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Sample records for adefovir dipivoxil adv

  1. Optimized combination therapies with adefovir dipivoxil (ADV) and lamivudine, telbivudine, or entecavir may be effective for chronic hepatitis B patients with a suboptimal response to ADV monotherapy

    PubMed Central

    Li, Xiangyong; Jie, Yusheng; You, Xu; Shi, Hong; Zhang, Min; Wu, Yuankai; Lin, Guoli; Li, Xinhua; Gao, Zhiliang; Chong, Yutian

    2015-01-01

    Objective: To identify high risk factors in chronic hepatitis B (CHB) patients for suboptimal response to adefovir dipivoxil (ADV) monotherapy, and to assess the efficacy of optimized therapy combining ADV with lamivudine (LAM), telbivudine (LdT), or entecavir (ETV) in patients with a suboptimal response to ADV alone. Methods: Suboptimal response to ADV monotherapy was defined as having a decline in serum hepatitis B virus (HBV) DNA level of more than 1 log compared to baseline, but with viremia still detectable (HBV DNA ≥ 100 IU/mL), after 48 weeks of therapy. All patients who received ADV monotherapy in our clinic were analyzed retrospectively. Both univariate and multivariate logistic regression models were applied for risk factor analysis. Patients who showed suboptimal response completed at least 12 months of optimized combination therapy consisting of ADV plus LAM, ADV plus LdT, ADV plus ETV, or continuous ADV monotherapy. The primary outcome measurement was complete viral suppression, indicated by a reduction of HBV DNA to undetectable levels (CVS, with HBV DNA < 100 IU/mL). Secondary outcome measures were HBeAg seroconversion for HBeAg-positive patients, HBsAg loss, alanine aminotransferase (ALT) normalization and virological breakthrough rates. Results: Of 521 patients who received ADV monotherapy, 170 showed a suboptimal response. These were grouped for continued therapy as follows: 34 in group A (continuous ADV monotherapy), 55 in group B (ADV plus LAM), 38 in group C (ADV plus LdT), and 43 in group D (ADV plus ETV). Using a logistic model, five conditions were identified as high risk factors for suboptimal response: presence of the tyrosine-methionine-aspartate-aspartate (YMDD) HBV DNA polymerase mutation; being HBeAg positive; having a high baseline level of HBV DNA; having a primary virological non-response to ADV; and [initial virological response] to ADV. After 48 weeks of ADV monotherapy, there were no withdrawn patients who had experienced side

  2. [Efficacy of the 96-week adefovir dipivoxil therapy in patients with chronic hepatitis B].

    PubMed

    Xu, Zhen; Chen, Lu-biao; Cao, Hong; Shu, Xin; Xu, Qi-huan; Li, Gang; Xie, Qi-feng

    2010-06-01

    To investigate the efficacy of the 96-week antiviral therapy with adefovir dipivoxil in patients with chronic hepatitis B. 80 patients with chronic hepatitis B received the antiviral therapy of adefovir dipivoxil (ADV, 10 mg/d). At the 12th week, 19 cases without early viral response (EVR, HBV DNA drop < 2 log10copies/ml) switched to the therapy of other nucleoside analogues. Aminotransferase (ALT) normalization, HBV DNA negative, HBeAg loss and HBeAg seroconvertion were accessed at the 96th week. At week 96, ALT normalization and HBV DNA negative in 61 patients with ADV therapy were 85.25% (52/61) and 95.08% (58/61); and HBeAg loss and HBeAg seroconvertion were 52.52% (17/33) and 42.42% (14/33) respectively. While for the other 19 patients switching to other nucleoside analogues, ALT normalization and HBV DNA negative came to 57.89% (11/19) and 68.42% (13/19). Both HBeAg loss and HBeAg seroconvertion were 58.33% (7/12). Long term ADV antiviral therapy is effective to inhibit HBV DNA replications and benefits patients with chronic hepatits B. Switching to another nucleoside analogue is an optimal alternative if there is no EVR at week 12 in ADV therapy.

  3. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.

    PubMed

    Marcellin, Patrick; Heathcote, E Jenny; Buti, Maria; Gane, Ed; de Man, Robert A; Krastev, Zahary; Germanidis, George; Lee, Sam S; Flisiak, Robert; Kaita, Kelly; Manns, Michael; Kotzev, Iskren; Tchernev, Konstantin; Buggisch, Peter; Weilert, Frank; Kurdas, Oya Ovung; Shiffman, Mitchell L; Trinh, Huy; Washington, Mary Kay; Sorbel, Jeff; Anderson, Jane; Snow-Lampart, Andrea; Mondou, Elsa; Quinn, Joe; Rousseau, Franck

    2008-12-04

    Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase. In two double-blind, phase 3 studies, we randomly assigned patients with hepatitis B e antigen (HBeAg)-negative or HBeAg-positive chronic HBV infection to receive tenofovir DF or adefovir dipivoxil (ratio, 2:1) once daily for 48 weeks. The primary efficacy end point was a plasma HBV DNA level of less than 400 copies per milliliter (69 IU per milliliter) and histologic improvement (i.e., a reduction in the Knodell necroinflammation score of 2 or more points without worsening fibrosis) at week 48. Secondary end points included viral suppression (i.e., an HBV DNA level of <400 copies per milliliter), histologic improvement, serologic response, normalization of alanine aminotransferase levels, and development of resistance mutations. At week 48, in both studies, a significantly higher proportion of patients receiving tenofovir DF than of those receiving adefovir dipivoxil had reached the primary end point (P<0.001). Viral suppression occurred in more HBeAg-negative patients receiving tenofovir DF than patients receiving adefovir dipivoxil (93% vs. 63%, P<0.001) and in more HBeAg-positive patients receiving tenofovir DF than patients receiving adefovir dipivoxil (76% vs. 13%, P<0.001). Significantly more HBeAg-positive patients treated with tenofovir DF than those treated with adefovir dipivoxil had normalized alanine aminotransferase levels (68% vs. 54%, P=0.03) and loss of hepatitis B surface antigen (3% vs. 0%, P=0.02). At week 48, amino acid substitutions within HBV DNA polymerase associated with phenotypic resistance to tenofovir DF or other drugs to treat HBV infection had not developed in any of the patients. Tenofovir DF produced a similar HBV DNA response in patients who had previously received lamivudine and in those who had not. The safety profile was similar for the two

  4. Modeling of autocatalytic hydrolysis of adefovir dipivoxil in solid formulations.

    PubMed

    Dong, Ying; Zhang, Yan; Xiang, Bingren; Deng, Haishan; Wu, Jingfang

    2011-04-01

    The stability and hydrolysis kinetics of a phosphate prodrug, adefovir dipivoxil, in solid formulations were studied. The stability relationship between five solid formulations was explored. An autocatalytic mechanism for hydrolysis could be proposed according to the kinetic behavior which fits the Prout-Tompkins model well. For the classical kinetic models could hardly describe and predict the hydrolysis kinetics of adefovir dipivoxil in solid formulations accurately when the temperature is high, a feedforward multilayer perceptron (MLP) neural network was constructed to model the hydrolysis kinetics. The build-in approaches in Weka, such as lazy classifiers and rule-based learners (IBk, KStar, DecisionTable and M5Rules), were used to verify the performance of MLP. The predictability of the models was evaluated by 10-fold cross-validation and an external test set. It reveals that MLP should be of general applicability proposing an alternative efficient way to model and predict autocatalytic hydrolysis kinetics for phosphate prodrugs.

  5. Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

    PubMed Central

    Lee, Yoon-Suk; Kim, Byung-Kook; Lee, Ho-Jae

    2016-01-01

    In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved. PMID:27247753

  6. Cost-effectiveness analysis of lamivudine, telbivudine, and entecavir in treatment of chronic hepatitis B with adefovir dipivoxil resistance.

    PubMed

    Wang, Guiliang; Liu, Yan; Qiu, Ping; Zhou, Shu-Feng; Xu, Linfang; Wen, Ping; Wen, Jianbo; Xiao, Xianzhong

    2015-01-01

    The purpose of this study was to analyze the cost-effectiveness of lamivudine (LMV), telbivudine (LdT), and entecavir (ETV) in treatment of chronic hepatitis B with adefovir dipivoxil (ADV) resistance. Two hundred and fifty-two patients were recruited and screened for resistance to ADV and randomly assigned into three groups: LMV + ADV, LdT + ADV, and ETV + ADV. The ratio of biochemical response, virological response, seroconversion of hepatitis Be antigen (HBeAg)/hepatitis Be antibody (HBeAb), viral breakthrough, and the cost and effectiveness of treatments were analyzed. A comparison of the results of the ratio of biochemical response, virological response and seroconversion of HBeAg/HBeAb, showed no statistical difference between the three groups, with the economic cost of LMV + ADV the lowest, LdT + ADV the middle, and ETV + ADV the highest. The side effects of the three plans are all rare and tolerable. LMV + ADV is the optimal rescue strategy, and LdT + ADV the alternative selection in the economically less developed regions, while ETV + ADV was used in the economically developed regions.

  7. [Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis].

    PubMed

    Buti, María; Rodríguez Frías, Francisco; Calleja, José Luis; Jardí, Rosendo; Pons, Fernando; Crespo, Javier; Casanovas, Teresa; Enríquez, Jaime; Carnicer, Fernando; Romero, Manuel; García Bengoechea, Manuel; Prieto, Martín; García Samaniego, Javier; Miras, Manuel; Pérez Roldán, Francisco; Rueda, Magdalena; Esteban, Rafael

    2007-10-27

    The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.

  8. Adefovir dipivoxil-induced Fanconi syndrome and its predictive factors: A study of 28 cases.

    PubMed

    Lin, Yong; Pan, Fan; Wang, Yingchao; Chen, Ziqian; Lin, Chun; Yao, Lvfeng; Zhang, Xin; Zhou, Rui; Pan, Chen

    2017-01-01

    The aim of the present study was to identify monitoring and prevention measures as well as predictive factors for early detection of renal toxicity associated with long-term administration of adefovir dipivoxil in order to avoid progression to Fanconi syndrome. Clinical data of 28 patients with Fanconi syndrome caused by long-term administration of adefovir dipivoxil for the treatment of chronic hepatitis B virus (HBV) infection were collected pre-and post-administration for analysis. Patients presented with fatigue, progressive systemic pain in multiple bones and joints, as well as difficulty in walking and pathological fractures in a number of severe cases. Laboratory examinations revealed hypophosphatemia, elevated serum cystatin C (Cys-C), elevated serum creatinine (SCr), reduced glomerular filtration rate (GFR), positive urinary protein, erythrocytes and glucose, as well as osteoporosis. In consequence, adefovir dipivoxil administration was stopped, and patients received concentrated divitamins, sodium phosphate syrup and calcitriol. Symptoms and abnormalities in laboratory examinations were significantly improved in all patients after 2-6 months. Therefore, serum phosphate, SCr, routine urine parameters, Cys-C and GFR should be monitored regularly in chronic HBV patients treated with adefovir dipivoxil. The following factors were identified as predictive of kidney damage and Fanconi syndrome: Age ≥40 years, living in rural areas, previous renal toxicity, estimated GFR (eGFR) <90 ml/min/1.73 m(2), hypertension, diabetes, cirrhosis and duration of adefovir dipivoxil treatment exceeding 24 months. The present results indicate that timely termination of adefovir dipivoxil treatment and replacement with other antiviral agents is critical once renal impairment appears, and that it is necessary to change to other antiviral agents and prolong the interval of administration according to the eGFR level.

  9. Adefovir dipivoxil-induced Fanconi syndrome and its predictive factors: A study of 28 cases

    PubMed Central

    Lin, Yong; Pan, Fan; Wang, Yingchao; Chen, Ziqian; Lin, Chun; Yao, Lvfeng; Zhang, Xin; Zhou, Rui; Pan, Chen

    2017-01-01

    The aim of the present study was to identify monitoring and prevention measures as well as predictive factors for early detection of renal toxicity associated with long-term administration of adefovir dipivoxil in order to avoid progression to Fanconi syndrome. Clinical data of 28 patients with Fanconi syndrome caused by long-term administration of adefovir dipivoxil for the treatment of chronic hepatitis B virus (HBV) infection were collected pre-and post-administration for analysis. Patients presented with fatigue, progressive systemic pain in multiple bones and joints, as well as difficulty in walking and pathological fractures in a number of severe cases. Laboratory examinations revealed hypophosphatemia, elevated serum cystatin C (Cys-C), elevated serum creatinine (SCr), reduced glomerular filtration rate (GFR), positive urinary protein, erythrocytes and glucose, as well as osteoporosis. In consequence, adefovir dipivoxil administration was stopped, and patients received concentrated divitamins, sodium phosphate syrup and calcitriol. Symptoms and abnormalities in laboratory examinations were significantly improved in all patients after 2–6 months. Therefore, serum phosphate, SCr, routine urine parameters, Cys-C and GFR should be monitored regularly in chronic HBV patients treated with adefovir dipivoxil. The following factors were identified as predictive of kidney damage and Fanconi syndrome: Age ≥40 years, living in rural areas, previous renal toxicity, estimated GFR (eGFR) <90 ml/min/1.73 m2, hypertension, diabetes, cirrhosis and duration of adefovir dipivoxil treatment exceeding 24 months. The present results indicate that timely termination of adefovir dipivoxil treatment and replacement with other antiviral agents is critical once renal impairment appears, and that it is necessary to change to other antiviral agents and prolong the interval of administration according to the eGFR level. PMID:28123560

  10. Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil.

    PubMed

    Delaney, William E

    2007-05-01

    Most chronic hepatitis B patients do not undergo a curative response to interferon-alpha or nucleoside/nucleotide-based regimens and require long-term therapy. Long-term safety, efficacy and resistance profiles of hepatitis B virus (HBV) drugs are therefore crucial issues for patient management. Adefovir dipivoxil is a nucleotide prodrug indicated for the treatment of patients with hepatitis B e antigen positive or hepatitis B e antigen negative chronic hepatitis B, lamivudine-resistant HBV infection, HBV infection pre- or post-liver transplantation, or HlV co-infection. Long-term data from clinical trials of up to 5 years duration of adefovir dipivoxil have recently become available and are reviewed here. These data demonstrate that adefovir dipivoxil therapy results in sustained efficacy and safety in the majority of patients after multiple years of treatment. The efficacy of adefovir dipivoxil in treating lamivudine-resistant HBV and the delayed emergence of adefovir resistance are key factors contributing to the durable response achieved in broad groups of chronic hepatitis B patients.

  11. Effects of 1α,25-Dihydroxyvitamin D3 on Intestinal Absorption and Disposition of Adefovir Dipivoxil and Its Metabolite, Adefovir, in Rats.

    PubMed

    Yoon, In-Soo; Son, Jun-Hyeng; Kim, Sang-Bum; Choi, Min-Koo; Maeng, Han-Joo

    2015-01-01

    The aim of this study was to investigate the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), an active form of vitamin D, on the oral absorption and disposition of adefovir dipivoxil (P-glycoprotein (P-gp) substrate) and its major active metabolite, adefovir (multidrug resistance-associated protein 4 (Mrp4) substrate), in rats. The pharmacokinetics of intravenous adefovir and oral adefovir dipivoxil was evaluated in control and 1,25(OH)2D3-treated rats. The intestinal absorption of adefovir dipivoxil was investigated through an in situ closed loop study, and the tissue distribution of adefovir after oral administration of adefovir dipivoxil was evaluated in the two groups. There was no significant difference in pharmacokinetic parameters of intravenous adefovir between the two groups. Importantly, the total area under the plasma concentration-time curve from time zero to time infinity (AUC), peak plasma concentration (Cmax) and extent of absolute oral bioavailability (F) of adefovir after oral administration of adefovir dipivoxil were significantly higher in 1,25(OH)2D3-treated rats than in control rats. In the in situ closed loop study, there was no significant difference in the remaining fraction of adefovir dipivoxil in the duodenum, jejunum and ileum loops between the two groups. In the tissue distribution study after oral administration of adefovir dipivoxil, the tissue-to-plasma partition coefficients of adefovir in the liver, brain, kidney, and intestine were significantly lower in the 1,25(OH)2D3-treated rats than in control rats. The present study indicates that 1,25(OH)2D3 treatment can enhance the oral absorption of adefovir dipivoxil, likely via the induction of basolateral Mrp4 function in rat intestine. However, the impact of 1,25(OH)2D3 treatment on the pharmacokinetics of intravenous adefovir was limited. These results could lead to further studies in clinically significant P-gp and/or MRP4-mediated 1,25(OH)2D3-drug interactions.

  12. Curative effect of combined lamivudine, adefovir dipivoxil, and stem cell transplantation on decompensated hepatitis B cirrhosis.

    PubMed

    Liu, L; Yan, Y; Zhou, J; Huang, L W; He, C P; Ling, K; Zhou, H C; Wen, Q M; Wang, X M

    2014-02-21

    This study assessed the clinical efficacy of lamivudine and adefovir dipivoxil combined with autologous bone marrow stem cell transplantation as treatment for patients with hepatitis B and decompensated liver cirrhosis. In total, 77 patients with hepatitis B and decompensated liver cirrhosis were randomly divided into two groups. Under general symptomatic and supportive treatment, the patients in group A (37 cases) were treated with lamivudine and adefovir dipivoxil, whereas those in group B (40 cases) were treated with autologous bone marrow stem cell transplantation in combination with lamivudine and adefovir dipivoxil. After 4 weeks of treatment, the liver function indicators and clinical signs and symptoms of the patients in group B improved more significantly than those of patients in group A. Lamivudine and adefovir dipivoxil in combination with autologous bone marrow stem cell transplantation effectively prevented hepatitis B virus infection and bone marrow stem cell damage. This combination treatment facilitates the differentiation of bone marrow stem cells into normal liver cells to restore liver structure and improve liver function, thereby improving the quality of life of patients.

  13. Absorption enhancement of adefovir dipivoxil by incorporating MCT and ethyl oleate complex oil phase in emulsion

    PubMed Central

    Li, Ping; Yu, Hong-zhen; Zhang, Xin-xin; Gan, Li; Zhu, Chun-liu; Gan, Yong

    2010-01-01

    Aim: To improve the oral absorption of adefovir dipivoxil (ADV) by employing MCT and the esterase inhibitor ethyl oleate (EO) as a complex oil phase in emulsion. Methods: EO was used as the esterase inhibitor, and its inhibitory effect on esterase activity was assessed in rat intestinal homogenates. ADV emulsions with or without EO were prepared. The emulsions' protective effect against intestinal metabolism was evaluated in rat luminal contents, ex vivo, as well as in vivo. Results: The IC50 of EO in intestinal mucosal homogenates was 2.2 mg/mL. The emulsions exhibited significant protective effects in rat luminal contents compared to a simple suspension (98.7%, 96.3%, 95.7% vs 74.7%, P<0.01). The permeability calculated from the emulsion containing EO was significantly different (11.4×10−6 vs 7.4/8.0×10−6, P<0.05) from the simple suspension or the emulsion without EO in an ex vivo assay. A bioavailability study in vivo revealed that emulsions containing both EO and MCT as a complex oil phase demonstrated 1.6- and 1.5-fold enhancements in area under the curve (AUC0–12) values (5358 vs 3386/3618, P<0.05), respectively, when compared with emulsions containing EO or MCT as a single oil phase. Conclusion: Heterotic lipid formulations (emulsions) with an esterase inhibitor (ie, EO) may be useful in protecting ester prodrugs from intestinal metabolism and increasing their oral bioavailability. PMID:20562905

  14. Efficacy of adefovir dipivoxil therapy in patients with chronic hepatitis B viral infection.

    PubMed

    Khan, M R; Chowdhury, M S; Saha, M; Roknuzzaman, S M; Mahmuduzzaman, M; Miah, A R; Roy, P K; Raihan, M A; Rahman, K M

    2014-10-01

    Hepatitis B virus (HBV) infection is a major public health problem in the world. About 30% of world population has serological evidence of HBV infection. The prevalence of chronic hepatitis B in Bangladesh is reported to be 7.8%. Several potentially effective agents with different mechanisms of action have entered clinical practice and adefovir dipivoxil is one of them. Studies on the efficacy of adefovir dipivoxil in Bangladeshi patients are lacking. This was a prospective study to find out the effect of one year adefovir therapy in patients with chronic hepatitis B virus infection who were HBeAg positive. Total number of patients included in this study was 68. Among them 53(77.94%) patients continued the therapy and completed follow up. At the end of one year of therapy, intention to treat analysis showed that the rate of response (HBeAg seroconversion and HBV DNA negative) was 37.73% which was comparable to the results obtained in other studies. There was major difference in the pre treatment serum ALT level between the responders and non-responders. Comparison of reduction of serum ALT level before treatment and after treatment showed that ALT level to be lower in both responder group and non responder group. Adefovir was effective in replicative HBV infection in Bangladeshi population. So we suggest that treatment can be started and subsequent follow up can be done in chronic HBV patients who are HBeAg positive without liver biopsy.

  15. A Simple and Specific Stability- Indicating RP-HPLC Method for Routine Assay of Adefovir Dipivoxil in Bulk and Tablet Dosage Form.

    PubMed

    Darsazan, Bahar; Shafaati, Alireza; Mortazavi, Seyed Alireza; Zarghi, Afshin

    2017-01-01

    A simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of adefovir dipivoxil (ADV).The chromatographic separation was performed on a C18 column using a mixture of acetonitrile-citrate buffer (10 mM at pH 5.2) 36:64 (%v/v) as mobile phase, at a flow rate of 1.5 mL/min. Detection was carried out at 260 nm and a sharp peak was obtained for ADV at a retention time of 5.8 ± 0.01 min. No interferences were observed from its stress degradation products. The method was validated according to the international guidelines. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 0.5-16 μg/mL; the regression coefficient was 0.9999and the linear regression equation was y = 24844x-2941.3. The detection (LOD) and quantification (LOQ) limits were 0.12 and 0.35 μg/mL, respectively. The results proved the method was fast (analysis time less than 7 min), precise, reproducible, and accurate for analysis of ADV over a wide range of concentration. The proposed specific method was used for routine quantification of ADV in pharmaceutical bulk and a tablet dosage form.

  16. Adefovir dipivoxil is less expensive than lamivudine and associated with similar prognosis in patients with hepatitis B virus-related hepatocellular carcinoma after radical resection

    PubMed Central

    Zhong, Jian-Hong; Ke, Yang; Zhu, Shao-Liang; Wang, Lin; Luo, Cheng-Piao; Gong, Wen-Feng; You, Xue-Mei; Ma, Liang; Xiang, Bang-De; Li, Le-Qun

    2016-01-01

    Aim Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. Methods We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n=155) or ADV (n=46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free, and overall survival, as well as antiviral medication costs. Results Despite significant improvement in HBV-DNA and alanine aminotransferase level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2, and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, and 56.4%) than in the ADV group (0%, 3.3%, and 14.5%; P<0.001). Overall survival at 1, 2, and 3 years after resection was similar for the LAM group (84.5%, 69.3%, and 64.6%) and the ADV group (84.1%, 77.8%, and 63.4%; P=0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, and 43.9%) and the ADV group (81.1%, 66.1%, and 53.0%; P=0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, and 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, and €5.6 per person per day) than in the ADV group (€2.2, €2.4, and €3.1 per person per day; all P<0.05). Conclusion ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective. PMID:27877054

  17. Thermodynamic and kinetic investigation on the crucial factors affecting adefovir dipivoxil-saccharin cocrystallization.

    PubMed

    Ma, Kun; Zhang, Ying; Kan, Hongliang; Cheng, Linfeng; Luo, Ling; Su, Qing; Gao, Jing; Gao, Yuan; Zhang, Jianjun

    2014-07-01

    The aim of this study was to perform a thermodynamic and kinetic investigation on the crucial factors affecting the cocrystallization between adefovir dipivoxil (AD) and saccharin (SAC). Phase solubility diagrams and ternary phase diagrams were constructed based on the solubility data of AD, SAC and their cocrystals in ethanol, isopropanol and ethyl acetate at different temperatures. The conductimetric method was used to determine the induction time. A quantitative and intuitive technique modified from dissolution testing was employed to investigate the cocrystallization kinetics. AD-SAC cocrystals exhibited different crystal habits but only one cocrystal polymorph was confirmed. The effects of several crucial factors, including the input amounts of two components, AD/SAC ratio, solvent and temperature, on the crystallization of single-component alone, cocrystal formation, cocrystal stability, supersaturation, nucleation, crystal growth and cocrystal yield were determined. Thermodynamic and kinetic parameters provided the rationale for this spontaneous cocrystallization system without the need of solvent evaporation and temperature change. This systemic investigation enriched the present understanding of thermodynamics and kinetics of cocrystals and built the groundwork for AD-SAC cocrystal scale-up.

  18. Novel polymorphic form of adefovir dipivoxil derived from polymer-directed crystallization.

    PubMed

    Lee, Min Kyung; Lee, Hyeseung; Kim, Il Won; Lee, Jonghwi

    2011-10-01

    Crystallization is an essential step in pharmaceutical processing. The discovery of a non-classical crystallization pathway would be a promising strategy to engineer the properties of drug crystalline particles for specific delivery conditions. Herein, polymer-directed crystallization was successfully employed to modify the characteristics of a model drug, adefovir dipivoxil (AD). Polyacrylic acid (PAA), ethyl cellulose (EC), and hydroxypropyl cellulose were added as active polymers to control the crystallization pathway of AD. Changes in crystal habit were observed in all cases. A novel polymorph was found after the addition of PAA and EC, and was confirmed by XRD and DSC results. In FTIR investigations, the crystals derived from PAA-directed crystallization showed strong interactions between PAA and AD. The polymer content in polymer-directed crystallization-derived powders varied from 7 to 24 wt%, and the presence of polymers lead to sustained release of AD. These results make polymer-directed crystallization a simple and efficient technique to engineer the physical and chemical properties of drug crystals.

  19. Experimental and molecular docking studies on DNA binding interaction of adefovir dipivoxil: Advances toward treatment of hepatitis B virus infections

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Falsafi, Monireh

    The toxic interaction of adefovir dipivoxil with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove binding mode. The binding constant of UV-visible and the number of binding sites were 3.33 ± 0.2 × 104 L mol-1and 0.99, respectively. The fluorimetric studies showed that the reaction between the drug and CT-DNA is exothermic (ΔH = 34.4 kJ mol-1; ΔS = 184.32 J mol-1 K-1). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of adefovir dipivoxil, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that adefovir strongly binds to groove of DNA by relative binding energy of docked structure -16.83 kJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with bio macromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

  20. Effect of adefovir dipivoxil on T cell immune function in the treatment of chronic hepatitis B and hepatocirrhosis

    PubMed Central

    Tian, Liting; Fu, Qilin; Huang, Fu

    2016-01-01

    The aim of the present study was to investigate the T cell immune function in chronic hepatitis B hepatocirrhosis patients at the compensated and decompensated stage following treatment with adefovir dipivoxil. A total of 104 patients diagnosed with hepatitis B hepatocirrhosis during the period from October 2013 to October 2014 were enrolled in the study. Among the cases, there were 56 cases at compensated stage, and another 48 at decompensated stage. Adefovir dipivoxil was administered for antiviral therapy (10 mg/time, 1 time/day, for a total of 24 weeks), and we compared the virus disappearance rate, liver function improvement and T cell immune function between the two groups before and after treatment. The difference between the virus disappearance rate in the two groups was not statistically significant (P>0.05). The decreased level of ALT decrease in the compensated group was significantly higher than that in the decompensated group, while the increased level of albumin in the compensated group was significantly higher as well. The differences showed statistical significance (P<0.05). After treatment, the level of CD4+ and CD4+/CD8+ ratio were higher than before treatment, while the level of CD8+ was lower after treatment than before treatment in the two groups. The differences all showed statistical significance (P<0.05). The CD4+CXCR5+ T follicular helper (TFH) cell level in the two groups was higher after treatment, as was interleukin-2 and interferon-γ. The differences all showed statistical significance (P<0.05). As for comparison between groups, the difference had no statistical significance (P>0.05). Adefovir dipivoxil treatment can improve T cell immune function at the compensated and decompensated stages in chronic hepatitis B hepatocirrhosis patients. This may be associated with virus disappearance and liver function improvement. PMID:27698751

  1. Effect of adefovir dipivoxil on T cell immune function in the treatment of chronic hepatitis B and hepatocirrhosis.

    PubMed

    Tian, Liting; Fu, Qilin; Huang, Fu

    2016-10-01

    The aim of the present study was to investigate the T cell immune function in chronic hepatitis B hepatocirrhosis patients at the compensated and decompensated stage following treatment with adefovir dipivoxil. A total of 104 patients diagnosed with hepatitis B hepatocirrhosis during the period from October 2013 to October 2014 were enrolled in the study. Among the cases, there were 56 cases at compensated stage, and another 48 at decompensated stage. Adefovir dipivoxil was administered for antiviral therapy (10 mg/time, 1 time/day, for a total of 24 weeks), and we compared the virus disappearance rate, liver function improvement and T cell immune function between the two groups before and after treatment. The difference between the virus disappearance rate in the two groups was not statistically significant (P>0.05). The decreased level of ALT decrease in the compensated group was significantly higher than that in the decompensated group, while the increased level of albumin in the compensated group was significantly higher as well. The differences showed statistical significance (P<0.05). After treatment, the level of CD4(+) and CD4(+)/CD8(+) ratio were higher than before treatment, while the level of CD8(+) was lower after treatment than before treatment in the two groups. The differences all showed statistical significance (P<0.05). The CD4(+)CXCR5(+) T follicular helper (TFH) cell level in the two groups was higher after treatment, as was interleukin-2 and interferon-γ. The differences all showed statistical significance (P<0.05). As for comparison between groups, the difference had no statistical significance (P>0.05). Adefovir dipivoxil treatment can improve T cell immune function at the compensated and decompensated stages in chronic hepatitis B hepatocirrhosis patients. This may be associated with virus disappearance and liver function improvement.

  2. The curative effect of adefovir dipivoxil treating HBeAg negative chronic hepatitis B and treating HBeAg positive chronic hepatitis B combining interferon α-2b.

    PubMed

    Gu, Junsheng; Sun, Ranran; Shen, Shen; Yu, Zujiang

    2015-07-01

    This study aimed to research the efficiency of adefovir dipivoxil in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B treatment and in combination with α-2b interferon in the treatment of HBeAg-positive chronic hepatitis B. A total of 102 cases of adult patients with HBeAg chronic hepatitis B were selected for testing. HBeAg negative chronic hepatitis B patients took 10mg adefovir dipivoxil capsules once daily, while positive chronic hepatitis B patients were randomly divided into either a treatment group or a control group. The treatment group was administrated with 10mg adefovir dipivoxil capsules, 1 time daily, and injected with 5 million U Recombinant Human Interferon α-2b through muscle every other day. The control group was treated with 10mg adefovir dipivoxil capsules, 1 time per day. We examined alanine aminotransferase (ALT) normalization and the Hepatitis B Virus (HBV)-DNA negative rate (undetectable rate), as well as, HBeAg / hepatitis B e antibody (HBeAb) sero-conversion rate to detect treatment effects. The results proved that after 6 months of medication therapy, the ALT normalization rate was 49.9% and the HBV-DNA negative conversion rate was 54.3%. 18 months into the treatment, showed an ALT normalization rate of 73.2%, while the HBV-DNA negative conversion rate grew to 76.8%. The use of adefovir dipivoxil treatment of the negative chronic HBV has a certain extent combined with α-2b Interferon therapy in treatment of HbeAg positive chronic hepatitis B. After a 48-week observation period, ALT normalization and HBV-DNA rate could not be measured, HBeAg/HBeAb sero-conversion rose higher, indicating that the treatment of the combined drugs is more efficient than taking adefovir dipivoxil by itself, and the data were comparable with the control group (P<0.05). Thus adefovir dipivoxil can greatly improve the restrain function to HBV-DNA and improve the immunity and control ability of the body, with obvious short-term effects, in combination

  3. [Virological response to adefovir dipivoxil predicts the long-term development of resistance in previously untreated patients with HBeAg-negative chronic hepatitis B].

    PubMed

    Suárez, Emilio; Gila, Ana; Figueruela, Blanca; Chueca, Natalia; Muñoz Rueda, Pilar; Puche, Beatriz; Fraga, Enrique; García, Federico; Martín, Juan Manuel; Andrade, Raúl J; Nogales, Carmen; Romero-Gómez, Manuel; Salmerón, Javier

    2011-02-01

    Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with more frequent development of resistance than in naïve patients. The virological response during treatment predicts the risk of developing resistance. The aims of this study were to assess the efficacy of adefovir dipivoxil treatment in naïve and lamivudine-resistant patients and to determine whether virological response predicts the development of adefovir resistance. This study included 82 patients with HBeAg-negative chronic hepatitis B (CHB) who received adefovir dipivoxil therapy. During active treatment, HBV-DNA values were determined by polymerase chain reaction; in addition, the presence of adefovir resistance-associated mutations was studied in cases of virological breakthrough. Virological response at 12 and 24 months was 59% and 73% in naive patients compared with 40% and 67% in lamivudine-resistant patients, whereas virological breakthrough at 24 months was 9.5% in naïve patients compared with 20% in lamivudine-resistant patients. A small percentage (4%) of patients with virological response at 12 months showed virological breakthrough between 12 and 40 months versus 29.4% of patients without virological response (P=.03). In lamivudine-resistant patients, virological response at 12 months was not a predictive factor for the development of virological breakthrough. Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with an increased tendency to develop virological breakthrough, which cannot be predicted by virological response at 12 months of treatment. In naive patients, an undetectable viral load at 12 months of treatment ensures the absence of virological breakthrough at 40 months of treatment. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  4. Effects of 1α,25-dihydroxyvitamin D3 on transport and metabolism of adefovir dipivoxil and its metabolites in Caco-2 cells.

    PubMed

    Maeng, Han-Joo; Chapy, Hélène; Zaman, Sarah; Pang, K Sandy

    2012-06-14

    Effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), natural ligand of the VDR, on the fates of adefovir dipivoxil (P-gp substrate) and its metabolites, mono(POM)-PMEA and adefovir (MRP4 substrate), were investigated in Caco-2 cells. After 1,25(OH)2D3-treatment, higher apical efflux of adefovir was observed after a 60 min incubation of adefovir divipoxil. Changes in these washout studies were predicted by a catenary model for the Caco-2 monolayer that described a higher MRP4 activity with 1,25(OH)2D3 treatment, as confirmed by Western blotting. Moreover, 1,25(OH)2D3 treatment (100 nM for 3 days) resulted in increased basolateral (B) to apical (A) (B-to-A) transport of adefovir dipivoxil but an unchanged A-to-B flux, rendering an elevated efflux ratio (EfR) (from 1.97 to 3.19). The EfR values in control and 1,25(OH)2D3-treated groups in these transport studies were reduced to 1.32 and 1.57, respectively, in the presence of verapamil (50 μM), the P-gp inhibitor. The B-to-A transport of the metabolite, adefovir, was increased in 1,25(OH)2D3-treated cells in the presence of verapamil, whereas the A-to-B and B-to-A transport of mono(POM)-PMEA remained unchanged. But the verapamil and 1,25(OH)2D3 treatments failed to alter rates of sequential metabolism of adefovir dipivoxil in cell lysate. The composite data established that 1,25(OH)2D3 treatment increased both P-gp and MRP4 transport activities without affecting the metabolism of adefovir dipivoxil by esterases. Moreover, an asymmetric appearance of metabolites, being higher with apical application, was observed. According to the catenary model, the asymmetry is suggestive that esterases are predominantly localized on the apical membrane and within the cell. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Mechanism study on stability enhancement of adefovir dipivoxil by cocrystallization: Degradation kinetics and structure-stability correlation.

    PubMed

    Lin, Rui-Zhen; Sun, Peng-Jie; Tao, Qian; Yao, Jia; Chen, Jia-Mei; Lu, Tong-Bu

    2016-03-31

    The purpose of this study is to determine the mechanism by which cocrystallization can enhance the stability of adefovir dipivoxil (AD), a diester prodrug of adefovir with known chemical stability problem. Three multi-component crystals of AD with biologically safe coformers, including gallic acid cocrystal hydrate (1:1:1), salicylate salt (1:1), and maleate salt (1:1) were prepared and characterized by thermal analysis, infrared spectroscopy, powder and single crystal X-ray diffraction. DVS measurements and stability tests were applied to evaluate the stability. The new crystalline phases exhibit improved stability compared to pure drug in the order AD gallic acid cocrystal>AD maleate>AD salicylate>AD form I. Degradation kinetics and structure-stability correlation studies demonstrate that the stability enhancement mechanism by cocrystallization involves (1) inhibition of hydrolysis of AD by replacement of drug-drug homosynthons by stronger drug-coformer heterosynthons at adenine fragments; (2) suppression of dimerization of AD by separation of adenine fragments by inserting coformers in crystal lattices; (3) further reducing rates of hydrolysis by forming hydrogen bonds with hydrate water at phosphoryl fragments. This study has important implications for use of cocrystallization approach to some easily degradable drugs in pharmaceutical.

  6. Deep Sequencing Analysis of HBV Genotype Shift and Correlation with Antiviral Efficiency during Adefovir Dipivoxil Therapy

    PubMed Central

    Shan, Youlan; Huang, Wenxiang; Zhang, Dazhi; Zen, Aizhong; Zhou, Xin; Zhao, Yao; Gong, Xuyang; Xu, Ge; Zhang, Xiuyu; Chen, Juan; Huang, Ailong

    2015-01-01

    Background Viral genotype shift in chronic hepatitis B (CHB) patients during antiviral therapy has been reported, but the underlying mechanism remains elusive. Methods 38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method. Results Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38%) increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT. Conclusions Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency. PMID:26110616

  7. Adefovir

    MedlinePlus

    ... long-term) hepatitis B infection (swelling of the liver caused by a virus) in patients who have ... chronic hepatitis B such as cirrhosis of the liver or liver cancer. Adefovir may not prevent the ...

  8. Detection of rtN236T and rtA181V/T mutations associated with resistance to adefovir dipivoxil in samples from patients with chronic hepatitis B virus infection by the INNO-LiPA HBV DR line probe assay (version 2).

    PubMed

    Osiowy, Carla; Villeneuve, Jean-Pierre; Heathcote, E Jenny; Giles, Elizabeth; Borlang, Jamie

    2006-06-01

    The nucleotide analog adefovir dipivoxil (ADV) is an effective antiviral treatment for chronic hepatitis B virus (HBV) infection, with resistance to ADV estimated to occur less frequently than resistance to lamivudine treatment. The detection of ADV resistance mutations is necessary during therapy to monitor and anticipate possible treatment failure. The INNO-LiPA HBV DR v2 (LiPA; Innogenetics, Ghent, Belgium) is a DNA hybridization line probe assay for the detection of HBV polymerase mutations associated with resistance to lamivudine and ADV. Evaluation of this assay to detect ADV resistance mutations was performed by analyzing 38 patients treated with ADV. Serial samples taken at 6-month intervals during treatment were available for most patients. A total of 124 samples were analyzed by both LiPA and sequencing. By LiPA analysis, 12 patients (31.5%) were found to have mutations associated with resistance to ADV (rtA181V/T and/or rtN236T). This contrasted with sequence analysis, which found nine patients (24%) with either or both mutations. Twice as many samples were rtN236T positive by LiPA (18 of 124) compared to sequence analysis (9 of 124). LiPA detected the rtN236T mutation at least 6 months earlier than its detection by sequencing in patients for whom consecutive serum samples were available. Although less sensitive, sequencing has the advantage of providing information on other polymerase mutations not represented on LiPA strips. The INNO-LiPA HBV DR v2 assay is a very sensitive and specific assay for the detection of the rtN236T mutation associated with resistance to ADV.

  9. Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis

    PubMed Central

    2014-01-01

    Background Currently, there is no consensus on the efficacy and resistance of de novo combination therapy versus monotherapy for treatment naive patients of chronic hepatitis B (CHB). Objectives The aim of this study was to evaluate the effectiveness and resistance of de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for nucleos(t)ide–naive patients with CHB. Study design Publications on the effectiveness and resistance of LAM plus ADV versus ETV monotherapy for nucleos(t)ide-naive patients with CHB were identified by a search of PubMed, Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e antigen seroconversion, and viroligic response were extracted and combined to obtain an integrated result. Viral resistance and safety were reviewed. Results Five eligible studies (328 patients in total) were included in the analysis. LAM plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12 weeks than that of ETV monotherapy. At 48 weeks, the combination group had superior viroligic response rates compared with ETV group (90.0% vs. 78.9%, P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates was not found. At week 96, LAM + ADV was more effective than ETV in ALT normalization [RR = 1. 11, 95% CI (1.02, 1.21), P =0.01] and HBeAg seroconversion [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was found in the virologic response (P =0.23). No viral resistance occurred in combination therapy and six patients in ETV group were experienced with viral breakthrough. Both groups were well tolerated. Conclusion The de novo LAM plus ADV combination therapy for treatment-naïve patients with CHB was greater than ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to 96 weeks. The rate of emergence of viral

  10. Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis.

    PubMed

    Akyildiz, Murat; Karasu, Zeki; Zeytunlu, Murat; Aydin, Unal; Ozacar, Tijen; Kilic, Murat

    2007-12-01

    Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.

  11. Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma.

    PubMed

    Takamura, Masaaki; Ichida, Takafumi; Ohkoshi, Shogo; Tsubata, Shunsuke; Osaki, Akihiko; Aoyagi, Tomoya; Nomoto, Minoru; Uehara, Kazuhiro; Terada, Haruo; Aoyagi, Yutaka

    2007-01-01

    We describe a 64-year-old man with decompensated hepatitis B virus (HBV)-related cirrhosis who became resistant to lamivudine. He was started on adefovir at 10 mg daily while continuing lamivudine therapy. Several months later, his liver function improved and subsequently his ascites disappeared. The serum HBV-DNA level became undetectable 11 months later. Twenty months after the start of additional treatment with adefovir, one hepatocellular carcinoma (HCC) was detected, and the patient underwent a successful hepatectomy. Our findings suggest that the addition of adefovir to ongoing lamivudine therapy is useful for improving liver function in patients with decompensated lamivudine-resistant HBV-related cirrhosis, allowing surgery for HCC.

