Vickers hardness of YNi2B2C under high pressure are further investigated. It is shown that the ductility of YNi2B2C increases with increasing pressure.

  12. Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis

    2012-01-01

    role in the pathogenesis of the disease. METHODS: In the present study, we used lentiviral vectors to efficiently knockdown CHMP2B by delivering microRNA embedded small hairpin RNAs. RESULTS: We show that CHMP2B can be efficiently knocked down in patient fibroblasts using an RNA interference approach......BACKGROUND: Frontotemporal dementia is the second most common form of young-onset dementia after Alzheimer's disease, and several genetic forms of frontotemporal dementia are known. A rare genetic variant is caused by a point mutation in the CHMP2B gene. CHMP2B is a component of the ESCRT......-III complex, which is involved in endosomal trafficking of proteins targeted for degradation in lysosomes. Mutations in CHMP2B result in abnormal endosomal structures in patient fibroblasts and patient brains, probably through a gain-of-function mechanism, suggesting that the endosomal pathway plays a central...

  13. Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects

    DEFF Research Database (Denmark)

    Ravnskjær, Kim; Hogan, Meghan F; Lackey, Denise

    2013-01-01

    assays, we show that histone H3 acetylation at Lys 9 (H3K9Ac) was elevated over gluconeogenic genes and contributed to increased hepatic glucose production during fasting and in diabetes. Dephosphorylation of CRTC2 promoted increased H3K9Ac through recruitment of the lysine acetyltransferase 2B (KAT2B......) and WD repeat-containing protein 5 (WDR5), a core subunit of histone methyltransferase (HMT) complexes. KAT2B and WDR5 stimulated the gluconeogenic program through a self-reinforcing cycle, whereby increases in H3K9Ac further potentiated CRTC2 occupancy at CREB binding sites. Depletion of KAT2B or WDR5...... decreased gluconeogenic gene expression, consequently breaking the cycle. Administration of a small-molecule KAT2B antagonist lowered circulating blood glucose concentrations in insulin resistance, suggesting that this enzyme may be a useful target for diabetes treatment....

  14. Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.

    Science.gov (United States)

    Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, Hayriye; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. Copyright © 2015 Federation of European Biochemical Societies

  15. Cytochrome P450 2B diversity and dietary novelty in the herbivorous, desert woodrat (Neotoma lepida.

    Directory of Open Access Journals (Sweden)

    Jael R Malenke

    Full Text Available Detoxification enzymes play a key role in plant-herbivore interactions, contributing to the on-going evolution of ecosystem functional diversity. Mammalian detoxification systems have been well studied by the medical and pharmacological industries to understand human drug metabolism; however, little is known of the mechanisms employed by wild herbivores to metabolize toxic plant secondary compounds. Using a wild rodent herbivore, the desert woodrat (Neotoma lepida, we investigated genomic structural variation, sequence variability, and expression patterns in a multigene subfamily involved in xenobiotic metabolism, cytochrome P450 2B (CYP2B. We hypothesized that differences in CYP2B expression and sequence diversity could explain differential abilities of woodrat populations to consume native plant toxins. Woodrats from two distinct populations were fed diets supplemented with either juniper (Juniperus osteosperma or creosote bush (Larrea tridentata, plants consumed by woodrats in their respective desert habitats. We used Southern blot and quantitative PCR to determine that the genomic copy number of CYP2B in both populations was equivalent, and similar in number to known rodent copy number. We compared CYP2B expression patterns and sequence diversity using cloned hepatic CYP2B cDNA. The resulting sequences were very diverse, and clustered into four major clades by amino acid similarity. Sequences from the experimental treatments were distributed non-randomly across a CYP2B tree, indicating unique expression patterns from woodrats on different diets and from different habitats. Furthermore, within each major CYP2B clade, sequences shared a unique combination of amino acid residues at 13 sites throughout the protein known to be important for CYP2B enzyme function, implying differences in the function of each major CYP2B variant. This work is the most comprehensive investigation of the genetic diversity of a detoxification enzyme subfamily in a

  16. KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth

    Directory of Open Access Journals (Sweden)

    Wang Y

    2018-01-01

    Full Text Available Yiwei Wang,1 Jin Zang,1 Dongyong Zhang,2 Zhenxiang Sun,1 Bo Qiu,2 Xiaojie Wang1 1Department of Human Anatomy, Shenyang Medical College, Huanggu District, Shenyang City, 2Department of Neurosurgery, First Affiliated Hospital of China Medical University, Heping District, Shenyang City, Liaoning Province, ChinaBackground: Gliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains poor. KDM2B is a histone lysine demethylase, which has been observed in multiple tumors. But the concrete role of KDM2B in gliomas remains to be further illustrated.Methods: The KDM2B expression in gliomas was detected with immunohistochemistry and Western blot assay. Furthermore, knockdown of KDM2B in U87 and U251 glioma cell lines, the proliferation capacity was evaluated by cell viability assay, colon formation assay and flow cytometry in vitro. Western blot assay was used to analyze the p21, EZH2 and cyclinD1 changes followed by knockdown of KDM2B.Results: KDM2B was upregulated in tissues of glioma patients, and the expression was correlated to cancer progression. Downregulation of KDM2B in U87 and U251 glioma cell lines inhibited cell proliferation and arrested cell cycle in G0/G1 phase. In addition, silencing KDM2B promoted the upregulation of p21 while reduced the expression of EZH2 and cyclinD1.Conclusion: Taken together, our results revealed that KDM2B might influence gliomas growth and act as a novel therapeutic target for glioma patients.Keywords: EZH2, glioma, KDM2B, P21

  17. Cloning and expression of a rat brain. alpha. sub 2B -adrenergic receptor

    Energy Technology Data Exchange (ETDEWEB)

    Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H. (Boston Univ. School of Medicine, MA (United States))

    1991-02-01

    The authors isolated a cDNA clone (RB{alpha}{sub 2B}) and its homologous gene (GR{alpha}{sub 2B}) encoding an {alpha}{sub 2B}-adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor ({alpha}{sub 2}-C4) and divergent from the rat kidney nonglycosylated {alpha}{sub 2B} subtype (RNG{alpha}{sub 2}). Transient expression of RB{alpha}{sub 2B} in COS-7 cells resulted in high-affinity saturable binding for ({sup 3}H)rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine {gt} yohimbine {gt} prazosin {gt} oxymetazoline, with a prazosin-to-oxymetazoline K{sub i} ratio of 0.34. This profile is characteristic of the {alpha}{sub 2B}-adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GR{alpha}{sub 2B} may be transcriptionally active. These findings show that rat brain expresses an {alpha}{sub 2B}-adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated {alpha}{sub 2B} subtype. Thus the rat expresses at least two divergent {alpha}{sub 2B}-adrenergic receptors.

  18. CDKN2B methylation is associated with carotid artery calcification in ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Shuyu Zhou

    2016-12-01

    Full Text Available Abstract Background Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B near chromosome 9p21 have been associated with both atherosclerosis and artery calcification, but the underlying mechanisms remained largely unknown. Considering that CDKN2A/2B is a frequently reported site for DNA methylation, this study aimed to evaluate whether carotid artery calcification (CarAC is related to methylation levels of CDKN2A/2B in patients with ischemic stroke. Methods DNA methylation levels of CDKN2A/2B were measured in 322 ischemic stroke patients using peripheral blood leukocytes. Methylation levels of 36 CpG sites around promoter regions of CDKN2A/2B were examined with BiSulfite Amplicon Sequencing. CarAC was quantified with Agatston score based on results of computed tomography angiography. Generalized liner model was performed to explore the association between methylation levels and CarAC. Results Of the 322 analyzed patients, 187 (58.1% were classified as with and 135 (41.9% without evident CarAC. The average methylation levels of CDKN2B were higher in patents with CarAC than those without (5.7 vs 5.4, p = 0.001. After adjustment for potential confounders, methylation levels of CDKN2B were positively correlated with cube root transformed calcification scores (β = 0.591 ± 0.172, p = 0.001 in generalized liner model. A positive correlation was also detected between average methylation levels of CDKN2B and cube root transformed calcium volumes (β = 0.533 ± 0.160, p = 0.001. Conclusions DNA methylation of CDKN2B may play a potential role in artery calcification.

  19. Validación de un ELISA para la cuantificación de las impurezas proteicas de la cepa hospedera en el principio activo de la vacuna recombinante cubana contra la hepatitis B

    Directory of Open Access Journals (Sweden)

    Eliana Pérez

    2014-04-01

    Full Text Available Se validó un inmunoensayo tipo sandwich de doble anticuerpo para cuantificar las impurezas proteicas de la cepa hospedera que pueden estar presentes en el principio activo de la vacuna cubana contra la hepatitis B. Se prepararon los reactivos biológicos empleados en el ELISA. Las proteínas de la cepa hospedera se obtuvieron bajo las mismas condiciones que el proceso de producción de la proteína recombinante hasta un paso de semipurificación o purificación primaria. Los antisueros dirigidos contra las proteínas de la cepa hospedera se generaron en conejos por un proceso de inmunización en cascada. Para la validación se analizaron los siguientes parámetros: linealidad, límite de detección y cuantificación, exactitud, rango y precisión. El ensayo establecido resultó específico, con una exactitud entre 89% y 109% para todos los tampones estudiados; se demostró un ajuste parabólico y un rango de trabajo entre 0,63 y 1,25 ng/mL, la repetibilidad y la precisión intermedia mostraron coeficientes de variación inferiores al 10 y 20% respectivamente.

  20. Elosulfase alfa enzyme replacement therapy attenuates disease progression in a non-ambulatory Japanese patient with Morquio A syndrome (case report

    Directory of Open Access Journals (Sweden)

    Misako Hiramatsu

    2017-12-01

    Full Text Available Enzyme replacement therapy (ERT with elosulfase alfa is the only approved therapy in Japan for patients with Morquio A syndrome, a lysosomal storage disorder inherited in an autosomal recessive fashion. The experience with ERT in severely affected, non-ambulatory patients has not been reported in previous studies. This case report describes clinical evidence for the 1-year efficacy and safety of ERT with elosulfase alfa in a severely affected, non-ambulatory, 47-year-old patient with Morquio A syndrome who needs intensive respiratory management. ERT with elosulfase alfa was well tolerated in this patient. Because of the possibility of potential hypersensitivity adverse events, special attention is needed when using ERT in patients with respiratory disorders. However, under the appropriate management of specialists, the patient in this case report showed significant respiratory improvement after starting ERT, and abdominal bloating was improved by gas evacuation. In addition, the patient was able to lift up her arms, reach behind her back, and move her legs slightly, and she recovered her grip strength. Her hearing loss improved and she could hear without a hearing aid. This report shows that ERT with elosulfase alfa can be used with appropriate respiratory care in patients with severe respiratory dysfunction.

  1. The ALFA4Hearing Model (At-a-Glance Labeling for Features of Apps for Hearing Health Care) to Characterize Mobile Apps for Hearing Health Care.

    Science.gov (United States)

    Paglialonga, Alessia; Pinciroli, Francesco; Tognola, Gabriella

    2017-10-12

    The aim of the study was to analyze, by using the ALFA4Hearing model (At-a-Glance Labeling for Features of Apps for Hearing Health Care), a sample of apps over a wide range of services in the hearing health care (HHC) domain in order to take a first picture of the current scenario of apps for HHC. We tested 120 apps, and we characterized them by using the ALFA4Hearing model, which includes 29 features in 5 components (Promoters, Services, Implementation, Users, and Descriptive Information). We analyzed (a) the distribution of the 29 features in the sample, (b) the relationship between the Implementation features and the Services provided by the apps, and (c) the distribution of the 29 features in apps for professional use. The analysis of our sample of apps by means of the ALFA4Hearing model highlighted interesting trends and emerging challenges. Also, results suggested many potential opportunities for research and clinical practice, such as greater involvement of stakeholders, improved evidence base, higher technical quality, and usability. The ALFA4Hearing model is able to represent, at a glance, a large amount of information about apps for HHC, highlighting trends and challenges. It might be useful to HHC professionals as a basis for app characterization and informed decision making.

  2. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    Science.gov (United States)

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. The influence of VO2(B nanobelts on thermal decomposition of ammonium perchlorate

    Directory of Open Access Journals (Sweden)

    Zhang Yifu

    2015-09-01

    Full Text Available The influence of vanadium dioxide VO2(B on thermal decomposition of ammonium perchlorate (AP has not been reported before. In this contribution, the effect of VO2(B nanobelts on the thermal decomposition of AP was investigated by the Thermo- Gravimetric Analysis and Differential Thermal Analysis (TG/DTA. VO2(B nanobelts were hydrothermally prepared using peroxovanadium (V complexes, ethanol and water as starting materials. The thermal decomposition temperatures of AP in the presence of I wt.%, 3 wt.% and 6 wt.% of as-obtained VO2<B nanobelts were reduced by 39 °C. 62 °C and 74 °C, respectively. The results indicated that VO2(B nanobelts had a great influence on the thermal decomposition temperature of AP Furthermore, the influence of the corresponding V2Os, which was obtained by thermal treatment of VO2(B nanobelts, on the thermal decomposition of AP was also investigated. The resufs showed that VO2(B nanobelts had a greater influence on the thermal decomposition temperature of AP than that of V2Os.

  4. Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a Neurodevelopmental Phenotype

    Directory of Open Access Journals (Sweden)

    Navin Mishra MD

    2016-03-01

    Full Text Available The GRIN2B (glutamate receptor, ionotropic, N-methyl- d -aspartate 2B gene, located in the short arm of chromosome 12, encoding the NR2B subunit of the N-methyl-D-aspartate receptor, has recently been recognized to play an important role in corticogenesis and brain plasticity. Deletions in the short arm of chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in developmental delay, whereas gain of function leads to epilepsy, and infantile spasms in particular. In addition, GRIN2B variants have been associated with autism spectrum disorder and schizophrenia. Here the authors report a child with global developmental delay, autistic behavioural features, central hypotonia, dysmorphic features and isolated congenital anomalies of the fingers and toes, and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving loss of several genes, including GRIN2B . This report and our review of the literature help clarify the distinct phenotypes associated with loss or gain of GRIN2B function.

  5. Lpar2b Controls Lateral Line Tissue Size by Regulating Yap1 Activity in Zebrafish

    Directory of Open Access Journals (Sweden)

    Xueqian Wang

    2018-02-01

    Full Text Available LPA signaling plays important roles during cell migration and proliferation in normal and pathological conditions. However, its role during sensory organ development remains unknown. Here we show a LPA receptor Lpar2b is expressed in the posterior lateral line primordium (pLLP and mechanosensory organs called neuromasts (NMs in zebrafish embryos. Lpar2b loss-of-function significantly reduces the number of NMs and hair cells in the posterior lateral line (pLL. Further analysis reveals that Lpar2b regulates the patterning and tissue size of the pLLP. Interestingly, we show that knocking down a Hippo effector Yap1 phenocopies the result of Lpar2b depletion, and Lpar2b regulates the phosphorylation and activity of Yap1 in the pLLP. Importantly, a phosphorylation-resistant Yap1 rescues pLLP size and NM number in Lpar2b-depleted embryos. Our results indicate Lpar2b controls primordium size and NM number by regulating Yap1 activity in the lateral line system.

  6. The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Michihiro Takahama

    2017-09-01

    Full Text Available Cyclic GMP-AMP synthase (cGAS is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5, in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING, the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis.

  7. Role of peroxynitrite induced structural changes on H2B histone by physicochemical method.

    Science.gov (United States)

    Khan, M Asad; Alam, Khursheed; Dixit, Kiran; Rizvi, M Moshahid A

    2016-01-01

    Histones are small highly conserved cationic proteins which bind DNA and remain confined in the nucleus. These histones are quite vulnerable to oxidizing and nitrating agents. Peroxynitrite is a powerful oxidant and nitrating agent present in the biological system. In this study, peroxynitrite-induced nitration and oxidation of H2B was assessed by various physicochemical techniques. The carbonyl content and dityrosine were markedly elevated in peroxynitrite-modified H2B histone as compared to the native histone. Cross-linking of H2B was evident on polyacrylamide gel electrophoresis. 3-Nitrotyrosine was present only in peroxynitrite-modified H2B revealed by HPLC. The results showed that peroxynitrite-mediated nitration and oxidation in H2B histone exhibited hyperchromicity, decrease of tyrosine fluorescence accompanied by increase in ANS-binding specific fluorescence, loss of β-sheet structure, appearance of new peak in FT-IR, increase in melting temperature and also loss of α-helix to produce a partially folded structure in comparison to intrinsically disordered structure of native H2B histone. We concluded that the H2B histone, a constituent of core histones, is highly sensitive to peroxynitrite and can adopt different structures under nitrosative and oxidative stress in order to protect the packaged DNA from the deleterious insult of peroxynitrite. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

    Science.gov (United States)

    Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

    2017-03-07

    Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10 6 /mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10 6 /mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

  9. Characterization of dermatoglyphics in PHOX2B-confirmed congenital central hypoventilation syndrome.

    Science.gov (United States)

    Todd, Emily S; Scott, Nicole M; Weese-Mayer, Debra E; Weinberg, Seth M; Berry-Kravis, Elizabeth M; Silvestri, Jean M; Kenny, Anna S; Hauptman, Susan A; Zhou, Lili; Marazita, Mary L

    2006-08-01

    Individuals with congenital central hypoventilation syndrome have characteristic variants in the PHOX2B gene (primarily polyalanine expansion mutations). The PHOX2B gene acts as a transcriptional activator in the promotion of pan-neuronal differentiation in the autonomic nervous system during early embryologic development, with a primary role in the sympathetic noradrenergic phenotype in vertebrates. Because sympathetic innervation has been hypothesized to affect the development of dermatoglyphic pattern types, we hypothesized that individuals with PHOX2B-confirmed congenital central hypoventilation syndrome would have characteristic dermatoglyphic patterning and that the dermatoglyphic phenotype would be related to the disease-defining PHOX2B genotype. Dermatoglyphic pattern type frequency, left/right symmetry, and genotype/phenotype correlation were assessed for 33 individuals with PHOX2B-confirmed congenital central hypoventilation syndrome and compared with published control data. Dermatoglyphic pattern type frequencies were altered in congenital central hypoventilation syndrome cases versus controls. In particular, there was an increase of arches in females and ulnar loops in males, with the largest differences for the left hand and for individuals with both congenital central hypoventilation syndrome and Hirschsprung disease. Dissimilarity scores between the congenital central hypoventilation syndrome and congenital central hypoventilation syndrome + Hirschsprung disease cases were not significantly different, nor were dissimilarity scores between all of the female and all of the male cases. No significant association was found between the number of polyalanine repeats in the PHOX2B genotypic category and dermatoglyphic pattern frequencies in the congenital central hypoventilation syndrome study groups. These results represent the first report describing specific dermatoglyphic patterning in congenital central hypoventilation syndrome and suggest a

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

    Science.gov (United States)

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

    2017-09-01

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

  11. O uso da drotrecogina alfa ativada na prática clínica e as atuais evidências Drotrecogin alfa activated in clinical practice and the current evidences

    Directory of Open Access Journals (Sweden)