  12. The Effect of Prophylactic Lamivudine plus Adefovir Therapy Compared with Lamivudine Alone in Preventing Hepatitis B Reactivation in Lymphoma Patients with High Baseline HBV DNA during Chemotherapy

    PubMed Central

    Wu, Shaoxu; Geng, Qirong; Huang, Huiqiang; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Duan, Huaxin; Rao, Huilan; Yao, Mengfei; Hu, Liyang

    2016-01-01

    Prophylactic antiviral therapy is essential for lymphoma patients with high baseline HBV DNA who undergo cytotoxic chemotherapy. However, there are limited data on the optimal options. The present study was designed to compare the efficacy of prophylactic lamivudine (LAM) with lamivudine plus adefovir dipivoxil (LAM+ADV) in preventing hepatitis B virus (HBV) reactivation in lymphoma with, pre-chemotherapy HBV DNA load ≥2000 IU/ml. We retrospectively analyzed the medical records of 86 lymphoma patients with baseline HBV DNA load ≥2000 IU/ml during chemotherapy and received LAM or LAM+ADV as prophylaxis between January 1, 2008 and November 30, 2014 at Sun Yat-sen University Cancer Center, China. Sixty-five patients received LAM and 21 received LAM+ADV. The rate was significantly lower in the LAM+ADV group compared with the LAM group for HBV reactivation (23.8% vs 55.4%; p = 0.012), while no difference was observed between the two groups in patients for HBV-related hepatitis (21.3% vs 33.3%; p   =  0.349), and chemotherapy disruption (10.9% vs 19.0%; p = 0.337). In a multivariate analysis of factors associated with HBV reactivation in these patients, LAM+ADV treatment and HBeAg negative were the independent protective factors. Therefore, LAM+ADV should be considered for antiviral prophylaxis in lymphoma patients with pre-chemotherapy HBV DNA load ≥2000 IU/ml. Further study is warranted to confirm these findings. PMID:27711135

  13. [A case of chronic hepatitis B with primary adefovir resistance].

    PubMed

    Yamazhan, Tansu; Sertöz, Rüçhan; Pullukçu, Hüsnü; Taşbakan, Meltem; Ulusoy, Sercan; Erensoy, Selda

    2007-04-01

    Implementation of antiviral therapy leads to the emergence of mutant strains during the treatment in chronic hepatitis B. Hepatitis B virus (HBV) with primary antiviral resistance may be rarely encountered. In this report, a chronic hepatitis B case who had never received adefovir dipivoxil but had primary adefovir resistance, was presented. HBeAg positive 25-year-old male patient was treated with interferon (IFN)-alpha (thrice a week 10 MU) and lamivudine (100 mg/daily) combination for one year. At the end of this treatment although HBV-DNA was under the detectable limit and ALT levels returned to normal, anti-HBe antibodies did not develop. During the course of lamivudin treatment on the third year virus was found to be resistant to lamivudin [FLM+YMDD+YIDD+YVDD (Inno-LiPA HBV DR, Innogenetics Ghent, Belgium)] and adefovir was added to the lamivudin therapy. At the end of eight months of combination therapy, ALT levels did not return to normal and HBV-DNA was still in detectable levels. On the 11th month resistance to adefovir was analysed and rtA181T mutation was found by DNA sequence analysis (Big Dye Terminator Cycle Sequencing kit, Applied Biosystems, USA). Since there had been no response to adefovir from the initiation of the therapy, primary adefovir resistance was suspected. Primary adefovir resistance was confirmed by the detection of the same mutation in pre-adefovir treatment serum sample of the patient. Lamivudin was re-added to the therapy, however, HBV-DNA still remained positive on the third month of this combination therapy. The patient got out of routine follow-up after this period.

  14. Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection.

    PubMed

    Shen, Yuequan; Zhukovskaya, Natalia L; Zimmer, Michael I; Soelaiman, Sandriyana; Bergson, Pamela; Wang, Chyung-Ru; Gibbs, Craig S; Tang, Wei-Jen

    2004-03-02

    Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high affinity (K(i) = 27 nM). A crystal structure of EF-CaM-PMEApp reveals that the catalytic site of EF forms better van der Waals contacts and more hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the approximately 10,000-fold higher affinity EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically approved drug that can block the action of an anthrax toxin. It can be used to address the role of EF in anthrax pathogenesis.

  15. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B.

    PubMed

    Wursthorn, Karsten; Lutgehetmann, Marc; Dandri, Maura; Volz, Tassilo; Buggisch, Peter; Zollner, Bernhard; Longerich, Thomas; Schirmacher, Peter; Metzler, Frauke; Zankel, Myrga; Fischer, Conrad; Currie, Graeme; Brosgart, Carol; Petersen, Joerg

    2006-09-01

    Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for persistent infection of hepatocytes. The aim of this study was to determine changes in intrahepatic cccDNA in patients with chronic hepatitis B (CH-B) during 48 weeks of antiviral therapy and its correlation to virological, biochemical, and histological parameters. Twenty-six HBsAg-positive CH-B patients received combination treatment with pegylated interferon alpha-2b (peg-IFN) and adefovir dipivoxil (ADV) for 48 weeks. Paired liver biopsies from before and at the end of treatment were analyzed for intrahepatic HBV-DNA. Median serum HBV-DNA had decreased by -4.9 log10 copies/mL at the end of treatment and was undetectable in 13 individuals (54%). Median intrahepatic total HBV-DNA and cccDNA had decreased by -2.2 and -2.4 log10, respectively. Changes in intracellular HBV-DNA positively correlated with HBsAg serum reduction and were accompanied by a high number of serological responders. Eight of 15 HBeAg-positive patients lost HBeAg, and five developed anti-HBe antibodies during treatment. These eight patients exhibited lower cccDNA levels before and at the end of therapy than did patients without HBeAg loss. Four patients developed anti-HBs antibodies. ALT normalized in 11 patients. The number of HBs-antigen- and HBc-antigen-positive hepatocytes was significantly lower after treatment, suggesting the involvement of cytolytic mechanisms. In conclusion, combination therapy with peg-IFN and ADV led to marked decreases in serum HBV-DNA and intrahepatic cccDNA, which was significantly correlated with reduced HBsAg.

  16. Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

    PubMed Central

    De Clercq, Erik

    2003-01-01

    The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily). PMID:14557287

  17. Entecavir plus adefovir combination therapy versus lamivudine add-on adefovir for lamivudine-resistant chronic hepatitis B: A meta-analysis.

    PubMed

    Zeng, Teng; Xu, Hua; Liu, Jun-Ying; Lei, Yu; Zhong, Shan; Zhou, Zhi

    2014-09-01

    To determine whether adefovir (ADV) in combination with entecavir (ETV) is more effective than with lamivudine (LAM) in patients with lamivudine-resistant chronic HBV infection, electronic databases were searched through May 10th, 2013 to obtain relevant trials which met the inclusion criteria. Meta-analysis was performed on randomized controlled trials (RCTs) and non-randomized studies. Four trials containing a total of 323 patients were included. Serum HBV DNA reductions after 3 and 6 months of treatment in the ETV + ADV group were greater than that of LAM + ADV group (mean difference (MD) = 0.90, 95% confidence interval (CI): 0.74-1.07, P < 0.00001; MD = 0.81, 95% CI: 0.57-1.06, P < 0.00001). The rate of 6 months HBV DNA undetectability with ETV and ADV was higher than that of LAM and ADV (relative risk (RR) = 1.63, 95% CI: 1.14-2.34, P < 0.007). There were higher rates of serum ALT normalization than those in LAM + ADV group after 6 months of treatment (RR = 1.40, 95% CI: 1.11-1.77, P < 0.005). The ETV + ADV group had lower viral breakthrough and genotypic mutation rates than LAM + ADV group after 12 months of treatment (RR = 0.24, 95% CI: 0.10-0.58, P = 0.002). The combination of ETV plus ADV is a more effective rescue therapy than LAM add-on ADV in patients with LAM-resistant HBV.

  18. Combination of lamivudine and adefovir without hepatitis B immune globulin is safe and effective prophylaxis against hepatitis B virus recurrence in hepatitis B surface antigen-positive liver transplant candidates.

    PubMed

    Gane, Edward J; Patterson, Scott; Strasser, Simone I; McCaughan, Geoffrey W; Angus, Peter W

    2013-03-01

    Without effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. Combination prophylaxis with hepatitis B immune globulin (HBIG) and lamivudine (LAM) reduces long-term recurrence rates below 10%; however, HBIG is costly and inconvenient to administer. We, therefore, conducted a multicenter, prospective study of outcomes with an HBIG-sparing regimen of LAM plus adefovir dipivoxil (ADV) initiated at the time of listing for liver transplantation and continued after transplantation. Twenty-six patients were recruited into this study at the time of listing for transplantation, and 20 subsequently underwent transplantation. Twelve of the 26 patients had LAM exposure before the study baseline, but none had LAM resistance. The median HBV viral load before the institution of antiviral therapy was approximately 4.0 log(10) IU/mL (range=2.3-7.5 log(10) IU/mL). To the 20 patients who underwent transplantation, 800 IU of intramuscular HBIG was given immediately after transplantation and daily for 7 days only (total HBIG dose=6400 IU). All transplant patients remained alive without HBV recurrence (they were negative for hepatitis B surface antigen, and HBV DNA was undetectable) after a median follow-up of 57 months after transplantation (range=27-83 months). The median serum creatinine level in these patients rose from 81 to 119 μmol/L over the course of the study. No patient required dose reduction or cessation. After the completion of this prospective study, the regimen was modified so that no perioperative HBIG was administered if the pretransplant serum HBV DNA level was suppressed below 3 log(10) IU/mL. Another 28 patients with HBV-related liver disease underwent transplantation (18 without HBIG). All remained alive and well without HBV recurrence after a median follow-up of 22 months after transplantation (range=10-58 months). In conclusion, a combination of

  19. Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

    PubMed

    Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

    2016-01-01

    Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

  20. Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients

    PubMed Central

    Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

    2016-01-01

    Background/aim Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). Methods To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. Results In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. Conclusion ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients. PMID:27041994

  1. In Vitro Antihepadnaviral Activities of Combinations of Penciclovir, Lamivudine, and Adefovir

    PubMed Central

    Colledge, Danni; Civitico, Gilda; Locarnini, Stephen; Shaw, Tim

    2000-01-01

    Penciclovir {9-[2-hydroxy-1-(hydroxymethyl)-ethoxymethyl]guanine [PCV]}, lamivudine ([−]-β-l-2′,3′-dideoxy-3′-thiacytidine [3TC]), and adefovir (9-[2-phosphonylmethoxyethyl]-adenine [PMEA]) are potent inhibitors of hepatitis B virus (HBV) replication. Lamivudine has recently received approval for clinical use against chronic human HBV infection, and both PCV and PMEA have undergone clinical trials against HBV in their respective prodrug forms {famciclovir and adefovir dipivoxil [bis-(POM)-PMEA]}. Since multidrug combinations are likely to be used to control HBV infection, investigation of potential interactions between PCV, 3TC, and PMEA is important. Primary duck hepatocyte cultures which were either acutely or congenitally infected with the duck hepatitis B virus (DHBV) were used to investigate in vitro interactions between PCV, 3TC, and PMEA. Here we show that the anti-DHBV effects of all the combinations containing PCV, 3TC, and PMEA are greater than that of each of the individual components and that their combined activities are approximately additive or synergistic. These results may underestimate the potential in vivo usefulness of PMEA-containing combinations, since there is evidence that PMEA has immunomodulatory activity and, at least in the duck model of chronic HBV infection, is capable of inhibiting DHBV replication in cells other than hepatocytes, the latter being unaffected by treatment with either PCV or 3TC. Further investigation of the antiviral activities of these drug combinations is therefore required, particularly since each of the component drugs is already in clinical use. PMID:10681317

  2. Bisamidate Prodrugs of 2-Substituted 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA, adefovir) as Selective Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis.

    PubMed

    Česnek, Michal; Jansa, Petr; Šmídková, Markéta; Mertlíková-Kaiserová, Helena; Dračínský, Martin; Brust, Tarsis F; Pávek, Petr; Trejtnar, František; Watts, Val J; Janeba, Zlatko

    2015-08-01

    Novel small-molecule agents to treat Bordetella pertussis infections are highly desirable, as pertussis (whooping cough) remains a serious health threat worldwide. In this study, a series of 2-substituted derivatives of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, adefovir), in their isopropyl ester bis(L-phenylalanine) prodrug form, were designed and synthesized as potent inhibitors of adenylate cyclase toxin (ACT) isolated from B. pertussis. The series consists of PMEA analogues bearing either a linear or branched aliphatic chain or a heteroatom at the C2 position of the purine moiety. Compounds with a small C2 substituent showed high potency against ACT without cytotoxic effects as well as good selectivity over human adenylate cyclase isoforms AC1, AC2, and AC5. The most potent ACT inhibitor was found to be the bisamidate prodrug of the 2-fluoro PMEA derivative (IC50 =0.145 μM). Although the bisamidate prodrugs reported herein exhibit overall lower activity than the bis(pivaloyloxymethyl) prodrug (adefovir dipivoxil), their toxicity and plasma stability profiles are superior. Furthermore, the bisamidate prodrug was shown to be more stable in plasma than in macrophage homogenate, indicating that the free phosphonate can be effectively distributed to target tissues, such as the lungs. Thus, ACT inhibitors based on acyclic nucleoside phosphonates may represent a new strategy to treat whooping cough.

  3. Comparison of the clinical outcomes between antiviral-naïve patients treated with entecavir and lamivudine-resistant patients receiving adefovir add-on lamivudine combination treatment

    PubMed Central

    Kim, Hong Joo; Park, Soo Kyung; Yang, Hyo Joon; Jung, Yoon Suk; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Choi, Kyu Yong

    2016-01-01

    Background/Aims To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. Methods This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. Results During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). Conclusion The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression. PMID:27729626

  4. ADV36 adipogenic adenovirus in human liver disease

    PubMed Central

    Trovato, Francesca M; Catalano, Daniela; Garozzo, Adriana; Martines, G Fabio; Pirri, Clara; Trovato, Guglielmo M

    2014-01-01

    Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment. PMID:25356033

  5. The relationship between capsid protein (VP2) sequence and pathogenicity of Aleutian mink disease parvovirus (ADV): a possible role for raccoons in the transmission of ADV infections.

    PubMed Central

    Oie, K L; Durrant, G; Wolfinbarger, J B; Martin, D; Costello, F; Perryman, S; Hogan, D; Hadlow, W J; Bloom, M E

    1996-01-01

    Aleutian mink disease parvovirus (ADV) DNA was identified by PCR in samples from mink and raccoons on commercial ranches during an outbreak of Aleutian disease (AD). Comparison of DNA sequences of the hypervariable portion of VP2, the major capsid protein of ADV, indicated that both mink and raccoons were infected by a new isolate of ADV, designated ADV-TR. Because the capsid proteins of other parvoviruses play a prominent role in the determination of viral pathogenicity and host range, we decided to examine the relationship between the capsid protein sequences and pathogenicity of ADV. Comparison of the ADV-TR hypervariable region sequence with sequences of other isolates of ADV revealed that ADV-TR was 94 to 100% related to the nonpathogenic type 1 ADV-G at both the DNA and amino acid levels but less than 90% related to other pathogenic ADVs like the type 2 ADV-Utah, the type 3 ADV-ZK8, or ADV-Pullman. This finding indicated that a virus with a type 1 hypervariable region could be pathogenic. To perform a more comprehensive analysis, the complete VP2 sequence of ADV-TR was obtained and compared with that of the 647-amino-acid VP2 of ADV-G and the corresponding VP2 sequences of the pathogenic ADV-Utah, ADV-Pullman, and ADV-ZK8. Although the hypervariable region amino acid sequence of ADV-TR was identical to that of ADV-G, there were 12 amino acid differences between ADV-G and ADV-TR. Each of these differences was at a position where other pathogenic isolates also differed from ADV-G. Thus, although ADV-TR had the hypervariable sequence of the nonpathogenic type 1 ADV-G, the remainder of the VP2 sequence resembled sequences of other pathogenic ADVs. Under experimental conditions, ADV-TR and ADV-Utah were highly pathogenic and induced typical AD in trios of both Aleutian and non-Aleutian mink, whereas ADV-Pullman was pathogenic only for Aleutian mink and ADV-G was noninfectious. Trios of raccoons experimentally inoculated with ADV-TR and ADV-Utah all became infected

  6. An Improved SEL Test of the ADV212 Video Codec

    NASA Technical Reports Server (NTRS)

    Wilcox, Edward P; Campola, Michael J.; Nadendla, Seshagiri; Kadari, Madhusudhan; Gigliuto, Robert A.

    2017-01-01

    Single-event effect (SEE) test data is presented on the Analog Devices ADV212. Focus is given to the test setup used to improve data quality and validate single-event latchup (SEL) protection circuitry.

  7. An Improved SEL Test of the ADV212 Video Codec

    NASA Technical Reports Server (NTRS)

    Wilcox, Edward P.; Campola, Michael J.; Nadendla, Seshagiri; Kadari, Madhusudhan; Gigliuto, Robert A.

    2017-01-01

    Single-event effect (SEE) test data is presented on the Analog Devices ADV212. Focus is given to the test setup used to improve data quality and validate single-event latch-up (SEL) protection circuitry.

  8. Intracellular concentrations determine the cytotoxicity of adefovir, cidofovir and tenofovir.

    PubMed

    Zhang, Xun; Wang, Ruduan; Piotrowski, Mary; Zhang, Hui; Leach, Karen L

    2015-02-01

    Lack of in vitro to in vivo translation is a major challenge in safety prediction during early drug discovery.One of the most common in vitro assays to evaluate the probability of a compound to cause adverse effects is a cytotoxicity assay. Cytotoxicity of a compound is often measured by dose–response curves assuming the administered doses and intracellular exposures are equal at the time of measurement.However, this may not be true for compounds with low membrane permeability or those which are substrates for drug transporters as intracellular concentrations are determined both by passive permeability and active uptake through drug transporters. We show here that three antiviral drugs, adefovir, cidofovir and tenofovir exhibit significantly increased cytotoxicity in HEK293 cells transfected with organic anion transporter (OAT) 1 and 3 compared to a lack of cytotoxicity in HEK293 wildtype cells. A further look at the media and intracellular drug concentrations showed that 24 h after dosing, all three drugs had higher intracellular drug concentrations than that of media in the HEK-OAT1 cells whereas the intracellular drug concentrations in the wildtype cells were much lower than the administered doses. Comparing cytotoxicity IC(50) values of adefovir, cidofovir and tenofovir based on administered doses and measured intracellular concentrations in HEK-OAT1 cells revealed that intracellular drug concentrations have significant impact on calculated IC(50) values. Tenofovir showed much less intrinsic cytotoxicity than adefovir and cidofovir using intracellular concentrations rather than media concentration. Our data suggest that for low permeable drugs or drugs that are substrates for drug transporters, the choice of cellular model is critical for providing an accurate determination of cytotoxicity.

  9. Cimicifuga foetida L. plus adefovir effectively inhibits the replication of hepatitis B virus in patients with chronic hepatitis B

    PubMed Central

    DAI, XIUFANG; YI, XIANFU; SUN, ZEQUN; RUAN, PENG

    2016-01-01

    The aim of the present study was to assess the anti-hepatitis B virus (HBV) effect of Cimicifuga foetida L. (C. foetida) in the patients with chronic hepatitis B (CHB). A total of 60 randomly selected patients with CHB were recruited and divided into groups I and II. The patients in group I received a monotherapy of adefovir (ADV), and the patients in group II received a combination therapy of ADV and C. foetida for >48 weeks. Intrahepatic (IH) HBV covalently closed circular DNA (cccDNA), serum HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase levels and serum interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels were quantified during the test. Following the treatment, a significant reduction of the median IH cccDNA level was identified in group II (P=0.017), but not in group I (P=0.05, and P=0.01 between the 2 groups), and a significant reduction of log10 HBsAg was identified in groups I (P=0.012) and II (P<0.0001, and P=0.20 between the 2 groups). A significant increase of the median serum IFN-γ level was found in group II (P=0.0005), but not in group I (P=0.06, and P=0.004 between the 2 groups), and a significant reduction of the median TGF-β level was identified in groups I (P<0.0001) and II (P<0.0001, and P=0.002 between the 2 groups). A total of 24 patients in group I, and 27 patients in group II achieved a sustained virological response (P=0.0386), and 20 patients in group I and 24 in group II achieved hepatitis B e antigen seroclearance (P=0.0442). In conclusion, C. foetida can effectively inhibit HBV transcription and replication in the patients by stimulating the release of the inflammatory cytokines, such as IFN-γ. PMID:27073640

  10. Cimicifuga foetida L. plus adefovir effectively inhibits the replication of hepatitis B virus in patients with chronic hepatitis B.

    PubMed

    Dai, Xiufang; Yi, Xianfu; Sun, Zequn; Ruan, Peng

    2016-04-01

    The aim of the present study was to assess the anti-hepatitis B virus (HBV) effect of Cimicifuga foetida L. (C. foetida) in the patients with chronic hepatitis B (CHB). A total of 60 randomly selected patients with CHB were recruited and divided into groups I and II. The patients in group I received a monotherapy of adefovir (ADV), and the patients in group II received a combination therapy of ADV and C. foetida for >48 weeks. Intrahepatic (IH) HBV covalently closed circular DNA (cccDNA), serum HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase levels and serum interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels were quantified during the test. Following the treatment, a significant reduction of the median IH cccDNA level was identified in group II (P=0.017), but not in group I (P=0.05, and P=0.01 between the 2 groups), and a significant reduction of log10 HBsAg was identified in groups I (P=0.012) and II (P<0.0001, and P=0.20 between the 2 groups). A significant increase of the median serum IFN-γ level was found in group II (P=0.0005), but not in group I (P=0.06, and P=0.004 between the 2 groups), and a significant reduction of the median TGF-β level was identified in groups I (P<0.0001) and II (P<0.0001, and P=0.002 between the 2 groups). A total of 24 patients in group I, and 27 patients in group II achieved a sustained virological response (P=0.0386), and 20 patients in group I and 24 in group II achieved hepatitis B e antigen seroclearance (P=0.0442). In conclusion, C. foetida can effectively inhibit HBV transcription and replication in the patients by stimulating the release of the inflammatory cytokines, such as IFN-γ.

  11. Floc Growth and Changes in ADV Acoustic Backscatter Signal

    NASA Astrophysics Data System (ADS)

    Rouhnia, M.; Keyvani, A.; Strom, K.

    2013-12-01

    A series of experiments were conducted to examine the effect of mud floc growth on the acoustic back-scatter signal recorded by a Nortek Vector acoustic Doppler velocimeter (ADV). Several studies have shown that calibration equations can be developed to link the backscatter strength with average suspended sediment concentration (SSC) when the sediment particle size distribution remains constant. However, when mud is present, the process of flocculation can alter the suspended particle size distribution. Past studies have shown that it is still unclear as to the degree of dependence of the calibration equation on changes in floc size. Part of the ambiguity lies in the fact that flocs can be porous and rather loosely packed and therefore might not scatter to the same extent as a grain of sand. In addition, direct, detailed measurements of floc size have not accompanied experiments examining the dependence of ADV backscatter and suspended sediment concentration. In this research, a set of laboratory experiments is used to test how floc growth affects the backscatter strength. The laboratory data is examined in light of an analytic model that was developed based on scatter theory to account for changes in both SSC and the floc properties of size and density. For the experiments, a turbulent suspension was created in a tank with a rotating paddle. Fixed concentrations of a mixture of kaolinite and montmorillonite were added to the tank in a step-wise manner. For each step, the flocs were allowed to grow to their equilibrium size before breaking the flocs with high turbulent mixing, adding more sediment, and then returning the mixing rate to a range suitable for the re-growth of flocs. During each floc growth phase, data was simultaneously collected at the same elevation in the tank using a floc camera to capture the changes in floc size, a Nortek Vector ADV for the acoustic backscatter, and a Campbell Scientific OBS 3+ for optical backscatter. Physical samples of the

  12. Three pharmaceuticals cocrystals of adefovir: Syntheses, structures and dissolution study

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoming; Sun, Fuxing; Zhang, Tingting; Jia, Jiangtao; Su, Hongmin; Wang, Chenhui; Zhu, Guangshan

    2015-11-01

    We report here three novel cocrystals, which are composed of adefovir as the API (Active Pharmaceutical Ingredient) with p-aminobenzoic acid (1, 2C8H12N5O4P·C7H6NO2·3H2O), 3,5-dihydroxybenzoic acid (2, C8H12N5O4P·C7H6O4·H2O) and 2,6-pyridinedicarboxlic acid (3, C8H12N5O4P·C7H5NO4) as CCFs (cocrystal formers) respectively by crystal engineering strategy. Their structures were characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD) analysis, thermogravimetric analyses (TGA), elemental analysis (EA) and infrared spectral analysis (IR). The analysis of single crystal X-ray diffraction demonstrate that cocrystal 1 and 2 form a strong hydrogen-bonded assembly through the phosphoric acids of API with water in the lattice and carboxylic acids of CCF respectively. Cocrystal 3 is formed in which the phosphoric acid groups of API are also held by the carboxylic acid groups of CCF. The PXRD results indicate their high purity of as-synthesized samples. The TGA, EA, IR and dissolution study of API and the cocrystals were also measured and discussed.

  13. Factors associated with the decrease in hepatitis B surface antigen titers following interferon therapy in patients with chronic hepatitis B: Is interferon and adefovir combination therapy effective?

    PubMed

    Yano, Yoshihiko; Seo, Yasushi; Hayashi, Hiroki; Hatazawa, Yuri; Hirano, Hirotaka; Minami, Akihiro; Kawano, Yuki; Saito, Masaya; Ninomiya, Toshiaki; Sugano, Masahiko; Yamada, Hajime; Kitajima, Naoto; Yoon, Seitetsu; Hayashi, Yoshitake

    2017-09-01

    The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P<0.05). Moreover, an increase in alanine aminotransferase (ALT) of >2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, P<0.05). The proportion of patients with a decrease in HBsAg was significantly greater in patients who received IFN monotherapy than in patients who received IFN and ADV combination therapy (43 vs. 29%, P<0.05). The present results revealed that the HBcr antigen titer before therapy and an on-treatment elevation of ALT (indicative of host instruction flare) are important factors associated with a decrease in HBsAg titers after IFN

  14. Rapid Detection of Hepatitis B Virus Variants Associated with Lamivudine and Adefovir Resistance by Multiplex Ligation-Dependent Probe Amplification Combined with Real-Time PCR

    PubMed Central

    Jia, Shuangrong; Wang, Feng; Li, Fake; Chang, Kai; Yang, Shaojun; Zhang, Kejun; Jiang, Wenbin; Shang, Ya

    2014-01-01

    Drug-resistant mutations of hepatitis B virus (HBV) are the major obstacles to successful therapy for chronic hepatitis B infection. Although there are many methods for detecting the antiviral drug-resistant mutations of HBV, their applications are restricted because of their shortcomings, such as low sensitivity, the time required, and the high cost. For this study, a multiplex ligation-dependent probe real-time PCR (MLP-RT-PCR) method was developed to simultaneously detect lamivudine (LAM)- and adefovir (ADV)-resistant HBV mutants (those with the mutations rtM204V/I, rtA181V/T, and rtN236T). The new method combined the high-throughput nature of multiplex ligation-dependent probe amplification (MLPA) with the rapid and sensitive detection of real-time PCR. In this report, MLP-RT-PCR was evaluated by detecting drug-resistant mutants in 116 patients with chronic hepatitis B infection. By MLP-RT-PCR analysis, LAM-resistant mutations were detected in 41 patients (35.3%), ADV-resistant mutations were detected in 17 patients (14.7%), and LAM- and-ADV-resistant mutations were detected in 5 patients (4.3%). Based on the results of MLP-RT-PCR, the mutations rtM204V, rtM204I, rtA181T, rtA181V, and rtN236T were 95.7% (111/116 patients), 98.3% (114/116 patients), 99.1% (115/116 patients), 98.3% (114/116 patients), and 99.1% (115/116 patients) concordant, respectively, with those of direct sequencing. The MLP-RT-PCR assay was more sensitive than direct sequencing for detecting mutations with low frequencies. Four samples containing the low-frequency (<10%) mutants were identified by MLP-RT-PCR and further confirmed by clonal sequencing. MLP-RT-PCR is a rapid and sensitive method that enables the detection of multidrug-resistant HBV mutations in clinical practice. PMID:24478474

  15. Single Event Effect Testing of the Analog Devices ADV212

    NASA Technical Reports Server (NTRS)

    Wilcox, Ted; Campola, Michael; Kadari, Madhu; Nadendla, Seshagiri R.

    2017-01-01

    The Analog Devices ADV212 was initially tested for single event effects (SEE) at the Texas AM University Cyclotron Facility (TAMU) in July of 2013. Testing revealed a sensitivity to device hang-ups classified as single event functional interrupts (SEFI), soft data errors classified as single event upsets (SEU), and, of particular concern, single event latch-ups (SEL). All error types occurred so frequently as to make accurate measurements of the exposure time, and thus total particle fluence, challenging. To mitigate some of the risk posed by single event latch-ups, circuitry was added to the electrical design to detect a high current event and automatically recycle power and reboot the device. An additional heavy-ion test was scheduled to validate the operation of the recovery circuitry and the continuing functionality of the ADV212 after a substantial number of latch-up events. As a secondary goal, more precise data would be gathered by an improved test method, described in this test report.

  16. 76 FR 255 - Amendments To Form ADV; Extension of Compliance Date

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... COMMISSION 17 CFR Parts 275 and 279 RIN 3235-AI17 Amendments To Form ADV; Extension of Compliance Date AGENCY: Securities and Exchange Commission. ACTION: Final rule; extension of compliance date. SUMMARY: The Securities and Exchange Commission is extending the compliance date for Part 2B of Form ADV, the brochure...

  17. Mechanism of Adefovir, Tenofovir and Entecavir Resistance: Molecular Modeling Studies of How A Novel Anti-HBV Agent (FMCA) Can Overcome the Drug Resistance.

    PubMed

    Rawal, R K; Konreddy, A K; Chu, C K

    2015-01-01

    Regardless of significant improvement in the area of anti-HBV therapy, resistance and cross-resistance against available therapeutic agents are the major consideration in drug discovery of new agents. The present study is to obtain the insight of the molecular basis of drug resistance conferred by the B and C domain mutations of HBV-polymerase on the binding affinity of four anti-HBV agents [Adefovir (ADV), Tenofovir (TNF), Entecavir (ETV) & 2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA)]. In this regard, homology modeled structure of HBV polymerase was used for minimization, conformational search and Glide XP docking followed by binding energy calculation on wild-type as well as on mutant HBV-polymerases (N236T, L180M+M204V+S202G & A194T). Our studies suggest a significant correlation between the fold resistances and the binding affinity of anti-HBV nucleosides. The domain B residue, L180 is indirectly associated with other active-site hydrophobic residues such as A87, F88 and M204, whereas the domain C residue, M204 is closely associated with sugar/pseudosugar ring positioning in the active site. These hydrophobic residues can directly influence the interaction of the incoming nucleoside triphosphates and change the binding efficacy. The carbohydrate ring part of natural substrate dATP, dGTP, FMCA and ETV, are occupied in similar passion in the grooves of HBV polymerase active site. The exocyclic double bond of Entecavir and FMCA occupies in the backside hydrophobic pocket (made by residues A87, F88, L180and M204), which enhances the overall binding affinity. Additional hydrogen bonding interaction of 2'-fluorine of FMCA with R41 residue of polymerase promotes a positive binding in wild-type as well as in ADVr, ETVr and TNFr with respect to that of entecavir.

  18. Bone Histology of Two Cases with Osteomalacia Related to Low-dose Adefovir

    PubMed Central

    Hiramatsu, Rikako; Ubara, Yoshifumi; Sawa, Naoki; Hasegawa, Eiko; Kawada, Masahiro; Imafuku, Aya; Sumida, Keiichi; Hoshino, Junichi; Takaichi, Kenmei

    2016-01-01

    We performed a bone histomorphometric analysis in two patients demonstrating Fanconi syndrome with hypophosphatemia, adefovir-related bone disease and chronic hepatitis B infection. Both patients had osteomalacia, but showed two different histological patterns. The osteoid volume of the patient without risedronate increased with [(osteoid volume/ bone volume)×100=18.6%]. However, the osteoid volume of the patient receiving risedronate without vitamin D analogue showed a greater increase of 53.8%. In both patients bone pain and hypophosphatemia subsided soon after the discontinuation of adefovir and the administration of phosphate derivative. These findings show that bisphosphonate may worsen this disease when this drug is administered without a vitamin D analogue. PMID:27746441

  19. Research Gaps and Technology Needs in Development of PHM for Passive AdvSMR Components

    SciTech Connect

    Meyer, Ryan M.; Ramuhalli, Pradeep; Coble, Jamie B.; Hirt, Evelyn H.; Mitchell, Mark R.; Wootan, David W.; Berglin, Eric J.; Bond, Leonard J.; Henager, Charles H.

    2014-01-01

    Advanced small modular reactors (AdvSMRs), which are based on modularization of advanced reactor concepts, may provide a longer-term alternative to traditional light-water reactors and near term small modular reactors (SMRs), which are based on integral pressurized water reactor (iPWR) concepts. SMRs are challenged economically due to losses in economy of scale, thus, there is increased motivation to reduce the controllable operations and maintenance (O&M) costs through automation technologies including prognostics health management (PHM) systems. In this regard, PHM systems have the potential to play a vital role in supporting the deployment of AdvSMRs and face several unique challenges with respect to implementation for passive AdvSMR components. This paper presents a summary of a research gaps and technical needs assessment performed for implementation of PHM for passive AdvSMR components. state-of-the-art in PHM.

  20. Research gaps and technology needs in development of PHM for passive AdvSMR components

    SciTech Connect

    Meyer, Ryan M.; Ramuhalli, Pradeep; Hirt, Evelyn H.; Mitchell, Mark R.; Wootan, David W.; Berglin, Eric J.; Henagar, Chuck H. Jr.; Coble, Jamie B.; Bond, Leonard J.

    2014-02-18

    Advanced small modular reactors (AdvSMRs), which are based on modularization of advanced reactor concepts, may provide a longer-term alternative to traditional light-water reactors and near-term small modular reactors (SMRs), which are based on integral pressurized water reactor (iPWR) concepts. SMRs are challenged economically because of losses in economy of scale; thus, there is increased motivation to reduce the controllable operations and maintenance costs through automation technologies including prognostics health management (PHM) systems. In this regard, PHM systems have the potential to play a vital role in supporting the deployment of AdvSMRs and face several unique challenges with respect to implementation for passive AdvSMR components. This paper presents a summary of a research gaps and technical needs assessment performed for implementation of PHM for passive AdvSMR components.

  1. Local-Level Prognostics Health Management Systems Framework for Passive AdvSMR Components. Interim Report

    SciTech Connect

    Ramuhalli, Pradeep; Roy, Surajit; Hirt, Evelyn H.; Pardini, Allan F.; Jones, Anthony M.; Deibler, John E.

    2014-09-12

    This report describes research results to date in support of the integration and demonstration of diagnostics technologies for prototypical AdvSMR passive components (to establish condition indices for monitoring) with model-based prognostics methods. The focus of the PHM methodology and algorithm development in this study is at the localized scale. Multiple localized measurements of material condition (using advanced nondestructive measurement methods), along with available measurements of the stressor environment, enhance the performance of localized diagnostics and prognostics of passive AdvSMR components and systems.

  2. Lamivudine/Adefovir Treatment Increases the Rate of Spontaneous Mutation of Hepatitis B Virus in Patients

    PubMed Central

    Pereira-Gómez, Marianoel; Bou, Juan-Vicente; Andreu, Iván; Sanjuán, Rafael

    2016-01-01

    The high levels of genetic diversity shown by hepatitis B virus (HBV) are commonly attributed to the low fidelity of its polymerase. However, the rate of spontaneous mutation of human HBV in vivo is currently unknown. Here, based on the evolutionary principle that the population frequency of lethal mutations equals the rate at which they are produced, we have estimated the mutation rate of HBV in vivo by scoring premature stop codons in 621 publicly available, full-length, molecular clone sequences derived from patients. This yielded an estimate of 8.7 × 10−5 spontaneous mutations per nucleotide per cell infection in untreated patients, which should be taken as an upper limit estimate because PCR errors and/or lack of effective lethality may inflate observed mutation frequencies. We found that, in patients undergoing lamivudine/adefovir treatment, the HBV mutation rate was elevated by more than sixfold, revealing a mutagenic effect of this treatment. Genome-wide analysis of single-nucleotide polymorphisms indicated that lamivudine/adefovir treatment increases the fraction of A/T-to-G/C base substitutions, consistent with recent work showing similar effects of lamivudine in cellular DNA. Based on these data, the rate at which HBV produces new genetic variants in treated patients is similar to or even higher than in RNA viruses. PMID:27649318

  3. De novo combination therapy adefovir plus lamivudine as a treatment for women of child-bearing age with HBeAg-positive chronic hepatitis B before pregnancy.

    PubMed

    Ma, Li-Na; Ding, Xiang-Chun; Liu, Xiao-Yan; Xu, Chun-Qiong; Liu, Shuai-Wei; Yan, Xie

    2014-03-01

    Substantial progress has been achieved in antiviral therapy for chronic hepatitis B; however, options for women of child-bearing age with HBeAg-positive chronic hepatitis B remain a challenge. In this study, we sought to determine whether de novo combination therapy of Adefovir plus Lamivudine was a super treatment for women of child-bearing age with HBeAg-positive chronic hepatitis B prior to conception. A total of 122 women patients of child-bearing age with HBeAg-positive chronic hepatitis B were randomly assigned to receive (i) 10 mg Adefovir plus 100 mg Lamivudine (64 patients) or (ii) 10 mg Adefovir monotherapy (58 patients), administrated orally once daily for 96 weeks. The therapeutic efficacy within each group was compared at weeks 48 and 96. The results showed that de novo combination therapy of Adefovir plus Lamivudine significantly reduced HBV-DNA detectability, and enhanced ALT normalization and HBeAg seroconversion in women of child-bearing age with HBeAg-positive chronic hepatitis B. No virological breakthrough and genotypic resistance were observed in the combination therapy group. Additionally, the combination therapy with Adefovir plus Lamivudine was well tolerated. This study suggests that de novo combination therapy of Adefovir plus Lamivudine offers a therapeutic advantage for women of child-bearing age with HBeAg-positive chronic hepatitis B when taken before conception.

  4. Concentration Measurements of Suspended Load using ADV with Influence of the Particle Size

    NASA Astrophysics Data System (ADS)

    Schwarzwälder, Kordula

    2017-04-01

    ADV backscatter data can be used under certain conditions to gain information about the concentrations of suspended loads. This was shown in many studies before (Fugate and Friedrichs 2002; Chanson et al 2008; Ha et al. 2009). This paper reports on a pre-study to investigate the influence of particle size on concentration measurements for suspended sediment load with ADV. The study was conducted in a flume in the Oskar-von-Miller-Institute using fresh water from a river including the natural suspended load. The ADV used in the experiments was a Vectrino Profiler (Nortek). In addition water samples were taken for TSS and TOC. For the measurements a surge was generated in the flume to ensure that also particles of larger size will be present in the water phase. The measurements and samples were taken during the whole surge event. Therefore we were able to find a good correlation between the backscatter data of the ADV and the TSS as well as TOC results. For the decreasing part of the flow event the concentration of TOC in the suspended load of the water phase is decreasing much slower than the TSS and results in a damped decrease of the backscatter values. This means that the results for concentration measurements might be slightly influenced by the size of the particles. Further evaluations of measurements conducted with a LISST SL (Sequoia) will be investigated to show the trend of the particle sizes during this process and fortify this result. David C. Fugate, Carl T. Friedrichs, Determining concentration and fall velocity of estuarine particle populations using ADV, OBS and LISST, Continental Shelf Research, Volume 22, Issues 11-13, 2002 H.K. Ha, W.-Y. Hsu, J.P.-Y. Maa, Y.Y. Shao, C.W. Holland, Using ADV backscatter strength for measuring suspended cohesive sediment concentration, Continental Shelf Research, Volume 29, Issue 10, 2009 Hubert Chanson, Maiko Takeuchi, Mark Trevethan, Using turbidity and acoustic backscatter intensity as surrogate measures of

  5. Choice of drugs in the treatment of chronic hepatitis B in pregnancy.

    PubMed

    Guclu, Ertugrul; Karabay, Oguz

    2013-03-14

    The selection of antiviral drugs for chronic hepatitis B (CHB) treatment in pregnancy is very difficult since none of the drugs have been approved for use in pregnancy. Transmission from mother to newborn remains the most frequent route of infection in mothers with high viral load and positive hepatitis B e antigen status, even with the use of appropriate prophylaxis with hepatitis B virus (HBV) immunoglobulin and HBV vaccination. We read from the article written by Yi et al that lamivudine treatment in early pregnancy was safe and effective. However, we could not understand why adefovir dipivoxil (ADV) was used in three pregnancy cases, since ADV has been classified as pregnancy category C. In pregnancy, telbivudine or tenofovir should be selected when the treatment of CHB is necessary, since these drugs have been classified as Food and Drug Administration pregnancy risk category B.

  6. The Acceptance of Dating Violence scale (ADV): Psychometric properties of the Spanish version.

    PubMed

    Fernández-González, Liria; Calvete, Esther; Orue, Izaskun

    2017-05-01

    The main aim of this study was to analyse the psychometric properties of the Spanish version of the Acceptance of Dating Violence (ADV) scale, which assesses attitudes that justify the use of aggression in adolescents’ dating relationships. A total of 1,579 high school students (49% girls) from Bizkaia (Spain), aged between 14 and 18 years (M = 15.79, SD = 1.16), completed this questionnaire along with the Irrational Beliefs Scale for Adolescents and the Conflict in Adolescent Dating Relationships Inventory. The factor analyses suggested a one-factor structure, which fits data well for both girls and boys. Moreover, the ADV showed good internal consistency (α = .83) and was related to general justification of violence and dating violence (perpetration and victimization). Boys (compared to girls) and adolescents who had had a dating relationship in the past year (compared to those who had not) displayed a higher acceptance of dating violence. The ADV is a useful, brief and easily applicable instrument for the assessment of attitudes toward dating violence.

  7. Evaluation of acoustic Doppler velocimetry (ADV) performance under various probe configurations

    NASA Astrophysics Data System (ADS)

    Liu, Da; Valyrakis, Manousos

    2017-04-01

    Acoustic Doppler velocimetry (ADV) is widely used as one of the most versatile and robust flow diagnostics tools for both laboratory and field studies across a range of research and applied themes spanning engineering eco-hydraulics and geomorphology. A range of specific ADV probes with varying specifications, are readily available for use by professionals and researchers. However, in practice using certain ADV equipment under certain default configurations can easily result in obtaining flow diagnostics that are non-representative of the real flow conditions. This appears to be true for most probes but even more those with which higher temporal resolution can be achieved - which many times is desired for assessing turbulence levels, amongst others. A preliminary examination revealed that there is a varying level of dependency on a number of the probes' configuration parameters, which even though detailed in the user manual, a definite guide for the user is lacking. Subsequently users of this equipment may end up underutilizing or using it in a manner that returns inaccurate results. There are little, if any, resources in obtaining a better understanding on how to use the probe effectively. To this goal a series of laboratory experiments are conducted, under the same open channel flow conditions, using a profiler (ADCP VectrinoII from Nortek®) aiming to cover the full range of probe configuration combinations that can be used in practice. For each experiment, single or multiple point measurements are taken to reconstruct velocity and turbulence intensity profiles. These are conducted at the same location (mid-channel) under the same flow conditions (referring to steady uniform flow and fully developed turbulence) for all probe configurations. In particular, the effect of tested parameters (including Range length, Range to fist cell, Sampling rate, Ping algorithm, Transmit pulse size and Cell size) on the sensitivity and accuracy of the obtained results is assessed

  8. Water-compatible molecularly imprinted polymer as a sorbent for the selective extraction and purification of adefovir from human serum and urine.