    Márcio Soares

    2008-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O debate sobre a segurança e eficácia da drotrecogina alfa (DrotAA encontra-se na ordem do dia, principalmente, em função dos resultados negativos observados em ensaios clínicos subseqüentes ao PROWESS e do impacto econômico no sistema de saúde relacionado ao custo elevado do fármaco. O objetivo deste estudo foi rever os principais estudos sobre a utilização da DrotAA em pacientes com sepse grave, com ênfase nas questões ligadas a sua eficácia e segurança. CONTEÚDO: Foram selecionados artigos sobre a utilização da DrotAA em pacientes com sepse publicados nos últimos dez anos no MedLine. Os seguintes unitermos foram utilizados: activated protein C; drotrecogin alfa; sepsis; septic shock; Xigris®. Estudos referenciados nos artigos selecionados na busca também foram utilizados. CONCLUSÕES: As taxas de letalidades e as complicações hemorrágicas associadas com o uso do fármaco foram maiores em grandes estudos observacionais do que aquelas descritas previamente nos ensaios clínicos. A luz dos resultados atualmente disponíveis, o uso da DrotAA deve ser reconsiderado até que novos ensaios clínicos possam subsidiar com informações adicionais sobre eficácia, segurança e na identificação dos subgrupos de pacientes com sepse grave que porventura possam ter benefício com o uso deste medicamento. A DrotAA deve servir de exemplo para que haja maior cautela com a rápida transposição de evidências ainda em construção para recomendações e diretrizes de tratamento de pacientes com sepse grave.BACKGROUND AND OBJECTIVES: The debate on efficacy and patient safety related to the use of drotrecogin alfa (DrotAA is timely, principally due to the negative results observed in clinical studies performed after the PROWESS study, and the economic cost-related impact of the drug on the healthcare system. The aim of this study was to review the main studies on the use of DrotAA in patients with severe

  12. Diversidad alfa y beta de la comunidad de reptiles en el complejo cenagoso de Zapatosa, Colombia

    Directory of Open Access Journals (Sweden)

    Guido Fabián Medina-Rangel

    2011-06-01

    Full Text Available La diversidad es una propiedad de las comunidades, permite describir, caracterizar y entender el funcionamiento de los ecosistemas. Para estudiar la riqueza, abundancia y el recambio de especies de reptiles entre hábitats circundantes al complejo cenagoso de Zapatosa, se realizaron cuatro salidas de campo (noviembre de 2006 y octubre de 2007. Se invirtieron 640h/hombre de muestreo repartido en cinco tipos de hábitat: bosque casmófito, bosque seco, bosque de ribera, palmar y sabana arbolada. Se encontraron 847 individuos de 48 especies, la familia más rica fue Colubridae, se registraron cinco especies endémicas y ocho con algún grado de amenaza en conservación a nivel nacional. El hábitat más diverso fue el bosque de ribera. La representatividad del muestreo en total y para cada hábitat fue superior al 80%, con excepción del palmar (Alfa and beta diversity of reptilian assemblages in Zapatosa wetland complex, Colombia. Diversity is a property of community that can described, characterized, and understood according to the functioning of ecosystems. To study the richness and local abundance and species replacement between habitats around the Zapatosa’s wetland complex (El Cesar Department, I carried out four field trips between November of 2006 and October of 2007. A total of 640 sampling hours/man analyzed five habitat types chasmophyte forest, dry forest, riparian forest, palm-grove and tree-lined savanna; with the exception of the palm-grove sampled at its 75%, the others were sampled up to their 80%. I found 847 reptiles that were distributed in 48 species. The group with the highest number of species was Colubridae with 14, followed by Gekkonidae with five. Five endemic species and eight with some conservation threat grade at a national level a re reported. The riparian forest was the richest and most abundant habitat with 34 species and 196 individuals. For each habitat, Colubridae had the highest number of species, followed by

  13. A B2B Digital Marketing Plan for a Micro Design Company

    OpenAIRE

    Yin, Zi

    2015-01-01

    This product-based thesis was made for a Finnish micro design company – 2.Elämä Design. The objective of the thesis is to create a strategic B2B digital marketing plan for 2.Elämä Design in order to help its business expansion in Finland and globally. The final product of the thesis is a handbook of B2B digital marketing 2.Elämä Design could put into use in 2015. The author set up five project tasks in order to accomplish the thesis project. Firstly a thorough literature review on B2B di...

  14. RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist

    OpenAIRE

    Bonhaus, Douglas W; Flippin, Lee A; Greenhouse, Robert J; Jaime, Saul; Rocha, Cindy; Dawson, Mark; Van Natta, Kristine; Chang, L K; Pulido-Rios, Tess; Webber, Andrea; Leung, Edward; Eglen, Richard M; Martin, Graeme R

    1999-01-01

    Efforts to define precisely the role of 5-HT2B receptors in normal and disease processes have been hindered by the absence of selective antagonists. To address this deficiency, we developed a series of naphthylpyrimidines as potentially useful 5-HT2B receptor antagonists.RS-127445 (2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine) was found to have nanomolar affinity for the 5-HT2B receptor (pKi=9.5±0.1) and 1,000 fold selectivity for this receptor as compared to numerous other receptor ...

  15. Using service design methods for B2b service brand concept development: Case company

    OpenAIRE

    Molina Escalante, Hugo

    2014-01-01

    A short time before this study was initiated, a small B2b service company had just began op-erating its business without a brand of it’s own. The company owners were looking to design an innovative brand for their business. The purpose of this thesis was to develop the brand for this service Company in the B2b context, using practical service design and Strategic design research methods. This thesis report represents a framework for developing a B2b service brand using research methods c...

  16. Exoelectron emission from surface layer of Li2B4O7 glass ceramics

    International Nuclear Information System (INIS)

    Kawamoto, Takamichi; Katsube, Shizuko; Yanagisawa, Hideo; Kikuchi, Riichi; Kawanishi, Masaharu.

    1984-01-01

    The thermally stimulated exoelectron emission (TESS) of Li 2 B 4 O 7 glass ceramics was investigated for its application to the dosimetric use. It has been found the TSEE glow patterns of Li 2 B 4 O 7 glass ceramics and of the thin layer of LiF evaporated on Li 2 B 4 O 7 glass ceramics depend on the kind of radiations irradiated. The TSEE glow pattern of the duplicated structure sample indicated a possibility of determining the dose of each kind of radiation separately in the mixed radiation field. (author)

  17. Efficacy and safety of enzyme-replacement-therapy with agalsidase alfa in 36 treatment-naïve Fabry disease patients.

    Science.gov (United States)

    Tsuboi, Kazuya; Yamamoto, Hiroshi

    2017-06-07

    Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the α-galactosidase A gene mutations. Enzyme-replacement-therapy (ERT) products for FD currently used include agalsidase alfa and agalsidase beta. There are many reports on efficacy and safety of ERT. However, most of the previous studies are done as a retrospective medical records analysis. The Japan Fabry Research - 002 (JFR-002) was a prospective observational clinical study of 36 ERT-naïve FD patients (14 men and 22 women) at baseline (BL) and after initiation of ERT with agalsidase alfa 0.2 mg/kg every two weeks, a median period 62.5 months. The parameters measured included globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso-Gb3), left ventricular mass index (LVMI), brain natriuretic peptide (BNP), high-sensitivity troponin I (hs-Trop I), estimated glomerular filtration rate (eGFR), and anti-agalsidase alfa IgG antibody formation. All parameters remained steady during ERT treatment period. BNP levels in 14 patients whose BL levels were within the normal range (<19.5 pg/mL) remained within the same range, while 22 patients whose BL levels were abnormally high (≥19.5 pg/mL) gradually showed decreased levels after start of ERT. Gb3 and Lyso-Gb3 levels remarkably decreased after the initiation of ERT and remained low. The JFR-002 suggests that agalsidase alfa is effective in maintaining organ function in FD patients, and that the incidence of infusion reactions related to the treatment with agalsidase alfa is low, indicating the good tolerability to this ERT. The JFR-002 was retrospectively registered at Japan Medical Association Center for Clinical Trials (Registration number: JMA-IIA00291 ) on May 19th, 2017.

  18. Estudios sobre alfa-amilasa en saliva como marcador de estrés en la especie humana y otras especies animales= Studies on salivary alpha-amylase as a maker of stress in human and different animal species

    OpenAIRE

    Fuentes Rubio, María

    2014-01-01

    OBJETIVOS 1. Evaluar el uso de la alfa amilasa salivar como marcador de estrés usando técnicas tradicionales (ensayos enzimáticos) en humana, usando como modelo experimental a estudiantes de veterinaria que tenían que realizar una presentación oral de un trabajo en lengua extranjera. 2. Evaluar el uso de la alfa amilasa salivar como marcador de estrés usando técnicas tradicionales (ensayos enzimáticos) en cerdos. 3. Implementar nuevos enfoques para la medición de la alfa-amilasa e...

  19. Electron Density and Temperature During the CHARGE-2B Sounding Rocket Mission

    National Research Council Canada - National Science Library

    Ernstmeyer, James

    1997-01-01

    The CHARGE-2B sounding rocket was launched from Poker Flats Research Range, Alaska, in March 1992 to investigate VLF electromagnetic radiation generated by a modulated electron beam in the ionosphere...

  20. Data of evolutionary structure change: 1YDVA-1AW2B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1YDVA-1AW2B 1YDV 1AW2 A B RKYFVAANWKCNGTLESIKSLTNSFNNLDFDPSKLDVVV...--- RHPVVMGNWKLNGSKEMVVDLLNGLNAELEGVTGVDVAVAPPALFVDLAERTLTEAGSAIILGA...confEVID> 0 1YDV A 1YDVA...> A 1YDVA IVKDTCGEKQA

  1. Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

    Science.gov (United States)

    Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

    2017-06-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

  2. Marine microbial biodiversity, bioinformatics and biotechnology (M2B3) data reporting and service standards.

    Science.gov (United States)

    Ten Hoopen, Petra; Pesant, Stéphane; Kottmann, Renzo; Kopf, Anna; Bicak, Mesude; Claus, Simon; Deneudt, Klaas; Borremans, Catherine; Thijsse, Peter; Dekeyzer, Stefanie; Schaap, Dick Ma; Bowler, Chris; Glöckner, Frank Oliver; Cochrane, Guy

    2015-01-01

    Contextual data collected concurrently with molecular samples are critical to the use of metagenomics in the fields of marine biodiversity, bioinformatics and biotechnology. We present here Marine Microbial Biodiversity, Bioinformatics and Biotechnology (M2B3) standards for "Reporting" and "Serving" data. The M2B3 Reporting Standard (1) describes minimal mandatory and recommended contextual information for a marine microbial sample obtained in the epipelagic zone, (2) includes meaningful information for researchers in the oceanographic, biodiversity and molecular disciplines, and (3) can easily be adopted by any marine laboratory with minimum sampling resources. The M2B3 Service Standard defines a software interface through which these data can be discovered and explored in data repositories. The M2B3 Standards were developed by the European project Micro B3, funded under 7(th) Framework Programme "Ocean of Tomorrow", and were first used with the Ocean Sampling Day initiative. We believe that these standards have value in broader marine science.

  3. Cyclic benzamidines as orally efficacious NR2B-selective NMDA receptor antagonists.

    Science.gov (United States)

    Nguyen, Kevin T; Claiborne, Christopher F; McCauley, John A; Libby, Brian E; Claremon, David A; Bednar, Rodney A; Mosser, Scott D; Gaul, Stanley L; Connolly, Thomas M; Condra, Cindra L; Bednar, Bohumil; Stump, Gary L; Lynch, Joseph J; Koblan, Kenneth S; Liverton, Nigel J

    2007-07-15

    A novel series of cyclic benzamidines was synthesized and shown to exhibit NR2B-subtype selective NMDA antagonist activity. Compound 29 is orally active in a carrageenan-induced rat hyperalgesia model of pain.

  4. Pre-LBA ABLE-2A and ABLE-2B Expedition Data

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: The ABLE 2A and 2B (Atmospheric Boundary Layer Experiments) data consists of estimates of the rate of exchange of a wide variety of aerosols and gases...

  5. Pre-LBA ABLE-2A and ABLE-2B Expedition Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The ABLE 2A and 2B (Atmospheric Boundary Layer Experiments) data consists of estimates of the rate of exchange of a wide variety of aerosols and gases between the...

  6. OS2_OSCAT_LEVEL_2B_OWV_COMP_12_V2:1

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset consists of the version 2 Level 2B science-quality ocean surface wind vector retrievals from the Oceansat-2 scatterometer (OSCAT), which was designed...

  7. Managing Innovation Through Social Media in B2B SME-Context

    DEFF Research Database (Denmark)

    Lutz, Salla; Madsen, Svend Ole; Brink, Tove

    2015-01-01

    This paper shed light on how social media application can enhance innovation management in SME B2B context. Our study employs a qualitative case study approach with four B2B SMEs for in-depth research in the period from October 2013 to October 2014. The B2B SME managers aim for open business model...... innovation. However, social media application is hindered due to lack of specific local knowledge, lack of knowledge on social media technicalities and bewilderedness on leadership approaches within the social media application. A contribution is hereby made to the B2B SME field, to the academic...... understanding an insight on social media application and open business model innovation....

  8. Boriding kinetics of Fe2B layers formed on AISI 1045 steel

    Directory of Open Access Journals (Sweden)

    Zuno-Silva J.

    2014-01-01

    Full Text Available In the present work, a diffusion model was suggested to study the growth kinetics of Fe2B layers grown on the AISI 1045 steel by the pack-boriding treatment. The generated boride layers were analyzed by optical microscopy and X-ray diffraction analysis. The applied diffusion model is based on the principle of mass conservation at the (Fe2B/ substrate interface. It was used to estimate the boron diffusion coefficients of Fe2B in the temperature range of 1123-1273 K. A validation of the model was also made by comparing the experimental Fe2B layer thickness obtained at 1253 K for 5 h of treatment with the predicted value. Basing on our experimental results, the boron activation energy was estimated as 180 kJ mol-1 for the AISI 1045 steel.

  9. High performance of solvothermally prepared VO2(B as anode for aqueous rechargeable lithium batteries

    Directory of Open Access Journals (Sweden)

    Milošević Sanja

    2015-01-01

    Full Text Available The VO2 (B was synthesized via a simple solvothermal route at 160oC in ethanol. The initial discharge capacity of VO2 (B anode, in saturated aqueous solution of LiNO3, was 177 mAh g-1 at a current rate of 50 mA g-1. After 50 cycles capacity fade was 4%, but from 20th-50th cycle no capacity drop was observed. The VO2 (B has shown very good cyclability at current rate of even 1000 mA g-1 with initial discharge capacity of 92 mAh g-1. The excellent electrochemical performance of VO2 (B was attributed to the stability of micro-nano structures to repeated intercalation /deintercalation process, very good electronic conductivity as well as the very low charge transfer resistance in the aqueous electrolyte. [Projekat Ministarstva nauke Republike Srbije, br. III45014

  10. QSCAT_LEVEL_2B_OWV_COMP_12:1

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the latest reprocessed version 3 of the Level 2B science-quality ocean surface wind vector retrievals from the QuikSCAT scatterometer. The...

  11. PEMBUATAN ETANOL DARI BIJI CEMPEDAK (Artocarpus champeden sp. DENGAN HIDROLISIS MENGGUNAKAN ENZIM ALFA AMILASE DAN GLUKOLASE FERMENTASI Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Wahyu Teguh Santoso

    2016-06-01

    Full Text Available Telah dilakukan penelitian yang bertujuan untuk mengetahui potensi dari biji cempedak (Artocarpus champedan sp. sebagai bahan baku pembuatan etanol, sekaligus mengetahui apakah variasi penambahan nutrisi ammonium sulfat dan lamanya waktu fermentasi dapat meningkatkan konsentrasi etanol yang dihasilakan. Proses hidrolisis pati dilakukan secara  enzimatis melalui tahap liquifikasi dan sakarifikasi dengan menggunakan enzim alfa-amilase dan glukolase yang akan mengkonversi pati menjadi glukosa. Hasil hidrolisis ditambahkan amonium sulfat sebagai sumber nutrisi dengan variasi 0,1 %, 0,3 % dan 0,5 % (b/v kemudian difermentasi dengan variasi waktu 4, 5 dan 6 hari. Konsentrasi etanol tertinggi berada pada penambahan nutrisi amonium sulfat 0,3 % (b/v dengan waktu fermentasi 6 hari sebesar 8,233 %   Kata Kunci: Etanol, Biji Cempedak (Artocarpus champedan sp. dan Fermentasi.

  12. Serotonin 2B Receptors in Mesoaccumbens Dopamine Pathway Regulate Cocaine Responses.

    Science.gov (United States)

    Doly, Stéphane; Quentin, Emily; Eddine, Raphaël; Tolu, Stefania; Fernandez, Sebastian P; Bertran-Gonzalez, Jesus; Valjent, Emmanuel; Belmer, Arnauld; Viñals, Xavier; Callebert, Jacques; Faure, Philippe; Meye, Frank J; Hervé, Denis; Robledo, Patricia; Mameli, Manuel; Launay, Jean-Marie; Maldonado, Rafael; Maroteaux, Luc

    2017-10-25

    Addiction is a maladaptive pattern of behavior following repeated use of reinforcing drugs in predisposed individuals, leading to lifelong changes. Common among these changes are alterations of neurons releasing dopamine in the ventral and dorsal territories of the striatum. The serotonin 5-HT 2B receptor has been involved in various behaviors, including impulsivity, response to antidepressants, and response to psychostimulants, pointing toward putative interactions with the dopamine system. Despite these findings, it remains unknown whether 5-HT 2B receptors directly modulate dopaminergic activity and the possible mechanisms involved. To answer these questions, we investigated the contribution of 5-HT 2B receptors to cocaine-dependent behavioral responses. Male mice permanently lacking 5-HT 2B receptors, even restricted to dopamine neurons, developed heightened cocaine-induced locomotor responses. Retrograde tracing combined with single-cell mRNA amplification indicated that 5-HT 2B receptors are expressed by mesolimbic dopamine neurons. In vivo and ex vivo electrophysiological recordings showed that 5-HT 2B -receptor inactivation in dopamine neurons affects their neuronal activity and increases AMPA-mediated over NMDA-mediated excitatory synaptic currents. These changes are associated with lower ventral striatum dopamine activity and blunted cocaine self-administration. These data identify the 5-HT 2B receptor as a pharmacological intermediate and provide mechanistic insight into attenuated dopamine tone following exposure to drugs of abuse. SIGNIFICANCE STATEMENT Here we report that mice lacking 5-HT 2B receptors totally or exclusively in dopamine neurons exhibit heightened cocaine-induced locomotor responses. Despite the sensitized state of these mice, we found that associated changes include lower ventral striatum dopamine activity and lower cocaine operant self-administration. We described the selective expression of 5-HT 2B receptors in a subpopulation of

  13. Mutations in SULT2B1 Cause Autosomal-Recessive Congenital Ichthyosis in Humans.

    Science.gov (United States)

    Heinz, Lisa; Kim, Gwang-Jin; Marrakchi, Slaheddine; Christiansen, Julie; Turki, Hamida; Rauschendorf, Marc-Alexander; Lathrop, Mark; Hausser, Ingrid; Zimmer, Andreas D; Fischer, Judith

    2017-06-01

    Ichthyoses are a clinically and genetically heterogeneous group of genodermatoses associated with abnormal scaling of the skin over the whole body. Mutations in nine genes are known to cause non-syndromic forms of autosomal-recessive congenital ichthyosis (ARCI). However, not all genetic causes for ARCI have been discovered to date. Using whole-exome sequencing (WES) and multigene panel screening, we identified 6 ARCI-affected individuals from three unrelated families with mutations in Sulfotransferase family 2B member 1 (SULT2B1), showing their causative association with ARCI. Cytosolic sulfotransferases form a large family of enzymes that are involved in the synthesis and metabolism of several steroids in humans. We identified four distinct mutations including missense, nonsense, and splice site mutations. We demonstrated the loss of SULT2B1 expression at RNA and protein levels in keratinocytes from individuals with ARCI by functional analyses. Furthermore, we succeeded in reconstructing the morphologic skin alterations in a 3D organotypic tissue culture model with SULT2B1-deficient keratinocytes and fibroblasts. By thin layer chromatography (TLC) of extracts from these organotypic cultures, we could show the absence of cholesterol sulfate, the metabolite of SULT2B1, and an increased level of cholesterol, indicating a disturbed cholesterol metabolism of the skin upon loss-of-function mutation in SULT2B1. In conclusion, our study reveals an essential role for SULT2B1 in the proper development of healthy human skin. Mutation in SULT2B1 leads to an ARCI phenotype via increased proliferation of human keratinocytes, thickening of epithelial layers, and altered epidermal cholesterol metabolism. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  14. Drivers of relationships affecting B2B firms in an e-commerce environment

    Directory of Open Access Journals (Sweden)

    Irene Samanta

    2014-09-01

    Full Text Available The advent of the internet has created numerous opportunities for B2B marketing professionals to enhance current marketing practices, including electronic relationships. However, the investigation of e-relationships and the factors that influence e-relationships in an internet environment is scant. Further, there appears to be no investigation of this phenomenon within the context of Greek B2B Medium-sized firms (MSF. Τhe research problem investigated in this research is: “Which drivers in B2B e-commerce use affect inter-firm relationships in medium-sized B2B firms?”. A framework for B2B e-commerce relationships in a changing and globalized environment was synthesised and integrated with the literature about relationship marketing to arrive at the following research issues: “How do relationship marketing drivers affect the management of B2B e-relationships?”. An explanatory quantitative research approach was used and quantitative data was collected from B2B firms in Greece, which represents a case of e-commerce progress during the last six years. Regarding social exchange, some important differences emerge where cooperation between B2B e-commerce firms is concerned. Suppliers engaged in electronic commerce are more committed and oriented to a long-term relationship than buyers, based on both previous and current experience with them. Confidence in the relationships, consistency and honesty with their obligations and the exchange of reliable, trustworthy information and advisory services between firms are important factors in the development and establishment of their e-relationships. The main contribution of this research is the development of a theoretical framework for e-relationships in medium-sized Β2Β firms. That framework is the first rigorously researched step towards understanding the importance of these powerful streams of relationship drivers in total, and the business activity of e-marketing and electronic relationships.

  15. Multiple endocrine neoplasias type 2B and RET proto-oncogene

    Directory of Open Access Journals (Sweden)

    Martucciello Giuseppe

    2012-03-01

    Full Text Available Abstract Multiple Endocrine Neoplasia type 2B (MEN 2B is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T. A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

  16. Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein.

    Directory of Open Access Journals (Sweden)

    Da Ao

    Full Text Available Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER, with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+ concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.

  17. Fluoxetine and all other SSRIs are 5-HT2B Agonists - Importance for their Therapeutic Effects

    OpenAIRE

    Peng, Liang; Gu, Li; Li, Baoman; Hertz, Leif

    2014-01-01

    Fluoxetine and other serotonin-specific re-uptake inhibitors (SSRIs) are generally thought to owe their therapeutic potency to inhibition of the serotonin transporter (SERT). However, research in our laboratory showed that it affects, with relatively high affinity the 5-HT2B receptor in cultured astrocytes; this finding was confirmed by independent observations showing that fluoxetine loses its ability to elicit SSRI-like responses in behavioral assays in mice in which the 5-HT2B receptor was...

  18. Deconstructing antiobesity compound action: requirement of serotonin 5-HT2B receptors for dexfenfluramine anorectic effects.

    OpenAIRE

    2010-01-01

    Abstract The now banned anorectic molecule, dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism and has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT2B receptors play important roles in dexfenfluramine-side effects, i.e. pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT2B receptors in dexfenfluramine-dependent ...

  19. Endogenous 5-HT2B receptor activation regulates neonatal respiratory activity in vitro

    OpenAIRE

    Günther , Silke; Maroteaux , Luc; Schwarzacher , Stephan W.

    2006-01-01

    International audience; An implication of 5-HT 2B receptors in central nervous system has not yet been clearly elucidated. We studied the role of different 5-HT 2 receptor subtypes in the medullary breathing center, the pre-Bötzinger complex, and on hypoglossal motoneur-ons in rhythmically active transversal slice preparations of neonatal rats and mice. Local microinjection of 5-HT 2 receptor agonists revealed tonic excitation of hypoglossal motoneurons. Excitatory effects of the 5-HT 2B rece...

  20. Magnetism and superconductivity in ErNi2B2C

    Indian Academy of Sciences (India)

    in modulation vector and harmonic content. Studies of the vortex lattice show the presence of a 45. ◦ reorientation transition and a distorted hexagonal to square transition as a function of applied field. Further distortions of the vortex lattice occur at TN, but no changes are seen at TF. Keywords. (RE)Ni2B2C; ErNi2B2C; vortex ...

  1. Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy.

    Science.gov (United States)

    Cavero, Icilio; Guillon, Jean-Michel

    2014-01-01

    The rhythmic opening and tightly closing of cardiac valve leaflets are cardiac cyclic events imposing to blood a unidirectional course along the vascular tree. Drugs with 5-HT2B agonism properties can seriously compromise this biological function critical for hemodynamic efficiency as their intrinsic pro-fibrotic effects can, with time, make valvular coaptation blood regurgitant. Cardiac valve anatomy, physiology and pathology as well as 5-HT2B receptor properties (coupling, effects mediated, biased agonism) are briefly exposed. Approaches to unveil 5-HT2B receptor liability of drug candidates are detailed. In silico computational models can rapidly probe molecules for chemical signatures associated with 5-HT2B receptor affinity. In vitro radioligand competition assays allow quantifying receptor binding capacity (Ki, IC50), the pharmacological nature (agonism, antagonism) of which can be ascertained from cytosolic second messenger (inositol phosphates, Ca(++), MAPK2) changes. Potencies calculated from the latter data may exhibit variability as they are dependent upon the readout measured and the experimental conditions (e.g., receptor density level of cell material expressing human 5-HT2B receptors). The in vivo valvulopathy effects of 5-HT2B receptor agonists can be assessed by echocardiographic measurements and valve histology in rats chronically treated with the candidate drug. Finally, safety margins derived from from nonclinical and clinical data are evaluated in terms of the readout, usefulness and scientific reliability. The Safety Pharmacology toolbox for detecting possible 5-HT2B receptor agonism liabilities of candidate drugs requires meticulous optimization and validation of all its (in silico, in vitro and in vivo) components to perfect its human predictability power. In particular, since 5-HT2B receptor agonism is biased in nature, the most predictive readout(s) of valvular liability should be identified and prioritized in keeping with best scientific

  2. An analysis of Common Missile and TOW 2B using the Janus combat simulation

    OpenAIRE

    Kruse, Rachel A.

    2002-01-01

    Approved for public release; distribution is unlimited. The US Army is currently developing a new close combat missile system, Common Missile, to replace the aging Tubelaunched, Optically-tracked, Wire-guided (TOW 2B) and HELLFIRE missile systems. The Common Missile will have a greater range and improved target acquisition capability over the current missile systems. The purpose of this thesis is to compare the performance of the Common Missile and the TOW 2B missile in a simulated ground ...

  3. Generation of an induced pluripotent stem cell line from a patient with hereditary multiple endocrine neoplasia 2B (MEN2B) syndrome with "highest risk" RET mutation.

    Science.gov (United States)

    Bennaceur-Griscelli, A; Hadoux, J; Féraud, O; Opolon, P; Divers, D; Gobbo, E; Schlumberger, M; Griscelli, F; Turhan, A G

    2017-08-01

    Multiple Endocrine Neoplasia Type 2B (MEN2B) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC) and pheochromocytoma. Currently, there is no satisfactory model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 918 who developed pheochromocytoma and MTC. These iPSC had normal karyotype, harboured the RET M918T mutation and expressed pluripotency hallmarks. A comprehensive pathological assessment of teratoma was performed after injection in immunodeficient mice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Localization of MOs and electronic populations in closo-carboranes 1, 5-C2B3H5 and 1,6-C2B4H6

    International Nuclear Information System (INIS)

    Semenov, S.G.

    1988-01-01

    We have analyzed the electronic populations of chemical bonds and atoms in the highly symmetric closo-carboranes 1,5-C 2 B 3 H 5 (I) and 1,6-C 2 B 4 H 6 (II). The overlap populations σ/sub XY/ are compared with the corresponding Mulliken indices. We note substantial nonadditivity of the populations σ/sub XY/ for closed three-center bonds BCB' and the closeness of the total overlap populations σ/sub t/ to its maximum value. We have established the localization of the natural MOs on the bonds CH, BH, and BCB', and for molecule I also on the CBC' bonds. The effects of conjugation of bonds in the closo-carborane polyhedron are apparent in the linear dependence of these MOs. The corresponding nonorthogonal hybrid AOs of carbon and boron are also linearly dependent. We have formulated the concept of unshared population of an atom

  5. Isolation of recombinant strains with enhanced pectinase production by protoplast fusion between Penicillium expansum and Penicillium griseoroseum Isolamento de linhagens recombinantes com maior produção de pectinases por meio de fusão de protoplastos entre Penicillium expansum e Penicillium griseoroseum

    Directory of Open Access Journals (Sweden)

    Maurilio Antonio Varavallo

    2007-03-01

    Full Text Available Protoplast fusion between complementary auxotrophic and morphological mutant strains of Penicillium griseoroseum and P. expansum was induced by polyethylene glycol and calcium ions (Ca2+. Fusant strains were obtained in minimal medium and a prototrophic strain, possibly diploid, was chosen for haplodization with the fungicide benomyl. Different recombinant strains were isolated and characterized for occurrence of auxotrophic mutations and pectinolytic enzyme production. The fusant prototrophic did not present higher pectinase production than the parental strains, but among 29 recombinants analyzed, four presented enhanced enzyme activities. The recombinant RGE27, which possesses the same auxotrophic and morphologic mutations as the P. griseoroseum parental strain, presented a considerable increase in polygalacturonase (3-fold and pectin lyase production (1.2-fold.Fusões de protoplastos entre linhagens mutantes auxotróficas e morfológicas complementares de Penicillium griseoroseum e P. expansum foram induzidas por polietilenoglicol e íons cálcio (Ca2+. Fusionantes foram obtidos em meio mínimo e uma linhagem prototrófica, possivelmente diplóide, foi selecionada para a haploidização com o fungicida benomil. Diferentes linhagens recombinantes foram isoladas e caracterizadas quanto à presença de mutações auxotróficas e a produção de enzimas pectinolíticas. O fusionante prototrófico não apresentou maior atividade de pectinases em relação às linhagens parentais, entretanto, entre 29 recombinantes analisados, quatro apresentaram maiores atividades enzimáticas. O recombinante RGE27, o qual possui as mesmas mutações auxotróficas e morfológicas que a linhagem parental de P. griseoroseum, apresentou um aumento considerável na produção de poligalacturonase (3 vezes e de pectina liase (1,2 vezes.

  6. Defective dendritic cell generation from monocytes is a potential reason for poor therapeutic efficacy of interferon α2b (IFNα2b) in cervical cancer.

    Science.gov (United States)

    Roy, Soumyabrata; Goswami, Shyamal; Bose, Anamika; Goswami, Kuntal Kanti; Sarkar, Koustav; Chakraborty, Krishnendu; Chakraborty, Tathagata; Pal, Smarajit; Haldar, Atanu; Basu, Parthasarathi; Biswas, Jaydip; Baral, Rathindranath

    2011-10-01

    Despite being a pleiotropic cytokine, the therapeutic potential of interferon α2b (IFNα2b) is debatable. Thus, the need for identifying predictive marker(s) for patients who are most likely to benefit from the treatment is pivotal for avoiding the exposure of nonresponsive patients to the toxicity of the treatment. To account for the attenuated efficacy of the drug, we have verified its dendritic cell (DC) maturating ability from monocytes of cervical cancer stage IIIB (CaCx-IIIB) patients. First, we evaluated the status of monocytes from CaCx-IIIB and healthy women by conducting flow cytometric studies of various activation markers and a cytokine analysis by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Immature DCs were then generated from these monocytes and matured with low-dose IFNα2b (1500 units/mL). A functional and phenotypic comparative analysis of these matured DCs was performed by flow cytometric, proliferative, cytotoxic, and enzyme-linked immunosorbent assays. Our study shows that monocytes isolated from CaCx-IIIB are impaired, and in vitro maturation with IFNα2b did not significantly improve the functional repertoire of DCs generated from these monocytes in comparison with healthy controls. This impairment of monocytes might be a plausible reason for the attenuated efficacy of this drug alone in treating CaCx-IIIB patients, and this imbalance of immune parameters associated with the stage of malignancy might be considered an effective marker to design a proper therapeutic regimen. Copyright © 2011 Mosby, Inc. All rights reserved.

  7. Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

    Science.gov (United States)

    Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E; Zheng, Qing Y

    2011-01-01

    Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans.

  8. Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

    Directory of Open Access Journals (Sweden)

    Bin Yang

    Full Text Available Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee mirrors craniofacial dysmorphology and otitis media in humans.

  9. Functional importance of a peripheral pocket in mammalian cytochrome P450 2B enzymes.

    Science.gov (United States)

    Jang, Hyun-Hee; Liu, Jingbao; Lee, Ga-Young; Halpert, James R; Wilderman, P Ross

    2015-10-15

    The functional importance of a peripheral pocket found in previously published X-ray crystal structures of CYP2B4 and CYP2B6 was probed using a biophysical approach. Introduction of tryptophan within the pocket of CYP2B4 at F202 or I241 leads to marked impairment of 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC) or 7-benzyloxyresorufin O-dealkylation efficiency; a similar substitution at F195, near the surface access to the pocket, does not affect these activities. The analogous CYP2B6 F202W mutant is inactive in the 7-EFC O-dealkylation assay. The stoichiometry of 7-EFC deethylation suggested that the decreased activity of F202W and I241W in CYP2B4 and lack of activity of F202W in CYP2B6 coincided with a sharp increase in the flux of reducing equivalents through the oxidase shunt to produce excess water. The results indicate that the chemical identity of residues within this peripheral pocket, but not at the mouth of the pocket, is important in substrate turnover and redox coupling, likely through effects on active site topology. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Silencing of Atp2b1 increases blood pressure through vasoconstriction.

    Science.gov (United States)

    Shin, Young-Bin; Lim, Ji Eun; Ji, Su-Min; Lee, Hyeon-Ju; Park, So-Yon; Hong, Kyung-Won; Lim, Mihwa; McCarthy, Mark I; Lee, Young-Ho; Oh, Bermseok

    2013-08-01

    Recent genome-wide association studies (GWASs) have identified 30 genetic loci that regulate blood pressure, increasing our understanding of the cause of hypertension. However, it has been difficult to define the causative genes at these loci due to a lack of functional analyses. In this study, we aimed to validate the candidate gene ATP2B1 in 12q21, variants near which have the strongest association with blood pressure in Asians and Europeans. ATP2B1 functions as a calcium pump to fine-tune calcium concentrations - necessary for repolarization following muscular contractions. We silenced Atp2b1 using an siRNA complex, injected into mouse tail veins. In treated mice, blood pressure rose and the mesenteric arteries increased in wall : lumen ratio. Moreover, the arteries showed enhanced myogenic responses to pressure, and contractile responses to phenylephrine increased compared with the control, suggesting that blood pressure is regulated by ATP2B1 through the contraction and dilation of the vessel, likely by controlling calcium concentrations in the resting state. These results support that ATP2B1 is the causative gene in the blood pressure-associated 12q21 locus and demonstrate that ATP2B1 expression in the vessel influences blood pressure.

  11. Itga2b regulation at the onset of definitive hematopoiesis and commitment to differentiation.

    Directory of Open Access Journals (Sweden)

    Stephanie Dumon

    Full Text Available Product of the Itga2b gene, CD41 contributes to hematopoietic stem cell (HSC and megakaryocyte/platelet functions. CD41 expression marks the onset of definitive hematopoiesis in the embryo where it participates in regulating the numbers of multipotential progenitors. Key to platelet aggregation, CD41 expression also characterises their precursor, the megakaryocyte, and is specifically up regulated during megakaryopoiesis. Though phenotypically unique, megakaryocytes and HSC share numerous features, including key transcription factors, which could indicate common sub-regulatory networks. In these respects, Itga2b can serve as a paradigm to study features of both developmental-stage and HSC- versus megakaryocyte-specific regulations. By comparing different cellular contexts, we highlight a mechanism by which internal promoters participate in Itga2b regulation. A developmental process connects epigenetic regulation and promoter switching leading to CD41 expression in HSC. Interestingly, a similar process can be observed at the Mpl locus, which codes for another receptor that defines both HSC and megakaryocyte identities. Our study shows that Itga2b expression is controlled by lineage-specific networks and associates with H4K8ac in megakaryocyte or H3K27me3 in the multipotential hematopoietic cell line HPC7. Correlating with the decrease in H3K27me3 at the Itga2b Iocus, we find that following commitment to megakaryocyte differentiation, the H3K27 demethylase Jmjd3 up-regulation influences both Itga2b and Mpl expression.

  12. Deficiência de alfa-1 antitripsina: diagnóstico e tratamento Alpha-1 antitrypsin deficiency: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Aquiles A Camelier

    2008-07-01

    Full Text Available A deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnóstico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiros a respeito da prevalência da doença ou da freqüência de ocorrência dos alelos deficientes. O subdiagnóstico também tem sido uma importante limitação tanto para o estudo da doença quanto para o tratamento adequado dos pacientes. Espera-se que a criação do Registro Internacional de Alfa-1 venha a resolver essas e outras importantes questões.Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical

  13. Competency-orientated brand cooperations of power supply companies in the B2B sector; Kompetenzorientierte Markenkooperationen von Energieversorgungsunternehmen im B2B-Kundenbereich

    Energy Technology Data Exchange (ETDEWEB)

    Peuser, M.M.

    2008-07-01

    On the basis of an extensive empirical study with B2B electricity users, the author of the book under consideration examines brand co-operations of power supply companies with companies not working in the area of energy production. Based on the view of various co-operation alternatives, impact relations and success-determining factors of influence in the area of B2B customers are identified. The term of the authority of an energy brand is discussed. Beside this, profiles of concrete brands of current power supply companies from the view of B2B customers are pointed out, and recommendations for the organization of brand co-operation and the structure of mark authority in practice are shown. This contribution is written for lecturers and students of the management economics with the emphasis of marketing and management as well as high-level personnel in the energy industry, who wants to develop strong mark authority by brand co-operation.

  14. Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon alfa-2a (40 kDa delivered via a disposable autoinjector device

    Directory of Open Access Journals (Sweden)

    Varunok P

    2011-11-01

    Full Text Available Peter Varunok1, Eric Lawitz2, Kimberly L Beavers3, Gary Matusow4, Ruby Leong5, Nathalie Lambert6, Coen Bernaards7, Jonathan Solsky5, Barbara J Brennan5, Cynthia Wat8, Anne Bertasso51Gastroenterology Associates, Poughkeepsie, NY, USA; 2Alamo Medical Research, San Antonio, TX, USA; 3Asheville Gastroenterology, Asheville, NC, USA; 4Gastroenterology Group, South Jersey, NJ, USA; 5Roche, Nutley, NJ, USA; 6Roche, Basel, Switzerland; 7Roche, San Francisco, CA, USA; 8Roche, Welwyn, UKBackground: Peginterferon alfa-2a (40 kDa is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device.Methods: In trial 1, 50 healthy adult subjects received one 180 µg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 µg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment.Results: In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation, and area under the concentration time curve (0–168 hours was 1996 ± 613 ng · hour

  15. Effect of NMDA NR2B antagonist on neuropathic pain in two spinal cord injury models.

    Science.gov (United States)

    Kim, Youngkyung; Cho, Hwi-young; Ahn, Young Ju; Kim, Junesun; Yoon, Young Wook

    2012-05-01

    N-Methyl-d-aspartate (NMDA) receptors are thought to play an important role in the processes of central sensitization and pathogenesis of neuropathic pain, particularly after spinal cord injury (SCI). NMDA antagonists effectively reduce neuropathic pain, but serious side effects prevent their use as therapeutic drugs. NMDA NR2B antagonists have been reported to effectively reduce inflammatory and neuropathic pain. In this study, we investigated the effects of NR2B antagonists on neuropathic pain and the expression of NR2B in the spinal cord in 2 SCI models. SCI was induced at T12 by a New York University impactor (contusion) or by sectioning of the lateral half of the spinal cord (hemisection). Ifenprodil (100, 200, 500, 1000nmol) and Ro25-6981 (20, 50, 100, 200nmol) were intrathecally injected and behavioral tests were conducted. Ifenprodil increased the paw withdrawal threshold in both models but also produced mild motor depression at higher doses. Ro25-6981 increased the mechanical nociceptive threshold in a dose-dependent manner without motor depression. NR2B expression was significantly increased on both sides at the spinal segments of L1-2 and L4-5 in the hemisection model but did not change in the contusion model. Increased expression of NR2B in the hemisection model was reduced by intrathecal ifenprodil. These results suggest that intrathecal NMDA NR2B antagonist increased the mechanical nociceptive threshold after SCI without motor depression. A selective subtype of NMDA receptor, such as NR2B, may be a more selective target for pain control because NMDA receptors play a crucial role in the development and maintenance of chronic pain. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  16. Implication of 5-HT(2B) receptors in the serotonin syndrome.