    PubMed

    Pourfarzib, Mojgan; Dinarvand, Rasoul; Akbari-Adergani, Behrouz; Mehramizi, Ali; Rastegar, Hossein; Shekarchi, Maryam

    2015-05-01

    A molecularly imprinted polymer has been synthesized to specifically extract adefovir, an antiviral drug, from serum and urine by dispersive solid-phase extraction before high-performance liquid chromatography with UV analysis. The imprinted polymers were prepared by bulk polymerization by a noncovalent imprinting method that involved the use of adefovir (template molecule) and functional monomer (methacrylic acid) complex prior to polymerization, ethylene glycol dimethacrylate as cross-linker, and chloroform as porogen. Molecular recognition properties, binding capacity, and selectivity of the molecularly imprinted polymers were evaluated and the results show that the obtained polymers have high specific retention and enrichment for adefovir in aqueous medium. The new imprinted polymer was utilized as a molecular sorbent for the separation of adefovir from human serum and urine. The serum and urine extraction of adefovir by the molecularly imprinted polymer followed by high-performance liquid chromatography showed a linear calibration curve in the range of 20-100 μg/L with excellent precisions (2.5 and 2.8% for 50 μg/L), respectively. The limit of detection and limit of quantization were determined in serum (7.62 and 15.1 μg/L), and urine (5.45 and 16 μg/L). The recoveries for serum and urine samples were found to be 88.2-93.5 and 84.3-90.2%, respectively.

  9. SACR ADVance 3-D Cartesian Cloud Cover (SACR-ADV-3D3C) product

    DOE Data Explorer

    Meng Wang, Tami Toto, Eugene Clothiaux, Katia Lamer, Mariko Oue

    2017-03-08

    SACR-ADV-3D3C remaps the outputs of SACRCORR for cross-wind range-height indicator (CW-RHI) scans to a Cartesian grid and reports reflectivity CFAD and best estimate domain averaged cloud fraction. The final output is a single NetCDF file containing all aforementioned corrected radar moments remapped on a 3-D Cartesian grid, the SACR reflectivity CFAD, a profile of best estimate cloud fraction, a profile of maximum observable x-domain size (xmax), a profile time to horizontal distance estimate and a profile of minimum observable reflectivity (dBZmin).

  10. Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice.

    PubMed

    Dai, M; Liu, J; Chen, D-E; Rao, Y; Tang, Z-J; Ho, W-Z; Dong, C-Y

    2012-02-01

    Clinical efficacy of current therapies for hepatocellular carcinoma (HCC) treatment is limited. Indole-3-acetic acid (IAA) is non-toxic for mammalian cells. Oxidative decarboxylation of IAA by horseradish peroxidase (HRP) leads to toxic effects of IAA. The purpose of this study was to investigate the effects of a novel gene-targeted enzyme prodrug therapy with IAA on hepatoma growth in vitro and in vivo mouse hepatoma models. We generated a plasmid using adenovirus to express HRP isoenzyme C (HRPC) with the HCC marker, alpha-fetoprotein (AFP), as the promoter (pAdv-AFP-HRPC). Hepatocellular cells were infected with pAdv-AFP-HRPC and treated with IAA. Cell death was detected using MTT assay. Hepatoma xenografts were developed in mice by injection of mouse hepatoma cells. The size and weight of tumors and organs were evaluated. Cell death in tumors was assessed using hematoxylin and eosin-stained tissue sections. HRPC expression in tissues was detected using Reverse Transcriptase-Polymerase Chain Reaction. IAA stimulated death of hepatocellular cells infected with pAdv-AFP-HRPC, in a dose- and time-dependent manner, but not in control cells. Growth of hepatoma xenografts, including the size and weight, was inhibited in mice treated with pAdv-AFP-HRPC and IAA, compared with that in control group. pAdv-AFP-HRPC/IAA treatment induced cell death in hepatoma xenografts in mice. HRPC gene expressed only in hepatoma, but not in other normal organs of mice. pAdv-AFP-HRPC/IAA treatment did not cause any side effects on normal organs. These findings suggest that pAdv-AFP-HRPC/IAA enzyme/prodrug system may serve as a strategy for HCC therapy.

  11. EVALUATION OF RANGE ESTIMATES FOR TOYOTA FCHV-ADV UNDER OPEN ROAD DRIVING CONDITIONS

    SciTech Connect

    Anton, D.; Wipke, K.; Sprik, S.

    2009-07-10

    The objective of this evaluation was to independently and objectively verify driving ranges of >400 miles announced by Toyota for its new advanced Fuel Cell Hybrid Vehicle (FCHV-adv) utilizing 70 MPa compressed hydrogen. To accomplish this, participants from both Savannah River National Laboratory (SRNL) and the National Renewable Energy Laboratory (NREL) witnessed and participated in a 2-vehicle evaluation with Toyota Motor Engineering & Manufacturing North America, Inc. (TEMA) over a typical open road route for over 11 hours in one day with all relevant data recorded. SRNL and TEMA first entered into discussions of verifying the range of the advanced Toyota Fuel Cell Hybrid Vehicle (FCHV-adv) in August 2008 resulting from reported 400+ mile range by Toyota. After extended negotiations, a CRADA agreement, SRNS CRADA No. CR-04-003, was signed on May 6, 2009. Subsequently, on June 30, 2009 SRNL and NREL participated in an all-day evaluation of the FCHV-adv with TEMA to determine the real-world driving range of this vehicle through on-road driving on an extended round-trip drive between Torrance and San Diego, California. SRNL and NREL observed the vehicles being refueled at Toyota's headquarters the day before the evaluation in Torrance, CA on June 29. At 8:00 AM on June 30, the vehicles departed Torrance north toward downtown Los Angeles, then west to the Pacific Coast Highway, and down to San Diego. After lunch the vehicles retraced their route back to Torrance. The traffic encountered was much heavier than anticipated, causing the vehicles to not return to Torrance until 9 PM. Each vehicle was driven by the same Toyota driver all day, with one SRNL/NREL observer in each vehicle the entire route. Data was logged by Toyota and analyzed by NREL. The maximum range of the FCHV-adv vehicles was calculated to be 431 miles under these driving conditions. This distance was calculated from the actual range of 331.5 miles during over 11 hours driving, plus 99.5 miles of

  12. Self-assembled drug delivery systems. Part 7: hepatocyte-targeted nanoassemblies of an adefovir lipid derivative with cytochrome P450-triggered drug release.

    PubMed

    Du, Lina; Wu, Lailong; Jin, Yiguang; Jia, Junwei; Li, Miao; Wang, Yu

    2014-09-10

    A novel strategy was used in the design of self-assembled drug delivery systems (SADDSs) in this study. The nanoassemblies of an amphiphilic adefovir lipid derivative were prepared and demonstrated to have the functions of hepatocyte targeting, enzyme-triggered drug release and high anti-hepatitis effect. An amphiphilic adefovir lipid derivative, N-lauroyl-1-(3-chlorophenyl)-1,3-propanyl phosphonyl adefovir (LCPA) was prepared and formed the nanoassemblies by injecting the mixture of LCPA and another amphiphilic polymer, d-galactide polyoxyethylene (20) cetyl ether (GPCE) (ca. 20:1, mol/mol) into water. The nanoassemblies were very stable and showed negative charge. LCPA was sensitive to the cytochrome P450 isozymes that were expressed predominantly in the hepatocytes to produce adefovir. GPCE contained a long hydrophilic chain and a galactose ligand targeting the asialoglycoprotein receptors overexpressed on the surface of hepatocytes. The nanoassemblies showed the long-circulating and liver targeting effects according to the results of pharmacokinetics, tissue distribution and fluorescence imagination after bolus intravenous administration of the nanoassemblies to the mice. The highly efficient hepatitis B treatment was achieved by 10 day continuous administration of the nanoassemblies to the HBV-infected mice. Many functions were combined in the nanoassemblies, including prodrug, molecular self-assembly, nanotechnology, long-circulating, hepatocyte targeting and hepatocyte over expressing enzyme-triggered drug release.

  13. Tenofovir has inferior efficacy in adefovir-experienced chronic hepatitis B patients compared to nucleos(t)ide-naïve patients

    PubMed Central

    Chung, Goh Eun; Cho, Eun Ju; Lee, Jeong-Hoon; Yoo, Jeong-ju; Lee, Minjong; Cho, Yuri; Lee, Dong Hyeon; Kim, Hwi Young; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan; Zoulim, Fabien

    2017-01-01

    Background/Aims A recent study reported that entecavir had inferior efficacy in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients compared to NA-naïve patients. We sought to compare the efficacy of tenofovir disoproxil fumarate (TDF) in NA-experienced and NA-naïve CHB patients. Methods We retrospectively enrolled 252 consecutive patients who had a serum hepatitis B virus (HBV) DNA level greater than 2,000 IU/mL at the initiation of TDF treatment and who received TDF for at least 6 months. Complete virologic suppression (CVS) was defined as undetectable serum HBV DNA. We generated a multivariate Cox proportional-hazard model to examine predictive factors that were independently associated with time to CVS. Results The mean age of patients was 48.2 years, and the cohort included 181 NA-naïve patients and 71 NA-experienced patients. The median duration of TDF treatment was 14.4 (interquartile range, 9.5-17.8) months. A total of 167 (92.3%) of 181 NA-naïve patients achieved CVS, and 60 (84.5%) of 71 NA-exposed patients achieved CVS. Forty-nine (89.1%) of 55 patients who previously took an NA aside from adefovir and 11 (68.8%) of 16 adefovir-experienced patients achieved CVS. In multivariable analysis, previous adefovir exposure significantly influenced time to CVS (hazard ratio, 0.37; 95% confidence interval, 0.19-0.72; P=0.003), after adjusting for HBeAg positivity, baseline HBV DNA level and cirrhosis. Conclusions Tenofovir had inferior efficacy in adefovir-experienced CHB patients compared to NA-naïve patients. The response of patients with previous adefovir exposure to TDF monotherapy should be monitored closely. PMID:28190329

  14. Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection.

    PubMed

    Fernández, J Alonso; Tapia, Lorena; Palomino, M Angélica; Larrañaga, Carmen; Peña, Mónica; Jaramillo, Héctor

    2005-01-01

    Adenovirus (ADV) and respiratory syncytial virus (RSV) are etiological agents of acute respiratory tract infection in infants. Long-term prognosis of ADV infection includes severe lung damage, bronchiectasis and hyperlucent lung, while RSV infection is associated with development of recurrent wheezing and subsequent asthma. These differences may be related to differences in the primary immune responses elicited by these viruses. In this paper, we investigated the type of cytokine responses and the magnitude of immune activation in ADV and RSV infections in infants. We examined plasma concentrations of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), soluble interleukin-2 receptor (sCD25) and soluble tumor necrosis factor receptor II (sTNFR-II) in previously healthy infants during the acute phase of primary ADV infection (n = 21) and RSV infection (n = 68), and in uninfected controls (n = 44). In ADV-infected infants, IFN-gamma plasma levels were significantly higher than those observed in RSV cases and the control group (p < 0.05). RSV cases did not show any differences in IFN-gamma plasma levels compared to the other groups. sCD25 levels were significantly higher in ADV- and RSV-infected infants than in controls (p < 0.0001), and higher in ADV than in RSV cases (p < 0.05). sTNFR-II levels were significantly higher in RSV- and ADV-infected infants than in controls (p < 0.0001, p < 0.05, respectively), and higher in RSV than in ADV infection (p < 0.05). No significant differences were observed in IL-10 plasma concentrations between the three groups. These results indicate that ADV and RSV infections in infants differ significantly with regard to the magnitude of production of interferon-gamma and soluble immune activation markers sCD25 and sTNFR-II. These immunological differences may be involved in the different clinical outcomes associated with these viral infections.

  15. Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal.

    PubMed

    Viganò, Mauro; Brocchieri, Alessandra; Spinetti, Angiola; Zaltron, Serena; Mangia, Giampaolo; Facchetti, Floriana; Fugazza, Alessandro; Castelli, Francesco; Colombo, Massimo; Lampertico, Pietro

    2014-12-01

    Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor widely used to treat patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. In the HBV monoinfection scenario, only two cases of TDF-associated Fanconi syndrome have been reported thus far. Here, we describe two additional patients with chronic hepatitis B (CHB) who developed a TDF-induced Fanconi syndrome that reverted after TDF withdrawal and had viral replication fully suppressed upon switching to entecavir (ETV). Though the overall risk of TDF associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular function should be monitored in patients exposed to TDF, especially when other renal risk factors or a history of previous exposure to adefovir dipivoxil (ADV) are present.

  16. AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study.

    PubMed

    Immonen, Arto; Vapalahti, Matti; Tyynelä, Kristiina; Hurskainen, Heleena; Sandmair, Anu; Vanninen, Ritva; Langford, Gillian; Murray, Neil; Ylä-Herttuala, Seppo

    2004-11-01

    Malignant glioma is a devastating brain tumor with no effective treatment. This randomised, controlled study involved 36 patients with operable primary or recurrent malignant glioma. Seventeen patients were randomized to receive AdvHSV-tk gene therapy (3 x 10(10) pfu) by local injection into the wound bed after tumor resection, followed by intravenous ganciclovir (GCV), 5 mg/kg twice daily for 14 days. The control group of 19 patients received standard care consisting of radical excision followed by radiotherapy in those patients with primary tumors. The primary end-point was survival as defined by death or surgery for recurrence. Secondary end-points were all-cause mortality and tumour progression as determined by MRI. Overall safety and quality of life were also assessed. Findings were also compared with historical controls (n = 36) from the same unit over 2 years preceding the study. AdvHSV-tk treatment produced a clinically and statistically significant increase in mean survival from 39.0 +/- 19.7 (SD) to 70.6 +/- 52.9 weeks (P = 0.0095, log-rank regression vs. randomized controls). The median survival time increased from 37.7 to 62.4 weeks. Six patients had increased anti-adenovirus antibody titers, without adverse effects. The treatment was well tolerated. It is concluded that AdvHSV-tk gene therapy with GCV is a potential new treatment for operable primary or recurrent high-grade glioma.

  17. Evolutionary trends of resistance mutational patterns of HBV reverse transcriptase over years (2002-2012) of different treatment regimens: The legacy of lamivudine/adefovir combination treatment.

    PubMed

    Vincenti, Donatella; Piselli, Pierluca; Solmone, Mariacarmela; D'Offizi, Gianpiero; Capobianchi, Maria R; Menzo, Stefano

    2017-03-16

    Antiviral therapy has revolutionized treatment of chronic HBV infections. First generation compounds, lamivudine and adefovir, displayed a high rate of treatment failures, and have been replaced by more potent compounds with high genetic barrier to resistance. However, the evolution of the virus towards resistance due the use of first generation compounds may still provide useful information for a better management of current antivirals. A single center sequence database including 705 HBV reverse transcriptase sequences from patients failing antiviral treatments (2002-2012) has been statistically analyzed to highlight viral evolution in relationship to the use of antiviral compounds and to their associations/sequencing in those years. The influence of viral genotypes and polymorphisms on resistance-related mutational patterns was also investigated. This study documents how, after the first years of antiviral therapy, the use of adefovir as an add-on strategy allowed a consistent reduction treatment failures. It also documents the effects of the initial misuse of entecavir in lamivudine experienced patients. In the latest years, the correct use of entecavir and the introduction of tenofovir allowed further curbing of resistance-related treatment failures, which virtually disappeared. Furthermore, the study allows a better understanding of how viral genotype (A vs D) conditions specific mutational pathways to resistance against lamivudine and entecavir, and demonstrates that the use of adefovir in lamivudine experienced patients is associated to peculiar mutational patterns, in particular A181V + F/Y221L. Despite some concern may arise for patients previously treated with lamivudine/adefovir, in sequence or combination, where the virus may have developed a lower genetic barrier against resistance to tenofovir, the outlook of antiviral treatment of HBV infection should be quite optimistic.

  18. Long-term efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients.

    PubMed

    Berg, Thomas; Zoulim, Fabien; Moeller, Bernd; Trinh, Huy; Marcellin, Patrick; Chan, Sing; Kitrinos, Kathryn M; Dinh, Phillip; Flaherty, John F; McHutchison, John G; Manns, Michael

    2014-04-01

    Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy. Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾ 1000 copies/ml despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾ 400 copies/ml (⩾ 69IU/ml) at or after week 24 could switch to open-label emtricitabine/tenofovir. Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/ml) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile. Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. The Neurospora Transcription Factor ADV-1 Transduces Light Signals and Temporal Information to Control Rhythmic Expression of Genes Involved in Cell Fusion

    PubMed Central

    Dekhang, Rigzin; Wu, Cheng; Smith, Kristina M.; Lamb, Teresa M.; Peterson, Matthew; Bredeweg, Erin L.; Ibarra, Oneida; Emerson, Jillian M.; Karunarathna, Nirmala; Lyubetskaya, Anna; Azizi, Elham; Hurley, Jennifer M.; Dunlap, Jay C.; Galagan, James E.; Freitag, Michael; Sachs, Matthew S.; Bell-Pedersen, Deborah

    2016-01-01

    Light and the circadian clock have a profound effect on the biology of organisms through the regulation of large sets of genes. Toward understanding how light and the circadian clock regulate gene expression, we used genome-wide approaches to identify the direct and indirect targets of the light-responsive and clock-controlled transcription factor ADV-1 in Neurospora crassa. A large proportion of ADV-1 targets were found to be light- and/or clock-controlled, and enriched for genes involved in development, metabolism, cell growth, and cell fusion. We show that ADV-1 is necessary for transducing light and/or temporal information to its immediate downstream targets, including controlling rhythms in genes critical to somatic cell fusion. However, while ADV-1 targets are altered in predictable ways in Δadv-1 cells in response to light, this is not always the case for rhythmic target gene expression. These data suggest that a complex regulatory network downstream of ADV-1 functions to generate distinct temporal dynamics of target gene expression relative to the central clock mechanism. PMID:27856696

  20. Testing the Snowpack Hypothesis for Gully Formation on Mars: Utilization of the Antarctic Dry Valleys (ADV) as a Terrestrial Analog

    NASA Astrophysics Data System (ADS)

    Morgan, G. A.

    2007-12-01

    The identification of young gullies on Mars suggests that liquid water has flowed across the martian surface during the recent climatic regime which has otherwise been considered to have been cold and dry. Research into the martian gullies suggest that water flow was concurrent with periods of higher obliquity, yet, no consensus has been reached regarding whether the water which eroded the gullies originated within internal confined aquifers or was sourced from surface/near-surface snow and ice deposits. We undertook research into gully formation in the ADV, a hyper-arid very cold polar desert which is considered the closest terrestrial analog to current Martian conditions. Our research identified two water sources: 1) perennial snow/ice deposits within the gully alcoves. 2). Annual accumulations of windblown snow trapped within the channels themselves. The melt produced by each source was found to be a function of: the local microclimatic zone, lithology, slopes and elevation. We also classified and mapped a range of meso-scale features (m to 10s of m scale) that can be compared to landforms identifiable within HiRISE images in order to further constrain gully formation processes and potential levels of recent activity on Mars. The exchange of salts between the runoff within the gullies and the surrounding ADV soils may also provide further insights into the generation of brines within polar deserts; this has important ramification regarding their development on Mars and the extent to which the freezing point can be depressed. Our findings demonstrate how gully erosion can take place in the absence of aquifer-fed sapping and within a region of low precipitation and thus provides further support for a surface source of water for the martian gullies. These results also underline the significance of snowmelt as a source of water for both ADV hydrological systems and ecosystems.

  1. Molecular identification of the advanced third-stage larvae (ADV L(3)) of Gnathostoma lamothei in Tabasco, Mexico.

    PubMed

    Hernández-Gómez, Raúl Enrique; Martínez-Salazar, Elizabeth Aurelia; López-Jiménez, Serapio; León-Règagnon, Virginia

    2010-03-01

    Advanced third-stage larvae (ADV L(3)) of Gnathostoma spp. were collected from the muscle tissue of three species of freshwater fish (i.e., Gobiomorus dormitor, Petenia splendida, and Parachromis managuensis) in Swamps of Centla, Tabasco, Mexico. Nine sequences of the ITS2 of the ribosomal DNA of Gnathostoma spp. were compared with sequences obtained from GenBank for G. binucleatum, G. lamothei, G. miyazakii, G. spinigerum, and G. turgidum. Sequences of the ADV L(3) from P. splendida (Isla Chinal), P. managuensis (Isla Chinal), and of two of the six larvae collected from G. dormitor (Tres Brazos), were identical to that of G. binucleatum (GenBank). Sequences from the other four larvae from G. dormitor (Tres Brazos) are identical to the sequence of G. lamothei (GenBank). This is the first record of the intermediate host of G. lamothei. The only species documented to cause human gnathostomiasis in the Americas is G. binucleatum. Our finding of G. binucleatum, and G. lamothei parasitizing the commercially important fish species, G. dormitor in Centla swamps, indicates the possibility of G. lamothei causing human gnathostomiasis in Mexico as well. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  2. A test of the ADV-based Reynolds flux method for in situ estimation of sediment settling velocity in a muddy estuary

    NASA Astrophysics Data System (ADS)

    Cartwright, Grace M.; Friedrichs, Carl T.; Smith, S. Jarrell

    2013-12-01

    Under conditions common in muddy coastal and estuarine environments, acoustic Doppler velocimeters (ADVs) can serve to estimate sediment settling velocity ( w s) by assuming a balance between upward turbulent Reynolds flux and downward gravitational settling. Advantages of this method include simple instrument deployment, lack of flow disturbance, and relative insensitivity to biofouling and water column stratification. Although this method is being used with increasing frequency in coastal and estuarine environments, to date it has received little direct ground truthing. This study compared in situ estimates of w s inferred by a 5-MHz ADV to independent in situ observations from a high-definition video settling column over the course of a flood tide in the bottom boundary layer of the York River estuary, Virginia, USA. The ADV-based measurements were found to agree with those of the settling column when the current speed at about 40 cm above the bed was greater than about 20 cm/s. This corresponded to periods when the estimated magnitude of the settling term in the suspended sediment continuity equation was four or more times larger than the time rate of change of concentration. For ADV observations restricted to these conditions, ADV-based estimates of w s (mean 0.48±0.04 mm/s) were highly consistent with those observed by the settling column (mean 0.45±0.02 mm/s). However, the ADV-based method for estimating w s was sensitive to the prescribed concentration of the non-settling washload, C wash. In an objective operational definition, C wash can be set equal to the lowest suspended solids concentration observed around slack water.

  3. Detection of relic gravitational waves in thermal case by using Adv.LIGO data of GW150914

    NASA Astrophysics Data System (ADS)

    Ghayour, Basem; Khodagholizadeh, Jafar

    2017-08-01

    The thermal spectrum of relic gravitational waves enhances the usual spectrum. Our analysis shows that there exist some chances for detection of the thermal spectrum in addition to the usual spectrum by comparison with sensitivity of Adv.LIGO of GW150914 and detector based on the maser light. The behavior of the inflation and reheating stages are often known as power law expansion like S(η )∝ η ^{1+β }, S(η )∝ η ^{1+β _s}, respectively, with constraints 1+β <0, 1+β s>0. The β and β _s have an unique effect on the shape of the spectrum. We find some values of the β and β _s by considering the mentioned comparison. As obtained, the results give us more information as regards the evolution of inflation and reheating stages.

  4. Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.

    PubMed

    Terao, Shuji; Shirakawa, Toshiro; Goda, Kazumasa; Kamidono, Sadao; Fujisawa, Masato; Gotoh, Akinobu

    2005-01-01

    Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model. In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days. The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 microM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model. The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.

  5. Work Domain Analysis of a Predecessor Sodium-cooled Reactor as Baseline for AdvSMR Operational Concepts

    SciTech Connect

    Ronald Farris; David Gertman; Jacques Hugo

    2014-03-01

    This report presents the results of the Work Domain Analysis for the Experimental Breeder Reactor (EBR-II). This is part of the phase of the research designed to incorporate Cognitive Work Analysis in the development of a framework for the formalization of an Operational Concept (OpsCon) for Advanced Small Modular Reactors (AdvSMRs). For a new AdvSMR design, information obtained through Cognitive Work Analysis, combined with human performance criteria, can and should be used in during the operational phase of a plant to assess the crew performance aspects associated with identified AdvSMR operational concepts. The main objective of this phase was to develop an analytical and descriptive framework that will help systems and human factors engineers to understand the design and operational requirements of the emerging generation of small, advanced, multi-modular reactors. Using EBR-II as a predecessor to emerging sodium-cooled reactor designs required the application of a method suitable to the structured and systematic analysis of the plant to assist in identifying key features of the work associated with it and to clarify the operational and other constraints. The analysis included the identification and description of operating scenarios that were considered characteristic of this type of nuclear power plant. This is an invaluable aspect of Operational Concept development since it typically reveals aspects of future plant configurations that will have an impact on operations. These include, for example, the effect of core design, different coolants, reactor-to-power conversion unit ratios, modular plant layout, modular versus central control rooms, plant siting, and many more. Multi-modular plants in particular are expected to have a significant impact on overall OpsCon in general, and human performance in particular. To support unconventional modes of operation, the modern control room of a multi-module plant would typically require advanced HSIs that would

  6. Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy.

    PubMed

    Lim, Lucy; Thompson, Alexander; Patterson, Scott; George, Jacob; Strasser, Simone; Lee, Alice; Sievert, William; Nicoll, Amanda; Desmond, Paul; Roberts, Stuart; Marion, Kaye; Bowden, Scott; Locarnini, Stephen; Angus, Peter

    2017-06-01

    Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study. A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily. Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma. Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Evaluating 2D models for fluvial bedform morphodynamics using flume experiments with profiling ADVs over a mobile sand bed

    NASA Astrophysics Data System (ADS)

    Mahon, R. C.; Naqshband, S.; McElroy, B. J.

    2016-12-01

    Bedforms are a primary observable topographic feature in most systems in which moving fluid interacts with a mobile sand bed. Their behavior is a classic morphodynamic problem in which local stress, transport, and topographic conditions result in complex local growth, migration, and deformation characteristics of forms. Numerous models exist describing individual relations between these conditions. However, models are commonly derived from small scale, limited measurements and theory. Measuring and describing the complete set of variables necessary for constraining the entire system has been hindered by instrumental limitations stemming from fine spatial and temporal scales of variability in all three components of the morphodynamic problem. We present a morphodynamic model resulting from the combination of existing descriptions of sediment entrainment/deposition as a function of local skin friction shear stress, a statement of conservation of sediment mass (Exner equation), and particle excursion lengths. This model is compared to data from flume experiments with a natural sand bed using repeat scans with a Nortek Vectrino II profiling acoustic Doppler velocimeter (ADV) mounted to a moving carriage. By utilizing the combination of three-component near bed velocity data coupled with bed topographic evolution along a two-dimensional transect we are able to fully constrain the three components of the morphodynamic system in a two-dimensional space. Initial qualitative results show that migration, growth, and decay of bedforms are consistent with expectation relative to the local gradients in near-bed shear stress conditions. The relation between topographic evolution and the local near-bed stress field, and the influence of cross-stream transport remain to be quantitatively assessed.

  8. MODFLOW-2000 : the U.S. Geological Survey modular ground-water model--documentation of the Advective-Transport Observation (ADV2) Package

    USGS Publications Warehouse

    Anderman, Evan R.; Hill, Mary Catherine

    2001-01-01

    Observations of the advective component of contaminant transport in steady-state flow fields can provide important information for the calibration of ground-water flow models. This report documents the Advective-Transport Observation (ADV2) Package, version 2, which allows advective-transport observations to be used in the three-dimensional ground-water flow parameter-estimation model MODFLOW-2000. The ADV2 Package is compatible with some of the features in the Layer-Property Flow and Hydrogeologic-Unit Flow Packages, but is not compatible with the Block-Centered Flow or Generalized Finite-Difference Packages. The particle-tracking routine used in the ADV2 Package duplicates the semi-analytical method of MODPATH, as shown in a sample problem. Particles can be tracked in a forward or backward direction, and effects such as retardation can be simulated through manipulation of the effective-porosity value used to calculate velocity. Particles can be discharged at cells that are considered to be weak sinks, in which the sink applied does not capture all the water flowing into the cell, using one of two criteria: (1) if there is any outflow to a boundary condition such as a well or surface-water feature, or (2) if the outflow exceeds a user specified fraction of the cell budget. Although effective porosity could be included as a parameter in the regression, this capability is not included in this package. The weighted sum-of-squares objective function, which is minimized in the Parameter-Estimation Process, was augmented to include the square of the weighted x-, y-, and z-components of the differences between the simulated and observed advective-front locations at defined times, thereby including the direction of travel as well as the overall travel distance in the calibration process. The sensitivities of the particle movement to the parameters needed to minimize the objective function are calculated for any particle location using the exact sensitivity

  9. Naturally occurring hepatitis B virus (HBV) variants with primary resistance to antiviral therapy and S-mutants with potential primary resistance to adefovir in Argentina.

    PubMed

    Cuestas, María L; Rivero, Cintia W; Minassian, María L; Castillo, Amalia I; Gentile, Emiliano A; Trinks, Julieta; León, Liliana; Daleoso, Graciela; Frider, Bernardo; Lezama, Carol; Galoppo, Marcela; Giacove, Gisela; Mathet, Verónica L; Oubiña, José R

    2010-07-01

    Hepatitis B virus (HBV) variants may either emerge in patients with chronic hepatitis B (CHB) as a result of positive selection pressure exerted by their own immune response, or during therapy with nucleos(t)ide analogues (NAs). Naturally occurring HBV variants with primary antiviral resistance are rarely observed. The aim of this study was to retrospectively analyze the (eventual) circulation of HBV variants with natural resistance to NAs currently used as therapy for CHB in Argentina. This study reports 13 cases of CHB-infected patients with natural antiviral resistance to at least one NA. Five of them were also carriers of S-variants that might escape the humoral immune system recognition with potential resistance to adefovir. In addition to the already reported A2 HBV subgenotype association to NAs natural resistance, E and F genotypes association to such resistance is described for the first time. These findings suggest that sequence analysis of the HBV reverse transcriptase might be an essential tool before starting antiviral therapy, in order to choose the proper NAs for optimizing the therapeutic management of chronically infected patients. Moreover, the circulation and transmission of S-mutants with resistance to such antiviral drugs should be of public health concern as they may represent an additional risk for the community. 2010 Elsevier B.V. All rights reserved.

  10. Examining the effect of length/width ratio on the hydro-dynamic behaviour in a DAF system using CFD and ADV techniques.

    PubMed

    Kwon, S B; Park, N S; Lee, S J; Ahn, H W; Wang, C K

    2006-01-01

    Dissolved air flotation (DAF) is a solid-liquid separation system that uses fine bubbles rising from the bottom to remove particles in water. In this study, we investigated the effect of L/W(L; length, W; width) on the hydrodynamic behavior in a DAF system using CFD (computational fluid dynamics) and ADV (acoustic Doppler velocimetry) technique. The factual full-scale DAF system, L/W ratio of 1:1, was selected and various UW ratio conditions (2:1, 3:1,4:1 and 5:1) were simulated with CFD. For modelling, 2-phase (gas-liquid) flow equations for the conservation of mass, momentum and turbulence quantities were solved using a Eulerian-Eulerian approach based on the assumption that a very small particle is applied in the DAF system. Also, for verification of CFD simulation results, we measured the actual velocity at some points in the full-scale DAF system with the ADV technique. Both the simulation and the measurement results were in good accordance with each other. We concluded that the L/W ratio and outlet geometry play an important role for flow pattern and fine bubble distribution in the flotation zone. In the ratio of 1:1, the dead zone is less than those in other cases. On the other hand, in the ratio of 5:1, the fine bubbles were more evenly distributed.

  11. Synthesis, characterization and biological activity of a niobium-substituted-heteropolytungstate on hepatitis B virus.

    PubMed

    Zhang, Hong; Qi, Yanfei; Ding, Yanhua; Wang, Juan; Li, Qingmei; Zhang, Jingzhou; Jiang, Yanfang; Chi, Xiumei; Li, Juan; Niu, Junqi

    2012-02-15

    To synthesise and characterize the polyoxometalate Cs(2)K(4)Na[SiW(9)Nb(3)O(40)]·H(2)O 1 for its anti-hepatitis B virus (HBV) properties by using the HepG2.2.15 cell. The methylthiazol tetrazolium assay was used to evaluate the growth inhibitory effect of Compound 1 on HepG2.2.15 cell. By using ELISA and real-time PCR, respectively, the presence of extracellular hepatitis B surface antigen (HBsAg), e antigen (HBeAg), and HBV DNA were measured. The levels of intracellular HBV DNA and mRNA were determined by using Southern blot or reverse-transcription-PCR, respectively. Intracellular distribution of antigen were measured by Western blot. A 1995 μmol/L concentration of the commercially-available hepatitis B drug, adefovir dipivoxil (ADV), was required to achieve 50% cytotoxicity against cultured cells (CC(50)) by day nine; in contrast, only 1747 μmol/L of Compound 1 was required for the same result. Treatment of HepG2.2.15 cells with Compound 1 effectively suppress the secretion of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. IC(50) values were determined to be 80 μmol/L for HBsAg, 75 μmol/L for HBeAg and 3.72 μmol/L for supernatant HBV DNA at day nine post-exposure, as opposed to 266, 296, 30.09 μmol/L, respectively, for ADV. Intracellular HBV DNA, mRNA and antigen were also found to be decreased by Compound 1. The same dose of ADV yielded a significantly less robust inhibitory effect. Compound 1 can clear HBV from hepatic cells and may represent a therapeutic agent to treat HBV infection.

  12. Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC.

    PubMed

    Zhou, Q; Chen, E; Chen, L; Nong, Y; Cheng, X; He, M; Tang, H

    2014-01-01

    The long-term benefits of antiviral treatment are limited by the resistance of hepatitis B virus (HBV). However, the effect of interferon (IFN)α treatment on drug-resistant HBVs is so far unknown. We, therefore, investigated the effects of IFN-α inducer poly-IC on the replication of HBV mutants resistant to drugs such as lamivudine (LAM), adefovir dipivoxil (ADV) and entecavir (ETV) in mice. HBV DNA and HBV DNA intermediate (RI) were employed as markers of the virus replication and 2',5'-oligoadenylate synthase (OAS) mRNA as a marker of IFN-α/β induction. Poly-IC inhibited wtHBV replication and increased levels of OAS mRNA. Compared to the wt virus, the capacity of virus replication was reduced in most LAMr and ETVr mutants except those with mutations rtM(204V+L180M+V173L), and was similary in the ADVr mutants except rt(A121V+N236T). The virus replication was reduced after poly-IC treatment with LAMr and ADVr mutants similary to the wt virus. In contrast, ETVr mutants were resistant to the poly-IC treatment. In conclusion, the capacity of HBV replication and the sensitivity to IFN therapy are influenced by drug-resistant mutations. The IFN therapy may effectively inhibit HBV replication in particular in patients with LAMr or ADVr mutations but not in patients with ETVr mutations.

  13. In vitro evaluation of 9-(2-phosphonylmethoxyethyl)adenine ester analogues, a series of anti-HBV structures with improved plasma stability and liver release.

    PubMed

    Liao, Sha; Fan, Shi-Yong; Liu, Qin; Li, Chang-Kun; Chen, Jia; Li, Jing-Lai; Zhang, Zhi-Wei; Zhang, Zhen-Qing; Zhong, Bo-Hua; Xie, Jian-Wei

    2014-11-01

    Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis and hepatocellular carcinoma, but few drugs are available for its treatment. Acyclic nucleoside phosphonates (ANPs) have remarkable antivirus activities but are not easily absorbed from the gastrointestinal tract and accumulate in the kidneys, resulting in nephrotoxicity. Therefore, there is a need to find effective liver site-specific prodrugs. The dipivaloyloxymethyl ester of 9-(2-phosphonylmethoxyethyl)adenine (PMEA)-adefovir dipivoxil (ADV)-is a first-line therapy drug for chronic hepatitis B with a low therapeutic index because of renal toxicity and low hepatic uptake. In this study, a series of PMEA derivatives were synthesized to enhance plasma stability and liver release. The metabolic stability of ADV (Chemical I) and its two analogues (Chemicals II and III) was evaluated in rat plasma and liver homogenate in vitro. An ion-pair reverse-phase HPLC-UV method and a hybrid ion trap and high-resolution time-of-flight mass spectrometry (LC-IT-TOF-MS) were used to evaluate the degradation rate of the analogues and to identify their intermediate metabolites, respectively. Chemicals I and II were hydrolyzed by cleavage of the C-O bond to give monoesters. Sufficient enzymatic activation in the liver homogenate through a relatively simple metabolic pathway, in addition to a favorable stability profile in rat plasma, made Chemical II an optimal candidate. Next, six analogues based on the structure of Chemical II were synthesized and evaluated in plasma and liver homogenate. Compared to Chemical II, these compounds generated less active PMEA levels in rat liver homogenate. Therefore, chemical modification of Chemical II may lead to new promising PMEA derivatives with enhanced plasma stability and liver activation.

  14. 75 FR 49233 - Amendments to Form ADV

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... Act, an adviser is a fiduciary whose duty is to serve the best interests of its clients, which... that relationship. \\3\\ Proxy Voting by Investment Advisers, Investment Advisers Act Release No. IA-2106... relationship that allows for broader access to other financial services and may seek an adviser with financial...

  15. Selected highlights from the 5th Conference on Retroviruses and Opportunistic Infections.

    PubMed

    Bartnof, H S

    1998-04-01

    The 5th Conference on Retroviruses and Opportunistic Infections included 837 abstracts and oral presentations on clinical and basic science aspects of HIV. A major theme of the conference was the effectiveness of newer anti-HIV therapies, and there were many sessions dealing with combination treatments, including six-drug treatments. Results of studies with several drugs, including abacavir, efavirenz, amprenavir, PMPA Prodrug, adefovir dipivoxil, hydroxyurea, and protease inhibitors in several combinations are summarized. Treatments for opportunistic infections, including MAC, CMV retinitis, herpesvirus, and tuberculosis, are also presented.

  16. Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B

    SciTech Connect

    Stoop, Jeroen N. . E-mail: j.n.stoop@erasmusmc.nl; Molen, Renate G. van der . E-mail: r.vandermolen@erasmusmc.nl; Kuipers, Ernst J. . E-mail: e.j.kuipers@erasmusmc.nl; Kusters, Johannes G. . E-mail: j.g.kusters@erasmusmc.nl; Janssen, Harry L.A. . E-mail: h.janssen@erasmusmc.nl

    2007-04-25

    Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were collected at baseline and during treatment. In parallel to the decline in viral load, we found a decline in circulating Treg, combined with an increase in HBV core antigen-specific IFN-{gamma} production and proliferation. The production of IL10 did not decrease during therapy. In conclusion, adefovir induced viral load reduction results in a decline of circulating Treg together with a partial recovery of the immune response.

  17. The intracellular activation of lamivudine (3TC) and determination of 2′-deoxycytidine-5′-triphosphate (dCTP) pools in the presence and absence of various drugs in HepG2 cells

    PubMed Central

    Kewn, Stephen; Hoggard, Patrick G; Sales, Sean D; Johnson, Mark A; Back, David J

    2000-01-01

    Aims Lamivudine (3TC, 2′-deoxy-3′-thiacytidine) requires intracellular metabolism to its active 5′-triphosphate, 3TC-5′-triphosphate (3TCTP), to inhibit the replication of hepatitis B virus (HBV). We have investigated the activation of 3TC, in the presence and absence of a range of compounds, in HepG2 cells. The intracellular levels of the endogenous competitor of 3TCTP, 2′-deoxycytidine-5′-triphosphate (dCTP), were also determined and 3TCTP/dCTP ratios calculated. Methods The effects of a number of compounds on 3TC (3H; 1 μM) phosphorylation were investigated by radiometric h.p.l.c. dCTP levels were determined using a template primer extension assay. 3TCTP/dCTP ratios were calculated from these results. Results The phosphorylation of 3TC was significantly increased in the presence of either hydroxyurea (HU), methotrexate (MTX), or fludarabine (FLU). For example, at 100 μm HU, control 3TCTP levels were increased to 361% of control, whereas at 100 μm FLU, control 3TCTP levels were increased to 155%. dCTP pools were significantly reduced in the presence of HU and FLU, at 100 μm concentrations only. However, for all the above three compounds investigated, the ratio of 3TCTP/dCTP was favourably enhanced (e.g. at 1 μm MTX, 255% of control). Neither ganciclovir (GCV), lobucavir (LCV), penciclovir (PCV), adefovir dipivoxil (ADV), nor foscarnet (FOS) had any significant effects on 3TC phosphorylation or dCTP pools. Conclusions These results suggest that the activity of 3TC may be potentiated when combined with one of the modulators studied. The lack of an interaction between 3TC and the other anti-HBV agents is reassuring. These in vitro studies can be used as an initial screen to examine potential interactions at the phosphorylation level. PMID:11136299

  18. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028170 (23 March 2011) --- NASA astronaut Andrew Feustel, STS-134 mission specialist, participates in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. The facility includes moving scenes of full-sized International Space Station components over a simulated Earth. Photo credit: NASA or National Aeronautics and Space Administration

  19. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028166 (23 March 2011) --- European Space Agency astronaut Roberto Vittori (right) and NASA astronaut Andrew Feustel, both STS-134 mission specialists, participate in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. The facility includes moving scenes of full-sized International Space Station components over a simulated Earth. Photo credit: NASA or National Aeronautics and Space Administration

  20. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028161 (23 March 2011) --- NASA astronauts Greg Chamitoff (foreground), STS-134 mission specialist; and Greg H. Johnson, pilot, participate in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. The facility includes moving scenes of full-sized International Space Station components over a simulated Earth. Photo credit: NASA or National Aeronautics and Space Administration

  1. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028163 (23 March 2011) --- NASA astronauts Greg Chamitoff (foreground), STS-134 mission specialist; and Greg H. Johnson, pilot, participate in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. The facility includes moving scenes of full-sized International Space Station components over a simulated Earth. Photo credit: NASA or National Aeronautics and Space Administration

  2. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028158 (23 March 2011) --- NASA astronaut Greg H. Johnson, STS-134 pilot, participates in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  3. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028160 (23 March 2011) --- NASA astronauts Greg H. Johnson (right), STS-134 pilot; and Greg Chamitoff, mission specialist, are pictured during an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  4. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028157 (23 March 2011) --- NASA astronaut Greg H. Johnson (left), STS-134 pilot; along with European Space Agency astronaut Roberto Vittori (second left) and NASA astronauts Andrew Feustel and Greg Chamitoff (seated), all mission specialists, participate in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  5. STS-134 crew during PDRS PRF ADV (AMS) traiining

    NASA Image and Video Library

    2011-03-23

    JSC2011-E-028173 (23 March 2011) --- European Space Agency astronaut Roberto Vittori (right) and NASA astronaut Andrew Feustel, both STS-134 mission specialists, participate in an exercise in the systems engineering simulator in the Avionics Systems Laboratory at NASA's Johnson Space Center. The facility includes moving scenes of full-sized International Space Station components over a simulated Earth. Photo credit: NASA or National Aeronautics and Space Administration

  6. Light-Emitting Diodes: Phosphorescent Nanocluster Light-Emitting Diodes (Adv. Mater. 2/2016).

    PubMed

    Kuttipillai, Padmanaban S; Zhao, Yimu; Traverse, Christopher J; Staples, Richard J; Levine, Benjamin G; Lunt, Richard R

    2016-01-13

    On page 320, R. R. Lunt and co-workers demonstrate electroluminescence from earth-abundant phosphorescent metal halide nanoclusters. These inorganic emitters, which exhibit rich photophysics combined with a high phosphorescence quantum yield, are employed in red and near-infrared light-emitting diodes, providing a new platform of phosphorescent emitters for low-cost and high-performance light-emission applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Tissue Boundaries: Mimicking Tissue Boundaries by Sharp Multiparameter Matrix Interfaces (Adv. Healthcare Mater. 15/2016).

    PubMed

    Sapudom, Jiranuwat; Rubner, Stefan; Martin, Steve; Pompe, Tilo

    2016-08-01

    Engineering interfaces of extracellular compartments mimicking native tissues is key to study cell behavior in a physiologically relevant context and for a successful translation of these new biomaterials engineering principles in regenerative and therapeutic applications. Tilo Pompe and co-workers demonstrate a strategy to engineer multiparameter matrix interfaces using a sequential reconstitution of two well-defined Collagen I based matrices on page 1861. Such matrix interfaces trigger cell migration directionality normal to the interface plane in dependence on matrix pore size.

  8. Nanoscale Electrodes: Nanoscale Electrodes for Flexible Electronics by Swelling Controlled Cracking (Adv. Mater. 30/2016).

    PubMed

    Zhao, Qiang; Wang, Wenjun; Shao, Jinyou; Li, Xiangming; Tian, Hongmiao; Liu, Lu; Mei, Xuesong; Ding, Yucheng; Lu, Bingheng

    2016-08-01

    The fabrication of nanospaced electrodes on a flexible substrate is a great challenge. W. Wang, J. Shao, and co-workers propose a novel approach to fabricate nanogap electrodes for flexible electronics using a swelling-controlled cracking method, which is described on page 6337. This method has the advantages of high applicability, parallel manufacturing capacity, and compatibility with flexible substrates. It provides a new way to create high-performance flexible electronics in a cost-efficient fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Artificial Synapses: Organometal Halide Perovskite Artificial Synapses (Adv. Mater. 28/2016).

    PubMed

    Xu, Wentao; Cho, Himchan; Kim, Young-Hoon; Kim, Young-Tae; Wolf, Christoph; Park, Chan-Gyung; Lee, Tae-Woo

    2016-07-01

    A synapse-emulating electronic device based on organometal halide perovskite thin films is described by T.-W. Lee and co-workers on page 5916. The device successfully emulates important characteristics of a biological synapse. This work extends the application of organometal halide perovskites to bioinspired electronic devices, and contributes to the development of neuromorphic electronics.

  10. Carbon Nanotubes: Printed Carbon Nanotube Electronics and Sensor Systems (Adv. Mater. 22/2016).

    PubMed

    Chen, Kevin; Gao, Wei; Emaminejad, Sam; Kiriya, Daisuke; Ota, Hiroki; Nyein, Hnin Yin Yin; Takei, Kuniharu; Javey, Ali

    2016-06-01

    Printed electronics and sensors enable new applications ranging from low-cost disposable analytical devices to large-area sensor networks. Recent progress in printed carbon nanotube electronics in terms of materials, processing, devices, and applications is discussed on page 4397 by A. Javey and co-workers. The research challenges and opportunities regarding the processing and system-level integration are also discussed for enabling of practical applications.

  11. Gold Nanocups: Colloidal Gold Nanocups with Orientation-Dependent Plasmonic Properties (Adv. Mater. 30/2016).

    PubMed

    Jiang, Ruibin; Qin, Feng; Liu, Yejing; Ling, Xing Yi; Guo, Jun; Tang, Minghua; Cheng, Si; Wang, Jianfang

    2016-08-01

    On page 6322, J. F. Wang and co-workers report a wet-chemistry method for the preparation of colloidal Au nanocups and their plasmonic properties. The Au nanocups are prepared through single-vertex-initiated Au deposition on PbS nano-octahedrons and subsequent selective dissolution of PbS. Owing to the orientation-dependent coupling strengths, the obtained Au nanocups display orientation-dependent plasmonic properties and Raman enhancements when deposited on substrates.

  12. Antimonene: Mechanical Isolation of Highly Stable Antimonene under Ambient Conditions (Adv. Mater. 30/2016).

    PubMed

    Ares, Pablo; Aguilar-Galindo, Fernando; Rodríguez-San-Miguel, David; Aldave, Diego A; Díaz-Tendero, Sergio; Alcamí, Manuel; Martín, Fernando; Gómez-Herrero, Julio; Zamora, Félix

    2016-08-01

    On page 6332, J. Gómez-Herrero, F. Zamora, and co-workers describe the isolation of antimonene, a new allotrope of antimony that consists of a single layer of atoms. They obtain antimonene flakes by the scotch tape method; these flakes are highly stable in ambient conditions and even when immersed in water. The 1.2 eV gap calculated in this study suggests potential applications in optoelectronics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine

  14. Clinical course of chronic hepatitis B patients receiving nucleos(t)ide analogues after virological breakthrough during monotherapy with lamivudine.

    PubMed

    De Francesco, Maria Antonia; Gargiulo, Franco; Spinetti, Angiola; Zaltron, Serena; Giagulli, Cinzia; Caccuri, Francesca; Castelli, Francesco; Caruso, Arnaldo

    2015-01-01

    Little is known about the optimal management of patients with chronic hepatitis B (CHB) who develop drug resistance. The aim of this study was to investigate the effectiveness of different drug regimens in chronically HBV-infected patients. HBV viral load was determined using a bDNA assay and the substitutions in HBV-DNA were studied by polymerase sequencing test. The study involved 38 patients who experienced a therapeutic failure to lamivudine (LAM). The sequential treatments used were: LAM + adefovir (ADV), LAM + tenofovir (TDF), entecavir (ETV) monotherapy, ADV monotherapy and TDF monotherapy. Similar activity against HBV replication was observed with all drug regimens. Of the patients treated with LAM, 44% developed resistance mutations. The rt M204I mutation was observed more frequently. Sequential ADV add-on LAM and TDF therapy induced the appearance of resistance in 3/18 (16.6%) and in 1/8 (5.5%) treated patients, respectively. Genotype D was the most prevalent (78.9%), followed by genotype A (13%), genotype E (5.2%) and genotype C (2.6%). Our study showed that baseline serum HBV DNA is an important predictor of virologic response and that virologic breakthrough is significantly associated with the insurgence of genotypic resistance.

  15. NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

    PubMed Central

    Shen, Xiaokun; Fu, Binqing; Liu, Yanyan; Guo, Chuang; Ye, Ying; Sun, Rui; Li, Jiabin; Tian, Zhigang; Wei, Haiming

    2016-01-01

    A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30+ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-γ+ CD107+ NK cells. In addition, the increase in NKp30+ NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-α-2b alone. However, in the non-responders, these NKp30+ NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30+ NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-α-2b therapy. PMID:27941937

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. Copyright 2005 Prous Science. All rights reserved.

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abciximab, acetylcysteine, adefovir dipivoxil, alfuzosin hydrochloride, aliskiren fumarate, alosetron hydrochloride, amlodipine besilate, apomorphine hydrochloride, atazanavir, atorvastatin, atorvastatin calcium, atrasentan; Basiliximab, beraprost sodium, bevacizumab, bivalirudin, botulinum toxin type A, botulinum toxin type B; Celecoxib, cetuximab, cilansetron, cilomilast; Daclizumab, darbepoetin alfa, docetaxel, duloxetine hydrochloride; Efalizumab, efavirenz, eletriptan,, entecavir, eplerenone, epoetin alfa, eptifibatide, esomeprazole magnesium. ezetimibe; Filgrastim, finasteride, fluvastatin sodium, follitropin alfa; Gemcitabine, gemeprost, ghrelin (human); HE-2000; Infliximab, 111In-Pentetreotide, interferon alfa-2 alpha, interferon alfa-2 beta, interferon beta-1 alpha, irbesartan, irinotecan hydrochloride; Ketamine hydrochloride; L-778123, lafutidine, lamivudine, lamivudine/zidovudine, latanoprost, letrozole, licofelone, lopinavir, losartan potassium, loxiglumide, lubeluzole; Magnesium sulfate, MeGLA, meloxicam, mycophenolate mofetil; NBI-6024, nelfinavir mesilate, nesiritide, nevirapine, niacin, NN-2211; Octreotide, orlistat; PC-515, peginterferon alfa-2 alpha, peginterferon alfa-2b, pemetrexed disodium, pibrozelesin hydrochloride, pimagedine, pirfenidone, pitavastatin calcium, premarin/trimegestone, prucalopride; Rabeprazole sodium; reboxetine, risedronate sodium, ritonavir, rituximab, rofecoxib, roflumilast, rosuvastatin calcium; Sertraline, sibutramine hydrochloride monohydrate, sildenafil citrate, spironolactone, stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride

  19. A cutting-edge view on the current state of antiviral drug development.

    PubMed

    De Clercq, Erik

    2013-11-01

    Prominent in the current stage of antiviral drug development are: (i) for human immunodeficiency virus (HIV), the use of fixed-dose combinations (FDCs), the most recent example being Stribild(TM); (ii) for hepatitis C virus (HCV), the pleiade of direct-acting antivirals (DAAs) that should be formulated in the most appropriate combinations so as to obtain a cure of the infection; (iii)-(v) new strategies (i.e., AIC316, AIC246, and FV-100) for the treatment of herpesvirus infections: herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), respectively; (vi) the role of a new tenofovir prodrug, tenofovir alafenamide (TAF) (GS-7340) for the treatment of HIV infections; (vii) the potential use of poxvirus inhibitors (CMX001 and ST-246); (viii) the usefulness of new influenza virus inhibitors (peramivir and laninamivir octanoate); (ix) the position of the hepatitis B virus (HBV) inhibitors [lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate (TDF)]; and (x) the potential of new compounds such as FGI-103, FGI-104, FGI-106, dUY11, and LJ-001 for the treatment of filoviruses (i.e., Ebola). Whereas for HIV and HCV therapy is aimed at multiple-drug combinations, for all other viruses, HSV, CMV, VZV, pox, influenza, HBV, and filoviruses, current strategies are based on the use of single compounds. © 2013 Wiley Periodicals, Inc.

  20. Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis.

    PubMed

    Kim, V; Abreu, R M; Nakagawa, D M; Baldassare, R M; Carrilho, F J; Ono, S K

    2016-03-01

    Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNα) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and LILACS--for randomized controlled trials evaluating PEG-IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies. © 2015 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

  1. Entecavir: a new treatment option for chronic hepatitis B.

    PubMed

    Zoulim, Fabien

    2006-05-01

    Because of the slow kinetics of viral clearance and the spontaneous genetic variability of hepatitis B virus (HBV), antiviral therapy of chronic hepatitis B remains a clinical challenge. Despite the recent development of lamivudine, adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic HBV infection, there is still a major need for new antiviral compounds. Entecavir, a guanosine analog, has been recently approved in US for the therapy of chronic hepatitis B and its registration is expected soon in Europe. Extensive studies have been performed to characterize its antiviral activity in enzymatic and tissue culture models, as well as in animal models of HBV infection. In clinical trails, entecavir administration was associated with a significantly more potent viral suppression compared to lamivudine, and a significant advantage in terms of biochemical and histological improvement compared to lamivudine. Entecavir was tolerated as well as lamivudine in these phase III trials. No case of resistance was detected after two years of therapy in nucleoside naive patients. Treatment of patients with lamivudine failure requires a higher dosage of entecavir and induces a significant decline in viraemia levels. However, 10% of these patients developed entecavir resistance after two years of therapy. The availability of entecavir as a new treatment option is providing clinicians more choice to keep both viral replication and liver disease under control. This provides new hope for improved treatment concepts for chronic HBV infection.

  2. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-12-01

    [Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant; Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib, Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab, Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human), Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab, Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin, Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir, Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride, Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles, Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate, Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone, Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban, Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin, Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide, Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate, Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost, Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib

  3. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  4. Bis[(2,2-dimethyl-propano-yloxy)meth-yl] {[2-(6-amino-9H-purin-9-yl)eth-oxy]meth-yl}phospho-nate-succinic acid (2/1).

    PubMed

    Jung, Sungyup; Ha, Jeong-Myeong; Kim, Il Won

    2012-03-01

    The title compound, C(20)H(32)N(5)O(8)P·0.5C(4)H(6)O(4), is composed of two 9-{2-[bis-(pivaloyloxymeth-oxy)phosphinylmeth-oxy]eth-yl}adenine, commonly known as adefovir dipivoxil (AD), mol-ecules linked to the carb-oxy-lic acid groups of succinic acid (SA). The asymmetric unit contains one mol-ecule of AD and half a mol-ecule of SA, which sits on an inversion center. Both adenine units in the two AD mol-ecules make AD-SA N-H⋯O and SA-AD O-H⋯N hydrogen bonds to SA. In addition, the inter-molecular AD-AD N-H⋯O-P hydrogen bond serves to stabilize the cocrystal. There is also a π-π stacking inter-action [inter-planar spacing 3.34 (19) Å] between adjacent inversion-related adenine groups.

  5. A screening strategy for the discovery of drugs that reduce C/EBPβ-LIP translation with potential calorie restriction mimetic properties

    PubMed Central

    Zaini, Mohamad A.; Müller, Christine; Ackermann, Tobias; Reinshagen, Jeanette; Kortman, Gertrud; Pless, Ole; Calkhoven, Cornelis F.

    2017-01-01

    An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA. We showed before that suppression of LIP in mice, reflecting reduced mTORC1-signaling at the C/EBPβ level, results in CR-type of metabolic improvements. Hence, we aim to find possibilities to pharmacologically down-regulate LIP in order to induce CR-mimetic effects. We engineered a luciferase-based cellular reporter system that acts as a surrogate for C/EBPβ-mRNA translation, emulating uORF-dependent C/EBPβ-LIP expression under different translational conditions. By using the reporter system in a high-throughput screening (HTS) strategy we identified drugs that reduce LIP. The drug Adefovir Dipivoxil passed all counter assays and increases fatty acid β-oxidation in a hepatoma cell line in a LIP-dependent manner. Therefore, these drugs that suppress translation into LIP potentially exhibit CR-mimetic properties. PMID:28198412

  6. Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure.

    PubMed

    Zoulim, Fabien; Białkowska-Warzecha, Jolanta; Diculescu, Mircea Mihai; Goldis, Adrian Eugen; Heyne, Renate; Mach, Tomasz; Marcellin, Patrick; Petersen, Jörg; Simon, Krzysztof; Bendahmane, Soumaya; Klauck, Isabelle; Wasiak, Wojciech; Janssen, Harry L A

    2016-09-01

    In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen. In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks. At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed. In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.

  7. A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients

    PubMed Central

    Liu, Kehui; Xiang, Xiaogang; Bao, Rebecca; Chen, Rong; Liu, Yunye; Xie, Jingdong; Guo, Qing; Bao, Shisan; Xie, Qing; Wang, Hui

    2016-01-01

    Entecavir (ETV) is a potent viral replication inhibitor for chronic hepatitis B (CHB) patients. To investigate the efficacy of ETV in Chinese nucleos(t)ide(NA)-experienced CHB patients. Among 89 CHB patients with ETV monotherapy for ≥6 months, 33/89 (37%) or 56/89 (73%) were NA-naïve or NA-experienced. During a median follow-up of 5.75 years, all NA-naïve CHB patients achieved VR without genotypic ETV-resistance. However, VR was observed in 50/56 (~90%) of NA-experienced CHB patients during a median follow-up of 4.75 years. Antiviral efficacy was not reduced in patients with previous lamivudine (LAM) with/without LAM-resistance (HR 0.465; 95% CI 0.196–1.100; p > 0.05) (HR 0.472; 95% CI 0.205–1.091; p > 0.05). Patients with a primary treatment failure to adefovir (ADV) had a reduced probability of achieving VR compared to NA-naïve (HR 0.496; 95% CI 0.287–0.857; p < 0.01). Previous ADV-experienced patients with a partial VR (HR 1.253; 95% CI 0.429–3.665; p > 0.05) did not influence antiviral response to ETV. The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance. ETV may still be an option in ADV-experienced patients with a partial VR, but not advised in patients with a primary treatment failure to ADV. PMID:27364728

  8. Wearable Strain Sensors: Carbonized Silk Fabric for Ultrastretchable, Highly Sensitive, and Wearable Strain Sensors (Adv. Mater. 31/2016).

    PubMed

    Wang, Chunya; Li, Xiang; Gao, Enlai; Jian, Muqiang; Xia, Kailun; Wang, Qi; Xu, Zhiping; Ren, Tianling; Zhang, Yingying

    2016-08-01

    A novel carbonized plain-weave silk-fabric-based wearable strain sensor is proposed by Y. Y. Zhang and co-workers on page 6640. The sensor can be stretched up to 500% with high sensitivity in a wide strain range and can be assembled into wearable devices for the detection of both large and subtle human activities, showing great potential in human-motion detection and robotics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Nanocarbon Paper: Flexible, High Temperature, Planar Lighting with Large Scale Printable Nanocarbon Paper (Adv. Mater. 23/2016).

    PubMed

    Bao, Wenzhong; Pickel, Andrea D; Zhang, Qing; Chen, Yanan; Yao, Yonggang; Wan, Jiayu; Fu, Kun Kelvin; Wang, Yibo; Dai, Jiaqi; Zhu, Hongli; Drew, Dennis; Fuhrer, Michael; Dames, Chris; Hu, Liangbing

    2016-06-01

    On page 4684, C. Dames, L. Hu and co-workers report highly efficient, broadband lighting from printed hybrid nanocarbon structures with carbon nanotubes and reduced graphene oxides. The fast response and excellent stability of the flexible lighting can find applications in a range of emerging applications where the shape and format, as well as being lightweight, are important. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Carbon Nanotubes: Ultrabreathable and Protective Membranes with Sub-5 nm Carbon Nanotube Pores (Adv. Mater. 28/2016).

    PubMed

    Bui, Ngoc; Meshot, Eric R; Kim, Sangil; Peña, José; Gibson, Phillip W; Wu, Kuang Jen; Fornasiero, Francesco

    2016-07-01

    A flexible membrane with sub-5 nm single-walled carbon nanotube (SWNT) pores is developed by F. Fornasiero and co-workers, as described on page 5871, for application as a key component of protective, yet breathable fabrics. The SWNTs are shown to enable exceptionally fast transport of water vapor under a concentration driving force. Thus, membranes having SWNTs as moisture-conductive pores feature outstanding breathability and provide a high degree of protection from biological threats by size exclusion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Microspheres: Microfluidic Generation of Monodisperse and Photoreconfigurable Microspheres for Floral Iridescence-Inspired Structural Colorization (Adv. Mater. 26/2016).

    PubMed

    Yeo, Seon Ju; Park, Kyung Jin; Guo, Kai; Yoo, Pil J; Lee, Seungwoo

    2016-07-01

    Flowering plants have advanced their colorization strategies to divide incoming white light into spatially sequenced vivid colors, especially by using 2D grating diffractive motifs. On page 5268, P. J. Yoo, S. Lee, and co-workers conceive a new idea for a microfluidic approach to mimic this wonderful biological strategy and its practical application to the color encoding of colloidal particles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Ferromagnetism: Sulfur Doping Induces Strong Ferromagnetic Ordering in Graphene: Effect of Concentration and Substitution Mechanism (Adv. Mater. 25/2016).

    PubMed

    Tuček, Jiří; Błoński, Piotr; Sofer, Zdeněk; Šimek, Petr; Petr, Martin; Pumera, Martin; Otyepka, Michal; Zbořil, Radek

    2016-07-01

    R. Zbořil and co-workers show that doping a graphene lattice with sulfur induces magnetic centers which display ferromagnetic order below ≈62 K. As described on page 5045, sulfur doping promotes magnetically active configurations resembling the gamma-thiothiapyrone motif. Enhanced magnetic properties of sulfur-doped graphene are attributed to two unpaired electrons from each sulfur atom injected into the graphene conducting band where they are delocalized between the S and C atoms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Cancer Immunotherapy: Comprehensive Mechanism Analysis of Mesoporous-Silica-Nanoparticle-Induced Cancer Immunotherapy (Adv. Healthcare Mater. 10/2016).

    PubMed

    Wang, Xiupeng; Li, Xia; Yoshiyuki, Kazuko; Watanabe, Yohei; Sogo, Yu; Ohno, Tadao; Tsuji, Noriko M; Ito, Atsuo

    2016-05-01

    A plain mesoporous silica (MS) nanoparticle without any immunomodulatory molecules enhances anti-cancer immunity in vivo. On page 1169, X.P. Wang, N. M. Tsuji, A. Ito and co-workers show that a plain MS nanoparticle promotes both Th1 and Th2 immune responses, and enhances the effector memory of CD4(+) and CD8(+) T cell populations in the three most important immune organs (bone marrow, lymph node and spleen) of mice. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Batteries: encapsulated monoclinic sulfur for stable cycling of li-s rechargeable batteries (adv. Mater. 45/2013).

    PubMed

    Moon, San; Jung, Young Hwa; Jung, Wook Ki; Jung, Dae Soo; Choi, Jang Wook; Kim, Do Kyung

    2013-12-03

    On page 6547 Do Kyung Kim, Jang Wook Choi and co-workers describe a highly aligned and carbon-encapsulated sulfur cathode synthesized with an AAO template that exhibits a high and long cycle life, and the best rate capability based on the complete encapsulation of sulfur (physical) and implementation of the monoclinic sulfur phase (chemical). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Phosphorene: Enhanced Photoresponse from Phosphorene-Phosphorene-Suboxide Junction Fashioned by Focused Laser Micromachining (Adv. Mater. 21/2016).

    PubMed

    Lu, Junpeng; Carvalho, Alexandra; Wu, Jing; Liu, Hongwei; Tok, Eng Soon; Neto, Antonio H Castro; Özyilmaz, Barbaros; Sow, Chorng Haur

    2016-06-01

    On page 4090, B. Özyilmaz, C. H. Sow, and co-workers use a focused laser beam to modify the surface of a phosphorene device. With a simple focused laser beam, a part of the phosphorene can be scanned and converted into phosphorene-suboxide species, leaving behind a functional and active phosphorene-phosphorene suboxide junction in the device. Once the junction is formed, the photoresponsivity and photocurrent distribution of the device can be significantly altered with a qualitative difference in behavior. Photovoltaic-like behavior is observed, which is not found in the pristine sample. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Pulsed Lasers: Pulsed Lasers Employing Solution-Processed Plasmonic Cu3- x P Colloidal Nanocrystals (Adv. Mater. 18/2016).

    PubMed

    Liu, Zeke; Mu, Haoran; Xiao, Si; Wang, Rongbin; Wang, Zhiteng; Wang, Weiwei; Wang, Yongjie; Zhu, Xiangxiang; Lu, Kunyuan; Zhang, Han; Lee, Shuit-Tong; Bao, Qiaoliang; Ma, Wanli

    2016-05-01

    Q. Bao, W. Ma and co-workers demonstrate the usage of plasmonic Cu3-x P colloidal nanocrystals as a new type of tunable saturable absorber for the generation of high-energy pulses in a fiber laser. As described on page 3535, these low-cost, solution-processed, next-generation nonlinear optical materials can be harnessed for applications in signal processing and optical communication. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Organosilica: Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic-Inorganic Hybridization into Frameworks (Adv. Mater. 17/2016).

    PubMed

    Chen, Yu; Shi, Jianlin

    2016-05-01

    Organic-inorganic hybrid materials can combine the advantages of organic and inorganic materials, and overcome their drawbacks accordingly. On page 3235, Y. Chen and J. L. Shi review and discuss research progress on the design, synthesis, structure, and composition control of organic-inorganic hybrid mesoporous organosilica nanoparticles (MONs). Extensive applications of MONs in nanotechnology, mainly in nanomedicine, nanocatalysis and nanofabrication are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Adv. Simulation for Additive Manufacturing: 11/2014 Wkshp. Report for U.S. DOE/EERE/AMO

    SciTech Connect

    Turner, John A.; Babu, Sudarsanam Suresh; Blue, Craig A.

    2015-07-01

    The overarching question for the workshop was as following: How do we best utilize advanced modeling and high-performance computing (HPC) to address key challenges and opportunities in order to realize the full potential of additive manufacturing; and what are the key challenges of additive manufacturing to which modeling and simulation can contribute solutions, and what will it take to meet these challenges?

  19. Flexible Electronics: High Pressure Chemical Vapor Deposition of Hydrogenated Amorphous Silicon Films and Solar Cells (Adv. Mater. 28/2016).

    PubMed

    He, Rongrui; Day, Todd D; Sparks, Justin R; Sullivan, Nichole F; Badding, John V

    2016-07-01

    On page 5939, J. V. Badding and co-workers describe the unrolling of a flexible hydrogenated amorphous silicon solar cell, deposited by high-pressure chemical vapor deposition. The high-pressure deposition process is represented by the molecules of silane infiltrating the small voids between the rolled up substrate, facilitating plasma-free deposition over a very large area. The high-pressure approach is expected to also find application for 3D nanoarchitectures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 3D Printing: 3D Printing of Shape Memory Polymers for Flexible Electronic Devices (Adv. Mater. 22/2016).

    PubMed

    Zarek, Matt; Layani, Michael; Cooperstein, Ido; Sachyani, Ela; Cohn, Daniel; Magdassi, Shlomo

    2016-06-01

    On page 4449, D. Cohn, S. Magdassi, and co-workers describe a general and facile method based on 3D printing of methacrylated macromonomers to fabricate shape-memory objects that can be used in flexible and responsive electrical circuits. Such responsive objects can be used in the fabrication of soft robotics, minimal invasive medical devices, sensors, and wearable electronics. The use of 3D printing overcomes the poor processing characteristics of thermosets and enables complex geometries that are not easily accessible by other techniques.

  1. Flexible Batteries: Hierarchical Assemblies of Carbon Nanotubes for Ultraflexible Li-Ion Batteries (Adv. Mater. 31/2016).

    PubMed

    Ahmad, Shahab; Copic, Davor; George, Chandramohan; De Volder, Michael

    2016-08-01

    An advanced battery architecture composed of 3D carbon nanotube (CNT) current collectors is used to mitigate stresses in flexible batteries. On Page 6705, C. George, M. De Volder, and co-workers describe the fabrication process and characteristics of this new generation of ultraflexible batteries, which show high rate and cyclablility. These batteries may find applications in the powering of flexible displays and logics.

  2. Liquid Metals: Stretchable, High-k Dielectric Elastomers through Liquid-Metal Inclusions (Adv. Mater. 19/2016).

    PubMed

    Bartlett, Michael D; Fassler, Andrew; Kazem, Navid; Markvicka, Eric J; Mandal, Pratiti; Majidi, Carmel

    2016-05-01

    An all-soft-matter composite consisting of liquid metal microdroplets embedded in a soft elastomer matrix is presented by C. Majidi and co-workers on page 3726. This composite exhibits a high dielectric constant while maintaining exceptional elasticity and compliance. The image shows the composite's microstructure captured by 3D X-ray imaging using a nano-computed tomographic scanner.

  3. Nanoparticle Assemblies: Nanoparticle Clusters: Assembly and Control Over Internal Order, Current Capabilities, and Future Potential (Adv. Mater. 27/2016).

    PubMed

    Stolarczyk, Jacek K; Deak, Andras; Brougham, Dermot F

    2016-07-01

    Clusters or assemblies of nanoparticles exhibit unique features which arise from the enhancement of properties of single nanoparticles or due to new collective properties. On page 5400, D. F. Brougham and co-workers review the role of nanoparticle interactions in controlling cluster formation, and classify the assembly mechanisms. Emerging applications for surface-enhanced Raman scattering (SERS), optical labeling, light harvesting, magnetic resonance imaging (MRI), hyperthermia, photocatalysis, enrichment, and separation are presented. Cover image by Christoph Hohmann, Nanosystems Initiative Munich (NIM).

  4. Perovskite Solar Cells: High Efficiency Pb-In Binary Metal Perovskite Solar Cells (Adv. Mater. 31/2016).

    PubMed

    Wang, Zhao-Kui; Li, Meng; Yang, Ying-Guo; Hu, Yun; Ma, Heng; Gao, Xing-Yu; Liao, Liang-Sheng

    2016-08-01

    On page 6695, X. Y. Gao, L.-S. Liao, and co-workers describe the fabrication of mixed Pb-In perovskite solar cells, using indium (III) chloride and lead (II) chloride with methylammonium iodide. A maximum power conversion efficiency as high as 17.55% is achieved owing to the high quality of the perovskites with multiple ordered crystal orientations. This work demonstrates the possibility of substituting the Pb (II) by using In (III), which opens a broad route to fabricating alloy perovskite solar cells with mitigated ecological impact. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Nanowires: Quantitative Probing of Cu(2+) Ions Naturally Present in Single Living Cells (Adv. Mater. 21/2016).

    PubMed

    Lee, Junho; Lee, Hwa-Rim; Pyo, Jaeyeon; Jung, Youngseob; Seo, Ji-Young; Ryu, Hye Guk; Kim, Kyong-Tai; Je, Jung Ho

    2016-06-01

    Quantitative probing of the Cu(2+) ions naturally present in single living cells is accomplished by a probe made from a quantum-dot-embedded-nanowire waveguide. After inserting the active nanowire-based waveguide probe into single living cells, J. H. Je and co-workers directly observe photoluminescence (PL) quenching of the embedded quantum dots by the Cu(2+) ions diffused into the probe as described on page 4071. This results in quantitative measurement of intracellular Cu(2+) ions.

  6. High-Resolution Electronics: Spontaneous Patterning of High-Resolution Electronics via Parallel Vacuum Ultraviolet (Adv. Mater. 31/2016).

    PubMed

    Liu, Xuying; Kanehara, Masayuki; Liu, Chuan; Sakamoto, Kenji; Yasuda, Takeshi; Takeya, Jun; Minari, Takeo

    2016-08-01

    On page 6568, T. Minari and co-workers describe spontaneous patterning based on the parallel vacuum ultraviolet (PVUV) technique, enabling the homogeneous integration of complex, high-resolution electronic circuits, even on large-scale, flexible, transparent substrates. Irradiation of PVUV to the hydrophobic polymer surface precisely renders the selected surface into highly wettable regions with sharply defined boundaries, which spontaneously guides a metal nanoparticle ink into a series of circuit lines and gaps with the widths down to a resolution of 1 μm. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Treatment Efficacy and Safety of Tenofovir-Based Therapy in Chronic Hepatitis B: A Real Life Cohort Study in Korea

    PubMed Central

    Ahn, Hyo Jun; Song, Myeong Jun; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    2017-01-01

    Background & Aims We evaluated the efficacy and safety of Tenofovir disoproxil fumarate (TDF)-based therapy in naïve and treatment-experienced chronic hepatitis B (CHB) patients for 96 weeks in Korean real life practice. Methods A total of 209 CHB patients with a prescription for TDF at the Seoul and Daejeon St. Mary’s hospitals were enrolled from December 2012 to October 2014. We compared the virological responses and evaluated the renal safety of treatment-naive and treatment-experienced patients. Results An overall complete virological response (CVR) was achieved in 80.4% and 84.6% of patients at weeks 48 and 96, respectively. In a subgroup analysis, CVR at week 96 was present in 88.4%, 75.0%, 75.5%, and 83.3% of participants in the lamivudine-resistant (LAM-R) group, adefovir-resistant (ADV-R) group, multidrug-resistant (MDR) group, and suboptimal response group, respectively. In a multivariate analysis, ADV-R, MDR, hepatitis B virus DNA, and hepatitis B e antigen were independent predictors for CVR. With regard to renal safety, diabetes mellitus, cirrhosis, and an initial low estimated glomerular filtration rate were independent factors affecting creatinine elevation (≥0.5 mg/dL). Moreover, two patients with DM and cirrhosis experienced TDF-related Fanconi syndrome. Conclusions TDF-based therapy demonstrated sustained viral suppression and favorable safety during a 2-year treatment period. The LAM-R and suboptimal response groups showed comparable efficacy to the naïve group, while the ADV-R and MDR groups were significantly associated with a low CVR. Close monitoring of renal safety should be mandatory when treating CHB patients receiving TDF, particularly those with DM and cirrhosis. PMID:28114428

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-09-01

    12B75, 274150; Abacavir sulfate/lamivudine, Abatacept, Ad2/HIF-1alpha, Adalimumab, Adefovir, Adefovir dipivoxil, AGN-201904-Z, AIDSVAX, Albinterferon alfa-2b, Alemtuzumab, Aliskiren fumarate, Alvimopan hydrate, Amlodipine besylate/atorvastatin calcium, Amlodipine besylate/Olmesartan medoxomil, Ammonium tetrathiomolybdate, Amodiaquine, Apaziquone, Aprepitant, Arsenic trioxide, Artesunate/Amodiaquine, Ascorbic acid, Atazanavir sulfate, Atazanavir/ritonavir, Atomoxetine hydrochloride, Atrigel-Leuprolide, Axitinib; Bevacizumab, Binodenoson, Bortezomib, Bovine lactoferrin; Calcipotriol/betamethasone dipropionate, Carisbamate, Certolizumab pegol, Ciclesonide, Conivaptan hydrochloride, CP-690550, CP-751871, Cypher; Dapivirine, Darbepoetin alfa, Darunavir, Dasatinib, del-1 Genemedicine, Denosumab, Desloratadine, Dexlansoprazole, DiabeCell, Drospirenone/ethinylestradiol, DTaP-HepB-IPV, Duloxetine hydrochloride, Dutasteride; Eculizumab, Eldecalcitol, Eletriptan, Emtricitabine, Entecavir, Eritoran tetrasodium, Ertapenem sodium, Escitalopram oxalate, Eslicarbazepine acetate, Esomeprazole magnesium, Estradiol acetate, Eszopiclone, ETEC vaccine, Etoricoxib, Exenatide, Ezetimibe; Fluticasone furoate, Fosmidomycin, Fosmidomycin/clindamycin; Glutamine; Heat Shock Protein 10, Hepatitis B hyperimmunoglobulin, HIV vaccine, Hochuekki-to, Human Albumin, Human papillomavirus vaccine; Immune globulin subcutaneous [human], IMP-321, Interferon omega, ISIS-301012, Istaroxime; Japanese encephalitis virus vaccine; Latanoprost/timolol maleate, Lenalidomide, Linaclotide acetate, Lumiracoxib, LY-517717; Malaria vaccine, MAS-063D, Meningitis B vaccine, Mepolizumab, Methylnaltrexone bromide, Micafungin sodium, MK-0822A, Morphine glucuronide, Morphine hydrochloride, Mycophenolic acid sodium salt; Natalizumab, Nesiritide, Norelgestromin/ethinyl estradiol, NT-201; Oblimersen sodium, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Omalizumab, Otamixaban; Paclitaxel nanoparticles

  9. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

    PubMed

    Ke, Weixia; Zhang, Chi; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

    2016-11-01

    Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. For Chinese chronic hepatitis B patients, ETV is still the most cost

  10. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  13. [Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016].

    PubMed

    Horváth, Gábor; Gerlei, Zsuzsanna; Gervain, Judit; Lengyel, Gabriella; Makara, Mihály; Pár, Alajos; Rókusz, László; Szalay, Ferenc; Tornai, István; Werling, Klára; Hunyady, Béla

    2017-02-01

    Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2017, 158(Suppl. 1) 23-35.

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331.

  17. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection.

    PubMed

    Buti, Maria; Tsai, Naoky; Petersen, Joerg; Flisiak, Robert; Gurel, Selim; Krastev, Zahary; Aguilar Schall, Raul; Flaherty, John F; Martins, Eduardo B; Charuworn, Prista; Kitrinos, Kathryn M; Subramanian, G Mani; Gane, Edward; Marcellin, Patrick

    2015-05-01

    Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks). We assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients. Patients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks). Of 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA < 69 IU/mL), 80.0 % achieved serum alanine aminotransferase normalization, and in HBeAg-positive patients, 84/154 (54.5 %) and 25/154 (11.8 %) achieved HBeAg and HBsAg loss, respectively. One/375 (0.3 %) HBeAg-negative patients achieved HBsAg loss. No resistance to TDF was detected through 7 years. During the open-label phase, grade 3/4 drug-related adverse events were uncommon (1.0 %); ten (1.7 %) patients had elevation of serum creatinine ≥ 0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336). Long-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.

  18. Rolling circle amplification, a powerful tool for genetic and functional studies of complete hepatitis B virus genomes from low-level infections and for directly probing covalently closed circular DNA.

    PubMed

    Margeridon, Séverine; Carrouée-Durantel, Sandra; Chemin, Isabelle; Barraud, Luc; Zoulim, Fabien; Trépo, Christian; Kay, Alan

    2008-09-01

    Complete characterization of the biological properties of hepatitis B virus (HBV) variants requires the generation of full-length genomes. The aim of this study was to develop new tools for the efficient full-length genome amplification of virus from samples with low viral loads. Rolling circle amplification (RCA) was used to amplify full-length HBV genomes from both sera and liver biopsy samples from chronic HBV carriers. Serum-derived relaxed circular HBV DNA could be amplified only after completion and ligation of plus-strand DNA. Covalently closed circular DNA (cccDNA) from liver biopsies could be amplified directly from as few as 13 copies, using RCA, followed by a full-length HBV PCR. Three serial liver biopsy samples were obtained from a lamivudine-resistant patient who cleared detectable serum HBV after adefovir dipivoxil was added to the lamivudine therapy and then seroconverted to anti-HBs. Only the genomes from the last biopsy specimen obtained after the emergence of lamivudine resistance contained the lamivudine resistance-associated mutations rtL180M and rtM204V ("rt" indicates reverse transcriptase domain). Defective genomes were also found in this biopsy sample. Genomes cloned from the liver biopsy specimens were transfected into HuH7 cells to study their replication competence and their susceptibility to lamivudine. RCA is a powerful tool for amplifying full-length HBV genomes and will be especially useful for the study of occult or inactive HBV infections and patients undergoing antiviral treatment. It can also be used to probe HBV cccDNA, the crucial intermediate in viral persistence and the archive of resistance mutations.

  19. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha.

    PubMed

    Cao, Zhenhuan; Liu, Yali; Ma, Lina; Lu, Junfeng; Jin, Yi; Ren, Shan; He, Zhimin; Shen, Chengli; Chen, Xinyue

    2017-10-01

    Hepatitis B surface antigen (HBsAg) clearance represents a clinical cure, although the clearance rate is extremely low. The aim of this study was to evaluate the feasibility and safety profiles of pegylated-interferon α-2a (PEG-IFNα-2a) as a therapeutic option for inactive HBsAg carriers. There were 144 inactive HBsAg carriers enrolled and divided into a therapeutic group (102 subjects) and a control group (42 subjects). PEG-IFNα-2a and PEG-IFNα-2a combined with adefovir dipivoxil were used for treatment group subjects with hepatitis B virus DNA <20 IU/mL and 20 IU/mL ≤ hepatitis B virus DNA < 2,000 IU/mL, respectively. Total therapy duration was no more than 96 weeks. HBsAg clearance and seroconversion rates at therapeutic weeks 48 and 96 were used to evaluate the therapeutic efficacy. Per protocol analysis showed that the HBsAg clearance rate and seroconversion rate in the treatment group were 29.8% and 20.2% at week 48 and increased to 44.7% and 38.3% at week 96, respectively. However, the HBsAg clearance rate in the control group was 2.4% at weeks 48 and 96, and no subject achieved seroconversion. The quantitative HBsAg levels and changes during the early period of treatment (at week 12 and week 24) as well as the alanine aminotransferase elevation at week 12 were strong predictors of HBsAg clearance. The adverse events were similar to those with treatment for chronic hepatitis B patients. High rates of HBsAg clearance and seroconversion could be achieved by PEG-IFNα-2a-based treatments and the treatments were relatively safe for inactive HBsAg carriers. (Hepatology 2017;66:1058-1066). © 2017 by the American Association for the Study of Liver Diseases.

  20. Photodetectors: Broad Detection Range Rhenium Diselenide Photodetector Enhanced by (3-Aminopropyl)Triethoxysilane and Triphenylphosphine Treatment (Adv. Mater. 31/2016).

    PubMed

    Jo, Seo-Hyeon; Park, Hyung-Youl; Kang, Dong-Ho; Shim, Jaewoo; Jeon, Jaeho; Choi, Seunghyuk; Kim, Minwoo; Park, Yongkook; Lee, Jaehyeong; Song, Young Jae; Lee, Sungjoo; Park, Jin-Hong

    2016-08-01

    The effects of triphenylphosphine (PPh3 ) and (3-amino-propyl)triethoxysilane (APTES) on a rhenium diselenide (ReSe2 ) photodetector are systematically studied by J.-H. Park and co-workers on page 6711 in comparison with a conventional MoS2 device. A very high performance ReSe2 photodetector is demonstrated, which has a broad photodetection range, high photoresponsivity (1.18 × 10(6) A W(-1) ), and fast photoswitching speed (rising/decaying time: 58/263 ms). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Conducting Membranes: Unprecedented Perovskite Oxyfluoride Membranes with High-Efficiency Oxygen Ion Transport Paths for Low-Temperature Oxygen Permeation (Adv. Mater. 18/2016).

    PubMed

    Zhu, Jiawei; Liu, Gongping; Liu, Zhengkun; Chu, Zhenyu; Jin, Wanqin; Xu, Nanping

    2016-05-01

    Perovskite oxyfluoride (ABO3-δ Fγ ) membranes for low-temperature oxygen permeation are reported by W. Jin and co-workers. As described on page 3511, using mixed ionic and electronic conducting (MIEC) oxides, this new type of membrane outperforms current state-of-the-art MIEC membranes and satisfies commercial requirements at low temperatures (<923 K). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Tumor Bioimaging: Morphology-Tailoring of a Red AIEgen from Microsized Rods to Nanospheres for Tumor-Targeted Bioimaging (Adv. Mater. 16/2016).

    PubMed

    Li, Yongsheng; Shao, Andong; Wang, Yao; Mei, Ju; Niu, Dechao; Gu, Jinlou; Shi, Ping; Zhu, Weihong; Tian, He; Shi, Jianlin

    2016-04-01

    Y. Li, W. Zhu, and co-workers develop a convenient and versatile "make-up" strategy to modulate the micro-sized rods of a near-infrared-emissive AIEgen probe integrated into nanospheres via a self-assembly encapsulation process, as presented on page 3187. The obtained nanospheres outperform microrods in terms of brightness, photostability, biocompatibility, tumor-accumulation, and targeting ability, making them perfect bioprobes for tumor-targeted bioimaging. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Flexible Electronics: Theoretical and Experimental Studies of Epidermal Heat Flux Sensors for Measurements of Core Body Temperature (Adv. Healthcare Mater. 1/2016).