    Science.gov (United States)

    Diaz, Silvina Laura; Maroteaux, Luc

    2011-09-01

    The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this disorder by forced swimming test (FST) and behavioral assessment in the open field. In FST, genetic (5-HT(2B)(-/-) mice) or pharmacological (antagonist RS127445 at 0.5 mg/kg) ablation of 5-HT(2B) receptors facilitated selective 5-HT reuptake inhibitors (SSRI)-induced increase of immobility time as well as expression of other symptoms related to 5-HT syndrome like hind limb abduction and Straub tail. Increase in immobility was also developed in FST by both wild type (WT) and 5-HT(2B)(-/-) mice after the administration of 5-HT(1A), 5-HT(2A) or 5-HT(2C) receptor agonists, 8-OH-DPAT (5 mg/kg), DOI (1 mg/kg), or WAY161503 (5 mg/kg), respectively. In contrast, the 5-HT(2B) receptor agonist BW723C86 (3 mg/kg) or 5-HT(1B) receptor agonist CGS12066A (2 mg/kg) decreased immobility time in both genotypes. The 5-HT syndrome induced by fluoxetine at high doses was blocked in WT and 5-HT(2B)(-/-) mice by administration of 5-HT(1A) and 5-HT(2C) receptor antagonists (WAY100635 0.5 mg/kg and SB242084 0.5 mg/kg) but not by the 5-HT(2A) receptor antagonist MDL100907 (1 mg/kg). By behavioral assessment, we confirmed that 5-HT(2B)(-/-) mice were more prone to develop 5-HT syndrome symptoms after administration of high dose of SSRIs or the 5-HT precursor 5-Hydroxytryptophan, 5-HTP, even if increases in 5-HT plasma levels were similar in both genotypes. This evidence suggests that the presence of 5-HT(2B) receptors hinders acute 5-HT toxicity once high levels of 5-HT are attained. Therefore, differential agonism

  17. Power Generation Unit of Nano-Satellites STUDSAT 2A/2B

    Science.gov (United States)

    Velayudhan, Sneha; Bhavana, K. H.; Ravi Kumar, H. M.; Ranjith, H. G.; Ghosh, Sujay

    2014-08-01

    STUDSAT 2A/2B [8] are the twin nano-satellites. Electrical power system is one of the most important subsystems of STUDSAT 2A/2B which provides conditioned power to all the subsystem. Power generating unit is one of the most important units in Electrical Power system. The power generation unit of STUDSAT-2A/2B consists of 3 solar panels out of which 2 are deployable and 1 is body mounted and a maximum Power point Tracker(MPPT).The total orbital period of STUDSAT-2A/2B is 98min.The sunlit period is about 63.8min.The power can be generated by the solar panels only during this period. Since the power generated by the solar panel is affected by the solar irradiation, temperature etc. It's difficult to generate the maximum power at all the point in an orbit, hence maximum power point trackers are used. These maximum power point trackers track the maximum power point on the solar panel using perturb and observe algorithm and hence maximum power is generated at all the points in an orbit.This paper presents the power profile for both body mounted and deployable solar panels. It gives a brief description of how the power generated by the solar cells is conditioned and the power protection unit with simulation results and testing results for the solar panel used in STUDSAT-2A/2B.

  18. Effects of nano bamboo charcoal on PAHs-degrading strain Sphingomonas sp. GY2B.

    Science.gov (United States)

    She, Bojia; Tao, Xueqin; Huang, Ting; Lu, Guining; Zhou, Zhili; Guo, Chuling; Dang, Zhi

    2016-03-01

    Nano bamboo charcoal (NBC) has been commonly used in the production of textiles, plastics, paint, etc. However, little is known regarding their effects towards the microorganisms. The effects of NBC on phenanthrene degrading strain Sphingomonas sp. GY2B were investigated in the present study. Results showed that the addition of NBC could improve the phenanthrene removal by Sphingomonas sp. GY2B, with removal efficiencies increased by 10.29-18.56% in comparison to the control at 24h, and phenanthrene was almost completely removed at 48h. With the presence of low dose of NBC (20 and 50mgL(-1)), strain GY2B displayed a better growth at 6h, suggesting that NBC was beneficial to the growth of GY2B and thus resulting in the quick removal of phenanthrene from water. However, the growth of strain GY2B in high dose of NBC (200mgL(-1)) was inhibited at 6h, and the inhibition could be attenuated and eliminated after 12h. NBC-effected phenanthrene solubility experiment suggested that NBC makes a negligible contribution to the solubilization of phenanthrene in water. Results of electronic microscopy analysis (SEM and TEM) indicated NBC may interact with the cell membrane, causing the enhanced membrane permeability and then NBC adsorbed on the membrane would enter into the cells. The findings of this work would provide important information for the future usage and long-term environmental risk assessment of NBC. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    Directory of Open Access Journals (Sweden)

    Wiebke Janssen

    2015-01-01

    Full Text Available Objective. The serotonin (5-HT pathway was shown to play a role in pulmonary hypertension (PH, but its functions in right ventricular failure (RVF remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist or SB204741 (5-HT2B receptor antagonist on right heart function and structure upon pulmonary artery banding (PAB in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid or SB204741 (5 mg/kg day. Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI, and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF.

  20. GluN2B in corticostriatal circuits governs choice learning and choice shifting

    Science.gov (United States)

    Brigman, Jonathan L.; Daut, Rachel; Wright, Tara; Gunduz-Cinar, Ozge; Graybeal, Carolyn; Davis, Margaret I.; Jiang, Zhihong; Saksida, Lisa; Jinde, Seiichiro; Pease, Matthew; Bussey, Timothy J.; Lovinger, David M.; Nakazawa, Kazu; Holmes, Andrew

    2013-01-01

    A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or become perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms subserving the instantiation of these processes are not well understood. We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic, and pharmacological approaches to study choice. We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal GluN2B gene deletion, or DS-restricted GluN2B antagonism, impaired choice learning, whereas cortical GluN2B deletion or OFC GluN2B antagonism impaired shifting. Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior. PMID:23831965

  1. Immunodiagnosis of tumors in vivo using radiolabeled monoclonal antibody A2B5

    Energy Technology Data Exchange (ETDEWEB)

    Reintgen, D.S.; Shimizu, K.; Coleman, E.; Briner, W.; Kitzmiller, J.; Eisenbarth, G.; Seigler, H.F.

    1983-07-01

    Recently a murine monoclonal antibody (A2B5) has been described that reacts with a membrane associated GQ ganglioside common to peptide secreting normal cells and tumors. In vitro binding data demonstrated the presence of this ganglioside on neurons, adrenal medulla, and pancreatic islets, along with neuroendocrine tumors such as insulinomas, pheochromocytomas, melanomas and neuroblastomas. Negative binding has previously been shown for tissue sections from liver, kidney, colon, lung, stomach, and tumors not derived from the neural crest. Because of the specificity at A2B5 in vitro, this monoclonal antibody was labeled with /sup 131/I for in vivo tumor localization studies. Daily radionuclear scans were obtained in 5 KX rats bearing the radiation induced rat insulinoma with disappearance of the label from the blood pool and concentration in the tumor so that by the fourth day, the only activity present by scan was in the insulinoma. In addition A2B5 also localized to five different human melanoma cells lines grown in nude mice with high tumor/blood levels compared to normal tissues, while no localization is seen in nudes carrying osteosarcomas, colon, bladder, and renal cell carcinomas. In addition antibody A2B5 did not concentrate in any normal tissue though the antigen is present on several. The finding that A2B5 reacts across species lines (mouse, rat, man) lends itself to obvious diagnostic and therapeutic possibilities.

  2. Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects.

    Science.gov (United States)

    Ravnskjaer, Kim; Hogan, Meghan F; Lackey, Denise; Tora, Laszlo; Dent, Sharon Y R; Olefsky, Jerrold; Montminy, Marc

    2013-10-01

    Circulating pancreatic glucagon is increased during fasting and maintains glucose balance by stimulating hepatic gluconeogenesis. Glucagon triggering of the cAMP pathway upregulates the gluconeogenic program through the phosphorylation of cAMP response element-binding protein (CREB) and the dephosphorylation of the CREB coactivator CRTC2. Hormonal and nutrient signals are also thought to modulate gluconeogenic gene expression by promoting epigenetic changes that facilitate assembly of the transcriptional machinery. However, the nature of these modifications is unclear. Using mouse models and in vitro assays, we show that histone H3 acetylation at Lys 9 (H3K9Ac) was elevated over gluconeogenic genes and contributed to increased hepatic glucose production during fasting and in diabetes. Dephosphorylation of CRTC2 promoted increased H3K9Ac through recruitment of the lysine acetyltransferase 2B (KAT2B) and WD repeat-containing protein 5 (WDR5), a core subunit of histone methyltransferase (HMT) complexes. KAT2B and WDR5 stimulated the gluconeogenic program through a self-reinforcing cycle, whereby increases in H3K9Ac further potentiated CRTC2 occupancy at CREB binding sites. Depletion of KAT2B or WDR5 decreased gluconeogenic gene expression, consequently breaking the cycle. Administration of a small-molecule KAT2B antagonist lowered circulating blood glucose concentrations in insulin resistance, suggesting that this enzyme may be a useful target for diabetes treatment.

  3. [Mutation of TFAP-2B gene in patients with patent ductus arteriosus].

    Science.gov (United States)

    Chen, Yi-wei; Zhao, Wu; Li, Fen; Ji, Wei; Fu, Qi-hua; Zhang, Zhi-fang; Wang, Jian

    2010-12-01

    To identify novel genetic mutations in Chinese patients with congenital patent ductus arteriosus (PDA). Clinical data and peripheral blood specimens from a kindred spanning 3 generations in which 5 of 16 individuals had PDA and a cohort of 95 unrelated subjects with PDA were collected, and 100 unrelated healthy individuals were included as controls. The coding exons and flanking introns of TFAP-2B gene were amplified by polymerase chain reaction (PCR) with specific primers. We aligned the acquired sequences with which publicized in GenBank by the aid of program BLAST. Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify the parts of TFAP-2B and sequencing was performed on PCR products forward and reversely directly. Sequencing of TFAP-2B identified that there was a splice-junction in intron 3 [intron 3(+5)G > A] and a 60 bp deletion was found in exon 3 by nested PCR. Additionally, a novel single nucleotide polymorphism (SNP) where a transition of guanine (G) to adenine (A) was identified at 34 bp front of transcription initiation site in TFAP-2B gene. There were significant differences in the prevalence of alleles G and A between controls and PDA patients (Z = -2.513, P = 0.012). We identified a novel splice-junction in TFAP-2B gene which might lead to hereditary PDA in a Chinese family. However, the mechanism by which this mutation results in PDA is still to be ascertained.

  4. Social Media within a B2B context : A qualitative study about how industrial corporations can use social media to maintain B2B relationships

    OpenAIRE

    Andersén, Sophia; Bengtsson, Annie; Gilén, Sandra

    2014-01-01

    The last thirty years there has been a dramatic change in relationship marketing. The use of computers connected to the Internet at work places has increased over time and social media is widely used in marketing strategies. Social media is a new phenomenon to communicate with each other, it enables market information based on individual consumer’s experiences. Therefore managers are seeking a way to incorporate social media into their strategies, but this is more common within B2C than B2B. ...

  5. The Adaptor Protein SH2B3 (Lnk) Negatively Regulates Neurite Outgrowth of PC12 Cells and Cortical Neurons

    Science.gov (United States)

    Wang, Tien-Cheng; Chiu, Hsun; Chang, Yu-Jung; Hsu, Tai-Yu; Chiu, Ing-Ming; Chen, Linyi

    2011-01-01

    SH2B adaptor protein family members (SH2B1-3) regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2. PMID:22028877

  6. IMMUNOMODULATING THERAPY BY RECOMBINANT ALPHA-2B INTERFERON AMONG CHILDREN WITH TIMOMEGALIA

    Directory of Open Access Journals (Sweden)

    L.A. Nikulin

    2007-01-01

    Full Text Available The study of the enlarged thymus gland syndrome is extremely important for understanding of the immune system formation and functioning mechanisms. the purpose of this study is to conduct clinical and immunological analysis of the children, suffering from the syndrome of the enlarged thymus gland II and III degrees, who received recombinant alpha2b interferon (in suppositories. The revealed changes in the immune sys tem during timomegalia are complex and conducive to the development of the infectious and inflammatory diseases among infants, thus, determining the necessity for the adequate immune correction. The application of the recombinant alpha 2b interferon among such children allows one to uncover the immunomodulating effects, normalizing the imbalances in the immune system of children with timomegalia.Key words: timomegalia, alpha 2b interferon, immunity, immune correction, children.

  7. Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

    DEFF Research Database (Denmark)

    Rohrer, Jonathan D; Ahsan, R Laila; Isaacs, Adrian M

    2009-01-01

    BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no ......BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease...... gene mutation carriers. CONCLUSIONS: This finding suggests that mutations in CHMP2B have widespread effects throughout the brain, leading to a neuro-anatomical signature distinct from other diseases in the frontotemporal lobar degeneration spectrum....

  8. The structure and the analytical potential energy function of NH2 (X2B1)

    International Nuclear Information System (INIS)

    Liu Yufang; Jiang Lijuan; Ma Heng; Sun Jinfeng

    2008-01-01

    This paper reports that the equilibrium structure of NH 2 has been optimized at the QCISD/6-311++G (3df, 3pd) level. The ground-state NH 2 has a bent (C 2v , X 2 B 1 ) structure with an angle of 103.0582°. The geometrical structure is in good agreement with the other calculational and experimental results. The harmonic frequencies and the force constants have also been calculated. Based on the group theory and the principle of microscopic reversibility, the dissociation limits of NH 2 (C 2v , X 2 B 1 ) have been derived. The potential energy surface of NH 2 (X 2 B 1 ) is reasonable. The contour lines are constructed, the structure and energy of NH 2 reappear on the potential energy surface

  9. Phenotypic and Transcriptomic Analysis of Nicotiana benthamiana Expressing Cucumber mosaic virus 2b gene

    Directory of Open Access Journals (Sweden)

    Seong-Han Sohn

    2015-09-01

    Full Text Available Cucumber mosaic virus possesses 2b gene known as a suppressor of post-transcriptional gene silencing (PTGS. To investigate its function and effect in plant, transgenic Nicotiana benethamiana expressing 2b gene was developed and analyzed in phenotypic characteristics and differential gene expression (DEG comparing with wild-type. Eight lines of transgenic plants (T0 were obtained with difficulty and showed severe deformed phenotypes in leaves, flowers, petioles and etc. Moreover, transgenic plants were hardly able to set seeds, but small amounts of seeds were barely produced in some of transgene-hemizygous plants. DEG analysis showed that transgenic plant ectopically accumulated diverse RNA transcripts at higher levels than wild-type probably due to the disturbance in RNA metabolism, especially of RNA decay, caused by 2b-mediated inhibition of PTGS. These ectopic accumulations of RNAs disrupt protein and RNA homeostasis and then subsequently lead to abnormal phenotypes of transgenic plants.

  10. Accessory nerve function after level 2b-preserving selective neck dissection.

    Science.gov (United States)

    Celik, Bilge; Coskun, Hakan; Kumas, Ferda F; Irdesel, Jale; Zarifoglu, Mehmet; Erisen, Levent; Onart, Selcuk

    2009-11-01

    The aim of this prospective study was to evaluate the relationship between accessory nerve functions and level 2b-preserving selective neck dissection. Forty-one necks of 30 patients with laryngeal cancer who underwent unilateral or bilateral level 2b-preserving neck dissections, between February 2003 and July 2005, were evaluated. Neck and shoulder movements and muscle strengths were examined and electroneuromyography (ENMG) was performed preoperatively at the postoperative 21st day and 6th month. Pathological anatomical findings at the postoperative 6th month were also evaluated. All shoulder movements and muscle strengths were preserved. Neck extension, rotation movements, and flexion strengths were restricted. ENMG values were affected moderately in the early postoperative period and improved slightly in the late postoperative period. None of the patients developed shoulder syndrome or adhesive capsulitis. Preserving level 2b during selective neck dissection decreases trauma to the accessory nerve and improves functional results. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.

  11. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  12. Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.

    Directory of Open Access Journals (Sweden)

    Raquel María Fernández

    Full Text Available Hirschsprung disease (HSCR is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neural crest derivatives, and heterozygous mutations cause a complex dysautonomia associating HSCR, Congenital Central Hypoventilation Syndrome (CCHS and neuroblastoma (NB in various combinations. In order to determine the role of PHOX2B in isolated HSCR, we performed a mutational screening in a cohort of 207 Spanish HSCR patients. Our most relevant finding has been the identification of a de novo and novel deletion (c.393_410del18 in a patient with HSCR. Results of in silico and functional assays support its pathogenic effect related to HSCR. Therefore our results support that PHOX2B loss-of-function is a rare cause of HSCR phenotype.

  13. [Antiviral activity of recombinant interferon-alpha-2b in combination with certain antioxidant].

    Science.gov (United States)

    Vasil'ev, A N; Deriabin, P G; Galegov, G A

    2011-01-01

    In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

  14. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  15. The Importance of Brand on B2B Markets: Expert Interviews with Hilti AG Managers

    Directory of Open Access Journals (Sweden)

    Martin Konečný

    2013-12-01

    Full Text Available This paper investigates the importance of brand building in the business-to-business world. Not only B2C companies must take branding into account and put it among their top priorities in order to survive and succeed on the market. The first part of the article deals with the theoretical background of brand importance and market specifics of B2B markets and results in the setting of two hypotheses. The following research has to find out how the managers of a pure business-to-business company perceive the importance of a brand; moreover, it has to evaluate the importance of eight specific brand building factors. Fourteen expert interviews document the growing of brands in the B2B market and their main aspects. At the end of the article, we will focus on future implications for B2B management.

  16. Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT 1A6 and 2B7

    Directory of Open Access Journals (Sweden)

    Xiao-Qi Ji

    2012-08-01

    Full Text Available Inhibition of UDP-glucuronosyltransferase (UGT isoforms can result in severe clinical results, including clinical drug-drug interactions (DDI and metabolic disorders of endogenous substances. The present study aims to investigate the inhibition of demethylzeylasteral (an important active component isolated from Tripterygium wilfordii Hook F. towards three important UGT isoforms UGT1A6, UGT1A9 and UGT2B7. The results showed that 100 μM of demethylzeylasteral exhibited strong inhibition towards UGT1A6 and UGT2B7, with negligible influence towards UGT1A9. Furthermore, Dixon and Lineweaver-Burk plots showed the inhibition of UGT1A6 and UGT2B7 by demethylzeylasteral was best fit to competitive inhibition, and the inhibition kinetic parameters (Ki were calculated to be 0.6 μM and 17.3 μM for UGT1A6 and UGT2B7, respectively. This kind of inhibitory effect need much attention when demethylzeylasteral and demethylzeyasteral-containing herbs (e.g., Tripterygium wilfordii Hook F. were co-administered with the drugs mainly undergoing UGT1A6, UGT2B7-catalyzed metabolism. However, when extrapolating the in vivo clinical results using our present in vitro data, many complex factors might affect final results, including the contribution of UGT1A6 and UGT2B7 to the metabolism of compounds, and the herbal or patients’ factors affecting the in vivo concentration of demethylzeylasteral.

  17. GRIN2B mediates susceptibility to intelligence quotient and cognitive impairments in developmental dyslexia.

    Science.gov (United States)

    Mascheretti, Sara; Facoetti, Andrea; Giorda, Roberto; Beri, Silvana; Riva, Valentina; Trezzi, Vittoria; Cellino, Maria R; Marino, Cecilia

    2015-02-01

    Developmental dyslexia (DD) is a complex heritable condition associated with impairments in multiple neurocognitive domains. Substantial heritability has been reported for DD and related phenotypes, and candidate genes have been identified. Recently, a candidate gene for human cognitive processes, that is, GRIN2B, has been found to be associated significantly with working memory in a German DD sample. In this study, we explored the contribution of six GRIN2B markers to DD and key DD-related phenotypes by association analyses in a sample of Italian nuclear families. Moreover, we assessed potential gene-by-environment interactions on DD-related phenotypes. We carried out a family-based association study to determine whether the GRIN2B gene influences both DD as a categorical trait and its related cognitive traits in a large cohort of 466 Italian nuclear families ascertained through a proband affected by DD. Moreover, we tested the role of the selected GRIN2B markers and a set of commonly described environmental moderators using a test for G×E interaction in sib pair-based association analysis of quantitative traits in 178 Italian nuclear families. Evidence for a significant association was found with the categorical diagnosis of DD, performance intelligence quotient, phonemic elision, and auditory short-term memory. No significant gene-by-environment effects were found. Our results add further evidence in support of GRIN2B contributing toward DD and deficits in DD. More specifically, our data support the view that GRIN2B influences DD as a categorical trait and its related quantitative phenotypes, thus shedding further light on the etiologic basis and the phenotypic complexity of this disorder.

  18. Common PHOX2B poly-alanine contractions impair RET gene transcription, predisposing to Hirschsprung disease.

    Science.gov (United States)

    Di Zanni, Eleonora; Adamo, Annalisa; Belligni, Elga; Lerone, Margherita; Martucciello, Giuseppe; Mattioli, Girolamo; Pini Prato, Alessio; Ravazzolo, Roberto; Silengo, Margherita; Bachetti, Tiziana; Ceccherini, Isabella

    2017-07-01

    HSCR is a congenital disorder of the enteric nervous system, characterized by the absence of neurons along a variable length of the gut resulting from loss-of-function RET mutations. Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by impaired response to hypercapnia and hypoxemia caused by heterozygous mutations of the PHOX2B gene, mostly polyalanine (polyA) expansions but also missense, nonsense, and frameshift mutations, while polyA contractions are common in the population and believed neutral. HSCR associated CCHS can present in patients carrying PHOX2B mutations. Indeed, RET expression is orchestrated by different transcriptional factors among which PHOX2B, thus suggesting its possible role in HSCR pathogenesis. Following the observation of HSCR patients carrying in frame trinucleotide deletions within the polyalanine stretch in exon 3 (polyA contractions), we have verified the hypothesis that these PHOX2B variants do reduce its transcriptional activity, likely resulting in a down-regulation of RET expression and, consequently, favouring the development of the HSCR phenotype. Using proper reporter constructs, we show here that the in vitro transactivation of the RET promoter by different HSCR-associated PHOX2B polyA variants has resulted significantly lower compared to the effect of PHOX2B wild type protein. In particular, polyA contractions do induce a reduced transactivation of the RET promoter, milder compared to the severe polyA expansions associated with CCHS+HSCR, and correlated with the length of the deleted trait, with a more pronounced effect when contractions are larger. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Copolimerização de 1,3-butadieno e alfa-olefinas com catalisadores à base de versatato de neodímio

    OpenAIRE

    Gustavo Monteiro da Silva

    2010-01-01

    Nesta Dissertação, foram realizadas reações de copolimerização de 1,3-butadieno com diferentes alfa-olefinas (1-hexeno, 1-octeno e 1-dodeceno) utilizando-se um sistema catalítico do tipo Ziegler-Natta ternário constituído por versatato de neodímio, hidreto de diisobutilalumínio e cloreto de t-butila. O sistema catalítico também foi avaliado em reações de homopolimerização com cada alfa-olefina. As condições reacionais, tanto da síntese do catalisador como das reações de polimerização, foram m...

  20. Progressive dysphagia in limb-girdle muscular dystrophy type 2B.

    LENUS (Irish Health Repository)

    Walsh, Richard

    2012-02-01

    Dysphagia has not been reported in genetically confirmed limb-girdle muscular dystrophy type 2B (LGMD2B). A 40-year-old woman reported exercise-induced calf pain at age 34, followed by progressive lower and upper limb weakness. At age 38, progressive dysphagia for solids, and subsequently liquids, ensued. Endoscopic and videofluoroscopic-radiological findings indicated a myopathic swallowing disorder. Molecular genetic analysis confirmed two dysferlin gene mutations consistent with a compound heterozygote state. Progressive dysphagia should be considered as part of the expanding dysferlinopathy phenotype.

  1. Developmental splicing deregulation in leukodystrophies related to EIF2B mutations.

    Directory of Open Access Journals (Sweden)

    Aurélia Huyghe

    Full Text Available Leukodystrophies (LD are rare inherited disorders that primarily affect the white matter (WM of the central nervous system. The large heterogeneity of LD results from the diversity of the genetically determined defects that interfere with glial cells functions. Astrocytes have been identified as the primary target of LD with cystic myelin breakdown including those related to mutations in the ubiquitous translation initiation factor eIF2B. EIF2B is involved in global protein synthesis and its regulation under normal and stress conditions. Little is known about how eIF2B mutations have a major effect on WM. We performed a transcriptomic analysis using fibroblasts of 10 eIF2B-mutated patients with a severe phenotype and 10 age matched patients with other types of LD in comparison to control fibroblasts. ANOVA was used to identify genes that were statistically significantly differentially expressed at basal state and after ER-stress. The pattern of differentially expressed genes between basal state and ER-stress did not differ significantly among each of the three conditions. However, 70 genes were specifically differentially expressed in eIF2B-mutated fibroblasts whatever the stress conditions tested compared to controls, 96% being under-expressed. Most of these genes were involved in mRNA regulation and mitochondrial metabolism. The 13 most representative genes, including genes belonging to the Heterogeneous Nuclear Ribonucleoprotein (HNRNP family, described as regulators of splicing events and stability of mRNA, were dysregulated during the development of eIF2B-mutated brains. HNRNPH1, F and C mRNA were over-expressed in foetus but under-expressed in children and adult brains. The abnormal regulation of HNRNP expression in the brain of eIF2B-mutated patients was concomitant with splicing dysregulation of the main genes involved in glial maturation such as PLP1 for oligodendrocytes and GFAP in astrocytes. These findings demonstrate a developmental

  2. Short syntheses of enantiopure calystegine B-2, B-3, and B-4

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Madsen, Robert

    2001-01-01

    Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps.......Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps....

  3. Implication of 5-HT2B receptors in the serotonin syndrome

    OpenAIRE

    Diaz, Silvina Laura; Maroteaux, Luc

    2011-01-01

    International audience; The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this dis...

  4. Uniaxial pressure effect on RENi2B2C (RE=Ho and Y)

    International Nuclear Information System (INIS)

    Kobayashi, Yoshihiko; Iwata, M.; Okamoto, T.; Takeya, H; Kuroki, K.; Suzuki, M.; Asai, K.

    2006-01-01

    We have investigated the uniaxial pressure (P) effect on RENi 2 B 2 C for RE=Ho and Y. On HoNi 2 B 2 C 2 , the antiferromagnetic (AF) transition temperature remarkably increases with applying P parallel to [110], suggesting that the stress along [110] stabilizes the AF ordering through the enhancement of the magnetic anisotropy of Ho moments. On the other hand, a pressure dependence of the superconducting transition temperature was not observed. The finding of the present experiment suggests that the AF interaction has no influence on the origin of the superconductivity in this system

  5. Evaluation of the Efficacy and Cross-Protective Immunity of Live-Attenuated Chimeric PCV1-2b Vaccine Against PCV2b and PCV2d Subtype Challenge in Pigs.

    Science.gov (United States)

    Huan, Changchao; Fan, Mingyu; Cheng, Qingru; Wang, Xiaobo; Gao, Qingqing; Wang, Wanbin; Gao, Song; Liu, Xiufan

    2018-01-01

    Porcine circovirus type 2 (PCV2) commercial vaccines are either inactivated PCV2 isolates or subunit vaccine based on the Cap protein of PCV2. Currently, no live-attenuated vaccines are yet available. Although the predominant circulating subtype worldwide is PCV2b, the emerging PCV2d subtype is also increasingly associated with PCV disease. In this study, piglets were inoculated with a live-attenuated chimeric PCV1-2b vaccine before challenged with PCV2b and PCV2d isolates. Thirty-two piglets were randomly divided into seven groups: negative (sham-vaccinated, sham-challenged), VAC+PCV2b (PCV1-2b vaccinated, PCV2b-challenged), VAC+PCV2d (PCV1-2b vaccinated, PCV2d-challenged), CHAL+PCV2b (sham-vaccinated, PCV2b-challenged), CHAL+PCV2d (sham-vaccinated, PCV2d-challenged), CV+PCV2b (commercial-vaccinated, PCV2b-challenged), and CV+PCV2d (commercial-vaccinated, PCV2d-challenged). The results showed that vaccinated challenged groups demonstrated high levels of anti-PCV2 antibody and reduced PCV2b and PCV2d loads both in serum and nasal swabs compared with the challenge-only groups. PCV2 DNA was detected in the superficial inguinal lymph nodes of only one pig in each of the VAC+PCV2b and VAC+PCV2d groups (group mean values, 10 1.81 and 10 1.77 genomic copies/g, respectively), which was significantly lower than those in CHAL+PCV2b and CHAL+PCV2d animals (group mean values, 10 11.65 and 10 10.60 genomic copies/g, respectively; P live-attenuated PCV1-2b vaccine was more effective than commercial vaccine. The live-attenuated PCV1-2b vaccine was effective in reducing PCV2b/PCV2d viremia, shedding, and tissue viral loads in vaccinated challenged pigs compared with challenge-only piglets, indicating that the PCV1-2b prototype vaccine is a good candidate for a live-attenuated vaccine against both PCV2b and PCV2d subtypes. And we first revealed that the live-attenuated PCV1-2b vaccine could protect piglets from challenge with either PCV2b or PCV2d equivalently.

  6. Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alfa-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

    Czech Academy of Sciences Publication Activity Database

    Khainar, A.; Latta, P.; Dražanová, Eva; Rudá-Kučerová, J.; Szabó, N.; Arab, A.; Hutter-Paier, B.; Havas, D.; Windisch, M.; Šulcová, A.; Starčuk jr., Zenon; Rektorová, I.

    2015-01-01

    Roč. 28, č. 4 (2015), 281-289 ISSN 1029-8428 R&D Projects: GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : diffusion kurtosis imaging * alfa-Synuclein * TNWT-61 * Parkinson’s disease * Transgenic mice * TBSS Subject RIV: BH - Optics, Masers, Lasers Impact factor: 3.140, year: 2015

  7. Influence of wool and thermo-binder fibers relative fractions on the adhesion of non-woven Alfa fibers reinforced unsaturated polyester hybrid composites

    Science.gov (United States)

    Amin Omri, Med; Triki, A.; Ben Hassen, Med; Arous, M.; Bulou, A.

    2016-10-01

    Alfa/wool/thermo-binder fibers hybrid composites were investigated in order to analyze adhesion state. Bearing in mind the chemical structure of wool and thermo-binder fibers, this study revealed a good compatibility between the reinforcement and the matrix. Dielectric measurements revealed the presence of two dielectric relaxations in the composite. The first relaxation was attributed to the α mode relaxation and the second one was associated with the conductivity noted for high temperature. This study allowed the analysis of the interfacial polarization effect using the Havrilliak-Negami model in the electric modulus formalism. The lowness of this relaxation intensity revealed a good adhesion of the fibers in the matrix. Differential Scanning Calorimetry (DSC) showed a slow decrease of the Tg glass transition temperature compared to the matrix, which could be explained by the existence of interactions between the fibers and the matrix. Vibrational analysis, based on FTIR measurements, showed a less hydrophilic character of Alfa fibers owing to a basic dissociation that occurs between the wool fibers and the water molecules associated with Alfa fibers. Furthermore, adhesion mechanism in the composite material was established by covalent and hydrogen bonds. Tensile testing performed on this composite confirmed that such adhesion was improved by increasing the thermo-binder fibers relative fraction.

  8. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  9. Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

    Science.gov (United States)

    Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

    2017-06-01

    This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged 0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

  10. Effect of corifollitropin alfa supplemented with or without LH on ovarian stimulation and embryo viability in rabbit.

    Science.gov (United States)

    Viudes-de-Castro, María Pilar; Marco-Jiménez, Francisco; Cedano-Castro, José Isaí; Vicente, José Salvador

    2017-08-01

    There is increasing interest in using rabbits for research as a laboratory model as well as for industrial production of meat, wool and fur. Superovulation in animals is used to produce a maximum number of transferable embryos per donor, in order to either support genetic improvement programs, ex situ conservation or to optimize other biotechnologies. Over time, the use of this biotechnology has shown variable outcomes as a consequence of several factors, such as the origin of exogenous hormone, posology and the effect of gonadotropins used simultaneously, the donor and the environment. The aim of this study was to compare the efficacy of a single injection of corifollitropin alfa (CTP), alone or supplemented with LH, versus a FSH standard protocol of five equal doses administered twice daily to superovulate rabbit does (20 per group and 29 control females). We determined: 1) the impact of this stimulation on in vitro development and mRNA expression at blastocyst stage and 2) in vivo embryo development and viability rate at birth of transferred embryos. Our outcomes showed that the ovulation rate was similar among the different ovarian stimulation groups, reaching more than fourfold the ovulation rate of a control doe. While rates of embryos developing to the blastocyst stage after 48 h of in vitro culture were similar between groups, the hatched blastocyst rate was higher for superovulated embryos from CTP group. Moreover, no significant differences among mRNA expression of OCT4, SOX2 and NANOG genes were detected. Nevertheless, embryos from ovarian stimulated does with CTP + LH showed significantly higher implantation rates and survival at birth among the different ovarian stimulation groups and similar to those in the control group. In conclusion, the results of this study suggest that a single injection of long acting corifollitropin alfa can be effectively used in rabbits to elicit a more than fourfold increase in ovulation rate compared to control

  11. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

    DEFF Research Database (Denmark)

    Clayton, Emma L.; Mancuso, Renzo; Nielsen, Troels Tolstrup

    2017-01-01

    Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like c...

  12. A2 /A2 B to B Renal Transplantation: Past, Present, and Future Directions.

    Science.gov (United States)

    Bryan, C F; Cherikh, W S; Sesok-Pizzini, D A

    2016-01-01

    One component of the new national kidney allocation system (KAS) in the United States that was implemented on December 4, 2014, was the allocation of kidneys from A2 and A2 B (A, non-A1 and AB, non-A1 B) deceased donors into blood group B candidates (A2 /A2 B → B). In so far as this is an important component of the new KAS that has the potential to further increase the access to transplantation for blood group B candidates on the waiting list, most of whom are minority candidates, we will review the body of evidence and historical perspectives that led to its inclusion in the new KAS. This review will also describe prospects for more widespread use of A2 /A2 B → B transplantation and a novel mechanism of humoral immunosuppression in B patients before and after transplantation with an A2 or A2 B kidney. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Exterior orientation of CBERS-2B imagery using multi-feature control and orbital data

    Science.gov (United States)

    Marcato Junior, J.; Tommaselli, A. M. G.

    2013-05-01

    The major contribution of this paper relates to the practical advantages of combining Ground Control Points (GCPs), Ground Control Lines (GCLs) and orbital data to estimate the exterior orientation parameters of images collected by CBERS-2B (China-Brazil Earth Resources Satellite) HRC (High-resolution Camera) and CCD (High-resolution CCD Camera) sensors. Although the CBERS-2B is no longer operational, its images are still being used in Brazil, and the next generations of the CBERS satellite will have sensors with similar technical features, which motivates the study presented in this paper. The mathematical models that relate the object and image spaces are based on collinearity (for points) and coplanarity (for lines) conditions. These models were created in an in-house developed software package called TMS (Triangulation with Multiple Sensors) with multi-feature control (GCPs and GCLs). Experiments on a block of four CBERS-2B HRC images and on one CBERS-2B CCD image were performed using both models. It was observed that the combination of GCPs and GCLs provided better bundle block adjustment results than conventional bundle adjustment using only GCPs. The results also demonstrate the advantages of using primarily orbital data when the number of control entities is reduced.

  14. Magnetic structures in RNi{sub 2}B{sub 2}C (R = Ho, Er) superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Stassis, C.; Goldman, A.I.; Dervenagas, P.; Zarestky, J.; Canfield, P.C.; Cho, B.K.; Johnston, D.C.; Sternlieb, B. [Iowa State Univ., Ames, IA (United States). Dept. of Physics and Astronomy; Sternlieb, B. [Brookhaven National Lab., Upton, NY (United States)

    1994-12-31

    Single crystal neutron diffraction techniques have been employed to study the evolution of magnetic structures in RNi{sub 2}B{sub 2}C compounds in an attempt to understand the relationship between magnetic ordering and superconductivity in several members of this series. For HoNi{sub 2}B{sub 2}C, below the superconducting transition (T{sub c} = 8 K), an incommensurate magnetic structure characterized by two wave vectors (0.585 a* and 0.915 c*) is found in a narrow temperature range between 4.7 K and 6 K. This is the same temperature range where bulk measurements find a deep minimum in the upper critical field, H{sub c2}. Below 4.7 K, HoNi{sub 2}B{sub 2}C is a simple collinear antiferromagnet. ErNi{sub 2}B{sub 2}C ({Tc} = 11 K) orders in an incommensurate modulated antiferromagnetic state characterized by an ordering wave vector 0.553 a* below 7 K, which coexists with superconductivity.

  15. Adhesive and Cohesive Strength in FeB/Fe2B Systems

    Science.gov (United States)

    Meneses-Amador, A.; Blancas-Pérez, D.; Corpus-Mejía, R.; Rodríguez-Castro, G. A.; Martínez-Trinidad, J.; Jiménez-Tinoco, L. F.

    2018-01-01

    In this work, FeB/Fe2B systems were evaluated by the scratch test. The powder-pack boriding process was performed on the surface of AISI M2 steel. The mechanical parameters, such as yield stress and Young's modulus of the boride layer, were obtained by the instrumented indentation technique. Residual stresses produced on the boride layer were estimated by using the x-ray diffraction (XRD) technique. The scratch test was performed in order to evaluate the cohesive/adhesive strength of the FeB/Fe2B coating. In addition, a numerical evaluation of the scratch test on boride layers was performed by the finite element method. Maximum principal stresses were related to the failure mechanisms observed by the experimental scratch test. Shear stresses at the interfaces of the FeB/Fe2B/substrate system were also evaluated. Finally, the results obtained provide essential information about the effect of the layer thickness, the residual stresses, and the resilience modulus on the cohesive/adhesive strength in FeB/Fe2B systems.

  16. Designing the marketing-sales interface in B2B firms

    NARCIS (Netherlands)

    Biemans, W.G.; Makovec Brencic, M.

    2007-01-01

    Purpose - This paper explores the marketing-sales interface in Dutch and Slovenian B2B firms. Design/methodology/approach - The study included 11 Dutch firms and ten Slovenian firms, with both samples as closely matched as possible. The firms were all manufacturers of physical products that operate

  17. 76 FR 3451 - Wage Methodology for the Temporary Non-agricultural Employment H-2B Program

    Science.gov (United States)

    2011-01-19

    ... unemployment rates among specific groups of vulnerable low-wage workers: Youth, Hispanics, and African..., unemployment-related issues, the incorporation or continuation of special procedures in the H-2B program... conditions below the established minimum levels, citing examples of high unemployment rates in industries in...