    PubMed

    Zhang, Yihui; Chad Webb, Richard; Luo, Hongying; Xue, Yeguang; Kurniawan, Jonas; Cho, Nam Heon; Krishnan, Siddharth; Li, Yuhang; Huang, Yonggang; Rogers, John A

    2016-01-01

    On page 119, J. A. Rogers and co-workers present theoretical approaches, modeling algorithms, materials, and device designs for the noninvasive measurement of core body temperature by using multiple differential temperature sensors that attach softly and intimately onto the surface of the skin. The image shows the construction of differential temperature sensors using thermally insulating foam as the separation material. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Intracellular Delivery: Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology (Adv. Healthcare Mater. 10/2016).

    PubMed

    Zhu, Xiaoyue; Yuen, Muk Fung; Yan, Li; Zhang, Zhenyu; Ai, Fujin; Yang, Yang; Yu, Peter K N; Zhu, Guangyu; Zhang, Wenjun; Chen, Xianfeng

    2016-05-01

    G. Zhu, W. Zhang, X. Chen, and co-workers show on page 1157 that diamond needle arrays can efficiently deliver biomolecules into living cells. The study paves the way to a wide application of the nanonneedle treatment by systematically investigating the influence of the treatment on metabolic signal pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Water Splitting: Strongly Coupled Nafion Molecules and Ordered Porous CdS Networks for Enhanced Visible-Light Photoelectrochemical Hydrogen Evolution (Adv. Mater. 24/2016).

    PubMed

    Zheng, Xue-Li; Song, Ji-Peng; Ling, Tao; Hu, Zhen Peng; Yin, Peng-Fei; Davey, Kenneth; Du, Xi-Wen; Qiao, Shi-Zhang

    2016-06-01

    T. Ling, X.-W. Du, S. Z. Qiao, and co-workers report strongly coupled Nafion molecules and ordered-porous CdS networks for visible-light water splitting. The image conceptually shows how the three-dimensional ordered structure effectively harvests incoming light. As described on page 4935, the inorganic CdS skeleton is homogeneously passivated by the organic Nafion molecules to facilitate hydrogen generation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Transition Metal Dichalcogenides: Morphological Engineering of CVD-Grown Transition Metal Dichalcogenides for Efficient Electrochemical Hydrogen Evolution (Adv. Mater. 29/2016).

    PubMed

    Ji, Qingqing; Zhang, Yu; Shi, Jianping; Sun, Jingyu; Zhang, Yanfeng; Liu, Zhongfan

    2016-08-01

    On page 6207, Y. Zhang, Z. Liu and co-workers describe morphologically engineered 2D-MoS2 for the facilitation of efficient hydrogen evolution reaction. Two pathways to achieve such a purpose are highlighted, either by non-equilibrium growth of MoS2 dendrites or by high-density nucleation of MoS2 nanoflakes directly on the electrode materials. Future research directions are also proposed and discussed to further enhance the efficiency of such unique catalysts. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Phosphorescent OLEDs: Sky-Blue Phosphorescent OLEDs with 34.1% External Quantum Efficiency Using a Low Refractive Index Electron Transporting Layer (Adv. Mater. 24/2016).

    PubMed

    Shin, Hyun; Lee, Jeong-Hwan; Moon, Chang-Ki; Huh, Jin-Suk; Sim, Bomi; Kim, Jang-Joo

    2016-06-01

    J.-J. Kim and co-workers achieve highly efficient blue organic light-emitting diodes (OLEDs) using a low-refractive-index layer. As described on page 4920, an external quantum efficiency over 34% is achieved, owing to the low refractive index of the materials. A milepost and a shining entrance of the castle are the metaphor indicating the way to highly efficient blue OLEDs. On the way to the castle, the depicted chemical structures serve as the light-emitting layer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Dye-Sensitized Solar Cells: The Future of Using Earth-Abundant Elements in Counter Electrodes for Dye-Sensitized Solar Cells (Adv. Mater. 20/2016).

    PubMed

    Briscoe, Joe; Dunn, Steve

    2016-05-01

    Sustainability is an important concept generating traction in the research community. To be really sustainable the full life cycle of a product needs to be carefully considered. A key aspect of this is using elements that are either readily recycled or accessible in the Earth's biosphere. Jigsawing these materials together in compounds to address our future energy needs represents a great opportunity for the current generation of researchers. On page 3802, S. Dunn and J. Briscoe summarize the performance of a selection of alternative materials to replace platinum in the counter electrodes of dye-sensitized solar cells.

  9. Microfluidics-Based Biosensors: A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays (Adv. Healthcare Mater. 11/2016).

    PubMed

    Li, Xiao; Liu, Xinyu

    2016-06-01

    The first microfluidic paper-based origami nano-biosensor featuring zinc oxide nanowires and an electrochemical impedance spectroscopy biosensing mechanism, for label-free, ultrasensitive immunoassays is reported by X. Li and X. Liu on page 1326. The sensor consists of cellulose paper, a carbon ink electrode, and zinc oxide nanowires directly grown on the top. Possible parallelization of assays and high storage stability render the sensor promising for clinical diagnostics applications.

  10. 3D Tissue Culturing: Tissue in Cube: In Vitro 3D Culturing Platform with Hybrid Gel Cubes for Multidirectional Observations (Adv. Healthcare Mater. 13/2016).

    PubMed

    Hagiwara, Masaya; Kawahara, Tomohiro; Nobata, Rina

    2016-07-01

    An in vitro 3D culturing platform enabling multidirectional observations of 3D biosamples is presented by M. Hagiwara and co-workers on page 1566. 3D recognition of a sample structure can be achieved by facilitating multi-directional views using a standard microscope without a laser system. The cubic platform has the potential to promote 3D culture studies, offering easy handling and compatibility with commercial culture plates at a low price tag. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. From channel-forming ionic liquid crystals exhibiting humidity-induced phase transitions to nanostructured ion-conducting polymer membranes (adv. Mater. 26/2013).

    PubMed

    Zhang, Heng; Li, Lei; Möller, Martin; Zhu, Xiaomin; Rueda, Jaime J Hernandez; Rosenthal, Martin; Ivanov, Dimitri A

    2013-07-12

    A novel wedge-shaped amphiphilic molecule bearing a sulfonate group at the tip displays humidity-induced phase transitions from a hexagonal columnar structure to a bicontinuous cubic phase. The mesophases can be frozen by photopolymerization of acrylic end-groups resulting in free-standing membranes with different topology of ionic nanochannels. The obtained membranes with a well-ordered ionic channel structure hold promise for applications in separation and catalysis.

  12. Conducting Fibers: Downsized Sheath-Core Conducting Fibers for Weavable Superelastic Wires, Biosensors, Supercapacitors, and Strain Sensors (Adv. Mater. 25/2016).

    PubMed

    Wang, Hongyan; Liu, Zunfeng; Ding, Jianning; Lepró, Xavier; Fang, Shaoli; Jiang, Nan; Yuan, Ninyi; Wang, Run; Yin, Qu; Lv, Wei; Liu, Zhongsheng; Zhang, Mei; Ovalle-Robles, Raquel; Inoue, Kanzan; Yin, Shougen; Baughman, Ray H

    2016-07-01

    Using intelligent textiles for clothing represents one possibility for weavable superelastic conducting fibers that can store energy, sense body motions, and detect biochemicals. On page 4998, S. Yin, R. H. Baughman, and co-workers demonstrate that these hair-like-diameter fibers, comprising buckled carbon nanotube sheaths on a rubber core, can be used as glucose sensors, supercapacitors, ultrafast strain sensors, and electrical interconnectors. The performance of these structures is maintained also under giant strain. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 3D Printing: 3D Printing of Conductive Complex Structures with In Situ Generation of Silver Nanoparticles (Adv. Mater. 19/2016).

    PubMed

    Fantino, Erika; Chiappone, Annalisa; Roppolo, Ignazio; Manfredi, Diego; Bongiovanni, Roberta; Pirri, Candido Fabrizio; Calignano, Flaviana

    2016-05-01

    On page 3712, E. Fantino, A. Chiappone, and co-workers fabricate conductive 3D hybrid structures by coupling the photo-reduction of metal precursors with 3D printing technology. The generated structures consist of metal nanoparticles embedded in a polymer matrix shaped into complex multilayered architectures. 3D conductive structures are fabricated with a digital light-processing printer incorporating silver salt into photocurable formulations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Corrigendum to "Dynamics of a flexible tethered satellite system utilising various materials for coplanar and non-coplanar models" [Adv. Space Res. 56 (2015) 648-663

    NASA Astrophysics Data System (ADS)

    Hong, Aaron Aw Teik; Varatharajoo, Renuganth

    2015-12-01

    The authors would like to thank Dr. N.A. Ismail for some of the discussions found in her thesis as these discussions have facilitated to achieve some of the results published in this article. Therefore, Ismail, N.A., "The Dynamics of a Flexible Motorised Momentum Exchange Tether (MMET)", PhD. thesis, University of Glasgow, UK, pp. 26-41, 2012 is cited accordingly herein. The thesis was missed out from the reference list in the original version of this article due to an oversight with no other intention. Similarly the thesis by Stevens, R.E., "Optimal Control of Electrodynamic Tether Satellites", PhD. thesis, Air Force Institute of Technology, USA, pp. 87-96, 2008 is referred for a further readership completeness.

  15. Cellular Microcultures: Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing (Adv. Healthcare Mater. 9/2016).

    PubMed

    McCracken, Joselle M; Badea, Adina; Kandel, Mikhail E; Gladman, A Sydney; Wetzel, David J; Popescu, Gabriel; Lewis, Jennifer A; Nuzzo, Ralph G

    2016-05-01

    R. Nuzzo and co-workers show on page 1025 how compositional differences in hydrogels are used to tune their cellular compliance by controlling their polymer mesh properties and subsequent uptake of the protein poly-l-lysine (green spheres in circled inset). The cover image shows pyramid micro-scaffolds prepared using direct ink writing (DIW) that differentially direct fibroblast and preosteoblast growth in 3D, depending on cell motility and surface treatment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Sensors: A Highly Sensitive Diketopyrrolopyrrole-Based Ambipolar Transistor for Selective Detection and Discrimination of Xylene Isomers (Adv. Mater. 21/2016).

    PubMed

    Wang, Bin; Huynh, Tan-Phat; Wu, Weiwei; Hayek, Naseem; Do, Thu Trang; Cancilla, John C; Torrecilla, Jose S; Nahid, Masrur Morshed; Colwell, John M; Gazit, Oz M; Puniredd, Sreenivasa Reddy; McNeill, Christopher R; Sonar, Prashant; Haick, Hossam

    2016-06-01

    An ambipolar organic field-effect transistor (OFET) based on poly(diketopyrrolopyrrole-terthiophene) (PDPPHD-T3) is shown by P. Sonar, H. Haick, and co-workers on page 4012 to sensitively detect xylene isomers at low to 40 ppm level in multiple sensing features. Combined with pattern-recognition algorithms, a sole ambipolar FET sensor, rather than arrays of sensors, is able to discriminate highly similar xylene structural isomers from each other.

  17. Photoacoustic Imaging: Semiconducting Oligomer Nanoparticles as an Activatable Photoacoustic Probe with Amplified Brightness for In Vivo Imaging of pH (Adv. Mater. 19/2016).

    PubMed

    Miao, Qingqing; Lyu, Yan; Ding, Dan; Pu, Kanyi

    2016-05-01

    Despite the great potential of photoacoustic imaging in the life sciences, the development of smart activatable photoacoustic probes remains elusive. On page 3662, K. Pu and co-workers report a facile nanoengineering approach based on semiconducting oligomer nano-particles to develop ratiometric photoacoustic probes with amplified brightness and enhanced sensing capability for accurate photoacoustic mapping of pH in the tumors of living mice.

  18. Photothermal Gene Delivery: Stimuli-Regulated Enzymatically Degradable Smart Graphene-Oxide-Polymer Nanocarrier Facilitating Photothermal Gene Delivery (Adv. Healthcare Mater. 15/2016).

    PubMed

    Kim, Hyunwoo; Kim, Jinhwan; Lee, Minkyung; Choi, Hee Cheul; Kim, Won Jong

    2016-08-01

    On page 1918, Won Jong Kim and co-workers use disulfide bonding for the rational design of graphene oxide (GO) based nanocarriers. In the lower left side, photothermally triggered gene release is illustrated in cancer cell. Polymer-detached GOis exocytosed, and subsequently gets into the macrophage (middle right). In the macrophage, peroxidase binds to GO, thus degrades it to small fragments which are fluorescent.

  19. Field-Effect Transistors: Ultrathin MXene-Micropattern-Based Field-Effect Transistor for Probing Neural Activity (Adv. Mater. 17/2016).

    PubMed

    Xu, Bingzhe; Zhu, Minshen; Zhang, Wencong; Zhen, Xu; Pei, Zengxia; Xue, Qi; Zhi, Chunyi; Shi, Peng

    2016-05-01

    A field-effect transistor (FET) based on ultrathin Ti3 C2 -MXene micropatterns is developed by C. Zhi, P. Shi, and co-workers, as described on page 3333. The FET can be utilized for label-free probing of small molecules in typical biological environments, e.g., for fast detection of action potentials in primary neurons. This device is produced with a microcontact printing technique, harnessing the unique advantages for easy fabrication.

  20. Solar Cells: Homo-Tandem Polymer Solar Cells with VOC >1.8 V for Efficient PV-Driven Water Splitting (Adv. Mater. 17/2016).

    PubMed

    Gao, Yangqin; Le Corre, Vincent M; Gaïtis, Alexandre; Neophytou, Marios; Hamid, Mahmoud Abdul; Takanabe, Kazuhiro; Beaujuge, Pierre M

    2016-05-01

    On page 3366, P. M. Beaujuge and co-workers describe homo-tandem solar cells constructed by stacking identical subcells solution-processed from blends of the wide-bandgap polymer donor PBDTTPD and the fullerene acceptor PCBM, which achieve power conversion efficiencies >8% and open-circuit voltages >1.8 V. The homo-tandem devices provide sufficient voltage to induce the dissociation of water in an electrochemical cell. The authors acknowledge Hyun Ho Hwang (Heno) for developing the artwork.

  1. Electrospun Scaffolds: Enhanced Lineage-Specific Differentiation Efficiency of Human Induced Pluripotent Stem Cells by Engineering Colony Dimensionality Using Electrospun Scaffolds (Adv. Healthcare Mater. 12/2016).

    PubMed

    Maldonado, Maricela; Ico, Gerardo; Low, Karen; Luu, Rebeccah J; Nam, Jin

    2016-06-01

    Electrospun scaffolds provide soft nanofibrous networks pliable by human induced pluripotent stem cells. J. Nam and co-workers show on page 1408 that such compliant scaffolding leads to the formation of stem cell colonies with a distinctive three-dimensional morphology. The morphological modulation resulted in the lineage-specific differentiation, suggesting a potential means to enhance translational applications of the stem cells.

  2. Atomic Layers: Tellurium-Assisted Epitaxial Growth of Large-Area, Highly Crystalline ReS2 Atomic Layers on Mica Substrate (Adv. Mater. 25/2016).

    PubMed

    Cui, Fangfang; Wang, Cong; Li, Xiaobo; Wang, Gang; Liu, Kaiqiang; Yang, Zhou; Feng, Qingliang; Liang, Xing; Zhang, Zhongyue; Liu, Shengzhong; Lei, Zhibin; Liu, Zonghuai; Xu, Hua; Zhang, Jin

    2016-07-01

    H. Xu, J. Zhang, and co-workers synthesize anisotropic 2D-layered rhenium disulfide with high crystal quality and uniform monolayer thickness. As described on page 5019, tellurium-assisted epitaxial growth on a mica substrate is chosen to generate such structures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

    PubMed Central

    Yang, Fu-Qiang; Rao, Gui-Rong; Wang, Gui-Qiang; Li, Yue-Qi; Xie, Yao; Zhang, Zhan-Qing; Deng, Cun-Liang; Mao, Qing; Li, Jun; Zhao, Wei; Wang, Mao-Rong; Han, Tao; Chen, Shi-Jun; Pan, Chen; Tan, De-Ming; Shang, Jia; Zhang, Ming-Xiang; Zhang, Yue-Xin; Yang, Ji-Ming; Chen, Guang-Ming

    2017-01-01

    AIM To assess the efficacy and safety of in vivo electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, n = 109) or LAM + placebo (control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12 (start of treatment with vaccine or placebo, SOT), 16, 24, and 36 (end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir (ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeAg seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy. PMID:28127204

  4. Cost-Effectiveness Comparison Between the Response-Guided Therapies and Monotherapies of Nucleos(t)ide Analogues for Chronic Hepatitis B Patients in China.

    PubMed

    Lai, Keng; Zhang, Chi; Ke, Weixia; Gao, Yanhui; Zhou, Shudong; Liu, Li; Yang, Yi

    2017-03-01

    Nucleos(t)ide analogue (NA) monotherapies are typically used as the primary treatment for chronic hepatitis B (CHB) patients, including lamivudine (LAM), telbivudine (TBV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF). For high-resistance NAs (LAM, TBV, ADV), they can generate excellent clinical outcomes by using response-guided therapy; however, their pharmacoeconomic profiles remain unclear in China. We aimed to evaluate the cost effectiveness between response-guided therapies and monotherapies of NAs for Chinese hepatitis B e-antigen (HBeAg)-positive and -negative CHB patients. We constructed a Markov model to simulate CHB progression associated with 12 treatment strategies using effectiveness and cost data from the published literature. We measured the lifetime costs, quality adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity (especially to extend the range of the TDF price) and probabilistic sensitivity analyses were used to explore the uncertainties of the model. For both HBeAg-positive and -negative patients, no treatment strategy generated the lowest lifetime costs (US$31,185-US$31,338) and QALYs (7.54-7.58). ETV and TDF monotherapies were not dominated by other treatments, whereas, the ICER of ETV monotherapy was the lowest (US$6112/QALY-US$8533/QALY). For each high-resistance NA, compared with its monotherapy, the ICERs of its response-guided therapies were below the willingness-to-pay threshold of US$22,833/QALY. Additionally, TDF monotherapy was the preferred treatment when its price dropped to US$1820/year or lower. Among 12 treatment strategies evaluated, ETV monotherapy is the most cost-effective treatment for treatment-naive CHB patients in China. The response-guided therapies of high-resistance NAs are more cost-effective than their monotherapies.

  5. Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China.

    PubMed

    Wu, Bin; Shen, Jinfang; Cheng, Huafeng

    2012-11-08

    Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB. A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results. In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system. In Chinese patients with LAM-resistant CHB, combination therapy is a more cost-effective option than the

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  7. Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues.

    PubMed

    Rapti, Irene; Hadziyannis, Stephanos

    2015-05-18

    Hepatocellular carcinoma (HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus (HBV) infection (CHB) is the most important etiologic factor of this tumor, accounting for the development of more than 50% of the cases in the world. Primary prevention of HCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204 (update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and

  8. On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B

    PubMed Central

    Gao, Yu-Hua; Meng, Qing-Hua; Zhang, Zhan-Qing; Zhao, Ping; Shang, Qing-Hua; Yuan, Quan; Li, Yao; Deng, Juan; Li, Tong; Liu, Xue-En; Zhuang, Hui

    2016-01-01

    AIM To investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS Seventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated. RESULTS Forty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA ≤ 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, P = 0.003) as well as its declined value (OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer < 1.3 lg PEIU/mL and its decreased value > 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, P = 0.013) as well as its declined value (OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer < -0.5 lg PEIU/mL combined with its declined value > 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928. CONCLUSION The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy. PMID:28008342

  9. A Cost-Utility and Cost-Effectiveness Analysis of Different Oral Antiviral Medications in Patients With HBeAg-Negative Chronic Hepatitis B in Iran: An Economic Microsimulation Decision Model

    PubMed Central

    Keshavarz, Khosro; Kebriaeezadeh, Abbas; Alavian, Seyed Moayed; Akbari Sari, Ali; Rezaei Hemami, Mohsen; Lotfi, Farhad; Hashemi Meshkini, Amir; Javanbakht, Mehdi; Keshvari, Maryam; Nikfar, Shekoufeh

    2016-01-01

    Background Although hepatitis B infection is the major cause of chronic liver disease in Iran, no studies have employed economic evaluations of the medications used to treat Iranian patients with chronic hepatitis B (CHB). Therefore, the cost-effectiveness of the different treatment options for this disease in Iran is unknown. Objectives The aim of this study was to compare the cost utility and cost-effectiveness of medication strategies tailored to local conditions in patients with HB e antigen (HBeAg)-negative CHB infection in Iran. Methods An economic evaluation of the cost utility of the following five oral medication strategies was conducted: adefovir (ADV), lamivudine (LAM), ADV + LAM, entecavir (ETV), and tenofovir (TDF). A Markov microsimulation model was used to estimate the clinical and economic outcomes over the course of the patient’s lifetime and based on a societal perspective. Medical and nonmedical direct costs and indirect costs were included in the study and life-years gained (LYG) and quality-adjusted life-years (QALY) were determined as measures of effectiveness. The results are presented in terms of the incremental cost-effectiveness ratio (ICER) per QALY or LYG. The model consisted of nine stages of the disease. The transition probabilities for the movement between the different stages were based on clinical evidence and international expert opinion. A probabilistic sensitivity analysis (PSA) was used to measure the effects of uncertainty in the model parameters. Results The results revealed that the TDF treatment strategy was more effective and less costly than the other options. In addition, TDF had the highest QALY and LYG in the HBeAg-negative CHB patients, with 13.58 and 21.26 (discounted) in all comparisons. The PSA proved the robustness of the model results. The cost-effectiveness acceptability curves showed that TDF was the most cost-effective treatment in 59% - 78% of the simulations of HBeAg-negative patients, with WTP thresholds

  10. Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China

    PubMed Central

    2012-01-01

    Background Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB. Methods A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results. Results In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system. Conclusion In Chinese patients with LAM-resistant CHB, combination therapy is a more

  11. A Cost-Utility and Cost-Effectiveness Analysis of Different Oral Antiviral Medications in Patients With HBeAg-Negative Chronic Hepatitis B in Iran: An Economic Microsimulation Decision Model.

    PubMed

    Keshavarz, Khosro; Kebriaeezadeh, Abbas; Alavian, Seyed Moayed; Akbari Sari, Ali; Rezaei Hemami, Mohsen; Lotfi, Farhad; Hashemi Meshkini, Amir; Javanbakht, Mehdi; Keshvari, Maryam; Nikfar, Shekoufeh

    2016-09-01

    Although hepatitis B infection is the major cause of chronic liver disease in Iran, no studies have employed economic evaluations of the medications used to treat Iranian patients with chronic hepatitis B (CHB). Therefore, the cost-effectiveness of the different treatment options for this disease in Iran is unknown. The aim of this study was to compare the cost utility and cost-effectiveness of medication strategies tailored to local conditions in patients with HB e antigen (HBeAg)-negative CHB infection in Iran. An economic evaluation of the cost utility of the following five oral medication strategies was conducted: adefovir (ADV), lamivudine (LAM), ADV + LAM, entecavir (ETV), and tenofovir (TDF). A Markov microsimulation model was used to estimate the clinical and economic outcomes over the course of the patient's lifetime and based on a societal perspective. Medical and nonmedical direct costs and indirect costs were included in the study and life-years gained (LYG) and quality-adjusted life-years (QALY) were determined as measures of effectiveness. The results are presented in terms of the incremental cost-effectiveness ratio (ICER) per QALY or LYG. The model consisted of nine stages of the disease. The transition probabilities for the movement between the different stages were based on clinical evidence and international expert opinion. A probabilistic sensitivity analysis (PSA) was used to measure the effects of uncertainty in the model parameters. The results revealed that the TDF treatment strategy was more effective and less costly than the other options. In addition, TDF had the highest QALY and LYG in the HBeAg-negative CHB patients, with 13.58 and 21.26 (discounted) in all comparisons. The PSA proved the robustness of the model results. The cost-effectiveness acceptability curves showed that TDF was the most cost-effective treatment in 59% - 78% of the simulations of HBeAg-negative patients, with WTP thresholds less than $14010 (maximum WTP per QALY

  12. Flexible Supercapacitors: A Simple Approach to Boost Capacitance: Flexible Supercapacitors Based on Manganese Oxides@MOFs via Chemically Induced In Situ Self-Transformation (Adv. Mater. 26/2016).

    PubMed

    Zhang, Yi-Zhou; Cheng, Tao; Wang, Yang; Lai, Wen-Yong; Pang, Huan; Huang, Wei

    2016-07-01

    W.-Y. Lai, H. Pang, W. Huang, and co-workers present a simple and effective method for transforming nanocubic MOFs (metal-organic frameworks) into MnOx -nanoflower-decorated MOFs. This liquid-phase method is metaphorically illustrated by the ocean background, as is the transformation process by the different cubes. The application of these materials in flexible supercapacitors is further described on page 5242. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Li-Ion Battery Cathodes: Enhancing Interfacial Bonding between Anisotropically Oriented Grains Using a Glue-Nanofiller for Advanced Li-Ion Battery Cathode (Adv. Mater. 23/2016).

    PubMed

    Kim, Hyejung; Lee, Sanghan; Cho, Hyeon; Kim, Junhyeok; Lee, Jieun; Park, Suhyeon; Joo, Se Hun; Kim, Su Hwan; Cho, Yoon-Gyo; Song, Hyun-Kon; Kwak, Sang Kyu; Cho, Jaephil

    2016-06-01

    The formation of a spinel Lix CoO2 layer in a Ni-rich secondary particle for lithium-ion batteries is reported by S. K. Kwak, J. Cho, and co-workers on page 4705, who find that the spinel-like Lix CoO2 layer, between layered primary particles, can enhance the mechanical strength of secondary particles by enhancing the interfacial binding energy among the grains. Moreover, the layer can effectively protect the unstable surface of the primary particles and offers a fast electron-ion pathway, resulting in overall enhancements of stability and kinetics in battery performance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Alzheimer Therapy: Photoactive g-C3 N4 Nanosheets for Light-Induced Suppression of Alzheimer's β-Amyloid Aggregation and Toxicity (Adv. Healthcare Mater. 13/2016).

    PubMed

    Chung, You Jung; Lee, Byung Il; Ko, Jong Wan; Park, Chan Beum

    2016-07-01

    The accumulation of β-amyloid peptides and their aggregation in brain is a hallmark of Alzheimer's disease. On page 1560 C. B. Park and co-workers describe a strong suppression effect of graphitic carbon nitride (g-C3 N4 ) toward β-amyloid aggregation under light-illumination. Photoexcited g-C3 N4 generates reactive oxygen species and blocks further β-amyloid aggregation by impacting conformational structure of β-amyloid, rendering it a promising material for Alzheimer therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Photothermal Therapy: Cancer Cell Internalization of Gold Nanostars Impacts Their Photothermal Efficiency In Vitro and In Vivo: Toward a Plasmonic Thermal Fingerprint in Tumoral Environment (Adv. Healthcare Mater. 9/2016).

    PubMed

    Espinosa, Ana; Silva, Amanda K A; Sánchez-Iglesias, Ana; Grzelczak, Marek; Péchoux, Christine; Desboeufs, Karine; Liz-Marzán, Luis M; Wilhelm, Claire

    2016-05-01

    Because the ultimate target for photothermal therapy is the cancer cell, heating performances must be evaluated intracellularly. On page 1040 C. Wilhelm and team provide the first in vitro and in vivo photothermal measurements in cancer cells with gold nanostars. They demonstrate that once nanostars are internalized within endosomes, heat generation can change significantly.

  16. Targeted Drug Delivery: Carbon-Quantum-Dots-Loaded Mesoporous Silica Nanocarriers with pH-Switchable Zwitterionic Surface and Enzyme-Responsive Pore-Cap for Targeted Imaging and Drug Delivery to Tumor (Adv. Healthcare Mater. 12/2016).

    PubMed

    Liu, Zhongning; Chen, Xin; Zhang, Xiaojin; Gooding, John Justin; Zhou, Yongsheng

    2016-06-01

    On page 1401 X. Chen, X. Zhang, Y. Zhou, and co-workers describe the synthesis of mesoporous silica nanocarriers with pH-switchable antifouling zwitterionic surfaces and blue fluorescence that are capable of enzyme-responsive drug release. The system combines tumor treatment and tracking. It shows great potential for cancer treatment, since it exhibits prolonged circulation in the blood system with zero premature release while offering selective cellular uptake, tumor labeling, and intracellular drug release in tumor tissue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Human Neuron Cultures: Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks (Adv. Healthcare Mater. 15/2016).

    PubMed

    Burbulla, Lena F; Beaumont, Kristin G; Mrksich, Milan; Krainc, Dimitri

    2016-08-01

    Dimitri Krainc, Milan Mrksich, and co-workers demonstrate the utility of microcontact printing technology for culturing of human neurons in defined patterns over extended periods of time on page 1894. This approach facilitates studies of neuronal development, cellular trafficking, and related mechanisms that require assessment of individual neurons and neuronal networks.

  18. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.

    PubMed

    Hammer, Scott M; Vaida, Florin; Bennett, Kara K; Holohan, Mary K; Sheiner, Lewis; Eron, Joseph J; Wheat, Lawrence Joseph; Mitsuyasu, Ronald T; Gulick, Roy M; Valentine, Fred T; Aberg, Judith A; Rogers, Michael D; Karol, Cheryl N; Saah, Alfred J; Lewis, Ronald H; Bessen, Laura J; Brosgart, Carol; DeGruttola, Victor; Mellors, John W

    2002-07-10

    Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge. To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen. Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks. Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States. A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL. Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil. Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility. Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P =.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270] vs 16% [33/211], respectively; P<.001). Baseline HIV-1 hypersusceptibility to efavirenz (< or = 0.4-fold difference in susceptibility compared

  19. Tumor Vascular Targeted Delivery of Polymer-conjugated Adenovirus Vector for Cancer Gene Therapy

    PubMed Central

    Yao, Xinglei; Yoshioka, Yasuo; Morishige, Tomohiro; Eto, Yusuke; Narimatsu, Shogo; Kawai, Yasuaki; Mizuguchi, Hiroyuki; Gao, Jian-Qing; Mukai, Yohei; Okada, Naoki; Nakagawa, Shinsaku

    2011-01-01

    Previously, we generated a cancer-specific gene therapy system using adenovirus vectors (Adv) conjugated to polyethylene glycol (Adv-PEG). Here, we developed a novel Adv that targets both tumor tissues and tumor vasculatures after systemic administration by conjugating CGKRK tumor vasculature homing peptide to the end of a 20-kDa PEG chain (Adv-PEGCGKRK). In a primary tumor model, systemic administration of Adv-PEGCGKRK resulted in ~500- and 100-fold higher transgene expression in tumor than that of unmodified Adv and Adv-PEG, respectively. In contrast, the transgene expression of Adv-PEGCGKRK in liver was about 400-fold lower than that of unmodified Adv, and was almost the same as that of Adv-PEG. We also demonstrated that transgene expression with Adv-PEGCGKRK was enhanced in tumor vessels. Systemic administration of Adv-PEGCGKRK expressing the herpes simplex virus thymidine kinase (HSVtk) gene (Adv-PEGCGKRK-HSVtk) showed superior antitumor effects against primary tumors and metastases with negligible side effects by both direct cytotoxic effects and inhibition of tumor angiogenesis. These results indicate that Adv-PEGCGKRK has potential as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both primary tumors and metastases. PMID:21673661

  20. HBeAg levels at week 24 predict response to 8 years of tenofovir in HBeAg-positive chronic hepatitis B patients.

    PubMed

    Wong, D; Littlejohn, M; Yuen, L; Jackson, K; Mason, H; Bayliss, J; Rosenberg, G; Gaggar, A; Kitrinos, K; Subramanian, M; Marcellin, P; Buti, M; Janssen, H L A; Gane, E; Locarnini, S; Thompson, A; Revill, P A

    2017-10-11

    Hepatitis B e antigen (HBeAg) seroconversion is a treatment endpoint for HBeAg-positive CHB, and a necessary precursor to HBsAg loss. Biomarkers that predict serological outcomes would be useful. To evaluate the utility of measuring HBeAg levels for predicting HBeAg seroconversion and HBsAg loss under long-term tenofovir (TDF) therapy. A total of 266 patients were enrolled into a phase III study of TDF vs adefovir (ADV) for 48 weeks in HBeAg-positive patients, followed by open-label TDF up to 384 weeks. Serum HBeAg levels were measured for subjects with samples available at both baseline and week 24 of treatment (n = 200). Analysis compared subjects who achieved HBeAg seroconversion by week 384 vs no HBeAg seroconversion. HBeAg seroconversion rate was 52% by week 384. Time to HBeAg seroconversion was 80 weeks (IQR: 36-162). HBeAg decline at week 24 was associated with HBeAg seroconversion (1.63 vs 0.90 log10 PEIU/mL, P = .002). The optimal threshold for identifying HBeAg seroconversion was HBeAg decline ≥2.2 log10 PEIU/mL at week 24, with HBeAg seroconversion achieved by 76% of patients, compared to 44% if HBeAg decline <2.2 log10 (P < .0001). HBeAg decline ≥2.2 log10 PEIU/mL at week 24 was associated with HBsAg loss in genotype A or D patients (38% vs 15%, P = .03). Precore/basal core promotor variants were associated with lower baseline HBeAg levels, but not HBeAg seroconversion. Decline in HBeAg levels by week 24 was associated with HBeAg seroconversion and HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with long-term TDF. © 2017 John Wiley & Sons Ltd.

  1. 77 FR 59026 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-25

    ... and Exchange Commission, Office of Investor ] Education and Advocacy, Washington, DC 20549-0213... extension and approval. Form ADV-E (17 CFR 279.8) is the cover sheet for certificates of accounting filed...

  2. 17 CFR 275.203-1 - Application for investment adviser registration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., substantial changes to Part II of Form ADV. Thus, the rules for preparing, delivering, and offering Part II...) When filed. Each Form ADV is considered filed with the Commission upon acceptance by the IARD....

  3. 78 FR 62778 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ...) (``Fee Schedule'') to add orders yielding Flag AA to the calculation of the average daily trading (``ADV... add orders yielding Flag AA to the calculation of the ADV threshold required to meet the MidPoint... orders yielding Flag AA (MidPoint Match Cross (same MPID)) to the calculation of the ADV threshold...

  4. 17 CFR 275.203A-5 - Transition rules.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... investment adviser registered with the Commission on July 21, 2011. (b) SEC-registered advisers—Form ADV... amendment to Form ADV (17 CFR 279.1) no later than March 30, 2012 and shall determine its assets under... registration with the Commission by filing Form ADV-W (17 CFR 279.2) no later than June 28, 2012. During this...

  5. 77 FR 39767 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ... rebate tier depends on an ETP Holder's ADV. Endnote 3 provides that ``ADV'' means, with respect to an ETP... occurred. Endnote 3 further clarifies that ``ADV'' as used with respect to the Exchange's Automatic.... Endnote 5, which is proposed to apply to each of the four rebate tiers in Order Delivery, provides that...

  6. Adolescent Dating Violence Prevention and Intervention in a Community Setting: Perspectives of Young Adults and Professionals

    ERIC Educational Resources Information Center

    Martsolf, Donna S.; Colbert, Crystal; Draucker, Claire B.

    2012-01-01

    Adolescent dating violence (ADV) is a significant community problem. In this study, we examine the perspectives of two groups (young adults who experienced ADV as teens and professionals who work with teens) on ADV prevention/intervention in a community context. We interviewed 88 young adults and 20 professionals. Our research team used Thorne's…

  7. Molecular Detection and Phylogenetic Characterization of Bat and Human Adenoviruses in Southern China.

    PubMed

    Zheng, Xue-Yan; Qiu, Min; Chen, Hui-Fang; Chen, Shao-Wei; Xiao, Jian-Peng; Jiang, Li-Na; Huo, Shu-Ting; Shi, Ting-Li; Ma, Li-Zhen; Liu, Shan; Zhou, Jun-Hua; Zhang, Qiong-Hua; Li, Xing; Chen, Zhong; Wu, Yi; Li, Jin-Ming; Guan, Wei-Jie; Xiong, Yi-Quan; Ma, Shu-Juan; Zhong, Xue-Shan; Ge, Jing; Cen, Shu-Wen; Chen, Qing

    2016-06-01

    Several novel adenoviruses (AdVs) have recently been identified in humans and other animal species. In this study, we report the molecular detection of and phylogenetically characterize bat and human AdVs detected in fecal or rectal swab samples collected in southern China. To detect AdVs, a 252-261 bp fragment of the DNA polymerase (DPOL) gene was amplified using nested PCR. A total of 520 rectal swab samples were collected from eight bat species in four geographic regions of southern China (Guangzhou, Yunfu, Huizhou, and Haikou city). Thirty-six (6.9%) samples from the following species tested positive for AdVs: Myotis ricketti, Miniopterus schreibersii, Scotophilus kuhlii, Taphozous melanopogon, Rhinolophus blythi, and Cynopterus sphinx. Eight novel AdVs were detected in 13.3% of the samples from C. sphinx. Of 328 fecal samples from patients with diarrhea, 16 (4.9%) were positive for classical human AdVs. Phylogenetic analysis showed that human AdVs shared low similarity (57.1-69.3%) with bat AdVs in deduced amino acid sequences of the AdV DPOL region. Thus, our study indicated that bat AdVs and human AdVs are species specific. As such, there is no evidence of cross-species transmission of AdV between bats and humans based on current data.

  8. Theranostic Performance of Acoustic Nanodroplet Vaporization-Generated Bubbles in Tumor Intertissue

    PubMed Central

    Ho, Yi-Ju; Yeh, Chih-Kuang

    2017-01-01

    Solid tumors with poorly perfused regions reveal some of the treatment limitations that restrict drug delivery and therapeutic efficacy. Acoustic droplet vaporization (ADV) has been applied to directly disrupt vessels and release nanodroplets, ADV-generated bubbles (ADV-Bs), and drugs into tumor tissue. In this study, we investigated the in vivo behavior of ADV-Bs stimulated by US, and evaluated the possibility of moving intertissue ADV-Bs into the poorly perfused regions of solid tumors. Intravital imaging revealed intertissue ADV-B formation, movement, and cavitation triggered by US, where the distance of intertissue ADV-B movement was 33-99 µm per pulse. When ADV-Bs were applied to tumor cells, the cell membrane was damaged, increasing cellular permeability or inducing cell death. The poorly perfused regions within solid tumors show enhancement due to ADV-B accumulation after application of US-triggered ADV-B. The intratumoral nanodroplet or ADV-B distribution around the poorly perfused regions with tumor necrosis or hypoxia were demonstrated by histological assessment. ADV-B formation, movement and cavitation could induce cell membrane damage by mechanical force providing a mechanism to overcome treatment limitations in poorly perfused regions of tumors. PMID:28529631

  9. Reply to the comments by Willem J. Zaadnoordijk on "An analytical solution for predicting the transient seepage from a subsurface drainage system" by P. Xin, H.C. Dan, T. Zhou, C. Lu, J. Kong, L. Li [Adv. Water Resour. 91 (2016) 1-10

    NASA Astrophysics Data System (ADS)

    Xin, Pei; Dan, Han-Cheng; Zhou, Tingzhang; Lu, Chunhui; Kong, Jun; Li, Ling

    2016-10-01

    We appreciate Willem J. Zaadnoordijk's comments, which led us to revisit the results in Xin et al. (2016). Zaadnoordijk (2016) solved numerically the Boussinesq equation-based (BE) model, Eq. (6) in Xin et al. (2016), and found that (1) the transient groundwater tables predicted by the numerical BE model didn't match Fig. 5b in Xin et al. (2016) and (2) with an adjusted effective specific yield (discussed further below), the BE model predicted similar results to the analytical solution that accounts for the unsaturated zone effects. We address these two points in the following. (1) The results of Fig. 5b in Xin et al. (2016) were calculated from the analytical solution with the unsaturated zone neglected. Although the governing equation of the saturated-unsaturated mathematical model presented in Xin et al. (2016) can be reduced to the Boussinesq equation with the unsaturated zone neglected (i.e., α and β approaching infinity), the application of the approximate analytical solution directly to this limiting condition incurs large errors as contained in Fig. 5b of Xin et al. (2016). In this reply we derive a new analytical solution separately for the BE model (detailed derivation given in the appendix) with such errors removed.

  10. Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

    ClinicalTrials.gov

    2017-03-28

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  11. Adenovirus as a gene therapy vector for hematopoietic cells.

    PubMed

    Marini, F C; Yu, Q; Wickham, T; Kovesdi, I; Andreeff, M

    2000-06-01

    Adenovirus (Adv)-mediated gene transfer has recently gained new attention as a means to deliver genes for hematopoietic stem cell (HSC) or progenitor cell gene therapy. In the past, HSCs have been regarded as poor Adv targets, mainly because they lack the specific Adv receptors required for efficient and productive Adv infection. In addition, the nonintegrating nature of Adv has prevented its application to HSC and bone marrow transduction protocols where long-term expression is required. There is even controversy as to whether Adv can infect hematopoietic cells at all. In fact, the ability of Adv to infect epithelium-based targets and its inability to effectively transfect HSCs have been used in the development of eradication schemes that use Adv to preferentially infect and "purge" tumor cell-contaminating HSC grafts. However, there are data supporting the existence of productive Adv infections into HSCs. Such protocols involve the application of cytokine mixtures, high multiplicities of infection, long incubation periods, and more recently, immunological and genetic modifications to Adv itself to enable it to efficiently transfer genes into HSCs. This is a rapidly growing field, both in terms of techniques and applications. This review examines the two sides of the Adv/CD34 controversy as well as the current developments in this field.

  12. Development of Multiplexed Real-Time Quantitative PCR Assay for Detecting Human Adenoviruses

    PubMed Central

    Huang, Meei-Li; Nguy, Long; Ferrenberg, James; Boeckh, Michael; Cent, Anne; Corey, Lawrence

    2008-01-01

    Adenoviruses (AdV) have been associated with a wide variety of human disease and are increasingly recognized as viral pathogens that can cause significant morbidity and mortality in immunocompromised patients. Early detection of AdV DNA in plasma and sterile fluids has been shown to be useful for identifying patients at risk for invasive AdV disease. Due to the large number of existing Adv types, few real-time quantitative AdV PCR assays published effectively cover all AdV types. We designed a series of AdV PCR primers and probes and empirically multiplexed them into two separate real-time PCR assays to quantitatively detect all 49 serotypes of human AdV (Types 1-49) available from ATCC. We then subsequently multiplexed all the primers and probes into one reaction. The sensitivity of these assays was determined to be less than 10 copies per reaction (500 copies/ml plasma). In a retrospective evaluation we detected all 84 clinical AdV isolates isolated in cell culture from patients undergoing hematopoietic stem cell transplant (HSCT) between 1981 and 1987. Prospective analysis of 46 consecutive clinical samples submitted for adenovirus testing showed greater sensitivity and equal specificity of the AdV PCR than viral culture. This real time PCR assay allows rapid, sensitive and specific quantification of all currently defined adenoviruses into either two or one multiplex assay for clinical samples. PMID:18707838

  13. Adolescent dating violence and Peplau's dimensions of the self.

    PubMed

    Draucker, Claire B; Cook, Christina B; Martsolf, Donna S; Stephenson, Pam S

    2012-01-01

    Adolescent dating violence (ADV) is a significant public health problem. Despite an association between ADV and lowered self-esteem, little research has examined identity issues in persons who have experienced ADV. To use Peplau's model of the dimensions of the self to describe identity concerns in those who experienced ADV. Verbatim comments that met Peplau's definitions of self-statements were extracted from the narratives of 50 young adults who had taken part in an ongoing qualitative study on ADV. The statements were coded into Peplau's dimensions using content analysis. 175 verbatim sentences were extracted from the narratives. The statements addressed 16 different personal characteristics, including strength, sociability, and aggressiveness. Individuals who have experienced ADV have a number of concerns related to self-concept. Recommendations are made regarding how these concerns may be addressed with investigative counseling, as described by Peplau.

  14. Replication of Aleutian Mink Disease Parvovirus In Vivo Is Influenced by Residues in the VP2 Protein

    PubMed Central

    Fox, James M.; McCrackin Stevenson, Mary A.; Bloom, Marshall E.

    1999-01-01

    Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink. Several ADV isolates have been identified which vary in the severity of the disease they elicit. The isolate ADV-Utah replicates to high levels in mink, causing severe Aleutian disease that results in death within 6 to 8 weeks, but does not replicate in Crandell feline kidney (CrFK) cells. In contrast, ADV-G replicates in CrFK cells but does not replicate in mink. The ability of the virus to replicate in vivo is determined by virally encoded determinants contained within a defined region of the VP2 gene (M. E. Bloom, J. M. Fox, B. D. Berry, K. L. Oie, and J. B. Wolfinbarger. Virology 251:288–296, 1998). Within this region, ADV-G and ADV-Utah differ at only five amino acid residues. To determine which of these five amino acid residues comprise the in vivo replication determinant, site-directed mutagenesis was performed to individually convert the amino acid residues of ADV-G to those of ADV-Utah. A virus in which the ADV-G VP2 residue at 534, histidine (H), was converted to an aspartic acid (D) of ADV-Utah replicated in CrFK cells as efficiently as ADV-G. H534D also replicated in mink, causing transient viremia at 30 days postinfection and a strong antibody response. Animals infected with this virus developed diffuse hepatocellular microvesicular steatosis, an abnormal accumulation of intracellular fat, but did not develop classical Aleutian disease. Thus, the substitution of an aspartic acid at residue 534 for a histidine allowed replication of ADV-G in mink, but the ability to replicate was not sufficient to cause classical Aleutian disease. PMID:10482625

  15. A phase 3, randomized, double-blind, placebo-controlled study of the safety and efficacy of the live, oral adenovirus type 4 and type 7 vaccine, in U.S. military recruits.

    PubMed

    Kuschner, Robert A; Russell, Kevin L; Abuja, Mary; Bauer, Kristen M; Faix, Dennis J; Hait, Howard; Henrick, Jennifer; Jacobs, Michael; Liss, Alan; Lynch, Julia A; Liu, Qi; Lyons, Arthur G; Malik, Mohammad; Moon, James E; Stubbs, Jeremiah; Sun, Wellington; Tang, Doug; Towle, Andrew C; Walsh, Douglas S; Wilkerson, Deborah

    2013-06-19

    Adenovirus (ADV) types 4 (ADV-4) and 7 (ADV-7) are presently the major cause of febrile acute respiratory disease (ARD) in U.S. military recruits. We conducted a multi-center, randomized, double-blind, placebo-controlled phase 3 study of the new vaccine to assess its safety and efficacy. Healthy adults at two basic training sites were randomly assigned to receive either vaccine (two enteric-coated tablets consisting of no less than 4.5 log10 TCID50 of live ADV-4 or ADV-7) or placebo in a 3:1 ratio. Volunteers were observed throughout the approximate eight weeks of their basic training and also returned for four scheduled visits. The primary endpoints were prevention of febrile ARD due to ADV-4 and seroconversion of neutralizing serum antibodies to ADV-7, which was not expected to circulate in the study population during the course of the trial. A total of 4151 volunteers were enrolled and 4040 (97%) were randomized and included in the primary analysis (110 were removed prior to randomization and one was removed after randomization due to inability to swallow tablets). A total of 49 ADV-4 febrile ARD cases were identified with 48 in the placebo group and 1 in the vaccine group (attack rates of 4.76% and 0.03%, respectively). Vaccine efficacy was 99.3% (95% CI, 96.0-99.9; P<0.001). Seroconversion rates for vaccine recipients for ADV-4 and ADV-7 were 94.5% (95% CI, 93.4-95.5%) and 93.8% (95% CI: 93.4-95.2%), respectively. The vaccine was well tolerated as compared to placebo. We conclude that the new live, oral ADV-4 and ADV-7 vaccine is safe and effective for use in groups represented by the study population. Published by Elsevier Ltd.

  16. Presence of antibodies against Aujeszky's disease virus in wild boar (Sus scrofa) in Slovenia.

    PubMed

    Vengust, Gorazd; Valencak, Zdravko; Bidovec, Andrej

    2005-10-01

    Serum samples from 427 hunter-killed wild boar (Sus scrofa) from Slovenia were tested for antibodies to Aujeszky's disease virus (ADV). Samples were collected throughout Slovenia and corresponded to 6.2% of the total harvest. Antibodies against ADV were detected in 111 sera (26%) using a commercial enzyme-linked immunosorbent assay (ELISA). Antibody prevalence increased significantly with age. This report describes the first evidence of ADV infection in wild boar populations in Slovenia.

  17. Fatal systemic adenoviral infection superimposed on pulmonary mucormycosis in a child with acute leukemia

    PubMed Central

    Seo, Yu Mi; Hwang-Bo, Seok; Kim, Seong koo; Han, Seung Beom; Chung, Nack-Gyun; Kang, Jin Han

    2016-01-01

    Abstract Background: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. Case summary: We report a case of a 15-year-old boy with a fatal systemic ADV infection. He had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia. He complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy. In spite of appropriate antibiotic and antifungal therapy, pneumonia was aggravated and gross hematuria was accompanied. A multiplex polymerase chain reaction test for respiratory viruses was positive for ADV in a blood sample, and a urine culture was positive for ADV. He received oral ribavirin, intravenous immunoglobulin, and intravenous cidofovir therapy; however, he eventually died. Relapsed leukemia, concurrent fungal pneumonia, and delayed cidofovir administration were considered the cause of the grave outcome in this patient. Conclusion: ADV may cause severe infections not only in allogeneic hematopoietic cell transplant recipients, but also in patients undergoing chemotherapy for acute leukemia. The risk factors for severe ADV infection in patients undergoing chemotherapy should be determined in the future studies, and early antiviral therapy should be administered to immune compromised patients with systemic ADV infection. PMID:27749571

  18. Studies on the sequential development of acute interstitial pneumonia caused by Aleutian disease virus in mink kits.

    PubMed Central

    Alexandersen, S; Bloom, M E

    1987-01-01

    We studied different parameters during the development of acute interstitial pneumonia in mink kits caused by neonatal infection with Aleutian disease virus (ADV). When histological lesions, presence of intranuclear inclusion bodies, and intranuclearly localized ADV antigen were correlated with levels of single-stranded virion and duplex replicative forms of ADV DNA in the different tissues, it was concluded that the lung, probably alveolar type II cells, is the major primary target for viral replication and cytopathology. The presence of the duplex dimeric replicative-form DNA, a strong marker of parvovirus replication, was also observed in low amount in the mesenteric lymph node, suggesting replication of ADV in this organ, although no viral cytopathology could be demonstrated. Moreover, a few intranuclear inclusion bodies were demonstrated in kidney and liver from affected kits, but intranuclearly localized ADV antigen could not be demonstrated in liver sections, and neither could duplex dimer replicative-form DNA, suggesting that these organs are nevertheless not a major site of ADV replication. When the data were compared with results previously reported for ADV-infected adult mink and ADV-infected permissive cell cultures, the data suggested that the pattern of ADV replication in alveolar type II cells is similar to that seen in infected cell cultures but that the replication in the other kit organs resembles the restricted pattern seen in adult mink. Images PMID:3023709

  19. Prognostics Health Management for Advanced Small Modular Reactor Passive Components

    SciTech Connect

    Meyer, Ryan M.; Ramuhalli, Pradeep; Coble, Jamie B.; Mitchell, Mark R.; Wootan, David W.; Hirt, Evelyn H.; Berglin, Eric J.; Bond, Leonard J.; Henager, Charles H.

    2013-10-18

    In the United States, sustainable nuclear power to promote energy security is a key national energy priority. Advanced small modular reactors (AdvSMR), which are based on modularization of advanced reactor concepts using non-light-water reactor (LWR) coolants such as liquid metal, helium, or liquid salt may provide a longer-term alternative to more conventional LWR-based concepts. The economics of AdvSMRs will be impacted by the reduced economy-of-scale savings when compared to traditional LWRs and the controllable day-to-day costs of AdvSMRs are expected to be dominated by operations and maintenance costs. Therefore, achieving the full benefits of AdvSMR deployment requires a new paradigm for plant design and management. In this context, prognostic health management of passive components in AdvSMRs can play a key role in enabling the economic deployment of AdvSMRs. In this paper, the background of AdvSMRs is discussed from which requirements for PHM systems are derived. The particle filter technique is proposed as a prognostics framework for AdvSMR passive components and the suitability of the particle filter technique is illustrated by using it to forecast thermal creep degradation using a physics-of-failure model and based on a combination of types of measurements conceived for passive AdvSMR components.

  20. 77 FR 49463 - National Science Board; Sunshine Act Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ....m. SUBJECT MATTER: Chairman's remarks, discussion of Advanced Laser Interferometer Gravitational Wave Observatory (AdvLIGO) Construction Project Change in Scope, and discussion of and action on closed...

  1. In-situ and Post-cure Surface Modification of PDMS Elastomers for Low Surface Energy Applications

    DTIC Science & Technology

    2014-12-01

    Iodide Water Superomniphobic fabrics via dip-coating Transparent Omniphobicity Oil / water emulsion gravity seperation Golovin et al., Ang. Chem., 2013...fluorodecyl8T8 POSS: Water adv/ rec = 124°/116° Hexadecaneadv/ rec = 80°/61° Distribution A: Approved for Public Release; Distribution Unlimited 12 F-POSS...Black diamonds in figures) 70 °C/4 hrs, 45 °C/17 hrs Pure fluorodecyl8T8 POSS: Water adv/ rec = 124°/116° Hexadecaneadv/ rec = 80°/61

  2. Smallpox Antiviral Drug

    DTIC Science & Technology

    2007-01-01

    Nevirapine 1996 HIV Delavirdine 1997 HIV Abacavir 1998 HIV Efavirenz 1998 HIV Tenofovir 2001 HIV Adefovirn dipivoxil 2002 HBV Emtricitabine 2003 HIV Acyclovir...toxicity, hair loss, and skin changes [De Benedittis et al., 2004]. The other approach to orthopoxvirus antiviral drug discovery is to screen new...Rouzioux C. 2004. Penetration of enfuvirtide, tenofovir, efavirenz , and protease inhibitors in the genital tract of HIV-1-infected men. Aids 18:1958

  3. Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions ▿ †

    PubMed Central

    Wevers, Diana; Metzger, Sonja; Babweteera, Fred; Bieberbach, Marc; Boesch, Christophe; Cameron, Kenneth; Couacy-Hymann, Emmanuel; Cranfield, Mike; Gray, Maryke; Harris, Laurie A.; Head, Josephine; Jeffery, Kathryn; Knauf, Sascha; Lankester, Felix; Leendertz, Siv Aina J.; Lonsdorf, Elizabeth; Mugisha, Lawrence; Nitsche, Andreas; Reed, Patricia; Robbins, Martha; Travis, Dominic A.; Zommers, Zinta; Leendertz, Fabian H.; Ehlers, Bernhard

    2011-01-01

    Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene. A plethora of novel AdV sequences were identified, representing at least 45 distinct AdVs. From the AdV-positive individuals, 29 nearly complete hexon genes were amplified and, based on phylogenetic analysis, tentatively allocated to all known human AdV species (Human adenovirus A to Human adenovirus G [HAdV-A to -G]) as well as to the only simian AdV species (Simian adenovirus A [SAdV-A]). Interestingly, five of the AdVs detected in great apes grouped into the HAdV-A, HAdV-D, HAdV-F, or SAdV-A clade. Furthermore, we report the first detection of AdVs in New World monkeys, clustering at the base of the primate AdV evolutionary tree. Most notably, six chimpanzee AdVs of species HAdV-A to HAdV-F revealed a remarkably close relationship to human AdVs, possibly indicating recent interspecies transmission events. PMID:21835802

  4. What's in a name?

    PubMed

    1999-01-01

    A table charts the various nomenclature of drugs used to treat HIV and AIDS. The common name, generic name, and brand name are given for several categories including NARTIs (NRTIs, "Nukes", Nucleoside analogue reverse transcriptase inhibitors), NNRTIs (Non-nucleoside reverse transcriptase inhibitors), and PIs (Protease Inhibitors). Other drugs listed are Hydroxyurea (anti-cancer drug) and preveon (Adefovir (Nucleotide)).

  5. Molecular characterization, phylogeny analysis and pathogenicity of a Muscovy duck adenovirus strain isolated in China in 2014

    USDA-ARS?s Scientific Manuscript database

    This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The ...

  6. Laser Hazards Bibliography

    DTIC Science & Technology

    1989-10-31

    Everson, R. W., and Schmidt, I., Protection against photic damage in retinitis pigmentosa , Adv Exp Med Biol, 77: 233-247 (1977). 3. Agarwal, L. P., and...Wolbarsht, M. L., Landers, M. B., Wadsworth, J. A., and Anderson, W. B., Retinitis pigmentosa : clinical management based on current concepts, Adv Exp...General Reviews ............ 230 D. Retinal Burns from Lasers ....... .................... 230 E. Corneal Injury

  7. A novel adenovirus of Western lowland gorillas (Gorilla gorilla gorilla).

    PubMed

    Wevers, Diana; Leendertz, Fabian H; Scuda, Nelly; Boesch, Christophe; Robbins, Martha M; Head, Josephine; Ludwig, Carsten; Kühn, Joachim; Ehlers, Bernhard

    2010-11-05

    Adenoviruses (AdV) broadly infect vertebrate hosts including a variety of primates. We identified a novel AdV in the feces of captive gorillas by isolation in cell culture, electron microscopy and PCR. From the supernatants of infected cultures we amplified DNA polymerase (DPOL), preterminal protein (pTP) and hexon gene sequences with generic pan primate AdV PCR assays. The sequences in-between were amplified by long-distance PCRs of 2-10 kb length, resulting in a final sequence of 15.6 kb. Phylogenetic analysis placed the novel gorilla AdV into a cluster of primate AdVs belonging to the species Human adenovirus B (HAdV-B). Depending on the analyzed gene, its position within the cluster was variable. To further elucidate its origin, feces samples of wild gorillas were analyzed. AdV hexon sequences were detected which are indicative for three distinct and novel gorilla HAdV-B viruses, among them a virus nearly identical to the novel AdV isolated from captive gorillas. This shows that the discovered virus is a member of a group of HAdV-B viruses that naturally infect gorillas. The mixed phylogenetic clusters of gorilla, chimpanzee, bonobo and human AdVs within the HAdV-B species indicate that host switches may have been a component of the evolution of human and non-human primate HAdV-B viruses.

  8. Efficient genome replication of hepatitis B virus using adenovirus vector: a compact pregenomic RNA-expression unit

    PubMed Central

    Suzuki, Mariko; Kondo, Saki; Yamasaki, Manabu; Matsuda, Norie; Nomoto, Akio; Suzuki, Tetsuro; Saito, Izumu; Kanegae, Yumi

    2017-01-01

    The complicated replication mechanisms of hepatitis B virus (HBV) have impeded HBV studies and anti-HBV therapy development as well. Herein we report efficient genome replication of HBV applying adenovirus vectors (AdVs) showing high transduction efficiency. Even in primary hepatocytes derived from humanized mice the transduction efficiencies using AdVs were 450-fold higher compared than those using plasmids. By using an expression unit consisting of the CMV promoter, 1.03-copy HBV genome and foreign poly(A) signal, we successfully generated an improved AdV (HBV103-AdV) that efficiently provided 58 times more pregenomic RNA than previously reported AdVs. The HBV103-AdV-mediated HBV replication was easily and precisely detected using quantitative real-time PCR in primary hepatocytes as well as in HepG2 cells. Notably, when the AdV containing replication-defective HBV genome of 1.14 copy was transduced, we observed that HBV DNA-containing circular molecules (pseudo-ccc DNA) were produced, which were probably generated through homologous recombination. However, the replication-defective HBV103-AdV hardly yielded the pseudo-ccc, probably because the repeated sequences are vey short. Additionally, the efficacies of entecavir and lamivudine were quantitatively evaluated using this system at only 4 days postinfection with HBV103-AdVs. Therefore, this system offers high production of HBV genome replication and thus could become used widely. PMID:28157182

  9. Adenoviruses C in non-hospitalized Mexican children older than five years of age with acute respiratory infection.

    PubMed

    Rosete, Dora P; Manjarrez, María Eugenia; Barrón, Blanca L

    2008-03-01

    Adenoviruses (AdV) are commonly involved in acute respiratory infections (ARI), which cause high morbidity and mortality in children. AdV are grouped in six species (A-F), which are associated with a wide range of diseases. The aim of this study was to identify the AdV species infecting non-hospitalized Mexican children with ARI symptoms, attending to the same school. For that, a PCR/RFLP assay was designed for a region of the hexon gene, which was chosen, based on the bioinformatical analysis of AdV genomes obtained from GenBank. A total of 100 children's nasopharyngeal samples were collected from January to June, 2005, and used for viral isolation in A549 cells and PCR/RFLP analysis. Only 15 samples produced cytopathic effect, and in all of them AdV C was identified. AdV C was also identified in eight additional nasopharyngeal samples which were negative for viral isolation. In summary, this outpatient population showed a rate of AdV infection of 23%, and only AdV C was detected.

  10. Adenovirus species C detection in children under four years of age with acute bronchiolitis or recurrent wheezing.

    PubMed

    Tórtora, Rosângela Prendin; Guimarães, Maria Angélica Arpon Marandino; de Souza, Leandro Magalhães; Santos, Isabela Arruda; Varella, Rafael Brandão; de Fátima Pombo March, Maria; da Cunha, Antonio Jose Ledo Alves; Sant' Anna, Clemax Couto

    2015-12-01

    Lower respiratory tract viral infection is an important cause of morbidity and mortality in children worldwide. Among viral etiological agents the human Adenovirus (AdV) has been associated to mild or severe respiratory tract infection. To detect the presence of human Adenovirus (AdV) in children with acute bronchiolitis or recurrent wheezing, describing their clinical features and determining Adenovirus species and AdV association to Respiratory Syncytial Virus (RSV), Human Metapneumovirus (MPV) and Parainfluenza virus (PIV). A total of 155 children bellow 48 months of age with acute bronchiolitis or recurrent wheezing were investigated for the presence of AdV, RSV, MPV and PIV in nasopharyngeal aspirate, by real-time PCR method. AdV, predominantly of species C, has been detected as the unique pathogen (AdVi) or in association to other pathogens (AdVa.), in 39/155 samples. Crackles were more frequent in children with AdV. RSVi was detected predominantly in children with acute bronchiolitis while AdVi and AdVa were detected more frequently in patients with recurrent wheezing. A small outbreak of AdV species C was observed in 2012 and 2013. AdV was detected more frequently in children with recurrent wheezing while RSVi was more frequent in infants with acute bronchiolitis. Published by Elsevier B.V.

  11. Adenovirus 36 and Obesity: An Overview

    PubMed Central

    Ponterio, Eleonora; Gnessi, Lucio

    2015-01-01

    There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed. PMID:26184280

  12. Adenovirus detection in Guthrie cards from paediatric leukaemia cases and controls

    PubMed Central

    Vasconcelos, G M; Kang, M; Pombo-de-Oliveira, M S; Schiffman, J D; Lorey, F; Buffler, P; Wiemels, J L

    2008-01-01

    Archived neonatal blood cards (Guthrie cards) from children who later contracted leukaemia and matched normal controls were assayed for adenovirus (AdV) C DNA content using two highly sensitive methods. In contrast to a previous report, AdV DNA was not detected at a higher frequency among neonates who later developed leukaemia, when compared with controls. PMID:19002185

  13. Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

    SciTech Connect

    Bejerman, Nicolás; Giolitti, Fabián; Breuil, Soledad de; Trucco, Verónica; Nome, Claudia; Lenardon, Sergio; Dietzgen, Ralf G.

    2015-09-15

    Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

  14. Adenovirus vectors lacking virus-associated RNA expression enhance shRNA activity to suppress hepatitis C virus replication

    NASA Astrophysics Data System (ADS)

    Pei, Zheng; Shi, Guoli; Kondo, Saki; Ito, Masahiko; Maekawa, Aya; Suzuki, Mariko; Saito, Izumu; Suzuki, Tetsuro; Kanegae, Yumi

    2013-12-01

    First-generation adenovirus vectors (FG AdVs) expressing short-hairpin RNA (shRNA) effectively downregulate the expressions of target genes. However, this vector, in fact, expresses not only the transgene product, but also virus-associated RNAs (VA RNAs) that disturb cellular RNAi machinery. We have established a production method for VA-deleted AdVs lacking expression of VA RNAs. Here, we showed that the highest shRNA activity was obtained when the shRNA was inserted not at the popularly used E1 site, but at the E4 site. We then compared the activities of shRNAs against hepatitis C virus (HCV) expressed from VA-deleted AdVs or conventional AdVs. The VA-deleted AdVs inhibited HCV production much more efficiently. Therefore, VA-deleted AdVs were more effective than the currently used AdVs for shRNA downregulation, probably because of the lack of competition between VA RNAs and the shRNAs. These VA-deleted AdVs might enable more effective gene therapies for chronic hepatitis C.

  15. 77 FR 63900 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... daily volume (``ADV'') of Customer \\5\\ electronic equity and exchange-traded fund (``ETF'') contracts... of Customer electronic equity and ETF contracts executed by an OFP on the Exchange (the ``Tiers... ADV is comprised of those equity and ETF option contracts that clear in the customer account type at...

  16. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain.

    PubMed

    Shim, Byoung-Shik; Stadler, Konrad; Nguyen, Huan Huu; Yun, Cheol-Heui; Kim, Dong Wook; Chang, Jun; Czerkinsky, Cecil; Song, Man Ki

    2012-09-21

    Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.

  17. Detection of Soft Gamma-Ray Emission from the Seyfert II Galaxy NGC 4507 by the OSSE Telescope (Preprint)

    DTIC Science & Technology

    1995-01-01

    botes1.tesre.bo.cnr.it G. Malaguti : 38045:: MALAGUTI , malaguti @icarus.tesre.bo.cnr.it E. Jourdain: 17424::ROQUES J.P. Roques: 17424::ROQUES W.N. Johnson...Press), 537 Awaki, H, and Koyama, K. 1993, Adv. Space Res. Vol. 13,N.12, 221 Bassani L., Malaguti G. and Palumbo G.G.C., 1995, Adv. Space Res., in

  18. Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

    PubMed Central

    2012-01-01

    Background Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. Results Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. Conclusion Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV. PMID:22995185

  19. Effects of Levels of Automation for Advanced Small Modular Reactors: Impacts on Performance, Workload, and Situation Awareness

    SciTech Connect

    Johanna Oxstrand; Katya Le Blanc

    2014-07-01

    The Human-Automation Collaboration (HAC) research effort is a part of the Department of Energy (DOE) sponsored Advanced Small Modular Reactor (AdvSMR) program conducted at Idaho National Laboratory (INL). The DOE AdvSMR program focuses on plant design and management, reduction of capital costs as well as plant operations and maintenance costs (O&M), and factory production costs benefits.

  20. Optimization and internalization mechanisms of PEGylated adenovirus vector with targeting peptide for cancer gene therapy.

    PubMed

    Yao, Xing-Lei; Yoshioka, Yasuo; Ruan, Gui-Xin; Chen, Yu-Zhe; Mizuguchi, Hiroyuki; Mukai, Yohei; Okada, Naoki; Gao, Jian-Qing; Nakagawa, Shinsaku

    2012-08-13

    We have previously developed a novel adenovirus vector (Adv) that targeted tumor tissues/vasculatures after systemic administration. The surface of this Adv is conjugated with CGKRK tumor homing peptide by the cross-linking reaction of polyethyleneglycol (PEG). In this study, we showed that the condition of PEG modification was important to minimize the gene expression in normal tissues after systemic treatment. When Adv was modified only with PEG-linked CGKRK, its luciferase expression was enhanced even in the liver tissue, as well as the tumor tissue. However, in the reaction with the mixture of non-cross-linking PEG and PEG-linked CGKRK, we found out that the best modification could suppress its gene expression in the liver, without losing that in the tumor. We also studied the internalization mechanisms of CGKRK-conjugated Adv. Results suggested that there is a specific interaction of the CGKRK peptide with a receptor at the cell surface enabling efficient internalization of CGKRK-conjugated Adv. The presence of cell-surface heparan sulfate is important receptor for the cellular binding and uptake of CGKRK-conjugated Adv. Moreover, macropinocytosis-mediated endocytosis is also important in endocytosis of CGKRK-conjugated Adv, aside from clathrin-mediated and caveolae-mediated endocytosis. These results could help evaluate the potentiality of CGKRK-conjugated Adv as a prototype vector with suitable efficacy and safety for systemic cancer gene therapy.

  1. Characteristics of Adenovirus Pneumonia in Korean Military Personnel, 2012–2016

    PubMed Central

    Yoon, Hee; Yoo, Hongseok; Park, Sung Bum

    2017-01-01

    Adenovirus (AdV) can cause severe pneumonia in non-immunocompromised host, but limited data exist on the distinctive characteristics of AdV pneumonia in non-immunocompromised patients. We evaluated distinctive clinico-laboratory and radiological characteristics and outcomes of AdV pneumonia (n = 179), compared with non-AdV pneumonia (n = 188) in Korean military personnel between 2012 and 2016. AdV pneumonia patients had a higher rate of consolidation with ground-glass opacity (101/152) in lobar distribution (89/152) on computed tomography (CT) (P < 0.001). Laboratory findings showed a higher incidence of unusual blood profiles such as leukopenia (55/179, P < 0.001) or thrombocytopenia (100/179, P < 0.001). The patients had more systemic symptoms such as myalgia (82/179, P = 0.001) or diarrhea (23/179, P < 0.001), compared with non-AdV pneumonia patients. Bacterial co-infection was identified in 28.5% of AdV pneumonia. Most of the AdV isolates typed (69/72, 95.8%) were AdV-55. Patients with a pneumonia severity index ≥ class III were more commonly observed in AdV pneumonia patients compared with non-AdV pneumonia patients (11.2% vs. 2.1%, P < 0.001), and time to clinical stabilization from admission was longer in the AdV pneumonia patients compared with the non-AdV pneumonia patients (3.8 vs. 2.6 days, P < 0.001). Mechanical ventilation (n = 6) was only required in AdV pneumonia patients, one of whom died due to AdV-55. Our data showed that AdV pneumonia in non-immunocompromised patients had distinct characteristics and most of the isolates typed in our study were AdV-55. It is suggested that AdV-55 is an important pathogen of pneumonia in Korean military personnel. PMID:28049240

  2. Ultrasound-triggered drug delivery using acoustic droplet vaporization

    NASA Astrophysics Data System (ADS)

    Fabiilli, Mario Leonardo

    The goal of targeted drug delivery is the spatial and temporal localization of a therapeutic agent and its associated bioeffects. One method of drug localization is acoustic droplet vaporization (ADV), whereby drug-laden perfluorocarbon (PFC) emulsions are vaporized into gas bubbles using ultrasound, thereby releasing drug locally. Transpulmonary droplets are converted into bubbles that occlude capillaries, sequestering the released drug within an organ or tumor. This research investigates the relationship between the ADV and inertial cavitation (IC) thresholds---relevant for drug delivery due to the bioffects generated by IC---and explores the delivery of lipophilic and hydrophilic compounds using PFC double emulsions. IC can positively and negatively affect ultrasound mediated drug delivery. The ADV and IC thresholds were determined for various bulk fluid, droplet, and acoustic parameters. At 3.5 MHz, the ADV threshold occurred at a lower rarefactional pressure than the IC threshold. The results suggest that ADV is a distinct phenomenon from IC, the ADV nucleus is internal to the droplet, and the IC nucleus is the bubble generated by ADV. The ADV triggered release of a lipophilic chemotherapeutic agent, chlorambucil (CHL), from a PFC-in-oil-in-water emulsion was explored using plated cells. Cells exposed to a CHL-loaded emulsion, without ADV, displayed 44% less growth inhibition than cells exposed to an equal concentration of CHL in solution. Upon ADV of the CHL-loaded emulsion, the growth inhibition increased to the same level as cells exposed to CHL in solution. A triblock copolymer was synthesized which enabled the formulation of stable water-in-PFC-in-water (W1/PFC/W2) emulsions. The encapsulation of fluorescein in the W1 phase significantly decreased the mass flux of fluorescein; ADV was shown to completely release the fluorescein from the emulsions. ADV was also shown to release thrombin, dissolved in the W1 phase, which could be used in vivo to extend

  3. Characteristics of Adenovirus Pneumonia in Korean Military Personnel, 2012-2016.

    PubMed

    Yoon, Hee; Jhun, Byung Woo; Kim, Hojoong; Yoo, Hongseok; Park, Sung Bum

    2017-02-01

    Adenovirus (AdV) can cause severe pneumonia in non-immunocompromised host, but limited data exist on the distinctive characteristics of AdV pneumonia in non-immunocompromised patients. We evaluated distinctive clinico-laboratory and radiological characteristics and outcomes of AdV pneumonia (n = 179), compared with non-AdV pneumonia (n = 188) in Korean military personnel between 2012 and 2016. AdV pneumonia patients had a higher rate of consolidation with ground-glass opacity (101/152) in lobar distribution (89/152) on computed tomography (CT) (P < 0.001). Laboratory findings showed a higher incidence of unusual blood profiles such as leukopenia (55/179, P < 0.001) or thrombocytopenia (100/179, P < 0.001). The patients had more systemic symptoms such as myalgia (82/179, P = 0.001) or diarrhea (23/179, P < 0.001), compared with non-AdV pneumonia patients. Bacterial co-infection was identified in 28.5% of AdV pneumonia. Most of the AdV isolates typed (69/72, 95.8%) were AdV-55. Patients with a pneumonia severity index ≥ class III were more commonly observed in AdV pneumonia patients compared with non-AdV pneumonia patients (11.2% vs. 2.1%, P < 0.001), and time to clinical stabilization from admission was longer in the AdV pneumonia patients compared with the non-AdV pneumonia patients (3.8 vs. 2.6 days, P < 0.001). Mechanical ventilation (n = 6) was only required in AdV pneumonia patients, one of whom died due to AdV-55. Our data showed that AdV pneumonia in non-immunocompromised patients had distinct characteristics and most of the isolates typed in our study were AdV-55. It is suggested that AdV-55 is an important pathogen of pneumonia in Korean military personnel.

  4. Draft Function Allocation Framework and Preliminary Technical Basis for Advanced SMR Concepts of Operations

    SciTech Connect

    Hugo, Jacques; Forester, John; Gertman, David; Joe, Jeffrey; Medema, Heather; Persensky, Julius; Whaley, April

    2013-08-01

    This report presents preliminary research results from the investigation into the development of new models and guidance for Concepts of Operations in advanced small modular reactor (AdvSMR) designs. AdvSMRs are nuclear power plants (NPPs), but unlike conventional large NPPs that are constructed on site, AdvSMRs systems and components will be fabricated in a factory and then assembled on site. AdvSMRs will also use advanced digital instrumentation and control systems, and make greater use of automation. Some AdvSMR designs also propose to be operated in a multi-unit configuration with a single central control room as a way to be more cost-competitive with existing NPPs. These differences from conventional NPPs not only pose technical and operational challenges, but they will undoubtedly also have regulatory compliance implications, especially with respect to staffing requirements and safety standards.

  5. In situ molecular hybridization for detection of Aleutian mink disease parvovirus DNA by using strand-specific probes: identification of target cells for viral replication in cell cultures and in mink kits with virus-induced interstitial pneumonia.

    PubMed Central

    Alexandersen, S; Bloom, M E; Wolfinbarger, J; Race, R E

    1987-01-01

    Strand-specific hybridization probes were utilized in in situ molecular hybridization specifically to localize replicative form DNA of Aleutian mink disease parvovirus (ADV). Throughout in vitro infection, duplex replicative form DNA of ADV was located in the cell nuclei. Single-stranded virion DNA and capsid proteins were present in the nuclei early in infection, but were later translocated to the cytoplasm. In neonatal mink, ADV causes acute interstitial pneumonia, and replicative forms of viral DNA were found predominantly in alveolar type II cells of the lung. Viral DNA was also found in other organs, but strand-specific probes made it possible to show that most of this DNA represented virus sequestration. In addition, glomerular immune complexes containing intact virions were detected, suggesting that ADV virions may have a role in the genesis of ADV-induced glomerulonephritis. Images PMID:3037104

  6. Acoustic Doppler velocimeter-induced acoustic streaming and its implications for measurement

    NASA Astrophysics Data System (ADS)

    Poindexter, C. M.; Rusello, P. J.; Variano, E. A.

    2011-05-01

    The acoustic Doppler velocimeter (ADV) is widely used for the characterization of fluid flow. Secondary flows ("acoustic streaming") generated by the ADV's acoustic pulses may affect the accuracy of measurements in experiments with small velocities. We assessed the impact of acoustic streaming on flow measurement using particle image velocimetry. The probes of two different ADVs were successively mounted in a tank of quiescent water. The probes' ultrasound emitters were aligned with a laser light sheet. Observed flow was primarily in the axial direction, accelerating from the ultrasound emitter and peaking within centimeters of the velocimeter sampling volume before dropping off. We measured the dependence of acoustic streaming velocity on ADV configuration, finding that different settings induce streaming ranging from negligible to more than 2.0 cm s-1. From these results, we describe cases where acoustic streaming affects velocity measurements and also cases where ADVs accurately measure their own acoustic streaming.

  7. Molecular characterization, phylogeny analysis and pathogenicity of a Muscovy duck adenovirus strain isolated in China in 2014.

    PubMed

    Zhang, Xinheng; Zhong, Yangjin; Zhou, Zhenhai; Liu, Yang; Zhang, Huanmin; Chen, Feng; Chen, Weiguo; Xie, Qingmei

    2016-06-01

    This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The results of the analyses were in conformity with AdV properties. The full genome sequence was determined and analyzed. The new isolate (named CH-GD-12-2014) shared over 91% sequence identity with duck AdV-2 representing the species Duck aviadenovirus B. The most important distinguishing feature between the two DAdV strains was the presence of a second fiber gene in the Chinese isolate. Phylogeny reconstruction confirmed the affiliation of the virus with goose and duck AdVs in the genus Aviadenovirus. Experimental infection resulted in embryo death, and intramuscular inoculation provoked morbidity and mortality among ducks and chickens.

  8. Atmospheric dump valve engineering analysis

    SciTech Connect

    Mendoza, B.; McNemar, P.

    1990-01-01

    This report documents the activities undertaken after the atmospheric dump valves (ADVs) failed to operate following a Unit 3 reactor trip. The activities consisted of testing valves in all three units, examining Palo Verde Nuclear Generating Station (PVNGS) history with the valves, determining causes for failures, and making recommendations. The PVNGS engineering departments performed an in-depth review of the history, operation, maintenance, and design of ADVs. A preliminary mathematical model of the valves' dynamic behavior was developed by Arizona State University. The corrective actions are designed to eliminate the anomalies noted with the Unit 1 and 3 ADVs. Subsequent monitoring and testing activities following the planned modifications will ensure the ADVs remain operable during modes required by the PVNGS technical specifications. Through this increased monitoring and testing program, the valve modifications will be evaluated to confirm that the required level of reliability has been reached for the ADVs. The specific failures have been evaluated and the causes determined.

  9. Molecular cloning of the Aleutian disease virus genome: expression of Aleutian disease virus antigens by a recombinant plasmid.

    PubMed Central

    Mayer, L W; Aasted, B; Garon, C F; Bloom, M E

    1983-01-01

    Three nonoverlapping segments representing approximately 80% of the 4.8-kilobase pair Aleutian disease virus (ADV-G) duplex genome were molecularly cloned into either bacteriophage M13mp9 (M13bm2 = 0.07 to 0.15 map unit; M13bm1 = 0.15 to 0.54 map unit) or plasmid pUC8 (pBM1 = 0.54 to 0.88 map units). In addition the 0.54- to 0.88-map unit segment of a Danish isolate of ADV (DK ADV) was also cloned into pUC8 (pBM2). The recombinant plasmids pBM1 and pBM2 induced expression of several polypeptides in Escherichia coli JM103 that were specifically recognized by sera from mink infected with ADV. The same three proteins with approximate molecular weights of 55,000, 34,000, and 27,000 were detected both by immune blotting and by immunoprecipitation of [35S]methionine-labeled JM103 (pBM1). None of these proteins were recognized in JM103 or JM103 (pUC8), nor were they detected by sera from normal mink. Purified pBM1 and pBM2 DNA appeared identical in size by gel analysis and contour length measurement, and electron microscopic heteroduplex mapping revealed no visible areas of heterology. However, restriction endonuclease mapping showed that pBM2 was different from pBM1, indicating that this segment of the ADV genome was similar but not identical for two strains of ADV (ADV-G and DK ADV). Furthermore, when cloned DNA from ADV-G was labeled with [32P]dCTP by nick translation, DNA relatedness to several field strains of ADV (Utah I, Pullman, and DK), but not to mink enteritis virus or cellular DNA, was shown by Southern blot hybridization. Images PMID:6313959

  10. Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA

    PubMed Central

    Almgren, Malin; Atkinson, Richard; He, Jia; Hilding, Agneta; Hagman, Emilia; Wolk, Alicja; Thorell, Anders; Marcus, Claude; Näslund, Erik; Östenson, Claes-Göran; Schalling, Martin; Lavebratt, Catharina

    2012-01-01

    Background Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ∼7% in 1992–1998 to 15–20% in 2002–2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals. PMID:22848557

  11. Genetic characterization of Aleutian mink disease viruses isolated in China.

    PubMed

    Li, Yanwu; Huang, Juan; Jia, Yun; Du, Yijun; Jiang, Ping; Zhang, Rui

    2012-08-01

    Aleutian mink disease virus (AMDV) is a parvovirus that causes an immune complex mediated disease in minks. To understand the genetic characterization of AMDV in China, the genomic sequences of three isolates, ADV-LN1, ADV-LN2, and ADV-LN3, from different farms in the Northern China were analyzed. The results showed that the lengths of genomic sequences of three isolates were 4,543, 4,566, and 4,566 bp, respectively. They shared only 95.5-96.3 % nucleotide identity with each other. The nucleotide and amino acid homology of genome sequence between the Chinese isolates and European or American strains (ADV-G, ADV-Utah1, and ADV-SL3) were 92.4-95.0 % and 92.1-93.8 %, respectively. The amino acid substitutions randomly distributed in the genome, especially NS gene. ADV-LN1 strain had a 9-amino-acid deletion at amino acid positions 70 and 72-79 in the VP1 gene, comparing with ADV-G strain; ADV-LN2 and ADV-LN3 strains had 1-amino-acid deletion at amino acid positions 70 in the VP1. Some potential glycosylation site mutations in VP and NS genes were also observed. Phylogenetic analysis results showed that the three strains belonged to two different branches based on the complete coding sequence of VP2 gene. However, they all were in the same group together with the strains from United States based on the NS1 sequence. It indicated that Chinese AMDV isolates had genetic diversity. The origin of the ancestors of the Chinese AMDV strains might be associated with the American strains.

  12. Single-strand conformation polymorphism analysis for the study of adenoviral diversity in urban rivers.

    PubMed

    Lee, Cheonghoon; Kim, Sang-Jong

    2010-05-01

    The diversity of human adenoviruses (AdVs) in river waters was studied by single-strand conformational polymorphism (SSCP) analysis. Water samples were collected between 2002 and 2003 from 4 rivers in the Gyeonggi Province, South Korea. Forty-six (79.3%) of the 58 samples were positive for AdVs as determined on PCR amplification. Nine different SSCP profiles (profiles A to I) were detected in all the AdVs-positive samples by SSCP analysis, and most of the AdVs-positive samples (38 of 46 samples; 82.6%) showed the SSCP profile D. Nine different sequences were obtained in the SSCP profiles; sequence alignments and phylogenetic analysis identified 5 different sequences that were closely related to the human AdV type 41, and the 4 different sequences that were closely related to human AdV types 3, 4, 12, and 40. Two AdVs genomic variants were detected (types 3 and 41 in A, types 12 and 41 in B, and 2 genomic variants of type 41 in C) in SSCP profiles A, B, and C, respectively. SSCP analysis could be a useful technique for the identification of genetic variants of AdVs and for studying AdVs diversity in urban rivers.

  13. Wild boar: an increasing concern for Aujeszky's disease control in pigs?

    PubMed Central

    2012-01-01

    Background The goal of this study was describing the temporal evolution of Aujeszky's disease virus (ADV) contact prevalence among Eurasian wild boar (Sus scrofa) populations under different management regimes and contact likelihoods with domestic pigs. Given the recent increase in wild boar abundance throughout Europe, we hypothesized that wild boar contact with ADV would remain stable in time even after significant reduction of ADV prevalence in domestic pigs. Results Sera from 1659 wild boar were collected from 2000 to 2010 within 6 areas of the Iberian Peninsula and tested for the presence of antibodies against ADV by ELISA. According to sampling date, wild boar were grouped into three time periods. ADV prevalence was compared through period both globally and by geographic area. Overall seroprevalence for the ten-year study period was 49.6 ± 2.4%. The highest seroprevalence was recorded in areas with intense wild boar management. The annual proportion of positive wild boar sampling sites remained stable through the study period, while the percentage of domestic pig AD positive counties decreased from 70% in 2003 to 1.7% in 2010. Conclusions Results presented herein confirmed our hypothesis that ADV would remain almost stable in wild boar populations. This evidences the increasing risk wild boar pose in the final stages of ADV eradication in pigs and for wildlife conservation. PMID:22251441

  14. Acoustic Droplet Vaporization in Biology and Medicine

    PubMed Central

    Pitt, William G.