  18. Molecular interactions between general anesthetics and the 5HT2B receptor.

    Science.gov (United States)

    Matsunaga, Felipe; Gao, Lu; Huang, Xi-Ping; Saven, Jeffery G; Roth, Bryan L; Liu, Renyu

    2015-01-01

    Serotonin modulates many processes through a family of seven serotonin receptors. However, no studies have screened for interactions between general anesthetics currently in clinical use and serotonergic G-protein-coupled receptors (GPCRs). Given that both intravenous and inhalational anesthetics have been shown to target other classes of GPCRs, we hypothesized that general anesthetics might interact directly with some serotonin receptors and thus modify their function. Radioligand binding assays were performed to screen serotonin receptors for interactions with propofol and isoflurane as well as for affinity determinations. Docking calculations using the crystal structure of 5-HT2B were performed to computationally confirm the binding assay results and locate anesthetic binding sites. The 5-HT2B class of receptors interacted significantly with both propofol and isoflurane in the primary screen. The affinities for isoflurane and propofol were determined to be 7.78 and .95 μM, respectively, which were at or below the clinical concentrations for both anesthetics. The estimated free energy derived from docking calculations for propofol (-6.70 kcal/mol) and isoflurane (-5.10 kcal/mol) correlated with affinities from the binding assay. The anesthetics were predicted to dock at a pharmacologically relevant binding site of 5HT2B. The molecular interactions between propofol and isoflurane with the 5-HT2B class of receptors were discovered and characterized. This finding implicates the serotonergic GPCRs as potential anesthetic targets.

  19. A process-stakeholder analysis of B2B industry standardisation

    NARCIS (Netherlands)

    Rodon, J.; Ramis-Pujol, J.; Christiaanse, E.

    2007-01-01

    Purpose - Interoperability standards are a crucial aspect in the development of B2B e-business. The aim of this paper is to understand how standardisation evolves by analysing the interplay between activities and stakeholders within the process. Unlike most of the IS research that focuses on the

  20. Satisfaction with virtual communities in B2B financial services: social dynamics, content and technology

    NARCIS (Netherlands)

    Chompis, E.; Bons, R.W.H.; van den Hooff, B.J.; Feldberg, J.F.M.; Horn, H.

    2014-01-01

    This study explores satisfaction with Virtual Communities in a Financial Services setting. Based on Expectancy Value Theory and the concept of Experiential Value we hypothesize that three sources of value drive user satisfaction in a B2B-VC: social ties, content and technology. We propose a

  1. CDKN2B gene rs1063192 polymorphism decreases the risk of glaucoma.

    Science.gov (United States)

    Hu, Zhenxian; He, Chenliang

    2017-03-28

    The aim of this meta-analysis was to evaluate the association between cyclin-dependent kinase Inhibitor-2B (CDKN2B) gene rs1063192 polymorphism and glaucoma risk. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 14 case-control studies involving 11,316 cases and 24,055 controls were included. Meta-analysis showed that CDKN2B gene rs1063192 polymorphism was associated with a decreased risk of glaucoma. Stratification analysis of ethnicity indicated that rs1063192 polymorphism decreased the risk of glaucoma among Caucasians and Asians. Stratification analysis by type of glaucoma revealed that rs1063192 polymorphism conferred a protective factor of primary open-angle glaucoma (POAG) and non-POAG. Stratification by source of controls uncovered an association between rs1063192 polymorphism and glaucoma in groups of population-based controls. In conclusion, this meta-analysis indicates that CDKN2B gene rs1063192 polymorphism is significantly associated with a decreased risk of glaucoma.

  2. Bedrock geology of DFDP-2B, central Alpine Fault, New Zealand

    NARCIS (Netherlands)

    Toy, Virginia Gail; Sutherland, Rupert; Townend, John; Allen, Michael John; Becroft, Leeza; Boles, Austin; Boulton, Carolyn; Carpenter, Brett M.; Cooper, Alan; Cox, Simon C.; Daube, Christopher; Faulkner, Daniel R.; Halfpenny, Angela; Kato, Naoki; Keys, Stephen; Kirilova, Martina; Kometani, Yusuke; Little, Timothy; Mariani, Elisabetta; Melosh, Benjamin; Menzies, Catriona D.; Morales, Luiz; Morgan, Chance; Mori, Hiroshi; Niemeijer, André|info:eu-repo/dai/nl/370832132; Norris, Richard; Prior, David J.; Sauer, Katrina; Schleicher, Anja M.; Shigematsu, Norio; Teagle, Damon A H; Tobin, Harold; Valdez, Robert; Williams, Jack; Yeo, Samantha; Baratin, Laura May; Barth, Nicolas; Benson, Adrian; Boese, Carolin; Célérier, Bernard; Chamberlain, Calum J.; Conze, Ronald; Coussens, Jamie; Craw, Lisa; Doan, Mai Linh; Eccles, Jennifer; Grieve, Jason; Grochowski, Julia; Gulley, Anton; Howarth, Jamie; Jacobs, Katrina; Janku-Capova, Lucie; Jeppson, Tamara; Langridge, Robert; Mallyon, Deirdre; Marx, Ray; Massiot, Cécile; Mathewson, Loren; Moore, Josephine; Nishikawa, Osamu; Pooley, Brent; Pyne, Alex; Savage, Martha K.; Schmitt, Doug; Taylor-Offord, Sam; Upton, Phaedra; Weaver, Konrad C.; Wiersberg, Thomas; Zimmer, Martin

    2017-01-01

    During the second phase of the Alpine Fault, Deep Fault Drilling Project (DFDP) in the Whataroa River, South Westland, New Zealand, bedrock was encountered in the DFDP-2B borehole from 238.5–893.2 m Measured Depth (MD). Continuous sampling and meso- to microscale characterisation of whole rock

  3. Using the Internet for B2B Activities: A Review and Future Directions for Research.

    Science.gov (United States)

    Gattiker, Urs E.; Perlusz, Stefano; Bohmann, Kristoffer

    2000-01-01

    Illustrates some of the challenges that electronic commerce practitioners and researchers face, focusing on business to business (B2B) transactions. Highlights include a conceptual framework of Web user behavior; purchasing context; socio-demographic characteristics; cultural factors; economic factors; attitudes toward information technology;…

  4. Managing Innovation Through Social Media in B2B SME-Context

    DEFF Research Database (Denmark)

    Lutz, Salla; Madsen, Svend Ole; Brink, Tove

    2015-01-01

    innovation. However, social media application is hindered due to lack of specific local knowledge, lack of knowledge on social media technicalities and bewilderedness on leadership approaches within the social media application. A contribution is hereby made to the B2B SME field, to the academic...

  5. Do self-service technologies affect interfirm relationships? A B2B perspective

    Directory of Open Access Journals (Sweden)

    Raechel Johns

    2014-11-01

    Full Text Available While considerable literature examines business-to business (B2B relationships, the impact of technology on these relationships has lacked attention. IT has impacted the way businesses operate in a B2B context as well as influencing services by altering the way services are delivered. To understand the way in which Internet technology has impacted these B2B services, it is essential to examine its impact not only on business processes but on business relationships too. One technology, enabled by modern Internet technologies, which is changing the nature of business relationships is the increased use of self-service technologies (SSTs or technology-enabled services, however, there is a shortage of research in the area in a B2B context. The discussion in this paper provides an overview of the impact of IT on business relationships, using Relationship Marketing theory to provide a theoretical framework. A qualitative study in the Australian banking industry provides findings relating to the theory. The findings of this study provide evidence that while traditional Relationship Marketing theory is still applicable for some business customers, new theory is required for business customers who do not seek relationships. With both practical and theoretical implications, the research detailed in this paper makes a useful contribution to the literature and indicates the necessity for further research to be developed which explores business customers who prefer to remain transaction-oriented, rather than develop interpersonal relationships.

  6. Combustion of Na2B4O7 + Mg + C to synthesis B4C powders

    International Nuclear Information System (INIS)

    Jiang Guojian; Xu Jiayue; Zhuang Hanrui; Li Wenlan

    2009-01-01

    Boron carbide powder was fabricated by combustion synthesis (CS) method directly from mixed powders of borax (Na 2 B 4 O 7 ), magnesium (Mg) and carbon. The adiabatic temperature of the combustion reaction of Na 2 B 4 O 7 + 6 Mg + C was calculated. The control of the reactions was achieved by selecting reactant composition, relative density of powder compact and gas pressure in CS reactor. The effects of these different influential factors on the composition and morphologies of combustion products were investigated. The results show that, it is advantageous for more Mg/Na 2 B 4 O 7 than stoichiometric ratio in Na 2 B 4 O 7 + Mg + C system and high atmosphere pressure in the CS reactor to increase the conversion degree of reactants to end product. The final product with the minimal impurities' content could be fabricated at appropriate relative density of powder compact. At last, boron carbide without impurities could be obtained after the acid enrichment and distilled water washing.

  7. Molecular dynamic simulation of complex NS2B-NS3 DENV2 ...

    African Journals Online (AJOL)

    Nissia

    2013-07-10

    Jul 10, 2013 ... Molecular dynamic simulation of complex NS2B-NS3. DENV2 protease with potential ... results provide conformational changes of enzyme-inhibitor complex that is shown by root-mean- square deviation (RMSD) values. ..... utilized MMFF94x and NVT (N=constant number,. V=volume, and T=temperature) ...

  8. Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids.

    Science.gov (United States)

    Zhao, Xianliang; Wu, Changwen; Peng, Xuanxian; Li, Hui

    2014-09-05

    Interferon (IFN) family is a large group of cytokines involved in innate immune response against various microorganisms. However, whether IFN functions in antimicrobial property by metabolic pathways is largely unknown. In the present study, GC-MS-based metabolome is investigated in humoral fluid of zebrafish (Danio rerio) which are exposed to three doses of IFN-α2b, designed as IFN-L, IFN-M, and IFN-H. Out of 67 compounds identified, 19, 28, and 29 differential abundances of metabolites are identified in the three groups compared with control, respectively. A total of 41 differential metabolites constructed IFN-dependent metabolome, in which 13 overlap among the three doses of IFN-α2b groups. These overlapped metabolites show that decreased alanine asparate and glutamate metabolic pathway, arginine and proline metabolic pathway, and increased purine metabolism form a characteristic feature in response to IFN-α2b. Further dose-related metabolites indicate that biosynthesis of unsaturated fatty acids is enriched only in IFN-M and IFN-H, which is related to high protection against bacterial infection. Exogenous fatty acids, especially unsaturated linoleic acid, may elevate the survival ability of zebrafish infected with extracellular pathogenic V. alginolyticus and intracellular pathogenic Edwardsiella tarda. These results disclose an unknown mechanism by which IFN-α2b protects host from microbial infections. Our findings highlight the ways to understand action of IFN in content of metabolic regulation.

  9. Development of radiotracers for imaging NR2B subtype NMDA receptors with positron emission tomography

    International Nuclear Information System (INIS)

    Labas, R.

    2007-01-01

    The aim of this thesis was to develop new radioactive tracers for imaging NR2B subtype NMDA receptors with positron emission tomography. Several compounds including 4-(4-fluoro-benzyl)piperidine and presenting interesting in vivo biological properties were the object of a labelling with a positrons emitter atom ( 11 C or 18 F)

  10. Improved serodiagnosis of cystic echinococcosis using the new recombinant 2B2t antigen.

    Directory of Open Access Journals (Sweden)

    Ana Hernández-González

    Full Text Available A standardized test for the serodiagnosis of human cystic echinococcosis (CE is still needed, because of the low specificity and sensitivity of the currently available commercial tools and the lack of proper evaluation of the existing recombinant antigens. In a previous work, we defined the new ELISA-B2t diagnostic tool for the detection of specific IgGs in CE patients, which showed high sensitivity and specificity, and was useful in monitoring the clinical evolution of surgically treated CE patients. Nevertheless, this recombinant antigen gave rise to false-negative results in a percentage of CE patients. Therefore, in an attempt to improve its sensitivity, we constructed B2t-derived recombinant antigens with two, four and eight tandem repeat of B2t units, and tested them by ELISA on serum samples of CE patients and patients with related parasites. The best diagnostic values were obtained with the two tandem repeat 2B2t antigen. The influence of several clinical variables on the performance of the tests was also evaluated. Finally, the diagnostic performance of the 2B2t-ELISA was compared with that of an indirect haemagglutination commercial test. The 2B2t recombinant antigen performed better than the HF and B2t antigens, and the IHA commercial kit. Therefore, this new 2B2t-ELISA is a promising candidate test for the serodiagnosis of CE in clinical settings.

  11. Evaluation of the 2b-RAD method for genomic selection in scallop breeding.

    Science.gov (United States)

    Dou, Jinzhuang; Li, Xue; Fu, Qiang; Jiao, Wenqian; Li, Yangping; Li, Tianqi; Wang, Yangfan; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2016-01-12

    The recently developed 2b-restriction site-associated DNA (2b-RAD) sequencing method provides a cost-effective and flexible genotyping platform for aquaculture species lacking sufficient genomic resources. Here, we evaluated the performance of this method in the genomic selection (GS) of Yesso scallop (Patinopecten yessoensis) through simulation and real data analyses using six statistical models. Our simulation analysis revealed that the prediction accuracies obtained using the 2b-RAD markers were slightly lower than those obtained using all polymorphic loci in the genome. Furthermore, a small subset of markers obtained from a reduced tag representation (RTR) library presented comparable performance to that obtained using all markers, making RTR be an attractive approach for GS purpose. Six GS models exhibited variable performance in prediction accuracy depending on the scenarios (e.g., heritability, sample size, population structure), but Bayes-alphabet and BLUP-based models generally outperformed other models. Finally, we performed the evaluation using an empirical dataset composed of 349 Yesso scallops that were derived from five families. The prediction accuracy for this empirical dataset could reach 0.4 based on optimal GS models. In summary, the genotyping flexibility and cost-effectiveness make 2b-RAD be an ideal genotyping platform for genomic selection in aquaculture breeding programs.

  12. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  13. A Cross-Industry Review of B2B Critical Success Factors.

    Science.gov (United States)

    Eid, Riyad; Trueman, Myfanwy; Ahmed, Abdel Moneim

    2002-01-01

    Presents a comprehensive review of B2B (business-to- business) international Internet marketing and identifies 21 critical success factors in five categories: marketing strategy, including management support, strategic goals, and collaboration; Web site factors, including Web site design; global factors, including multilanguage sites and cultural…

  14. Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Alazhary, Nevin M; Shafik, Roxan E; Shafik, Hanan E; Kamel, Mahmoud M

    2015-01-01

    The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression- free survival (PFS) (p-value=0.245). Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

  15. Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication

    International Nuclear Information System (INIS)

    Gabet, Anne-Sophie; Moules, Vincent; Sibon, David; Nass, Catharie C.; Mortreux, Franck; Mauclere, Philippe; Gessain, Antoine; Murphy, Edward L.; Wattel, Eric

    2006-01-01

    As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population

  16. On the critical success factors for B2B e-marketplace

    Directory of Open Access Journals (Sweden)

    Sareh Ahmad Khan Beige

    2015-01-01

    Full Text Available Advancement of network technology, quick growth of Internet and Internet based solutions lead many firms to apply online processes as well as electronic businesses. Internet based B2B E-C requires applying Internet and affiliated technologies for exchanging products, services and information. Implementation of business to business (B2B requires long-term commitment of organizations. Carrying out research in this field is regarded as very important issue for recognizing effective factors on successful implementation and execution of B2B and determining current status of organization. This research deals with studying effective critical factors on successful implementation and execution of B2B. Factors are recognized through studying literature review and IT experts. Then, through case study (studying a vehicle manufacturing firm and by using analytical network process (ANP, the importance of factor and their rank are determined. The factors that are regarded at this research are including: culture, commitment and support of senior management, government support, purposes, organizational strategies, trust, partial advantage and technical infrastructure. Results of research show that support and commitment of senior management are the highest priority factors.

  17. KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions

    Directory of Open Access Journals (Sweden)

    Cemil Kerimoglu

    2017-07-01

    Full Text Available Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment. Our findings point to the distinct functions of even closely related histone-modifying enzymes and provide essential insight for the development of more efficient and specific epigenetic therapies against brain diseases.

  18. Magnetism and superconductivity in ErNi 2 B 2 C

    Indian Academy of Sciences (India)

    We have performed a series of neutron diffraction experiments from the magnetic order and the vortex lattice in single crystal ErNi2B2C. The incommensurate magnetic structure develops additional even harmonics below the `ferromagnetic' ordering temperature, F of 2.3 K. This feature and the existence of rods of diffuse ...

  19. Mission and Sustainability of Informatics for Integrating Biology and the Bedside (i2b2).

    Science.gov (United States)

    Murphy, Shawn; Wilcox, Adam

    2014-01-01

    A visible example of a successfully disseminated research project in the healthcare space is Informatics for Integrating Biology and the Bedside, or i2b2. The project serves to provide the software that can allow a researcher to do direct, self-serve queries against the electronic healthcare data form a hospital. The goals of these queries are to find cohorts of patients that fit specific profiles, while providing for patient privacy and discretion. Sustaining this resource and keeping its direction has always been a challenge, but ever more so as the ten year National Centers for Biomedical Computing (NCBCs) sunset their funding. Building on the i2b2 structures has helped the dissemination plans for grants leveraging it because it is a disseminated national resource. While this has not directly increased the support of i2b2 internally, it has increased the ability of institutions to leverage the resource and generally leads to increased institutional support. The successful development, use, and dissemination i2b2 has been significant in clinical research and informatics. Its evolution has been from a local research data infrastructure to one disseminated more broadly than any other product of the National Centers for Biomedical Computing, and an infrastructure spawning larger investments than were originally used to create it. Throughout this, there were two main lessons about the benefits of dissemination: that people have great creativity in utilizing a resource in different ways and that broader system use can make the system more robust. One option for long-term sustainability of the central authority would be to translate the function to an industry partner. Another option currently being pursued is to create a foundation that would be a central authority for the project. Over the past 10 years, i2b2 has risen to be an important staple in the toolkit of health care researchers. There are now over 110 hospitals that use i2b2 for research. This open

  20. Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

    Energy Technology Data Exchange (ETDEWEB)

    Peters, L.M.; Demmel, S. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Pusch, G.; Buters, J.T.M. [ZAUM — Center of Allergy and Environment, Helmholtz Zentrum München/Technische Universität München, Biedersteiner Str. 29, 80802 München (Germany); Thormann, W. [Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Murtenstrasse 35, 3010 Bern (Switzerland); Zielinski, J. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Leeb, T. [Institute of Genetics, Vetsuisse Faculty, University Bern, Bremgartenstr. 109, 3012 Bern (Switzerland); Mevissen, M. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Schmitz, A., E-mail: andrea.schmitz@vetsuisse.unibe.ch [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland)

    2013-01-01

    Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V{sub max} for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and K{sub m} was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC{sub 50} of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP

  1. M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

    Science.gov (United States)

    Tsuchimoto, Yusuke; Asai, Akira; Tsuda, Yasuhiro; Ito, Ichiaki; Nishiguchi, Tomoki; Garcia, Melanie C; Suzuki, Sumihiro; Kobayashi, Makiko; Higuchi, Kazuhide; Suzuki, Fujio

    2015-12-01

    Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγ(null) mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12(+)IL-10(-)CD163(-)CD14(+) cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1(+)CD163(+)CD14(+) cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12(-)IL-10(-)CCL1(-)CD163(-)CD14(+) cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes. Copyright © 2015 by The American Association of Immunologists, Inc.

  2. Atmospheric circulation of eccentric hot Jupiter HAT-P-2B

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Nikole K. [Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Showman, Adam P. [Department of Planetary Sciences and Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Marley, Mark S., E-mail: nklewis@mit.edu [NASA Ames Research Center 245-3, Moffett Field, CA 94035 (United States)

    2014-11-10

    The hot Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full orbit phase curves at 3.6, 4.5 and 8.0 μm, which is likely due to a chemical process not captured by our current atmospheric models for HAT-P-2b. Further modeling and observational efforts focused on understanding the chemistry of HAT-P-2b's atmosphere are needed and could provide key insights into the interplay between radiative, dynamical, and chemical processes in a wide range of exoplanet atmospheres.