    2013-01-01

    This paper reviews the literature regarding the use of acoustic droplet vaporization (ADV) in clinical applications of imaging, embolic therapy, and therapeutic delivery. ADV is a physical process in which the pressure waves of ultrasound induce a phase transition that causes superheated liquid nanodroplets to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other functions. ADV of perfluoropentane was used extensively in imaging for preclinical trials in the 1990s, but its use declined rapidly with the advent of other imaging agents. In the last decade, ADV was proposed and explored for embolic occlusion therapy, drug delivery, aberration correction, and high intensity focused ultrasound (HIFU) sensitization. Vessel occlusion via ADV has been explored in rodents and dogs and may be approaching clinical use. ADV for drug delivery is still in preclinical stages with initial applications to treat tumors in mice. Other techniques are still in preclinical studies but have potential for clinical use in specialty applications. Overall, ADV has a bright future in clinical application because the small size of nanodroplets greatly reduces the rate of clearance compared to larger contrast agent bubbles and yet provides the advantages of ultrasonographic contrast, acoustic cavitation, and nontoxicity of conventional perfluorocarbon contrast agent bubbles. PMID:24350267

  15. Components of Adenovirus Genome Packaging

    PubMed Central

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  16. Adenoviral E4 34K protein interacts with virus packaging components and may serve as the putative portal.

    PubMed

    Ahi, Yadvinder S; Hassan, Ahmed O; Vemula, Sai V; Li, Kunpeng; Jiang, Wen; Zhang, Guang Jun; Mittal, Suresh K

    2017-08-08

    Studies on dsDNA bacteriophages have revealed that a DNA packaging complex assembles at a special vertex called the 'portal vertex' and consists of a portal, a DNA packaging ATPase and other components. AdV protein IVa2 is presumed to function as a DNA packaging ATPase. However, a protein that functions as a portal is not yet identified in AdVs. To identify the AdV portal, we performed secondary structure analysis on a set of AdV proteins and compared them with the clip region of the portal proteins of bacteriophages phi29, SPP1 and T4. Our analysis revealed that the E4 34K protein of HAdV-C5 contains a region of strong similarity with the clip region of the known portal proteins. E4 34K was found to be present in empty as well as mature AdV particles. In addition, E4 34K co-immunoprecipitates and colocalizes with AdV packaging proteins. Immunogold electron microscopy demonstrated that E4 34K is located at a single site on the virus surface. Finally, tertiary structure prediction of E4 34K and its comparison with that of single subunits of Phi29, SPP1 and T4 portal proteins revealed remarkable similarity. In conclusion, our results suggest that E4 34K is the putative AdV portal protein.

  17. The relationship between adenovirus-36 seropositivity, obesity and metabolic profile in Turkish children and adults.

    PubMed

    Karamese, M; Altoparlak, U; Turgut, A; Aydogdu, S; Karamese, S Aksak

    2015-12-01

    Obesity potentially arising from viral infection is known as 'infectobesity'. The latest reports suggest that adenovirus-36 (Adv36) is related to obesity in adults and children. Our aim was not only to determine the Adv36 seropositivity in both obese and non-obese children and adults, but also to investigate correlations between antibody positivity and serum lipid profiles. Both Adv36 positivity and tumour-necrosis-factor-alpha, leptin and interleukin-6 levels were detected in blood samples collected from 146 children and 130 adults by ELISA. Fasting plasma triglycerides, total cholesterol and low-density lipoprotein levels were also measured. Adv36 positivity was determined to be 27·1% and 6% in obese and non-obese children and 17·5% and 4% in obese and non-obese adults, respectively. There was no difference with regard to total cholesterol, low-density lipoprotein, triglyceride, tumour-necrosis-factor-alpha and interleukin-6 levels (P > 0·05). However, there was a significant difference between groups in terms of leptin levels (P < 0·05). We determined the prevalence of Adv36 positivity in obese children and adults. Our results showed that Adv36 may be an obesity agent for both adults and children, parallel with current literature data. However, the available data on a possible relationship between Adv36 infection and obesity both in children and adults do not completely solve the problem.

  18. Association of adenovirus 36 infection with obesity-related gene variants in adolescents.

    PubMed

    Dušátková, L; Zamrazilová, H; Aldhoon Hainerová, I; Atkinson, R L; Sedláčková, B; Lee, Z P; Včelák, J; Bendlová, B; Kunešová, M; Hainer, V

    2015-01-01

    Both, common gene variants and human adenovirus 36 (Adv36) are involved in the pathogenesis of obesity. The potential relationship between these two pathogenic factors has not yet been investigated. The aim of our study was to examine the association of obesity susceptibility loci with Adv36 status. Genotyping of ten gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and analysis of Adv36 antibodies was performed in 1,027 Czech adolescents aged 13.0-17.9 years. Variants of two genes (PCSK1 and BDNF) were associated with Adv36 seropositivity. A higher prevalence of Adv36 antibody positivity was observed in obesity risk allele carriers of PCSK1 rs6232, rs6235 and BDNF rs4923461 vs. non-carriers (chi(2)=6.59, p=0.010; chi(2)=7.56, p=0.023 and chi(2)=6.84, p=0.033, respectively). The increased risk of Adv36 positivity was also found in PCSK1 variants: rs6232 (OR=1.67, 95 % CI 1.11-2.49, p=0.016) and rs6235 (OR=1.34, 95 % CI 1.08-1.67, p=0.010). PCSK1 rs6232 and BDNF rs925946 variants were closely associated with Adv36 status in boys and girls, respectively (chi(2)=5.09, p=0.024; chi(2)=7.29, p=0.026). Furthermore, PCSK1 rs6235 risk allele was related to Adv36 seropositivity (chi(2)=6.85, p=0.033) in overweight/obese subgroup. In conclusion, our results suggest that obesity risk variants of PCSK1 and BDNF genes may be related to Adv36 infection.

  19. Antiviral activity of eight commonly used medicinal plants in Taiwan.

    PubMed

    Chiang, Lien-Chai; Cheng, Hua-Yew; Liu, Mei-Chi; Chiang, Wen; Lin, Chun-Ching

    2003-01-01

    In an effort to find new antiviral agents from natural products, hot water extracts of eight traditionally used medicinal plants in Taiwan were investigated in vitro for their activities against adenoviruses (ADV) and herpes simplex viruses (HSV). Results demonstrated that all extracts exhibited antiviral activity with different degrees of potency. Only two extracts were active in suppressing both HSV and ADV infections. Three extracts inhibited only ADV infection whereas one extract blocked only HSV infection. These results suggested that the aforementioned medicinal plants merit further investigation.

  20. Detection of Aleutian disease virus by loop-mediated isothermal amplification.

    PubMed

    Zhang, Zhuo; Wang, Bin; Hu, Shouping; Zhang, Jiaoer; He, Xijun; Zheng, Shimin

    2015-09-01

    In this study, a loop-mediated isothermal amplification (LAMP) assay was developed and optimized for the detection of Aleutian disease virus (ADV) in minks. The amplification could be completed within 45 min under isothermal condition by employing a set of six ADV genome-specific primers. The amplification results could be visualized directly with the naked eye by using fluorescent dye. Comparative experiments showed that the LAMP assay is superior to conventional polymerase chain reaction for the detection of both experimental and field samples. Results of current study indicated that the LAMP assay is a rapid and reliable technique for routine diagnosis of ADV infection in minks.

  1. On Enhancing Risk Monitors for Advanced Small Modular Reactors

    SciTech Connect

    Coble, Jamie B.; Coles, Garill A.; Meyer, Ryan M.; Ramuhalli, Pradeep

    2013-08-01

    Advanced small modular reactors (AdvSMRs) can contribute to safe, sustainable, and carbon-neutral energy production. However, the economics of AdvSMRs suffer from the loss of economy-of-scale for both construction and operation. The controllable day-to-day costs of AdvSMRs are expected to be dominated by operations and maintenance (O&M) costs. These expenses could potentially be managed through optimized scheduling of O&M activities for components, reactor modules, power blocks, and the full plant. Accurate, real-time risk assessment with integrated health monitoring of key active components can support scheduling of both online and offline inspection and maintenance activities.

  2. Compact, Robust Chips Integrate Optical Functions

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Located in Bozeman, Montana, AdvR Inc. has been an active partner in NASA's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Langley Research Center engineers partnered with AdvR through the SBIR program to develop new, compact, lightweight electro-optic components for remote sensing systems. While the primary customer for this technology will be NASA, AdvR foresees additional uses for its NASA-derived circuit chip in the fields of academic and industrial research anywhere that compact, low-cost, stabilized single-frequency lasers are needed.

  3. Brincidofovir clearance of acyclovir-resistant herpes simplex virus-1 and adenovirus infection after stem cell transplantation.

    PubMed

    Voigt, S; Hofmann, J; Edelmann, A; Sauerbrei, A; Kühl, J-S

    2016-10-01

    Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance. A subsequent Epstein-Barr virus disease with relevant meningoencephalitis responded to rituximab.

  4. Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug–Drug Interactions

    PubMed Central

    Mandíková, Jana; Volková, Marie; Pávek, Petr; Navrátilová, Lucie; Hyršová, Lucie; Janeba, Zlatko; Pavlík, Jan; Bárta, Pavel; Trejtnar, František

    2016-01-01

    Entecavir (ETV) is one of the most potent agents for the treatment of the hepatitis B viral infection. The drug is principally eliminated by the kidney. The goal of this study was to investigate the potential of ETV to interact in vitro with the renal SLC transporters hOAT1, hOCT2, hCNT2 and hCNT3. Potential drug–drug interactions of ETV at the renal transporters with antiviral drugs known to be excreted by the kidney (adefovir, tenofovir, cidofovir) as well as transporter-dependent cytotoxicity were also examined. Interactions with the selected transporters along with cytotoxicity were studied in several transiently transfected cellular models using specific substrates and inhibitors. ETV was found to be both a substrate and inhibitor of hOAT1 (IC50 = 175.3 μM), hCNT2 (IC50 = 241.9 μM) and hCNT3 (IC50 = 278.4 μM) transporters, although it interacted with the transporters with relatively low affinities. ETV inhibited the cellular uptake of adefovir, tenofovir, and cidofovir by hOAT1; however, effective inhibition was shown at ETV concentrations exceeding therapeutic levels. In comparison with adefovir, tenofovir, and cidofovir, ETV displayed no transporter-mediated cytotoxicity in cells transfected with hOAT1, hCNT2, and hCNT3. No significant interaction of ETV with hOCT2 was detected. The study demonstrates interactions of ETV with several human renal transporters. For the first time, an interaction of ETV with the hCNTs was proved. We show that the potency of ETV to cause nephrotoxicity and/or clinically significant drug-drug interactions related to the tested transporters is considerably lower than that of adefovir, tenofovir, and cidofovir. PMID:26779022

  5. The design and characterization of wideband spline-profiled feedhorns for Advanced ACTPol

    NASA Astrophysics Data System (ADS)

    Simon, Sara M.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Coughlin, Kevin P.; Duff, Shannon M.; Gallardo, Patricio A.; Henderson, Shawn W.; Hills, Felicity B.; Ho, Shuay-Pwu Patty; Hubmayr, Johannes; Josaitis, Alec; Koopman, Brian J.; McMahon, Jeff J.; Nati, Federico; Newburgh, Laura; Niemack, Michael D.; Salatino, Maria; Schillaci, Alessandro; Schmitt, Benjamin L.; Staggs, Suzanne T.; Vavagiakis, Eve M.; Ward, Jonathan; Wollack, Edward J.

    2016-07-01

    Advanced ACTPol (AdvACT) is an upgraded camera for the Atacama Cosmology Telescope (ACT) that will measure the cosmic microwave background in temperature and polarization over a wide range of angular scales and five frequency bands from 28-230 GHz. AdvACT will employ four arrays of feedhorn-coupled, polarization- sensitive multichroic detectors. To accommodate the higher pixel packing densities necessary to achieve Ad- vACT's sensitivity goals, we have developed and optimized wideband spline-profiled feedhorns for the AdvACT multichroic arrays that maximize coupling efficiency while carefully controlling polarization systematics. We present the design, fabrication, and testing of wideband spline-profiled feedhorns for the multichroic arrays of AdvACT.

  6. DM-2 Chilling

    NASA Image and Video Library

    How do you chill down 1.4 million pounds of solid rocket fuel in the hot Utah desert? Lots of air conditioning! Learn how ATK chilled down DM-2, the second Ares first stage development motor in adv...

  7. Partial characterization of new adenoviruses found in lizards.

    PubMed

    Ball, Inna; Behncke, Helge; Schmidt, Volker; Geflügel, F T A; Papp, Tibor; Stöhr, Anke C; Marschang, Rachel E

    2014-06-01

    In the years 2011-2012, a consensus nested polymerase chain reaction was used for the detection of adenovirus (AdV) infection in reptiles. During this screening, three new AdVs were detected. One of these viruses was detected in three lizards from a group of green striped tree dragons (Japalura splendida). Another was detected in a green anole (Anolis carolinensis). A third virus was detected in a Jackson's chameleon (Chamaeleo jacksonii). Analysis of a portion of the DNA-dependent DNA polymerase genes of each of these viruses revealed that they all were different from one another and from all previously described reptilian AdVs. Phylogenetic analysis of the partial DNA polymerase gene sequence showed that all newly detected viruses clustered within the genus Atadenovirus. This is the first description of AdVs in these lizard species.

  8. Assembly and Integration Process of the First High Density Detector Array for the Atacama Cosmology Telescope

    NASA Technical Reports Server (NTRS)

    Li, Yaqiong; Choi, Steve; Ho, Shuay-Pwu; Crowley, Kevin T.; Salatino, Maria; Simon, Sara M.; Staggs, Suzanne T.; Nati, Federico; Wollack, Edward J.

    2016-01-01

    The Advanced ACTPol (AdvACT) upgrade on the Atacama Cosmology Telescope (ACT) consists of multichroicTransition Edge Sensor (TES) detector arrays to measure the Cosmic Microwave Background (CMB) polarization anisotropies in multiple frequency bands. The first AdvACT detector array, sensitive to both 150 and 230 GHz, is fabricated on a 150 mm diameter wafer and read out with a completely different scheme compared to ACTPol. Approximately 2000 TES bolometers are packed into the wafer leading to both a much denser detector density and readout circuitry. The demonstration of the assembly and integration of the AdvACT arrays is important for the next generation CMB experiments, which will continue to increase the pixel number and density. We present the detailed assembly process of the first AdvACT detector array.

  9. Screening ecological impacts of environmental surface waters using cell-based metabolomics

    EPA Science Inventory

    Anthropogenic chemicals are routinely detected in aquatic ecosystems downstream from wastewater treatment plants (WWTPs), industrial and agricultural operations, and numerous other sources. Various studies have shown that exposure to such complex chemical mixtures can produce adv...

  10. Assembly and Integration Process of the First High Density Detector Array for the Atacama Cosmology Telescope

    NASA Technical Reports Server (NTRS)

    Li, Yaqiong; Choi, Steve; Ho, Shuay-Pwu; Crowley, Kevin T.; Salatino, Maria; Simon, Sara M.; Staggs, Suzanne T.; Nati, Federico; Wollack, Edward J.

    2016-01-01

    The Advanced ACTPol (AdvACT) upgrade on the Atacama Cosmology Telescope (ACT) consists of multichroicTransition Edge Sensor (TES) detector arrays to measure the Cosmic Microwave Background (CMB) polarization anisotropies in multiple frequency bands. The first AdvACT detector array, sensitive to both 150 and 230 GHz, is fabricated on a 150 mm diameter wafer and read out with a completely different scheme compared to ACTPol. Approximately 2000 TES bolometers are packed into the wafer leading to both a much denser detector density and readout circuitry. The demonstration of the assembly and integration of the AdvACT arrays is important for the next generation CMB experiments, which will continue to increase the pixel number and density. We present the detailed assembly process of the first AdvACT detector array.

  11. The Design and Characterization of Wideband Spline-profiled Feedhorns for Advanced Actpol

    NASA Technical Reports Server (NTRS)

    Simon, Sara M.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Coughlin, Kevin P.; Duff, Shannon M.; Gallardo, Patricio A.; Henderson, Shawn W.; Hills, Felicity B.; Ho, Shuay-Pwu Patty; Hubmayr, Johannes; Josaitis, Alec; Koopman, Brian J.; McMahon, Jeff J.; Nati, Federico; Newburgh, Laura; Niemack, Michael D.; Salatino, Maria; Schillaci, Alessandro; Wollack, Edward J.

    2016-01-01

    Advanced ACTPol (AdvACT) is an upgraded camera for the Atacama Cosmology Telescope (ACT) that will measure the cosmic microwave background in temperature and polarization over a wide range of angular scales and five frequency bands from 28-230 GHz. AdvACT will employ four arrays of feedhorn-coupled, polarization- sensitive multichroic detectors. To accommodate the higher pixel packing densities necessary to achieve Ad- vACTs sensitivity goals, we have developed and optimized wideband spline-profiled feedhorns for the AdvACT multichroic arrays that maximize coupling efficiency while carefully controlling polarization systematics. We present the design, fabrication, and testing of wideband spline-profiled feedhorns for the multichroic arrays of AdvACT.

  12. Screening ecological impacts of environmental surface waters using cell-based metabolomics

    EPA Science Inventory

    Anthropogenic chemicals are routinely detected in aquatic ecosystems downstream from wastewater treatment plants (WWTPs), industrial and agricultural operations, and numerous other sources. Various studies have shown that exposure to such complex chemical mixtures can produce adv...

  13. Assembly and integration process of the first high density detector array for the Atacama Cosmology Telescope

    NASA Astrophysics Data System (ADS)

    Li, Yaqiong; Choi, Steve; Ho, Shuay-Pwu; Crowley, Kevin T.; Salatino, Maria; Simon, Sara M.; Staggs, Suzanne T.; Nati, Federico; Ward, Jonathan; Schmitt, Benjamin L.; Henderson, Shawn; Koopman, Brian J.; Gallardo, Patricio A.; Vavagiakis, Eve M.; Niemack, Michael D.; McMahon, Jeff; Duff, Shannon M.; Schillaci, Alessandro; Hubmayr, Johannes; Hilton, Gene C.; Beall, James A.; Wollack, Edward J.

    2016-07-01

    The Advanced ACTPol (AdvACT) upgrade on the Atacama Cosmology Telescope (ACT) consists of multichroic Transition Edge Sensor (TES) detector arrays to measure the Cosmic Microwave Background (CMB) polarization anisotropies in multiple frequency bands. The first AdvACT detector array, sensitive to both 150 and 230 GHz, is fabricated on a 150 mm diameter wafer and read out with a completely different scheme compared to ACTPol. Approximately 2000 TES bolometers are packed into the wafer leading to both a much denser detector density and readout circuitry. The demonstration of the assembly and integration of the AdvACT arrays is important for the next generation CMB experiments, which will continue to increase the pixel number and density. We present the detailed assembly process of the first AdvACT detector array.

  14. The Crossbyton project

    NASA Astrophysics Data System (ADS)

    Reichert, J. D.

    1980-05-01

    The Analog Design Verification System (ADVS), the largest single solar collector built, was tested. Referred to as the Solar Gridiron or Bowl Concept, it employs a stationary mirror, with tracking accomplished by the mirror.

  15. Ether lipid-ester prodrugs of acyclic nucleoside phosphonates: activity against adenovirus replication in vitro.

    PubMed

    Hartline, Caroll B; Gustin, Kortney M; Wan, William B; Ciesla, Stephanie L; Beadle, James R; Hostetler, Karl Y; Kern, Earl R

    2005-02-01

    The acyclic nucleoside phosphonate cidofovir (CDV) and its closely related analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine ([S]-HPMPA) have been reported to have activity against many adenovirus (AdV) serotypes. A new series of orally active ether lipid-ester prodrugs of CDV and of (S)-HPMPA that have slight differences in the structure of their lipid esters were evaluated, in tissue-culture cells, for activity against 5 AdV serotypes. The results indicated that, against several AdV serotypes, the most active compounds were 15-2500-fold more active than the unmodified parent compounds and should be evaluated further for their potential to treat AdV infections in humans.

  16. Disruption of the Coxsackievirus and Adenovirus Receptor-Homodimeric Interaction Triggers Lipid Microdomain- and Dynamin-dependent Endocytosis and Lysosomal Targeting*

    PubMed Central

    Salinas, Sara; Zussy, Charleine; Loustalot, Fabien; Henaff, Daniel; Menendez, Guillermo; Morton, Penny E.; Parsons, Maddy; Schiavo, Giampietro; Kremer, Eric J.

    2014-01-01

    The coxsackievirus and adenovirus receptor (CAR) serves as a docking factor for some adenovirus (AdV) types and group B coxsackieviruses. Its role in AdV internalization is unclear as studies suggest that its intracellular domain is dispensable for some AdV infection. We previously showed that in motor neurons, AdV induced CAR internalization and co-transport in axons, suggesting that CAR was linked to endocytic and long-range transport machineries. Here, we characterized the mechanisms of CAR endocytosis in neurons and neuronal cells. We found that CAR internalization was lipid microdomain-, actin-, and dynamin-dependent, and subsequently followed by CAR degradation in lysosomes. Moreover, ligands that disrupted the homodimeric CAR interactions in its D1 domains triggered an internalization cascade involving sequences in its intracellular tail. PMID:24273169

  17. The Design and Characterization of Wideband Spline-profiled Feedhorns for Advanced Actpol

    NASA Technical Reports Server (NTRS)

    Simon, Sara M.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Coughlin, Kevin P.; Duff, Shannon M.; Gallardo, Patricio A.; Henderson, Shawn W.; Hills, Felicity B.; Ho, Shuay-Pwu Patty; hide

    2016-01-01

    Advanced ACTPol (AdvACT) is an upgraded camera for the Atacama Cosmology Telescope (ACT) that will measure the cosmic microwave background in temperature and polarization over a wide range of angular scales and five frequency bands from 28-230 GHz. AdvACT will employ four arrays of feedhorn-coupled, polarization- sensitive multichroic detectors. To accommodate the higher pixel packing densities necessary to achieve Ad- vACTs sensitivity goals, we have developed and optimized wideband spline-profiled feedhorns for the AdvACT multichroic arrays that maximize coupling efficiency while carefully controlling polarization systematics. We present the design, fabrication, and testing of wideband spline-profiled feedhorns for the multichroic arrays of AdvACT.

  18. Antibody-Forming Cells and Serum Hemolysin Responses of Pastel and Sapphire Mink Inoculated with Aleutian Disease Virus

    PubMed Central

    Lodmell, Donald L.; Bergman, R. Kaye; Hadlow, William J.

    1973-01-01

    The effect of Aleutian disease virus (ADV) on serum hemolysin titers and antibody-forming cells in lymph nodes and spleens of sapphire and pastel mink inoculated with goat erythrocytes (G-RBC) was investigated. ADV injected 1 day after primary antigenic stimulation with G-RBC did not depress the immune responses of either color phase for a period of 26 days. However, when G-RBC were injected 47 days after ADV, both the number of antibody-forming cells and hemolysin titers were more markedly depressed in sapphire than in pastel mink. The results are discussed in relation to the greater susceptibility of sapphire mink and the variable susceptibility of pastel mink to the Pullman isolate of ADV. PMID:4584051

  19. 75 FR 69507 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-12

    ... Endnote 3 of the Fee Schedule, ``Liquidity Adding ADV'') is less than 25 million shares (``Tier 1''); a... (``TCADV''). As set forth in Explanatory Endnote 13, TCADV means average daily volume reported by all...

  20. What Would They Do? Parents' Responses to Hypothetical Adolescent Dating Violence Situations.

    PubMed

    Weisz, Arlene N; Black, Beverly M; Hawley, Alicia C

    2017-04-01

    Although adolescent dating violence (ADV) is recognized as a significant public health problem, little is known about how parents respond to it. This article analyzes exploratory, qualitative data from a public opinion survey of 529 Midwestern, U. S. parents' ideas about how they would respond to a daughter victimized by ADV. It examines differing responses between mothers and fathers across 3 vignettes. Most parents viewed the ADV as serious, meriting deeper discussions with the daughter, boyfriend, or his parents. Many planned to handle the incident by trying to end the adolescents' relationship, talking to the boyfriend, or informing the daughter about ADV. These findings can help prevention workers show how knowledge about parents' typical reactions can help parents modulate their responses to increase effective communication with adolescents.

  1. Nuclear Import of Adenovirus DNA Involves Direct Interaction of Hexon with an N-Terminal Domain of the Nucleoporin Nup214

    PubMed Central

    Ragues, Jessica; Guan, Tinglu; Bégu, Dominique; Wodrich, Harald; Kann, Michael; Nemerow, Glen R.; Gerace, Larry

    2014-01-01

    ABSTRACT In this study, we characterized the molecular basis for binding of adenovirus (AdV) to the cytoplasmic face of the nuclear pore complex (NPC), a key step during delivery of the viral genome into the nucleus. We used RNA interference (RNAi) to deplete cells of either Nup214 or Nup358, the two major Phe-Gly (FG) repeat nucleoporins localized on the cytoplasmic side of the NPC, and evaluated the impact on hexon binding and AdV infection. The accumulation of purified hexon trimers or partially disassembled AdV at the nuclear envelope (NE) was observed in digitonin-permeabilized cells in the absence of cytosolic factors. Both in vitro hexon binding and in vivo nuclear import of the AdV genome were strongly reduced in Nup214-depleted cells but still occurred in Nup358-depleted cells, suggesting that Nup214 is a major binding site of AdV during infection. The expression of an NPC-targeted N-terminal domain of Nup214 in Nup214-depleted cells restored the binding of hexon at the NE and the nuclear import of protein VII (pVII), indicating that this region is sufficient to allow AdV binding. We further narrowed the binding site to a 137-amino-acid segment in the N-terminal domain of Nup214. Together, our results have identified a specific region within the N terminus of Nup214 that acts as a direct NPC binding site for AdV. IMPORTANCE AdVs, which have the largest genome of nonenveloped DNA viruses, are being extensively explored for use in gene therapy, especially in alternative treatments for cancers that are refractory to traditional therapies. In this study, we characterized the molecular basis for binding of AdV to the cytoplasmic face of the NPC, a key step for delivery of the viral genome into the nucleus. Our data indicate that a 137-amino-acid region of the nucleoporin Nup214 is a binding site for the major AdV capsid protein, hexon, and that this interaction is required for viral DNA import. These findings provide additional insight on how AdV exploits the

  2. Expression of pIX gene induced by transgene promoter: possible cause of host immune response in first-generation adenoviral vectors.

    PubMed

    Nakai, Michio; Komiya, Kazuo; Murata, Masashi; Kimura, Toru; Kanaoka, Masaharu; Kanegae, Yumi; Saito, Izumu

    2007-10-01

    First-generation (FG) adenoviral vectors (AdVs) have been widely used not only for gene therapy but also for basic studies. Because vectors of this type lack the E1A gene that is essential for the expression of other viral genes, their expression levels in target cells have been considered low. However, we found that the viral pIX gene, located immediately downstream of the inserted expression unit of the transgene, was significantly coexpressed with the transgene in cells infected with FG AdV. Whereas CAG and SRalpha promoters activated the pIX promoter considerably through their enhancer effects, the EF1alpha promoter hardly did. Moreover, when the expression unit was inserted in the rightward orientation, not only the pIX protein but also a fusion protein consisting of the N-terminal part of transgene product and pIX were sometimes coexpressed with the transgene product through an aberrant splicing mechanism. In in vivo experiments, a LacZ-expressing AdV bearing the CAG promoter caused an elevation of alanine aminotransferase, but an AdV bearing the EF1alpha promoter produced no detectable levels. Whereas the FG AdV expressing human growth hormone under the control of the CAG promoter maintained a high hormone level for less than 1 month, the FG AdV under the control of the EF1alpha promoter maintained a high level for at least 6 months. These results suggest that pIX coexpression may be one of the main causes of AdV-induced immune responses, and that the EF1alpha promoter is probably valuable for the long-term expression of FG AdV. Thus, the in vivo utility of FG AdV should be reevaluated.

  3. Technical Needs for Prototypic Prognostic Technique Demonstration for Advanced Small Modular Reactor Passive Components

    SciTech Connect

    Meyer, Ryan M.; Coble, Jamie B.; Hirt, Evelyn H.; Ramuhalli, Pradeep; Mitchell, Mark R.; Wootan, David W.; Berglin, Eric J.; Bond, Leonard J.; Henager, Charles H.

    2013-05-17

    This report identifies a number of requirements for prognostics health management of passive systems in AdvSMRs, documents technical gaps in establishing a prototypical prognostic methodology for this purpose, and describes a preliminary research plan for addressing these technical gaps. AdvSMRs span multiple concepts; therefore a technology- and design-neutral approach is taken, with the focus being on characteristics that are likely to be common to all or several AdvSMR concepts. An evaluation of available literature is used to identify proposed concepts for AdvSMRs along with likely operational characteristics. Available operating experience of advanced reactors is used in identifying passive components that may be subject to degradation, materials likely to be used for these components, and potential modes of degradation of these components. This information helps in assessing measurement needs for PHM systems, as well as defining functional requirements of PHM systems. An assessment of current state-of-the-art approaches to measurements, sensors and instrumentation, diagnostics and prognostics is also documented. This state-of-the-art evaluation, combined with the requirements, may be used to identify technical gaps and research needs in the development, evaluation, and deployment of PHM systems for AdvSMRs. A preliminary research plan to address high-priority research needs for the deployment of PHM systems to AdvSMRs is described, with the objective being the demonstration of prototypic prognostics technology for passive components in AdvSMRs. Greater efficiency in achieving this objective can be gained through judicious selection of materials and degradation modes that are relevant to proposed AdvSMR concepts, and for which significant knowledge already exists. These selections were made based on multiple constraints including the analysis performed in this document, ready access to laboratory-scale facilities for materials testing and measurement, and

  4. A Novel Platform to Study the Effect of Small-scale Turbulent Density Fluctuations on Underwater Imaging in the Ocean

    DTIC Science & Technology

    2015-04-29

    camera and optical target mounted on a 5m-long frame, along with several Nortek Vector Acoustic Doppler Velocimeter and PME Conductivity -Temperature...BOTEX. the array free-fall through the water column. In the present study, we settled on the use of Acoustic Doppler Velocimeters (ADVs) and high...as optical target (bottom). a Nortek Vector Acoustic Doppler Velocimeter (ADV) and PME Conductivity–Temperature (CT) mi- crostructure probe

  5. Measuring Turbulence from Moored Acoustic Doppler Velocimeters. A Manual to Quantifying Inflow at Tidal Energy Sites

    SciTech Connect

    Kilcher, Levi; Thomson, Jim; Talbert, Joe; DeKlerk, Alex

    2016-03-01

    This work details a methodology for measuring hub height inflow turbulence using moored acoustic Doppler velocimiters (ADVs). This approach is motivated by the shortcomings of alternatives. For example, remote velocity measurements (i.e., from acoustic Doppler profilers) lack sufficient precision for device simulation, and rigid tower-mounted measurements are very expensive and technically challenging in the tidal environment. Moorings offer a low-cost, site-adaptable and robust deployment platform, and ADVs provide the necessary precision to accurately quantify turbulence.

  6. Surface Grafting of Thermoresponsive Microgel Nanoparticles (Postprint)

    DTIC Science & Technology

    2011-01-01

    and cell immobilization, as biosensors, and for in vivo drug delivery .33,34,36,49–53 PNIPAM-containing microgels have been synthesized and...2007, 25, 577–583. 51 J. Jagur-Grodzinski, Polym. Adv. Technol., 2010, 21, 27–47.Soft Matter52 M. Hamidi, A. Azadi and P. Rafiei,Adv. Drug Delivery ...prospective applications in micro- and nanofluidics, biocompatible materials, controlled drug release, nano- and biotribology, controlled cell growth

  7. Small Hepatocellular Carcinoma With Low Tumor Marker Expression Benefits More From Anatomical Resection Than Tumors With Aggressive Biology.

    PubMed

    Jung, Dong-Hwan; Hwang, Shin; Lee, Young-Joo; Kim, Ki-Hun; Song, Gi-Won; Ahn, Chul-Soo; Moon, Deok-Bog; Lee, Sung-Gyu

    2017-08-23

    We assessed prognostic advantage of anatomical resection (AR) over nonanatomical resection (NAR) for hepatocellular carcinoma (HCC) according to multiplication of α-fetoprotein, des-γ-carboxyprothrombin, and tumor volume (ADV) scores. Superiority of AR over NAR is debated. ADV score is surrogate marker of postresection prognosis for solitary HCC. This study included 1572 patients who underwent curative resection for solitary HCC of 2.0 to 5.0 cm between 2006 and 2014. Preoperative patient profiles were not statistically different between AR and NAR groups. In 1324 naïve patients without preoperative treatment, AR group showed lower recurrence rates (P = 0.003) and higher patient survival rates (P = 0.012) than NAR group. AR group showed lower recurrence rates in patients with ADV ≤5 log (P ≤ 0.046). ADV scores >4 log and >3 log were independent risk factors for tumor recurrence and patient survival in treatment-naïve patients, respectively. In treatment-naïve group with preserved hepatic functional reserve, AR group showed lower recurrence rates in patients with ADV ≤4 log (P = 0.026). Absence of microvascular invasion also showed lower recurrence rates (P = 0.007) in AR group. In 248 patients with preoperative treatment, AR group showed lower recurrence rates (P = 0.001) and higher patient survival rates (P = 0.006). AR group showed lower recurrence rates in patients with ADV ≤4 log (P < 0.001) and higher survival rates in patients with ADV ≤5 log (P ≤ 0.043). Prognostic benefit of AR was evident in patients with ADV score ≤4 log or absence of microvascular invasion. Patients with less aggressive tumor biology benefit more from AR than NAR, thus being reasonably indicated for AR.

  8. Laser Hazards Bibliography, January 1991

    DTIC Science & Technology

    1991-01-31

    retinitis pigmentosa , Adv Exp Med Biol, 77: 233-247 (1977). 3. Agarwal, L. P., and Malik, S. R. K., Solar retinitis , Br J Ophth, 43: 366-370 (1959). 4. Al... Retinitis pigmentosa : clinical management based on current concepts, Adv Exp Med Biol, 77: 181-195 (1977). 557. Wolbarsht, M. L., Safe Ocular Levels for IR...270 C. Optical Radiation Hazards - General Reviews ............ 271 D. Retinal Burns from Lasers

  9. Air Evacuation and Its Effect on Theater and Zone of Interior Hospitalization Requirements

    DTIC Science & Technology

    1947-10-13

    34:,; invalided home. 9 Medical Service- Communication Zone, Subj~ct 4308, Adv Sheet, par 8, p. 12 10 Historical Review, WuV II, Apend P, P• 58 11 FM...Service in Communication Zone", Apend 4 to Adv Sheet, par 9, p.26 25 liiJiil FM 8-35, par 102 f. 26 Maj Gen Kirk, op. cit. PP• 27-29 -12- skilled

  10. Defense Planning and Programming Categories: A Special Tool for Special Needs. Volume 3. Appendix E. Proposed Expanded DPPC Structure

    DTIC Science & Technology

    1990-04-01

    DEVELOPMENT - ADVANCED DEVELOPMENT 0603542N Radiological Control OAC RESEARCH & DEVELOPMENT - ADVANCED DEVELOPMENT 0603550N LINK DOGWOOD GAC RESEARCH...0604705N CHALK BANYAN GAD RESEARCH & DEVELOPMENT - ENGINEERING DEVELOPMENT 0604706A Radiological Defense Equipment (H) GAD RESEARCH & DEVELOPMENT...Elect Warfare Adv Bev GA RESEARCH & DEVELOPMENT 6e32O07A Aircraft Avionics Equipaent (H) GA RESEARCH i DEVELOPMENT 0603207F Adv Fire Ctl//Msl Tech (H

  11. Optics, Acoustics and Stress in Situ (OASIS)

    DTIC Science & Technology

    2012-09-30

    seafloor bedform measurements (Rotary Sidescan and Pencil-beam sonars ) APPROACH Our project is focused on obtaining direct measurements of the...September 2011, showing Pulse Coherent Doppler Profiler (PCDP), Imagenex rotary sidescan sonar , Imagenex 2- axis rotary pencil beam sonar , Aquatec ABS and...Nortek Vector ADVs. Rotary Pencil Beam Sonar Rotary Sidescan Sonar PCDP ABS ADVs 5 Figure 3. Rotary Sidescan Image showing 70 cm

  12. Armament for the Army in Transition Session II Interim Brigade Combat Team (IBCT) & Legacy Force Systems

    DTIC Science & Technology

    2001-06-18

    Coco Director, Adv Sys Concepts Office TACOM–ARDEC, Picatinny, NJ Tank-automotive & Armaments COMmand Session Co-Chairs: Mr. Donald...Program Element Number Author(s) Del Coco , Gene; Howe, Donald Project Number Task Number Work Unit Number Performing Organization Name(s) and...SESSION CHAIRMAN 0800 HOURS MR. GENE DEL COCO CHIEF, TACOM-ARDEC ADV. SYSTEMS CONCEPTS DIR MR. DONALD HOWE BCT PROGRAM, DIR. FOR GM-GDLS, DEFENSE

  13. Prevalence of neutralising antibodies against adenoviruses in lizards and snakes.

    PubMed

    Ball, Inna; Ofner, Sabine; Funk, Richard S; Griffin, Chris; Riedel, Ulf; Möhring, Jens; Marschang, Rachel E

    2014-10-01

    Adenoviruses (AdVs) are relatively common in lizards and snakes, and several genetically distinct AdVs have been isolated in cell culture. The aims of this study were to examine serological relationships among lizard and snake AdVs and to determine the frequency of AdV infections in these species. Isolates from a boa constrictor (Boa constrictor), a corn snake (Pantherophis gutattus) and a central bearded dragon (Pogona vitticeps), and two isolates from helodermatid lizards (Heloderma horridum and H. suspectum) were used in neutralisation tests for the detection of antibodies in plasma from 263 lizards from seven families (including 12 species) and from 141 snakes from four families (including 28 species) from the USA and Europe. Most lizard and snake samples had antibodies against a range of AdV isolates, indicating that AdV infection is common among these squamates. Neutralisation tests with polyclonal antibodies raised in rabbits demonstrated serological cross-reactivity between both helodermatid lizard isolates. However, squamate plasma showed different reactions to each of these lizard isolates in neutralisation tests. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Development and validation of a novel hydrolysis probe real-time polymerase chain reaction for agamid adenovirus 1 in the central bearded dragon (Pogona vitticeps).

    PubMed

    Fredholm, Daniel V; Coleman, James K; Childress, April L; Wellehan, James F X

    2015-03-01

    Agamid adenovirus 1 (AgAdv-1) is a significant cause of disease in bearded dragons (Pogona sp.). Clinical manifestations of AgAdv-1 infection are variable and often nonspecific; the manifestations range from lethargy, weight loss, and inappetence, to severe enteritis, hepatitis, and sudden death. Currently, diagnosis of AgAdv-1 infection is achieved through a single published method: standard nested polymerase chain reaction (nPCR) and sequencing. Standard nPCR with sequencing provides reliable sensitivity, specificity, and validation of PCR products. However, this process is comparatively expensive, laborious, and slow. Probe hybridization, as used in a TaqMan assay, represents the best option for validating PCR products aside from the time-consuming process of sequencing. This study developed a real-time PCR (qPCR) assay using a TaqMan probe-based assay, targeting a highly conserved region of the AgAdv-1 genome. Standard curves were generated, detection results were compared with the gold standard conventional PCR and sequencing assay, and limits of detection were determined. Additionally, the qPCR assay was run on samples known to be positive for AgAdv-1 and samples known to be positive for other adenoviruses. Based on the results of these evaluations, this assay allows for a less expensive, rapid, quantitative detection of AgAdv-1 in bearded dragons.

  15. In vitro anti-herpes simplex viruses and anti-adenoviruses activity of twelve traditionally used medicinal plants in Taiwan.

    PubMed

    Chiang, Lien-Chai; Cheng, Hua-Yew; Liu, Mei-Chi; Chiang, Wen; Lin, Chun-Ching

    2003-11-01

    As an effort to search for new antiviral agents from traditional medicine, the hot water (HW) extract of twelve traditionally used medicinal plants in Taiwan was evaluated for their in vitro anti-herpes simplex viruses (HSV; including HSV-1 and HSV-2) and anti-adenoviruses (ADV; including ADV-3, ADV-8 and ADV-11) activities with a XTT-based colorimetric assay. Results showed that the tested HW extracts exhibited anti-HSV and anti-ADV activities at different magnitudes of potency. Among the twelve medicinal plants, Boussingaultia gracilis var. pseudobaselloides (Basellaceae) and Serissa japonica (Rubiaceae) possessed broad spectrum of antiviral activity. Ardisia squamulosa (Myrsinaceae) and Artemisai princeps var. orientalis (Compositae) were more effective in inhibiting ADV-8 replication than the other four viruses. Cell cytotoxic assay demonstrated that all tested HW extracts had CC50 values higher than their EC50 values. It was concluded that the twelve traditionally used medicinal plants in Taiwan possessed antiviral activity, and some of them merit further investigation.

  16. Immunoglobulin classes of Aleutian disease virus antibody.

    PubMed Central

    Porter, D D; Porter, H G; Suffin, S C; Larsen, A E

    1984-01-01

    Aleutian disease virus (ADV) persistently infects mink and causes marked hypergammaglobulinemia. Immunoglobulin class-specific antisera were used to define the total immunoglobulin of each class by radial immunodiffusion and the immunoglobulin class of ADV-specific antibody by immunofluorescence in experimentally and naturally infected mink. Electrophoretic gamma globulin closely reflects the immunoglobulin G (IgG) level in mink, and the majority of the increased immunoglobulin and ADV antibody in infected mink is IgG. IgM becomes elevated within 6 days after infection, reaches peak levels by 15 to 18 days, and returns to normal by 60 days after infection. The first ADV antibody demonstrable is IgM, and most mink have virus-specific IgM antibody for at least 85 days postinfection. Serum IgA levels in normal mink are not normally distributed, and ADV infection causes a marked elevation of IgA. Low levels of ADV-specific IgA antibody can be shown throughout the course of infection. Failure of large amounts of virus-specific IgG antibody to inhibit the reaction of virus-specific IgM and IgA antibodies suggests that the various classes of antibodies are directed against spatially different antigenic determinants. The IgM and IgA were shown not to be rheumatoid factors. PMID:6319283

  17. Evidence of restricted viral replication in adult mink infected with Aleutian disease of mink parvovirus.

    PubMed Central

    Alexandersen, S; Bloom, M E; Wolfinbarger, J

    1988-01-01

    Strand-specific hybridization probes were used in in situ molecular hybridization specifically to localize cells containing replicative intermediates of Aleutian disease of mink parvovirus (ADV). When adult mink of Aleutian genotype were infected with ADV Utah I, the largest number of cells positive for viral replication (i.e., containing replicative-form DNA and RNA) were found in the mesenteric lymph nodes and spleens at 10 days after infection. The localization of positive cells in the middle of germinal centers suggested that they were B lymphoblasts. Circulating leukocytes and bone marrow cells also contained viral RNA, but the levels of replicative-form DNA were below detectability. The levels of viral DNA and RNA in adult mink cells replicating ADV were decreased compared with those in permissively infected cell cultures or neonatal mink, suggesting that the replication of ADV in adult mink might be semipermissive or restricted at some early stage of viral gene expression. The low level of viral replication and transcription in lymphoid cells might provide a mechanism for the development of immune disorders and for the maintenance of persistent infection. Single-stranded virion DNA was found in other organs, but the strand-specific probes made it possible to show that this DNA represented virus sequestration. In addition, glomerular immune complexes containing virion DNA were detected, suggesting that ADV virions, or perhaps free DNA, may have a role in the development of ADV-induced glomerulonephritis. Images PMID:2833604

  18. Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1.