  3. Uso de una conantokina y anticuerpos policlonales para identificar la subunidad NR2B del receptor

    Directory of Open Access Journals (Sweden)

    Leonardo Lareo,†

    2010-12-01

    Full Text Available Objetivo. Proponer una metodología de identificación de la subunidad NR2B, mediante el uso de conantokina G, así como una adecuada extracción de la subunidad NR2B. Materiales y métodos. Se ensayaron dos metodologías para la extracción de la subunidad NR2B de cerebro de rata adulta, la primera buscó la extracción de la subunidad a partir de la membrana mediante la utilización del detergente deoxicolato de sodio y la segunda, garantizó primero la solubilización y eliminación de proteínas citoplasmáticas para luego realizar la extracción de la subunidad mediante el uso del mismo detergente, a partir del pellet generado en la centrifugación del extracto obtenido. Adicionalmente se biotiniló la conantokina G para evaluar su eficiencia en la identificación de la subunidad y comparar los resultados con los obtenidos por metodologías tradicionales como DOT-BLOT, WESTERN-BLOT, ELISA e Inmunohistoquímica. Resultados. La segunda metodología mostró mayor extracción de NR2B por lo que se seleccionó para la realización de los extractos posteriores. Los ensayos de identificación con la conantokina biotinilada evidenciaron interferencia en el reconocimiento, haciéndose necesaria la identificación de la presencia de la subunidad NR2B mediante el uso de anticuerpos policlonales en los ensayos mencionados. Conclusiones. Se propone que hay un impedimento de tipo estérico en el marcaje de la conantokina con la biotina lo que no favorece la interacción de este péptido con la subunidad.

  4. Kidney function and 24-hour proteinuria in patients with Fabry disease during 36 months of agalsidase alfa enzyme replacement therapy: a Brazilian experience.

    Science.gov (United States)

    Thofehrn, Scheila; Netto, Cristina; Cecchin, Cláudia; Burin, Maira; Matte, Ursula; Brustolin, Sílvia; Nunes, Ane Cláudia Fernandes; Coelho, Janice; Tsao, Marylin; Jardim, Laura; Giugliani, Roberto; Barros, Elvino José Guardão

    2009-01-01

    Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/ 1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >or= 90 mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73 m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73 m(2), and stage V as < 15 mL/min/1.73 m(2). Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions

  5. Using Product Variables of Business- to-Business (B2B) Media to Assess the Impacts of Social Media

    OpenAIRE

    Zhang, Dan

    2016-01-01

    An original approach uses the three variables of timeliness, confidentiality, and utility of business-to-business (B2B) media products to study the impacts of social media. Interviews with B2B media practitioners in the UK reveal that social media have partially and weakly influenced the timeliness and confidentiality variables but have no effect on the basic utility of B2B media. Social media formats are therefore not so much in competition with B2B media, more a useful tool. B2B media pract...

  6. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa.

    Science.gov (United States)

    Olivennes, F; Trew, G; Borini, A; Broekmans, F; Arriagada, P; Warne, D W; Howles, C M

    2015-03-01

    In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited (23 centres: nine European countries and Chile); 200 women were randomized (CONSORT [n = 96]; standard dosing [n = 104]). Significantly lower mean daily (121.5 versus 167.4 IU; P CONSORT group. Clinical pregnancy rates were CONSORT (36.0%) and standard dosing (35.5%); estimated difference (confidence interval 0.6%; -13.5 to 14.6). Ovarian hyperstimulation syndrome occurred in 6.3% and 12.5% of patients in the CONSORT and standard-dosing groups, respectively. The primary efficacy analysis found a significantly lower mean [SD] number of oocytes retrieved in the CONSORT (10.0 [5.6]; P = 0.037) versus standard-dosing group (11.8 [5.3]). Although the CONSORT calculator was statistically inferior to standard dosing in the number of oocytes retrieved, clinical pregnancy rates (fresh embryo transfers) were similar in both groups, and incidence of ovarian hyperstimulation syndrome was lower in the CONSORT group. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Study of forward elastic $pp$ scattering at $\\sqrt{s}=8\\text{ TeV}$ with the ALFA detector

    CERN Document Server

    Stark, Simon Holm; Hansen, Jørgen Beck

    The elastic $pp$ scattering data analyzed in this thesis was taken at the LHC with the ALFA detector at $\\sqrt{s}=8\\text{ TeV}$ with a $\\beta^*=1\\text{ km}$ collision optics which gave access to the Coulomb-Nuclear-Interference region. An improved procedure was used to fit the observed number of elastic events as a function of the four-momentum transfer with a simulation based on theoretical expectations including experimental effects. The data can not exclude any of the investigated parametrizations for the modulus of the nuclear amplitude. The fit results for the total $pp$ cross section, $\\sigma_\\text{tot}$, and the ratio of the real to imaginary forward elastic scattering amplitude, $\\rho$, are: \\begin{align*} \\sigma_\\text{tot} &= 99.1\\pm 0.3 \\text{ (stat.)}\\pm1.6\\text{ (syst.)} \\text{ mb}\\;,\\\\ \\rho &= 0.166\\pm0.017\\text{ (stat.)}\\pm0.019\\text{ (syst.)}\\;, \\end{align*} which are in agreement with previous measurements. As part of the analysis, the detector distance to the beam was determined with ...

  8. Um imunoensaio rápido para a detecção de alfa-trembolona em urina bovina

    Directory of Open Access Journals (Sweden)

    Keila Maria Roncato Duarte

    2006-12-01

    Full Text Available O Brasil está entre os países que mantêm o uso de anabolizantes proibido, o que gera dificuldades muito grandes no monitoramento destas substâncias, uma vez que possui o maior rebanho bovino. Contudo, diversas substâncias são largamente utilizadas, entre as quais o acetato de trembolona. Com o consentimento do Ministério da Agricultura, Pecuária e Abastecimento, foram produzidos anticorpos policlonais para um teste baseado em ELISA ("enzyme linked immunosorbent assay" capazes de detectar acetato de trembolona na urina de bovinos tratados com trembolona. O teste apresentou baixo custo e de fácil execução para a detecção de alfa-trembolone, o principal metabólito na absorção do acetato de trembolona, liberado na urina dos animais. Os resultados foram similares aos obtidos com o "kit" comercial usado pelo Ministério da Agricultura, Pecuária e Abastecimento do Brasil.

  9. Proton-Proton Central Exclusive Pion Production at $\\sqrt{13}$ TeV with the ALFA and ATLAS Detector

    CERN Document Server

    Bols, Emil Sorensen

    The cross section for proton-proton central exclusive dipion production, $pp\\rightarrow p + \\pi^+ \\pi^- + p$, has been measured at the center of mass energy $\\sqrt{s}=13\\mathrm{TeV}$, where double Pomeron exchange is expected to dominate. The LHC was used to create the central diffractive events, and all the final state particles were measured using the ATLAS and ALFA detector. After correcting for detector inefficiencies and proton acceptance using the Donnachie-Landshoff model with $\\alpha'=0.126\\mathrm{GeV}^{-2}$ and $\\epsilon=0.085$, the cross section was found to be: \\begin{equation} \\sigma_{pp\\rightarrow p+\\pi^+\\pi^-+p}=18.754\\pm0.048(\\mathrm{stat}.)\\pm0.770(\\mathrm{syst}.)\\mu\\mathrm{b} , \\quad |\\eta_{\\pi}| 100\\mathrm{MeV} \\end{equation} The invariant mass spectrum of the pions has been analyzed in order to extract the widths and masses of the $f_0(500)$, $f_0(980)$, $f_2(1275)$ and $f_0(1500)$ mesons. A correlation between the two outgoing protons has been observed, which is not in agreement with Pom...

  10. Comparing effects of Beractant and Poractant alfa in decreasing mortality rate due to respiratory distress syndrome in premature infants

    Directory of Open Access Journals (Sweden)

    Saeidi R

    2011-02-01

    Full Text Available "nBackground: Exogenous natural and synthetic surfactants is a rescue treatment for respiratory distress syndrome (RDS. The goals of the study were to compare the clinical response and side-effects of two frequently used surfactants, poractant alfa (Curosurf and beractant (Survanta, for the treatment of respiratory distress syndrome in preterm infants."n "nMethods: This clinical trial study was performed during a two-year period in the Neonatal Intensive Care Unit of Ghaem Hospital in Mashhad, Iran. Sample size calculated by a 95% confidence and power of 80, included 104 premature neonates, 74 in survanta and 30 in curosurf groups. The level of statistical significance was considered to be < 0.05."n "nResults: There were no statistically significant differences between the infants treated by survanta or cursurf groups regarding their mean gestational age (30.58 Vs. 29.00 weeks and birth weight (1388 Vs. 1330 g, (p=0.3 There were also no significant differences between the two groups regarding incidences of broncho- pulmonary dysplasia (BPD (40.5% Vs. 40%, intraventricular hemorrhage (IVH grades III/IV (13.5% Vs. 13.3%, pneumothorax (both 20%, patent ductus arteriosus (PDA (28/3% Vs. 20% or death (28% Vs. 26.6% on the 28th day postpartum."n "nConclusion: This study showed that survanta and curosurf had similar therapeutic effects in the treatment of neonatal respiratory distress syndrome.

  11. Study of forward elastic pp scattering at √ s = 8 TeV with the ALFA detector

    DEFF Research Database (Denmark)

    Stark, Simon Holm

    The elastic proton-proton scattering data analyzed in this thesis was taken at the LHC with the ALFA detector at sqrt(s) = 8 TeV with a beta* collision optics which gave access to the Coulomb-Nuclear-Interference region. An improved procedure was used to fit the observed number of elastic events......_tot, and the ratio of the real to imaginary forward elastic scattering amplitude, rho, are: sigma_tot = 99.1 +/- 0.3 (stat.) +/- 1.6 (syst.) mb rho = 0.166 +/- 0.017 (stat.) +/- 0.019 (syst.) which are in agreement with previous measurements. As part of the analysis, the detector distance to the beam was determined...... with an improved method. A new background estimation procedure was developed and also implemented in the determination of the elastic track reconstruction efficiency. The experience gained in this thesis was used to optimize the experimental settings for a new data taking at sqrt(s) = 13 TeV with beta* = 2.5 km...

  12. Impaired Ventilatory and Thermoregulatory Responses to Hypoxic Stress in Newborn Phox2b Heterozygous Knock-Out Mice

    Science.gov (United States)

    Ramanantsoa, Nelina; Matrot, Boris; Vardon, Guy; Lajard, Anne-Marie; Voituron, Nicolas; Dauger, Stéphane; Denjean, André; Hilaire, Gérard; Gallego, Jorge

    2011-01-01

    The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/− pups and their wild-type littermates (Phox2b+/+) to hypoxia (10% O2) or hypercapnia (8% CO2) under thermoneutral (33°C) or cold (26°C) conditions. We found that Phox2b+/− pups showed less normoxic ventilation (VE) in the cold than Phox2b+/+ pups. Phox2b+/− pups also showed lower oxygen consumption (VO2) in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/− pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in Phox2b+/− pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments. PMID:21977017

  13. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

  14. Reaction and reorientation of electronically excited H[sub 2](B)

    Energy Technology Data Exchange (ETDEWEB)

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H[sub 2], HD, and D[sub 2] B [sup 1][Sigma][sub u][sup +] by [sup 4]He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H[sub 2], HD and D[sub 2] (B [sup 1][Sigma][sub u][sup +]. v[prime]=0, J[prime]=1, M[sub J]=0) in collisions with He, Ne, Ar and H[sub 2](X [sup 1][Sigma][sub g][sup +]) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250[plus minus]40 cm[sup [minus]1], and the difference in the H-H stretching frequencies between H[sub 2](B) and the H[sub 2]-He complex at the barrier to reaction is 140[plus minus]80 cm[sup [minus]1]. The effective cross sections for angular momentum reorientation in collisions of H[sub 2], HD, D[sub 2] with He and Ne were found to be about 30 [Angstrom][sup 2] and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D[sub 2] in collisions with Ar were 10.6[plus minus]2.0 and 13.9[plus minus]3.0 [Angstrom][sup 2], respectively. Reorientation of D[sub 2](B) in collisions with room temperature H[sub 2](X) occurs with a 7.6[plus minus]3.4 [Angstrom][sup 2] cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H[sub 2](B) and D[sub 2](B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  15. Photoelectron Spectroscopy Study of [Ta2B6]-: a Hexagonal Bipyramdial Cluster

    Science.gov (United States)

    Jian, Tian; Li, Weili; Romanescu, Constantin; Wang, Lai-Sheng

    2014-06-01

    It has been a long-sought goal in cluster science to discover stable atomic clusters as building blocks for cluster-assembled nanomaterials, as exemplified by the fullerenes and their subsequent bulk syntheses.[1,2] Clusters have also been considered as models to understand bulk properties, providing a bridge between molecular and solid-state chemistry.[3] Herein we report a joint photoelectron spectroscopy and theoretical study on the [Ta2B6]- and [Ta2B6] clusters.[4] The photoelectron spectrum of [Ta2B6]- displays a simple spectral pattern and a large HOMO-LUMO gap, suggesting its high symmetry. Theoretical calculations show that both the neutral and anion are D6h pyramidal. The chemical bonding analyses for [Ta2B6] revealed the nature of the B6 and Ta interactions and uncovered strong covalent bonding between B6 and Ta. The D6h-[TaB6Ta] gaseous cluster is reminiscent of the structural pattern in the ReB6X6Re core in the [(Cp*Re)2B6H4Cl2] and the TiB6Ti motif in the newly synthesized Ti7Rh4Ir2B8 solid-state compound.[5,6] The current work provides an intrinsic link between a gaseous cluster and motifs for solid materials. Continued investigations of the transition-metal boron clusters may lead to the discovery of new structural motifs involving pure boron clusters for the design of novel boride materials. Reference [1] H.W. Kroto, J. R. Heath, S. C. OBrien, R. F. Curl, R. E. Smalley, Nature 1985, 318, 162 - 163. [2] W. Krtschmer, L. D. Lamb, K. Fostiropoulos, D. R. Huffman, Nature 1990, 347, 354 - 358. [3] T. P. Fehlner, J.-F. Halet, J.-Y. Saillard, Molecular Clusters: A Bridge to Solid-State Chemitry, Cambridge University Press, UK, 2007. [4] W. L. Li, L. Xie, T. Jian, C. Romanescu, X. Huang, L.-S. Wang, Angew. Chem. Int. Ed. 2014, 126, 1312 - 1316. [5] B. Le Guennic, H. Jiao, S. Kahlal, J.-Y. Saillard, J.-F. Halet, S. Ghosh, M. Shang, A. M. Beatty, A. L. Rheingold, T. P. Fehlner, J. Am. Chem. Soc. 2004, 126, 3203 - 3217. [6] B. P. T. Fokwa, M. Hermus, Angew

  16. MAT2B promotes adipogenesis by modulating SAMe levels and activating AKT/ERK pathway during porcine intramuscular preadipocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Cunzhen; Chen, Xiaochang; Wu, Wenjing; Wang, Wusu; Pang, Weijun; Yang, Gongshe, E-mail: gsyang999@hotmail.com

    2016-05-15

    Intramuscular fat (IMF) has been demonstrated as one of the crucial factors of livestock meat quality. The MAT2B protein with MAT2α catalyzes the formation of methyl donor S- adenosylmethionine (SAMe) to mediate cell metabolism including proliferation and apoptosis. However, the regulatory effect of MAT2B on IMF deposition is still unclear. In this study, the effect of MAT2B on adipogenesis and its potential mechanism during porcine intramuscular preadipocyte differentiation was studied. The results showed that overexpression of MAT2B promoted adipogenesis and significantly up-regulated the mRNA and protein levels of adipogenic marker genes including FASN, PPARγ and aP2, consistently, knockdown of MAT2B inhibited lipid accumulation and down-regulated the mRNA and protein levels of the above genes. Furthermore, flow cytometry and EdU-labeling assay indicated that MAT2B regulate adipogenesis was partly due to influence intracellular SAMe levels and further affect cell clonal expansion. Also, increased expression of MAT2B activated the phosphorylations of AKT and ERK1/2, whereas knockdown of MAT2B blocked AKT signaling and repressed the phosphorylation of ERK1/2. Moreover, the inhibitory effect of LY294002 (a specific PI3K inhibitor) on the activities of AKT and ERK1/2 was partially recovered by overexpression of MAT2B in porcine intramuscular adipocytes. Finally, Co-IP experiments showed that MAT2B can directly interact with AKT. Taken together, our findings suggested that MAT2B acted as a positive regulator through modifying SAMe levels as well as activating AKT/ERK signaling pathway to promote porcine intramuscular adipocyte differentiation. - Highlights: • MAT2B up-regulates the expression of adipogenic marker genes and promotes porcine intramuscular preadipocyte differentiation. • MAT2B influences intracellular SAMe levels and further affects cell clonal expansion. • MAT2B interacts with AKT and activates AKT/ERK signaling pathway.

  17. The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells

    DEFF Research Database (Denmark)

    Karpiuk, Oleksandra; Najafova, Zeynab; Kramer, Frank

    2012-01-01

    Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly...... understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction...... during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation....

  18. A systematic analysis of the Braitenberg vehicle 2b for point-like stimulus sources

    International Nuclear Information System (INIS)

    Rañó, Iñaki

    2012-01-01

    Braitenberg vehicles have been used experimentally for decades in robotics with limited empirical understanding. This paper presents the first mathematical model of the vehicle 2b, displaying so-called aggression behaviour, and analyses the possible trajectories for point-like smooth stimulus sources. This sensory-motor steering control mechanism is used to implement biologically grounded target approach, target-seeking or obstacle-avoidance behaviour. However, the analysis of the resulting model reveals that complex and unexpected trajectories can result even for point-like stimuli. We also prove how the implementation of the controller and the vehicle morphology interact to affect the behaviour of the vehicle. This work provides a better understanding of Braitenberg vehicle 2b, explains experimental results and paves the way for a formally grounded application on robotics as well as for a new way of understanding target seeking in biology. (paper)

  19. The preliminary processing and analysis of LPR Channel-2B data from Chang'E-3

    Science.gov (United States)

    Zhao, Na; Zhu, PeiMin; Yang, KeSi; Yuan, YueFeng; Guo, ShiLi

    2014-12-01

    The Lunar Penetrating Radar (LPR) carried by Chang'E-3 has imaged the shallow subsurface of the landing site at the northern Mare Imbrium. The antenna B of the Channel-2 onboard the LPR (LPR Channel-2B) has collected more than 2000 traces of usable raw data. Because of the low resolution and noise of the raw data, only a few shallow geological structures are visible. To improve the resolution and the signal-to-noise ratio of the LPR data, we processed the LPR data including amplitude compensation, filtering, and deconvolution processes. The processing results reveal that the data processing in this study not only improves the signal-to-noise ratio of the LPR Channel-2B data but also makes the geological structures vivid. The processing results will lay the foundation for the subsequent geological interpretation and physical property inversion of lunar materials.

  20. Graphene nanoscrolls encapsulated TiO2 (B) nanowires for lithium storage

    Science.gov (United States)

    Li, Xinlu; Zhang, Yonglai; Li, Tongtao; Zhong, Qineng; Li, Hongyi; Huang, Jiamu

    2014-12-01

    Graphene nanoscrolls encapsulated TiO2 (B) nanowires have been fabricated through a self-scrolling and template-free process for the first time. Transmission electron microscope images reveal that graphene tightly encompassed TiO2 (B) nanowires to construct nanoscrolled architectures. Cyclic voltammetry demonstrates that pseudocapacitive behavior dominates fast lithium storage rather than diffusion-controlled insertion in the hybrids. Galvanostatic cycling tests show that the reversible specific capacity of the hybrids remains 153 mAh g-1 after 300 cycles at 10 C with capacity retention of 94%. The excellent lithium storage performance can be attributed to the unique nanoscrolled structure, which provides abundant channels for lithium ions transport, as well as accommodates volume variation during fast lithiation and delithiation.

  1. Electronic structure study of TiB2 and Ti2B

    Science.gov (United States)

    Vashistha, M.; Kabra, K.; Vyas, V.; Sharma, G.

    2015-06-01

    In this paper, the electronic properties of TiB2 and Ti2B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke's scheme are considered to treat the correlation and exchange effects respectively. TiB2 crystallizes in the hexagonal AlB2 type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti2B described in this paper is isomorphous to the body centered tetragonal (Al2Cu - type) structure with space group I4/mcm.

  2. Electronic structure study of TiB{sub 2} and Ti{sub 2}B

    Energy Technology Data Exchange (ETDEWEB)

    Vashistha, M., E-mail: vashistmanju690@gmail.com; Vyas, V. [Department of Physics, Banasthali University, Banasthali-304022 (India); Kabra, K.; Sharma, G. [Department of Pure and Appied Physics, University of Kota, Rajasthan-324010 (India)

    2015-06-24

    In this paper, the electronic properties of TiB{sub 2} and Ti{sub 2}B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke’s scheme are considered to treat the correlation and exchange effects respectively. TiB{sub 2} crystallizes in the hexagonal AlB{sub 2} type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti{sub 2}B described in this paper is isomorphous to the body centered tetragonal (Al{sub 2}Cu - type) structure with space group I4/mcm.

  3. B2B SME Management of Antecedents to the Application of Social Media

    DEFF Research Database (Denmark)

    Brink, Tove

    2017-01-01

    This paper elucidates how business-to-business (B2B) small and medium-sized enterprises (SMEs) can manage antecedents to the application of social media for potential contributions to their business. This in-depth qualitative research study was conducted at four plastic-producing SMEs from October...... 2013 to October 2014, with follow-up interviews in October 2015. The findings reveal two important antecedents to the application of social media that overcome the gap between acknowledging the usefulness of social media and its actual limited application in practical B2B contexts. First, open...... collaborative business model innovation is needed to apply social media in local business processes. Second, central and distributed leadership must be integrated to create ownership and responsibility across the SME organisation and beyond to customers and partners. These findings differ from the social media...

  4. Characteristics of the brand building on the business (B2B market

    Directory of Open Access Journals (Sweden)

    Gligorijević Mirjana

    2011-01-01

    Full Text Available This paper analyzes the characteristics of the brand building in the business (B2B market. Branding strategy at the business market is complex and difficult to implement because of the many limiting factors. Building a brand in the business market is marked by very specific characteristics of industrial products. The value of B2B brands is built through functional characteristics and performances of the product (functional values and emotional value, which together guarantee the delivery a unique experience of business customers. All marketing mix tools can be considered to be branding instruments. The purpose of this paper is to emphasize the importance of applying a branding strategy on business market.

  5. Producción de la proteína de choque térmico HSC70 Recombinante en Escherichia Coli BL21 (DE3 para generar anticuerpos policlonales

    Directory of Open Access Journals (Sweden)

    Rocio Cely Castro

    2006-07-01

    Full Text Available Antecedentes. Los organismos vivos responden al estrés aumentando la síntesis de proteínas. El estrés por choque térmico ha sido el más estudiado y las proteínas que se inducen, se han denominado genéricamente como proteínas de choque térmico. Objetivo.En este trabajo se establecieron las condiciones óptimas de producción de la proteína HSC70, expresada en E.coli BL21 (DE3 y de los anticuerpos policlonales que permitan identificarla. Material y métodos. Mediante varios ensayos se establecieron las concentraciones óptimas del agente inductor isopropil- -D-thiogalacto­piranosido (PTG, del inóculo bacteriano, de empleo de los plásmidos de expresión pET-3a y pET-28a (+; y el método más eficiente para la recuperación de las formas soluble o insoluble de la proteína y de anticuerpos policlonales que la identifiquen. Resultados. Encontramos que el inóculo de cinco colonias con IPTG (2mM en tubos con cinco mililitros de medio modificado e incubadas por 24 horas a 37°C con agitación constante (200 r.p.m y tratamiento de sonicación, produce el mejor rendimiento de HSC70. La calidad de la proteína inducida se estableció mediante "Western blotting". Conclusión. La proteína recombinante así obtenida permitió, generar anticuerpos policlonales que a su vez permiten detectar la proteína HSC70 natural en la membrana citoplasmática de diferentes células por inmunofluorescencia, en ELISA, en Western Blot y en pruebas de bloqueo de infección de rotavirus.

  6. Caracterização da imunogenicidade das proteínas recombinantes Virb9, Virb10 e fator termo instável de Elongação de Peptídeos de Anaplasma marginale em camundongos

    Directory of Open Access Journals (Sweden)

    Ana Beatriz Canevari Castelão

    2012-10-01

    Full Text Available Considerando as limitações dos atuais métodos de controle contra a anaplasmose bovina, o desenvolvimento de uma vacina efetiva se faz necessário. A partir do advento da análise genômica e proteômica, novas proteínas de membrana de Anaplasma marginale foram identificadas como possíveis candidatas a componentes de uma vacina, tais como, VirB9,VirB10 e Fator Termo Instavél de Elongação de Peptídeos (EF-Tu. Embora estas proteínas ainda não estejam bem caracterizadas na membrana de A. marginale, a produção destas na forma recombinante (rVirB 9, rVirB10 e rEF-Tutem sido realizada, mas as mesmas ainda não foram exploradas em formulações vacinais. Neste trabalho, avaliou-se ouso de rVirB9, rVirB10 e rEF-Tu emulsionadas em adjuvante Montanide em camundongos. Nas condições testadas, verificou-se a indução de forte resposta imune humoral com a produção de IgG1 e IgG2a, sendo que as proporções dos níveis de produção destas subclasses indicam predomínio de IgG1. Entretanto, esplenócitos de animais, que foram injetados com rVirB9 ou rVirB10, produziram interferon-gama acima do limite de detecção do ensaio após estimulação in vitro, sinalizando assim resposta celular específica. Assim, novas avaliações serão realizadas com a finalidade de modular o perfil de resposta imune obtido em bovinos e avaliar a proteção contra A. marginale.

  7. Digestibilidade e ganhos em peso de ovinos alimentados com diferentes fontes de volumosos e recebendo somatotropina recombinante bovina (rBST Digestibility and live weight gain of lambs fed different forages and administration of recombinant bovine somatotropin (rBST

    Directory of Open Access Journals (Sweden)

    Jane Maria Bertocco Ezequiel

    1999-01-01

    Full Text Available O objetivo deste trabalho foi avaliar os efeitos da aplicação de 20 mg de somatotropina recombinante bovina (rBST de liberação lenta, em períodos de 14 e 28 dias, sobre a ingestão de matéria seca, os coeficientes de digestibilidade de matéria seca (MS, fibra em detergente ácido (FDA, proteína bruta (PB e energia bruta (EB, o balanço de nitrogênio e o ganho de peso diário, em rações à base de silagem de milho, cana-de-açúcar ou bagaço hidrolisado e concentrado. Foi usado um total de 24 borregos mestiços, não-castrados, com média de 4 a 5 meses de idade e 22 ± 2 kg de PV. Não houve efeito da rBST na ingestão de matéria seca, nas digestibilidades de PB e FDA, no balanço de nitrogênio e no ganho de peso diário dos borregos. A digestibilidade da energia bruta foi influenciada pela aplicação de rBST, quando os diferentes volumosos ou períodos pós-aplicação hormonal foram considerados, porém, somente foi observado efeito da ação hormonal sobre a digestibilidade de MS nas dietas à base de silagem de milho.The objective of this work was to evaluate the effect of the administration of 20 mg of slow liberation bovine somatotropin (rBST on the dry matter intake and on the digestibility coefficient of dry matter (MS, acid detergent fiber, crude protein, crude energy, nitrogen balance and the daily weight gain in lambs fed diets based on corn silage, sugar cane or hydrolyzed bagasse and concentrate. Twenty-four crossbred lambs, averaging 4-5 months of age and 22 + 2 kg LW, were used. There was no effect of the rBST on the dry matter intake, the digestibilities of crude protein, acid detergent fiber, the nitrogen balance and the daily weight gain of the lambs. The gross energy digestibility was affected by the rBST administration when different forages or periods post hormonal administration were considered, however, the effect of the hormonal action was observed only on the dry matter digestibility of corn silage diets.

  8. Dinâmica folicular em cabras da raça Toggenburg em lactação tratadas ou não com somatotropina bovina recombinante Follicular dynamics of lactating Toggenburg does treated with recombinant bovine somatotropin

    Directory of Open Access Journals (Sweden)

    E.A.M. Amorim

    2007-12-01

    Full Text Available Avaliou-se o efeito da injeção de somatotropina bovina recombinante (r-bST sobre o ciclo estral de cabras. Foram utilizadas 24 fêmeas da raça Toggenburg, distribuídas em dois tratamentos: T1 (n=12, cabras tratadas com r-bST; e T2 (n=12, cabras tratadas com solução salina (controle. A partir da primeira injeção do tratamento, acompanhou-se o ciclo dos animais em estro até o estro subseqüente. O comprimento médio do ciclo estral e o período interovulatório não diferiram (P>0,05 entre os tratamentos. Foram verificados ciclos estrais de duas, três e quatro ondas de crescimento folicular. Não houve diferença (P>0,05 entre os tratamentos quanto ao número de ondas do ciclo estral. O número de folículos detectados com diâmetro >3mm nas cabras do T1 foi maior (P0,05. A r-bST não alterou a dinâmica folicular de cabras lactantes da raça Toggenburg, mas promoveu o aumento do número de folículos recrutados ³3mm durante o ciclo estral.The effect of the r-bST injection was evaluated on the goats estrous cycles. Twenty-four Toggenburg does were used in two treatments: T1 (n=12 treated with r-bST; and T2 (n=12 treated with saline solution (control. After the first r-bST injection, the estrous cycles were checked between two estrus. The estrous cycle length and interovulatory period of the goats did not differ between treatments (P>0.05. Estrous cycles with two, three and four waves of follicular growth were observed. The number of waves during the estrous cycle were not affected by the r-bST treatment (P>0.05. The number of 3mm follicles was different between T1 and T2 (P0.05 between treatments. The r-bST did not affect the ovarian response during the estrous cycle. The r-bST not affected the follicular dynamic of Toggenburg lactating does, but increased the number of emerging follicles >3mm during the estrous cycle.

  9. Immobilized Ionic Liquid-Catalyzed Synthesis of Pyrano[3,2-b]indole Derivatives

    Directory of Open Access Journals (Sweden)

    Saman Damavandi

    2012-01-01

    Full Text Available An ionic liquid-catalyzed synthesis of 2-amino-4,5-dihydro-4-arylpyrano[3,2-b]indole-3-carbonitrile derivatives through a novel three-component condensation of 3-hydroxyindole, aromatic aldehydes and malononitrile in the presence of silica supported ionic liquid of [pmim]HSO4SiO2 (silica supported 1-methyl-3-(triethoxysilylpropylimidazolium hydrogensulfate as an efficient catalyst is described.

  10. Structural Relaxation in Fe78Nb2B20 Amorphous Alloy Studied by Moessbauer Spectroscopy

    International Nuclear Information System (INIS)

    Kansy, J.; Hanc, A.; Rasek, J.; Haneczok, G.; Pajak, L.; Stoklosa, Z.; Kwapulinski, P.

    2011-01-01

    It was shown that soft magnetic properties of Fe 78 Nb 2 B 20 amorphous alloy can be significantly improved by applying 1-h annealing at temperature 623 K (permeability increases even about 8 times). The Moessbauer Spectroscopy technique indicated that the optimized microstructure (corresponding to the maximum magnetic permeability) is free of iron nanograins and should be attributed to annealing out of free volume and a reduction of internal stresses i.e. to the relaxed amorphous phase. (authors)

  11. De novo multiple endocrine neoplasia type 2B with noncardiogenic pulmonary edema as the presenting symptom.

    Science.gov (United States)

    Sato, Haruhiro; Suzuki, Yasuhiro; Fukasawa, Maki; Yasuda, Masanori; Osamura, Robert Yoshiyuki

    2006-08-01

    Multiple endocrine neoplasia (MEN) type 2B is a rare hereditary disorder characterized by medullary thyroid carcinoma, pheochromocytoma, and neuroma. Early signs of MEN 2B are usually neuroma, gastrointestinal problems, and medullary thyroid carcinoma. Noncardiogenic pulmonary edema is rare as a presenting symptom. We report a 31-year-old male who was admitted to our hospital because of noncardiogenic pulmonary edema. He was 168 cm in height, weighed 55 kg, and had an arm span of 166 cm. No marfanoid habitus was evident, but thickened lips and tongue neuroma were present. Chronic constipation had been present since childhood, and the patient had a two-year history of untreated hypertension. Noncardiogenic pulmonary edema and toxic megacolon were noted, and abdominal computed tomography revealed bilateral adrenal tumors. Ultrasonography of the thyroid showed two mass lesions. Intubation and mechanical ventilation were performed because of severe hypoxemia. Endocrinological examinations showed high levels of serum and urinary fractionated catecholamines, serum calcitonin, serum carcinoembryonic antigen, and serum intact parathyroid hormone. It was suggested that the high level of catecholamine from pheochromocytoma had caused the pulmonary edema. RET gene analysis showed a codon 918 mutation in exon 16 resulting in an ATG (methionine) to ACG (threonine) substitution, but analysis of the patient's parents showed the wild type. Therefore, the patient was diagnosed as having de novo MEN 2B. He underwent laparoscopic bilateral adrenectomy and total thyroidectomy. However, the values of serum calcitonin and CEA did not decrease to the normal ranges. Patients with early-stage MEN 2B have distinct characteristics that can aid early detection of the disease, thus possibly allowing them to be saved.

  12. Multiple endocrine neoplasia 2B: Differential increase in enteric nerve subgroups in muscle and mucosa

    Science.gov (United States)

    Hutson, John M; Farmer, Pam J; Peck, Cristal J; Chow, Chung W; Southwell, Bridget R

    2017-01-01

    Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit. Control transverse colon was from the normal margin of Hirschsprung (HSCR) colon (4-year-old) and a child with familial adenomatous polyposis (FAP, 12 year). Myenteric ganglia were increased in size to as wide as the circular muscle. There was a large increase in nerve cells and nerve fibres. ChAT-, NOS-, VIP- and SP-immunoreactive nerve fibres all increased in the myenteric ganglia. NOS-IR nerves preferentially increased in the muscle, while VIP and SP increased in submucosal ganglia and mucosal nerve fibres. The density of ICC was normal. RET overactivation in MEN2B lead to a large increase in intrinsic nerve fibres in the myenteric and submucosal ganglia, with a relative increase in NOS-IR nerve fibres in the circular muscle and VIP and SP in the submucosal ganglia and mucosa. The changes were associated with severe constipation resulting in colectomy at 4 years. PMID:28868184

  13. Determining the frequencies of B1, B2, B3 and E alleles of the ...

    African Journals Online (AJOL)

    The allelic frequencies of the B1, B2, B3 and E alleles were 0.927, 0.073, 0.390, and 0.272, respectively. B1 and B2 alleles did not affect milk yield and composition. B3 allele had significant effects on protein, fat, total solid (TS), solid not fat (SNF), casein and lactose percentages, but not on lactose yield. E allele significantly ...

  14. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  15. Novel Synthesis of the TiO2(B) Multilayer Templated Films

    Czech Academy of Sciences Publication Activity Database

    Procházka, Jan; Kavan, Ladislav; Zukalová, Markéta; Frank, Otakar; Kalbáč, Martin; Zukal, Arnošt; Klementová, Mariana; Carbone, D.; Graetzel, M.

    2009-01-01

    Roč. 21, č. 8 (2009), s. 1457-1464 ISSN 0897-4756 R&D Projects: GA MŠk LC510; GA AV ČR IAA400400804; GA AV ČR KAN200100801; GA AV ČR KAN100500652 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z40320502 Keywords : TiO2(B) * synthesis * films Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.368, year: 2009

  16. Small-Angle Neutron Scattering and Magnetization Study of HoNi2B2C

    OpenAIRE

    Ramazanoglu, M.; Laver, M.; Yagmurcu, A.; Choi, E. -M.; Lee, S. -I.; Knigavko, A.; Gaulin, B. D.

    2014-01-01

    The superconducting and magnetic properties of HoNi2B2C single crystals are investigated through transport, magnetometry and small-angle neutron scattering measurements. In the magnetic phases that enter below the superconducting critical temperature, the small-angle neutron scattering data uncover networks of magnetic surfaces. These likely originate from uncompensated moments e.g. at domain walls pinned to crystallographic grain boundaries. The field and temperature dependent behaviour appe...

  17. Debesų kompiuterijos paslaugų teikimo optimizavimas B2B modelyje

    OpenAIRE

    Ciechanavičiūtė, Kamilė

    2017-01-01

    The optimization of cloud computing provision in a Business to Business (B2B) model is highly desirable in today’s dynamic global business environment. The business workflows between business partners, suppliers and consumers need to be highly adaptable to changing business needs. As businesses move from a static to a dynamic environment, cloud computing provides a highly scalable, elastic and cost effective compute platform to run both, traditional platform 2 applications as well as the plat...

  18. Lithiation Thermodynamics and Kinetics of the TiO2(B) Nanoparticles.

    Science.gov (United States)

    Hua, Xiao; Liu, Zheng; Fischer, Michael G; Borkiewicz, Olaf; Chupas, Peter J; Chapman, Karena W; Steiner, Ullrich; Bruce, Peter G; Grey, Clare P

    2017-09-27

    TiO 2 (B) has attracted considerable attention in recent years because it exhibits the largest capacity among all studied titania polymorphs, with high rate performance for Li intercalation being achieved when this material is nanostructured. However, due to the complex nature of its lithiation mechanism and practical challenges in probing Li structure in nanostructured materials, a definitive understanding of the lithiation thermodynamics has yet to be established. A comprehensive mechanistic investigation of the TiO 2 (B) nanoparticles is therefore presented using a combination of in situ/operando X-ray pair distribution function (PDF) and electrochemical techniques. The discharge begins with surface reactions in parallel with Li insertion into the subsurface of the nanoparticles. The Li bulk insertion starts with a single-phase reaction into the A2 site, a position adjacent to the b-channel. A change of the Li diffusion pathway from that along this open channel to that along the c-direction is likely to occur at the composition of Li 0.25 TiO 2 until Li 0.5 TiO 2 is attained, leading to a two-step A2-site incorporation with one step kinetically distinct from the other. Subsequent Li insertion involves the C' site, a position situated inside the channel, and follows a rapid two-phase reaction to form Li 0.75 TiO 2 . Due to the high diffusion barrier associated with the further lithiation, Li insertion into the A1 site, another position adjacent to the channel neighboring the A2 sites, is kinetically restricted. This study not only explores the lithiation reaction thermodynamics and mechanisms of nanoparticulate TiO 2 (B) but also serves as a strong reference for future studies of the bulk phase, and for future calculations to study the Li transport properties of TiO 2 (B).

  19. Modelling Supply Chain Management in B2B E-Commerce Systems

    OpenAIRE

    Asmuni, Idris

    2014-01-01

    Applying supply chain management in e-commerce systems has been a need for enterprise to win the competition global in a term of customer-oriented market. Although investing in supply chain technology demand high costs and resources, many companies attempt to strengthen business function with systems application under ERP packages and other systems related. This paper discusses about B2B e-commerce modelling as an integral part of E-Business in supply chain company activities. Some critical ...

  20. Interdependence of magnetism and superconductivity in the borocarbide TmNi2B2C

    DEFF Research Database (Denmark)

    Nørgaard, K.; Eskildsen, M.R.; Andersen, N.H.

    2000-01-01

    We have discovered anew antiferromagnetic phase in TmNi2B2C by neutron diffraction. The ordering vector is Q(A) = (0.48,0,0) and the phase appears shove a critical in-plans magnetic field of 0.9 T. The field was applied in order to test the assumption that the zero-field magnetic structure at Q...