    PubMed

    Davie, Neil J; Gerasimovskaya, Evgenia V; Hofmeister, Stephen E; Richman, Aaron P; Jones, Peter L; Reeves, John T; Stenmark, Kurt R

    2006-06-01

    The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel. In addition, hypoxia-activated AdvFBs produced ET-1, suggesting a paracrine role for this pro-angiogenic molecule in these processes. When co-cultured on Matrigel, AdvFBs and VVECs self-assembled into heterotypic cord-like networks, a process augmented by hypoxia but attenuated by either selective endothelin receptor antagonists or oligonucleotides targeting prepro-ET-1 mRNA. From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia.

  19. Chemistry and Mineralogy of Antarctica Dry Valley Soils: Implications for Mars

    NASA Technical Reports Server (NTRS)

    Quinn, J. E.; Golden, D. C.; Graff, T. G.; Ming, D. W.; Morris, R. V.; Douglas, S.; Kounaves, S. P.; McKay, C. P.; Tamppari, L, K.; Smith, P. H.; hide

    2011-01-01

    The Antarctic Dry Valleys (ADV) comprise the largest ice-free region of Antarctica. Precipitation almost always occurs as snow, relative humidity is frequently low, and mean annual temperatures are about -20 C. The ADV soils have previously been categorized into three soil moisture regimes: subxerous, xerous and ultraxerous, based on elevation and climate influences. The subxerous regime is predominately a coastal zone soil, and has the highest average temperature and precipitation, while the ultraxerous regime occurs at high elevation (>1000 m) and have very low temperature and precipitation. The amounts and types of salts present in the soils vary between regions. The nature, origin and significance of salts in the ADV have been previously investigated. Substantial work has focused on soil formation in the ADVs, however, little work has focused on the mineralogy of secondary alteration phases. The dominant weathering process in the ADV region is physical weathering, however, chemical weathering has been well documented. The objective of this study was to characterize the chemistry and mineralogy, including the alteration mineralogy, of soils from two sites, a subxerous soil in Taylor Valley, and an ultraxerous soil in University Valley. The style of aqueous alteration in the ADVs may have implications for pedogenic processes on Mars.

  20. Construction and characterization of adenoviral vectors for the delivery of TALENs into human cells.

    PubMed

    Holkers, Maarten; Cathomen, Toni; Gonçalves, Manuel A F V

    2014-09-01

    Transcription activator-like effector nucleases (TALENs) are designed to cut the genomic DNA at specific chromosomal positions. The resulting DNA double strand break activates cellular repair pathways that can be harnessed for targeted genome modifications. TALENs thus constitute a powerful tool to interrogate the function of DNA sequences within complex genomes. Moreover, their high DNA cleavage activity combined with a low cytotoxicity make them excellent candidates for applications in human gene therapy. Full exploitation of these large and repeat-bearing nucleases in human cell types will benefit largely from using the adenoviral vector (AdV) technology. The genetic stability and the episomal nature of AdV genomes in conjunction with the availability of a large number of AdV serotypes able to transduce various human cell types make it possible to achieve high-level and transient expression of TALENs in numerous target cells, regardless of their mitotic state. Here, we describe a set of protocols detailing the rescue, propagation and purification of TALEN-encoding AdVs. Moreover, we describe procedures for the characterization and quantification of recombinant viral DNA present in the resulting AdV preparations. The protocols are preceded by information about their underlying principles and applied in the context of second-generation capsid-modified AdVs expressing TALENs targeted to the AAVS1 "safe harbor" locus on human chromosome 19.

  1. Pulmonary Artery Adventitial Fibroblasts Cooperate with Vasa Vasorum Endothelial Cells to Regulate Vasa Vasorum Neovascularization

    PubMed Central

    Davie, Neil J.; Gerasimovskaya, Evgenia V.; Hofmeister, Stephen E.; Richman, Aaron P.; Jones, Peter L.; Reeves, John T.; Stenmark, Kurt R.

    2006-01-01

    The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel. In addition, hypoxia-activated AdvFBs produced ET-1, suggesting a paracrine role for this pro-angiogenic molecule in these processes. When co-cultured on Matrigel, AdvFBs and VVECs self-assembled into heterotypic cord-like networks, a process augmented by hypoxia but attenuated by either selective endothelin receptor antagonists or oligonucleotides targeting prepro-ET-1 mRNA. From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia. PMID:16723696

  2. THE ROLE OF INERTIAL CAVITATION IN ACOUSTIC DROPLET VAPORIZATION

    PubMed Central

    Fabiilli, Mario L.; Haworth, Kevin J.; Fakhri, Nasir H.; Kripfgans, Oliver D.; Carson, Paul L.; Fowlkes, J. Brian

    2011-01-01

    The vaporization of a superheated droplet emulsion into gas bubbles using ultrasound – termed acoustic droplet vaporization (ADV) – has potential therapeutic applications in embolotherapy and drug delivery. The optimization of ADV for therapeutic applications can be enhanced by understanding the physical mechanisms underlying ADV, which are currently not clearly elucidated. Acoustic cavitation is one possible mechanism. This paper investigates the relationship between the ADV and inertial cavitation (IC) thresholds (measured as peak rarefactional pressures) by studying parameters that are known to influence the IC threshold. These parameters include bulk fluid properties such as gas saturation, temperature, viscosity, and surface tension; droplet parameters such as degree of superheat, surfactant type, and size; and acoustic properties such as pulse repetition frequency and pulse width. In all cases the ADV threshold occurred at a lower rarefactional pressure than the IC threshold indicating that the phase-transition occurs before IC events. The viscosity and temperature of the bulk fluid are shown to influence both thresholds directly and inversely, respectively. An inverse trend is observed between threshold and diameter for droplets in the 1 to 2.5 μ range. Based on a choice of experimental parameters, it is possible to achieve ADV with or without IC. PMID:19473917

  3. DELIVERY OF WATER-SOLUBLE DRUGS USING ACOUSTICALLY-TRIGGERED, PERFLUOROCARBON DOUBLE EMULSIONS

    PubMed Central

    Fabiilli, Mario L.; Lee, James A.; Kripfgans, Oliver D.; Carson, Paul L.; Fowlkes, J. Brian

    2010-01-01

    Purpose Ultrasound can be used to release a therapeutic payload encapsulated within a perfluorocarbon (PFC) emulsion via acoustic droplet vaporization (ADV), a process whereby the PFC phase is vaporized and the agent is released. ADV-generated microbubbles have been previously used to selectively occlude blood vessels in vivo. The coupling of ADV-generated drug delivery and occlusion has therapeutically, synergistic potentials. Methods Micron-sized, water-in-PFC-in-water (W1/PFC/W2) emulsions were prepared in a two-step process using perfluoropentane (PFP) or perfluorohexane (PFH) as the PFC phase. Fluorescein or thrombin was contained in the W1 phase. Results Double emulsions containing fluorescein in the W1 phase displayed a 5.7±1.4 fold and 8.2±1.3 fold increase in fluorescein mass flux, as measured using a Franz diffusion cell, after ADV for the PFP and PFH emulsions, respectively. Thrombin was stably retained in four out of five double emulsions. For three out of five formulations tested, the clotting time of whole blood decreased, in a statistically significant manner (p < 0.01), when incubated with thrombin-loaded emulsions exposed to ultrasound compared to emulsions not exposed to ultrasound. Conclusions ADV can be used to spatially and temporally control the delivery of water-soluble compounds formulated in PFC double emulsions. Thrombin release could extend the duration of ADV-generated, microbubble occlusions. PMID:20872050

  4. Current and future disease progression of the chronic HCV population in the United States.

    PubMed

    Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

    2013-01-01

    Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  5. Investigation of enteric adenovirus and poliovirus removal by coagulation processes and suitability of bacteriophages MS2 and φX174 as surrogates for those viruses.

    PubMed

    Shirasaki, N; Matsushita, T; Matsui, Y; Marubayashi, T; Murai, K

    2016-09-01

    We evaluated the removal of enteric adenovirus (AdV) type 40 and poliovirus (PV) type 1 by coagulation, using water samples from 13 water sources for drinking water treatment plants in Japan. The behaviors of two widely accepted enteric virus surrogates, bacteriophages MS2 and φX174, were compared with the behaviors of AdV and PV. Coagulation with polyaluminum chloride (PACl, basicity 1.5) removed AdV and PV from virus-spiked source waters: the infectious AdV and PV removal ratios evaluated by means of a plaque-forming-unit method were 0.1-1.4-log10 and 0.5-2.4-log10, respectively. A nonsulfated high-basicity PACl (basicity 2.1) removed infectious AdV and PV more efficiently than did other commercially available PACls (basicity 1.5-2.1), alum, and ferric chloride. The MS2 removal ratios tended to be larger than those of AdV and PV, partly because of differences in the hydrophobicities of the virus particles and the sensitivity of the virus to the virucidal activity of PACl; the differences in removal ratios were not due to differences in the surface charges of the virus particles. MS2, which was more hydrophobic than the other viruses, was inactivated during coagulation with PACl. Therefore, MS2 does not appear to be an appropriate surrogate for AdV and PV during coagulation. In contrast, because φX174, like AdV and PV, was not inactivated during coagulation, and because the hydrophobicity of φX174 was similar to or somewhat lower than the hydrophobicities of AdV and PV, the φX174 removal ratios tended to be similar to or somewhat smaller than those of the enteric viruses. Therefore, φX174 is a potential conservative surrogate for AdV and PV during coagulation. In summary, the surface hydrophobicity of virus particles and the sensitivity of the virus to the virucidal activity of the coagulant are probably important determinants of the efficiency of virus removal during coagulation.

  6. Analysis of Aleutian disease virus infection in vitro and in vivo: demonstration of Aleutian disease virus DNA in tissues of infected mink.

    PubMed Central

    Bloom, M E; Race, R E; Aasted, B; Wolfinbarger, J B

    1985-01-01

    Aleutian disease virus (ADV) infection was analyzed in vivo and in vitro to compare virus replication in cell culture and in mink. Initial experiments compared cultures of Crandell feline kidney (CRFK) cells infected with the avirulent ADV-G strain or the highly virulent Utah I ADV. The number of ADV-infected cells was estimated by calculating the percentage of cells displaying ADV antigen by immunofluorescence (IFA), and several parameters of infection were determined. Infected cells contained large quantities of viral DNA (more than 10(5) genomes per infected cell) as estimated by dot-blot DNA-DNA hybridization, and much of the viral DNA, when analyzed by Southern blot hybridization, was found to be of a 4.8-kilobase-pair duplex monomeric replicative form (DM DNA). Furthermore, the cultures contained 7 to 67 fluorescence-forming units (FFU) per infected cell, and the ADV genome per FFU ratio ranged between 2 X 10(3) and 164 X 10(3). Finally, the pattern of viral antigen detected by IFA was characteristically nuclear, although cytoplasmic fluorescence was often found in the same cells. Because no difference was noted between the two virus strains when cultures containing similar numbers of infected cells were compared, it seemed that both viruses behaved similarly in infected cell culture. These data were used as a basis for the analysis of infection of mink by virulent Utah I ADV. Ten days after infection, the highest levels of viral DNA were detected in spleen (373 genomes per cell), mesenteric lymph node (MLN; 750 genomes per cell), and liver (373 genomes per cell). In marked contrast to infected CRFK cells, the predominant species of ADV DNA in all tissues was single-stranded virion DNA; however, 4.8-kilobase-pair DM DNA was found in MLN and spleen. This observation suggested that MLN and spleen were sites of virus replication, but that the DNA found in liver reflected sequestration of virus produced elsewhere. A final set of experiments examined MLN taken

  7. Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study.

    PubMed

    Sabin, M A; Burgner, D; Atkinson, R L; Pei-Lun Lee, Z; Magnussen, C G; Cheung, M; Kähönen, M; Lehtimäki, T; Jokinen, E; Laitinen, T; Hutri-Kähönen, N; Viikari, J S A; Juonala, M; Raitakari, O T

    2015-11-01

    Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity. Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult. Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21-31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs. 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age. Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

  8. Expression of Aleutian mink disease parvovirus proteins in a baculovirus vector system.

    PubMed Central

    Christensen, J; Storgaard, T; Bloch, B; Alexandersen, S; Aasted, B

    1993-01-01

    We have previously published a detailed transcription map of Aleutian mink disease parvovirus (ADV) and proposed a model for the translation of the two virion structural proteins (VP1 and VP2) and three nonstructural proteins (NS-1, NS-2, and NS-3) (S. Alexandersen, M. E. Bloom, and S. Perryman, J. Virol. 62:3684-3994, 1988). To verify and further characterize this model, we cloned the predicted open reading frames for NS-1, NS-2, NS-3, VP1-VP2, and VP2 alone into a recombinant baculovirus and expressed them in Sf9 insect cells. Expression of VP1-VP2 or VP2 alone in cDNA and in the genomic form was achieved. The expressed proteins had molecular weights similar to those of the corresponding proteins of wild-type ADV-G, although the ratio of VP1 to VP2 was altered. The recombinant baculovirus-expressed ADV VP1 and VP2 showed nuclear localization in Sf9 cells and were able to form particles indistinguishable, by electron microscopy, from wild-type virus. The large nonstructural protein, NS-1, showed predominantly nuclear localization in Sf9 cells when analyzed by immunofluorescence and had a molecular weight similar to that of wild-type ADV NS-1. Moreover, expression of NS-1 in Sf9 cells caused a change in morphology of the cells and resulted in 10-times-lower titers of recombinant baculovirus during infection, suggesting a cytostatic or cytotoxic action of this protein. The smaller NS-2 gene product seems to be located in the cytoplasm. When analyzed by Western immunoblotting, NS-2 comigrated with an approximately 16-kDa band seen in lysates of ADV-infected feline kidney cells. The putative NS-3 gene product exhibited a diffuse distribution in Sf9 cells and had a molecular weight of approximately 10,000. All of the expressed ADV-encoded proteins were recognized by sera from ADV-infected mink. Thus, expression of ADV cDNAs allowed assignment of the different mRNAs to the viral proteins observed during ADV infection in cell culture and supported our previously proposed

  9. Turbulence Measurements from Compliant Moorings. Part I: Motion Characterization

    DOE PAGES

    Harding, Samuel; Kilcher, Levi; Thomson, Jim

    2017-06-01

    High-fidelity measurements of turbulence in the ocean have long been challenging to collect, in particular in the middle of the water column. In response, a measurement technique has been developed to deploy an acoustic Doppler velocimeter (ADV) to midwater locations on a compliant mooring. A variety of instrumentation platforms have been deployed as part of this work with a range of dynamic motion characteristics. The platforms discussed herein include the streamlined StableMoor buoy (SMB), the Tidal Turbulence Mooring (TTM) system based on a conventional 0.9-m spherical buoy, and a 100-lb sounding weight suspended from the stern of a research vessel.more » The ADV head motion is computed from inertial motion sensors integrated into an ADV, and the spectra of these signals are investigated to quantify the motion of each platform. The SMB with a single ADV head mounted on the nose provided the most stable platform for the measurement of tidal turbulence in the inertial subrange for flow speeds exceeding 1.0 m s-1. The modification of the SMB with a transverse wing configuration for multiple ADVs showed a similar frequency response to the nose configuration in the horizontal plane but with large contamination in the vertical direction as a result of platform roll. While the ADV motion on the TTM was significant in the horizontal directions, the vertical motion of this configuration was the most stable of all configurations tested. The sounding weight measurements showed the greatest motion at the ADV head but are likely to be influenced by both prop-wash and vessel motion.« less

  10. Turbulence Measurements from Compliant Moorings - Part I: Motion Characterization

    DOE PAGES

    Harding, Samuel; Kilcher, Levi; Thomson, Jim

    2017-06-20

    High-fidelity measurements of turbulence in the ocean have long been challenging to collect, in particular in the middle of the water column. In response, a measurement technique has been developed to deploy an Acoustic Doppler Velocimeter (ADV) to mid-water locations on a compliant mooring. A variety of instrumentation platforms have been deployed as part of this work with a range of dynamic motion characteristics. The platforms discussed herein include the streamlined StableMoor™ buoy (SMB), the Tidal Turbulence Mooring (TTM) system based on a conventional 0.9 m spherical buoy, and a 100 lb sounding weight suspended from the stern of amore » research vessel. The ADV head motion is computed from inertial motion sensors integrated into an ADV, and the spectra of these signals are investigated to quantify the motion of each platform. The SMB with a single ADV head mounted on the nose provided the most stable platform for the measurement of tidal turbulence in the inertial sub-range for flow speeds exceeding 1:0 ms-1. The modification of the SMB with a transverse wing configuration for multiple ADVs showed a similar frequency response to the nose configuration in the horizontal plane but with large contamination in the vertical direction as a result of platform roll. While the ADV motion on the TTM was significant in the horizontal directions, the vertical motion of this configuration was the most stable of all configurations tested. The sounding weight measurements showed the greatest motion at the ADV head but are likely to be influenced by both prop-wash and vessel motion.« less

  11. Expression of Coxsackie-Adenovirus receptor (CAR) in the developing mouse olfactory system.

    PubMed

    Venkatraman, Giri; Behrens, Maik; Pyrski, Martina; Margolis, Frank L

    2005-09-01

    Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use of adenoviruses (AdV) as gene delivery vectors. OSNs are the first order neurons in the olfactory system and the initial site of odor detection. They are highly susceptible to adenovirus infection although the mechanism is poorly understood. The Coxsackie-Adenovirus receptor (CAR) and members of the integrin family have been implicated in the process of AdV infection in various systems. Multiple serotypes of AdV efficiently bind to the CAR, leading to entry and infection of the host cell by a mechanism that can also involve integrins. Cell lines that do not express CAR are relatively resistant, but not completely immune to AdV infection, suggesting that other mechanisms participate in mediating AdV attachment and entry. Using in situ hybridization and western blot analyses, we show that OSNs and olfactory bulbs (OB) of mice express abundant CAR mRNA at embryonic and neonatal stages, with progressive diminution during postnatal development. By contrast to the olfactory epithelium (OE), CAR mRNA is still present in the adult mouse OB. Furthermore, despite a similar postnatal decline, CAR protein expression in the OE and OB of mice continues into adulthood. Our results suggest that the robust AdV infection observed in the postnatal olfactory system is mediated by CAR and that expression of even small amounts of CAR protein as seen in the adult rodent, permits efficient AdV infection and entry. CAR is an immunoglobulin domain-containing protein that bears homology to cell-adhesion molecules suggesting the possibility that it may participate in organization of the developing olfactory system.

  12. Modulation of lung inflammation by the Epstein-Barr virus protein Zta

    PubMed Central

    Guenther, James F.; Cameron, Jennifer E.; Nguyen, Hong T.; Wang, Yu; Sullivan, Deborah E.; Shan, Bin; Lasky, Joseph A.; Flemington, Erik K.

    2010-01-01

    Several studies have implicated gamma-herpesviruses, particularly Epstein-Barr virus (EBV), in the progression of idiopathic pulmonary fibrosis. The data presented here examine the possible role that EBV plays in the potentiation of this disease by evaluating the pulmonary response to expression of the EBV lytic transactivator protein Zta. Expression of Zta in the lungs of mice via adenovirus-mediated delivery (Adv-Zta) produced profibrogenic inflammation that appeared most pronounced by day 7 postexposure. Relative to mice exposed to control GFP-expressing adenovirus (Adv-GFP), mice exposed to Adv-Zta displayed evidence of lung injury and a large increase in inflammatory cells, predominantly neutrophils, recovered by bronchoalveolar lavage (BAL). Cytokine and mRNA profiling of the BAL fluid and cells recovered from Adv-Zta-treated mice revealed a Th2 and Th17 bias. mRNA profiles from Adv-Zta-infected lung epithelial cells revealed consistent induction of mRNAs encoding Th2 cytokines. Coexpression in transient assays of wild-type Zta, but not a DNA-binding-defective mutant Zta, activated expression of the IL-13 promoter in lung epithelial cells, and detection of IL-13 in Adv-Zta-treated mice correlated with expression of Zta. Induction of Th2 cytokines in Zta-expressing mice corresponded with alternative activation of macrophages. In cell culture and in mice, Zta repressed lung epithelial cell markers. Despite the profibrogenic character at day 7, the inflammation resolves by 28 days postexposure to Adv-Zta without evidence of fibrosis. These observations indicate that the EBV lytic transactivator protein Zta displays activity consistent with a pathogenic role in pulmonary fibrosis associated with herpesvirus infection. PMID:20817778

  13. A long-term serological survey on Aujeszky's disease virus infections in wild boar in East Germany.

    PubMed

    Pannwitz, G; Freuling, C; Denzin, N; Schaarschmidt, U; Nieper, H; Hlinak, A; Burkhardt, S; Klopries, M; Dedek, J; Hoffmann, L; Kramer, M; Selhorst, T; Conraths, F J; Mettenleiter, T; Müller, T

    2012-02-01

    Between 1985 and 2008, a total of 102,387 wild boar sera originating from Eastern Germany covering an area of 108 589 km2 were tested for the presence of Aujeszky's disease virus (ADV)-specific antibodies. From 1985 until 1991 and from 1992 until 2008, wild boar sera were exclusively investigated using either conventional seroneutralization assays (n=39 621) or commercial gB and full antigen ELISAs (n=62,766), respectively. Spatial-temporal analysis revealed an increasing ADV seroprevalence from 0·4% to 15·9%, on average, during the 24-year observation period that went along with a continuous spread of the infection in a western direction. During 2006 and 2008, 18% of the 66 affected districts had ADV seroprevalences >30%. There was a significant correlation between ADV seroprevalence and the hunting index of population density (HIPD) of wild boar in the entire study area, although this did not hold true for some regions. Seroprevalences did not differ between sexes but were age-dependent. East Germany has been officially free of Aujeszky's disease (pseudorabies) in domestic pigs since 1985. Although a risk for domestic pigs cannot be completely ruled out, experience has shown that ADV in domestic pigs could be eliminated although the virus was present in the wild boar population. Despite increasing ADV seroprevalence in the East German wild boar population no spillover infections from wild boar to domestic pigs have been reported. To further trace ADV infections in the wild boar population in Germany, a nationwide serological monitoring programme should be implemented.

  14. Risk assessment and cost-effectiveness analysis of Aujeszky's disease virus introduction through breeding and fattening pig movements into Spain.

    PubMed

    Martínez-López, B; Carpenter, T E; Sánchez-Vizcaíno, J M

    2009-07-01

    Movement of infected animals is considered the most likely route of Aujeszky's disease virus (ADV) introduction into free areas and the main obstacle to eradicating Aujeszky's disease (AD) in those areas, which have achieved a low prevalence (>0 and < or =10%) status. For this reason, the Spanish AD control and eradication program has established measures to enhance security in animal movements in an attempt to protect areas with free or low prevalence status; however, no studies have quantified the effectiveness of the current or alternative ADV introduction prevention measures. We performed a probabilistic risk assessment and cost-effectiveness analysis, using Monte Carlo simulation, to evaluate the probability of introducing ADV-infected animals into free or low prevalence areas under the Spanish AD control and eradication program. We found the mean probability of introducing ADV-infected animals, when breeding pigs were quarantined but not tested prior to shipment, is likely (up to 21%), representing 13.6 times higher risk than when breeding pigs were tested prior to shipment. The strategy of testing pigs on fattening farms 15 days prior to shipment and using a sample size sufficient to detect a prevalence of 5% with a 95% of confidence, could reduce the probability of introducing ADV-infected animals by 91% with no additional cost. Similarly, testing pigs on breeding and fattening farms using a sample size sufficient to detect a prevalence of 1% with a 95% of confidence, could reduce the probability of introducing ADV-infected animals by 99%, but with an increased cost of 81%. Results reported in this study identify factors that contribute to risk of ADV introduction and should aid the control and eradication of AD in Spain.

  15. Scavenging dissolved oxygen via acoustic droplet vaporization

    PubMed Central

    Radhakrishnan, Kirthi; Holland, Christy K.; Haworth, Kevin J.

    2016-01-01

    Acoustic droplet vaporization (ADV) of perfluorocarbon emulsions has been explored for diagnostic and therapeutic applications. Previous studies have demonstrated that vaporization of a liquid droplet results in a gas microbubble with a diameter 5 to 6 times larger than the initial droplet diameter. The expansion factor can increase to a factor of 10 in gassy fluids as a result of air diffusing from the surrounding fluid into the microbubble. This study investigates the potential of this process to serve as an ultrasound-mediated gas scavenging technology. Perfluoropentane droplets diluted in phosphate-buffered saline (PBS) were insonified by a 2 MHz transducer at peak rarefactional pressures lower than and greater than the ADV pressure amplitude threshold in an in vitro flow phantom. The change in dissolved oxygen (DO) of the PBS before and after ADV was measured. A numerical model of gas scavenging, based on conservation of mass and equal partial pressures of gases at equilibrium, was developed. At insonation pressures exceeding the ADV threshold, the DO of air-saturated PBS decreased with increasing insonation pressures, dropping as low as 25% of air saturation within 20 s. The decrease in DO of the PBS during ADV was dependent on the volumetric size distribution of the droplets and the fraction of droplets transitioned during ultrasound exposure. Numerically predicted changes in DO from the model agreed with the experimentally measured DO, indicating that concentration gradients can explain this phenomenon. Using computationally modified droplet size distributions that would be suitable for in vivo applications, the DO of the PBS was found to decrease with increasing concentrations. This study demonstrates that ADV can significantly decrease the DO in an aqueous fluid, which may have direct therapeutic applications and should be considered for ADV-based diagnostic or therapeutic applications. PMID:26964964

  16. Scavenging dissolved oxygen via acoustic droplet vaporization.

    PubMed

    Radhakrishnan, Kirthi; Holland, Christy K; Haworth, Kevin J

    2016-07-01

    Acoustic droplet vaporization (ADV) of perfluorocarbon emulsions has been explored for diagnostic and therapeutic applications. Previous studies have demonstrated that vaporization of a liquid droplet results in a gas microbubble with a diameter 5-6 times larger than the initial droplet diameter. The expansion factor can increase to a factor of 10 in gassy fluids as a result of air diffusing from the surrounding fluid into the microbubble. This study investigates the potential of this process to serve as an ultrasound-mediated gas scavenging technology. Perfluoropentane droplets diluted in phosphate-buffered saline (PBS) were insonified by a 2 MHz transducer at peak rarefactional pressures lower than and greater than the ADV pressure amplitude threshold in an in vitro flow phantom. The change in dissolved oxygen (DO) of the PBS before and after ADV was measured. A numerical model of gas scavenging, based on conservation of mass and equal partial pressures of gases at equilibrium, was developed. At insonation pressures exceeding the ADV threshold, the DO of air-saturated PBS decreased with increasing insonation pressures, dropping as low as 25% of air saturation within 20s. The decrease in DO of the PBS during ADV was dependent on the volumetric size distribution of the droplets and the fraction of droplets transitioned during ultrasound exposure. Numerically predicted changes in DO from the model agreed with the experimentally measured DO, indicating that concentration gradients can explain this phenomenon. Using computationally modified droplet size distributions that would be suitable for in vivo applications, the DO of the PBS was found to decrease with increasing concentrations. This study demonstrates that ADV can significantly decrease the DO in an aqueous fluid, which may have direct therapeutic applications and should be considered for ADV-based diagnostic or therapeutic applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. [Investigation of the presence and subgroups of adenoviruses in nasopharyngeal samples of military recruits with respiratory tract infections].

    PubMed

    Sener, Kenan; Yapar, Mehmet; Güney, Cakir; Kubar, Ayhan; Kiliç, Abdullah; Altayli, Ertan; Başustaoğlu, Ahmet Celal

    2009-01-01

    Adenoviruses (AdV) are important pathogens primarily associated to respiratory infections of children and military staff even though it is also associated to many clinical manifestations, such as cystitis, conjunctivitis, diarrhea, hepatitis, myocarditis, and encephalitis. The goals of this study were to detect and type acute respiratory disease associated AdV isolates among military trainees in a selected region without an evidence of an outbreak. Throat swab samples were obtained during February 2006-March 2006 period, from 180 military male trainees aged 20-29, who were presented with respiratory tract symptoms and an oral temperature of > or = 38.0 degrees C. All specimens were tested by HEp-2 cell culture and real-time TaqMan PCR with AdV specific primers and probes. Positive cell culture results, presented as AdV-specific cytopathic effects, were confirmed by real-time polymerase chain reaction (PCR). AdV subgroup differentiation were performed using conventional PCR assays with the primer set specific for subgroup B, C or E. Subgroup specific PCR products were restricted with Mspl enzyme in order to check whether they were specific or not. AdV positivity was detected in 8 (4.4%) samples by cell culture and in 9 (5.0%) by the real-time PCR. All culture positive samples were also positive by real-time PCR. Eight of the nine real-time PCR-positive specimens were found to be in the subgroup E (this group contains only AdV type 4) and the results were confirmed with restriction enzyme analysis. One isolate could not be typed with the available primers. These data indicated that both real-time TaqMan PCR and restriction enzyme analysis provide sensitive and specific tools for AdV detection and subgroup differentiation for throat swab specimens. It can be concluded that since the prevalence of AdV infections was low in the study group, AdV infections were not considered as a vaccine requiring health problem in Turkish armed forces, however, larger scale studies

  18. Clinical Impact of Mixed Respiratory Viral Infection in Children with Adenoviral Infection

    PubMed Central

    Seo, Young Eun

    2016-01-01

    Background Although adenovirus (ADV) infection occurs steadily all year round in Korea and the identification of respiratory viral coinfections has been increasing following the introduction of multiplex real-time polymerase chain reaction tests, the clinical impact of viral coinfection in children with ADV infection has rarely been reported. Materials and Methods Medical records of children diagnosed with ADV infection were retrospectively reviewed. The enrolled children were divided into two groups based on the identified respiratory viruses: ADV group and coinfection group. Clinical and laboratory parameters were compared between the two groups. Results In total, 105 children (60 males and 45 females) with a median age of 29 months (range: 0-131 months) diagnosed with an ADV infection were enrolled. Fever (99.0%) was by far the most frequent symptom, followed by respiratory (82.9%), and gastrointestinal (22.9%) symptoms. Upper and lower respiratory tract infections were diagnosed in 56 (53.3%), and 32 (30.5%) children, respectively. Five (4.8%) children received oxygen therapy, and no child died due to ADV infection. Coinfection was diagnosed in 32 (30.5%) children, with rhinovirus (46.9%), and respiratory syncytial virus (21.9%) being the most frequent. The proportions of children younger than 24 months (P <0.001), with underlying medical conditions (P = 0.020), and diagnosed with lower respiratory tract infection (P = 0.011) were significantly higher in the coinfection group than in the ADV group. In a multivariate analysis, only the younger age was significantly associated with coinfection (P <0.001). Although more children in the coinfection group received oxygen therapy (P = 0.029), the duration of fever and hospitalization was not significantly different between the two groups. Conclusion Respiratory viral coinfection with ADV occurred more frequently in children younger than 24 months of age compared with children aged 24 months or older. Respiratory

  19. Arctic decadal variability in a warming world

    NASA Astrophysics Data System (ADS)

    van der Linden, Eveline C.; Bintanja, Richard; Hazeleger, Wilco

    2017-06-01

    Natural decadal variability of surface air temperature might obscure Arctic temperature trends induced by anthropogenic forcing. It is therefore imperative to know how Arctic decadal variability (ADV) will change as the climate warms. In this study, we evaluate ADV characteristics in three equilibrium climates with present-day, double, and quadrupled atmospheric CO2 forcing. The dominant region of variability, which is located over the Barents and Greenland Sea at present, shifts to the central Arctic and Siberian regions as the climate warms. The maximum variability in sea ice cover and surface air temperature occurs in the CO2 doubling climate when sea ice becomes more vulnerable to melt over vast stretches of the Arctic. Furthermore, the links between dominant atmospheric circulation modes and Arctic surface climate characteristics vary strongly with climate change. For instance, a positive Arctic Oscillation index is associated with a colder Arctic in warmer climates, instead of a warmer Arctic at present. Such changing relationships are partly related to the retreat of sea ice because altered wind patterns influence the sea ice distribution and hence the associated local surface fluxes. The atmospheric pressure distributions governing ADV and the associated large-scale dynamics also change with climate warming. The changing character of the ADV shows that it is vital to consider (changes in) ADV when addressing Arctic warming in climate model projections.

  20. Turbulence Measurements from Compliant Moorings. Part II: Motion Correction

    DOE PAGES

    Kilcher, Levi F.; Thomson, Jim; Harding, Samuel; ...

    2017-06-20

    Acoustic Doppler velocimeters (ADVs) are a valuable tool for making high-precision measurements of turbulence, and moorings are a convenient and ubiquitous platform for making many kinds of measurements in the ocean. However, because of concerns that mooring motion can contaminate turbulence measurements and that acoustic Doppler profilers make middepth velocity measurements relatively easy, ADVs are not frequently deployed from moorings. This work demonstrates that inertial motion measurements can be used to reduce motion contamination from moored ADV velocity measurements. Three distinct mooring platforms were deployed in a tidal channel with inertial-motion-sensor-equipped ADVs. In each case, motion correction based on themore » inertial measurements reduces mooring motion contamination of velocity measurements. The spectra from these measurements are consistent with other measurements in tidal channels and have an f–5/3 slope at high frequencies - consistent with Kolmogorov's theory of isotropic turbulence. Motion correction also improves estimates of cross spectra and Reynolds stresses. A comparison of turbulence dissipation with flow speed and turbulence production indicates a bottom boundary layer production-dissipation balance during ebb and flood that is consistent with the strong tidal forcing at the site. Finally, these results indicate that inertial-motion-sensor-equipped ADVs are a valuable new tool for making high-precision turbulence measurements from moorings.« less

  1. High-Density Superconducting Cables for Advanced ACTPol

    NASA Technical Reports Server (NTRS)

    Pappas, C. G.; Austermann, J.; Beall, J. A.; Duff, S. M.; Gallardo, P. A.; Grace, E.; Henderson, S. W.; Ho, S. P.; Koopman, B. J.; Li, D.; McMahon, J.; Nati, F.; Niemack, M. D.; Niraula, P.; Salatino, M.; Schillaci, A.; Schmitt, B. L.; Simon, S. M.; Staggs, S. T.; Vavagiakis, E. M.; Ward, J. T.; Wollack, E. J.

    2016-01-01

    Advanced ACTPol (AdvACT) is an upcoming Atacama Cosmology Telescope (ACT) receiver upgrade, scheduled to deploy in 2016, that will allow measure- ment of the cosmic microwave background polarization and temperature to the highest precision yet with ACT. The AdvACT increase in sensitivity is partly provided by an increase in the number of transition-edge sensors (TESes) per array by up to a factor of two over the current ACTPol receiver detector arrays. The high-density AdvACT TES arrays require 70 µ m pitch superconducting flexible cables (flex) to connect the detec- tor wafer to the first-stage readout electronics. Here, we present the flex fabrication process and test results. For the flex wiring layer, we use a 400-nm-thick sputtered alu- minum film. In the center of the cable, the wiring is supported by a polyimide substrate, which smoothly transitions to a bare (uncoated with polyimide) silicon substrate at the ends of the cable for a robust wedge wire-bonding interface. Tests on the first batch of flex made for the first AdvACT array show that the flex will meet the requirements for AdvACT, with a superconducting critical current above 1 mA at 500 mK, resilience to mechanical and cryogenic stress, and a room temperature yield of 97%.

  2. Mechanical Design and Development of TES Bolometer Detector Arrays for the Advanced ACTPol Experiment

    NASA Technical Reports Server (NTRS)

    Ward, Jonathan T.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Crowley, Kevin T.; Devlin, Mark J.; Duff, Shannon M.; Gallardo, Patricio M.; Henderson, Shawn W.; Ho, Shuay-Pwu Patty; Hilton, Gene; Hubmayr, Johannes; Khavari, Niloufar; Klein, Jeffrey; Koopman, Brian J.; Li, Dale; McMahon, Jeffrey; Mumby, Grace; Nati, Federico; Wollack, Edward J.

    2016-01-01

    The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling 5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150 mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline pro le leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modi ed to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.

  3. Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways

    PubMed Central

    Coleman, Ilsa; Lakely, Bryce; Coleman, Roger; Larson, Sandy; Aguirre-Ghiso, Julio A.; Xia, Jing; Gulati, Roman; Nelson, Peter S.; Montgomery, Bruce; Lange, Paul; Snyder, Linda A.; Vessella, Robert L.; Morrissey, Colm

    2014-01-01

    Cancer dormancy refers to the prolonged clinical disease-free time between removal of the primary tumor and recurrence, which is common in prostate cancer (PCa), breast cancer, esophageal cancer, and other cancers. PCa disseminated tumor cells (DTC) are detected in both patients with no evidence of disease (NED) and advanced disease (ADV). However, the molecular and cellular nature of DTC is unknown. We performed a first-in-field study of single DTC transcriptomic analyses in cancer patients to identify a molecular signature associated with cancer dormancy. We profiled eighty-five individual EpCAM+/CD45− cells from the bone marrow of PCa patients with NED or ADV. We analyzed 44 DTC with high prostate-epithelial signatures, and eliminated 41 cells with high erythroid signatures and low prostate epithelial signatures. DTC were clustered into 3 groups: NED, ADV_1, and ADV_2, in which the ADV_1 group presented a distinct gene expression pattern associated with the p38 stress activated kinase pathway. Additionally, DTC from the NED group were enriched for a tumor dormancy signature associated with head and neck squamous carcinoma and breast cancer. This study provides the first clinical evidence of the p38 pathway as a potential biomarker for early recurrence and an attractive target for therapeutic intervention. PMID:25301725

  4. Mechanical designs and development of TES bolometer detector arrays for the Advanced ACTPol experiment

    NASA Astrophysics Data System (ADS)

    Ward, Jonathan T.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Crowley, Kevin T.; Devlin, Mark J.; Duff, Shannon M.; Gallardo, Patricio A.; Henderson, Shawn W.; Ho, Shuay-Pwu Patty; Hilton, Gene; Hubmayr, Johannes; Khavari, Niloufar; Klein, Jeffrey; Koopman, Brian J.; Li, Dale; McMahon, Jeffrey; Mumby, Grace; Nati, Federico; Niemack, Michael D.; Page, Lyman A.; Salatino, Maria; Schillaci, Alessandro; Schmitt, Benjamin L.; Simon, Sara M.; Staggs, Suzanne T.; Thornton, Robert; Ullom, Joel N.; Vavagiakis, Eve M.; Wollack, Edward J.

    2016-07-01

    The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling 5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150 mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline profile leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.

  5. High-Density Superconducting Cables for Advanced ACTPol

    NASA Astrophysics Data System (ADS)

    Pappas, C. G.; Austermann, J.; Beall, J. A.; Duff, S. M.; Gallardo, P. A.; Grace, E.; Henderson, S. W.; Ho, S. P.; Koopman, B. J.; Li, D.; McMahon, J.; Nati, F.; Niemack, M. D.; Niraula, P.; Salatino, M.; Schillaci, A.; Schmitt, B. L.; Simon, S. M.; Staggs, S. T.; Stevens, J. R.; Vavagiakis, E. M.; Ward, J. T.; Wollack, E. J.

    2016-07-01

    Advanced ACTPol (AdvACT) is an upcoming Atacama Cosmology Telescope (ACT) receiver upgrade, scheduled to deploy in 2016, that will allow measurement of the cosmic microwave background polarization and temperature to the highest precision yet with ACT. The AdvACT increase in sensitivity is partly provided by an increase in the number of transition-edge sensors (TESes) per array by up to a factor of two over the current ACTPol receiver detector arrays. The high-density AdvACT TES arrays require 70 \\upmu m pitch superconducting flexible cables (flex) to connect the detector wafer to the first-stage readout electronics. Here, we present the flex fabrication process and test results. For the flex wiring layer, we use a 400-nm-thick sputtered aluminum film. In the center of the cable, the wiring is supported by a polyimide substrate, which smoothly transitions to a bare (uncoated with polyimide) silicon substrate at the ends of the cable for a robust wedge wire-bonding interface. Tests on the first batch of flex made for the first AdvACT array show that the flex will meet the requirements for AdvACT, with a superconducting critical current above 1 mA at 500 mK, resilience to mechanical and cryogenic stress, and a room temperature yield of 97 %.

  6. Preferential and Bidirectional Labeling of the Rubrospinal Tract with Adenovirus-GFP for Monitoring Normal and Injured Axons

    PubMed Central

    Wang, Xiaofei; Smith, George M.

    2011-01-01

    Abstract The rodent rubrospinal tract (RST) has been studied extensively to investigate regeneration and remodeling of central nervous system (CNS) axons. Currently no retrograde tracers can specifically label rubrospinal axons and neurons (RSNs). The RST can be anterogradely labeled by injecting tracers into the red nucleus (RN), but accurately locating the RN is a technical challenge. Here we developed a recombinant adenovirus carrying a green fluorescent protein reporter gene (Adv-GFP) which can preferentially, intensely, and bi-directionally label the RST. When Adv-GFP was injected into the second lumbar spinal cord, the GFP was specifically transported throughout the entire RST, with peak labeling seen at 2 weeks post-injection. When Adv-GFP was injected directly into the RN, GFP was anterogradely transported throughout the RST. Following spinal cord injury (SCI), injection of Adv-GFP resulted in visualization of GFP in transected, spared, or sprouted RST axons bi-directionally. Thus Adv-GFP could be used as a novel tool for monitoring and evaluating strategies designed to maximize RST axonal regeneration and remodeling following SCI. PMID:21299337

  7. Controlling O&M Costs of Advanced SMRs using Prognostics and Enhanced Risk Monitoring

    SciTech Connect

    Ramuhalli, Pradeep; Hirt, Evelyn H.; Coles, Garill A.; Meyer, Ryan M.; Coble, Jamie B.; Wood, Richard T.

    2014-02-25

    Advanced small modular reactors (AdvSMRs) can contribute to safe, sustainable, and carbon-neutral energy production. The economics of small reactors (including AdvSMRs) will be impacted by the reduced economy-of-scale savings when compared to traditional light water reactors. The most significant controllable element of the day-to-day costs involves operations and maintenance (O&M). Enhancing affordability of AdvSMRs through technologies that help control O&M costs will be critical to ensuring their practicality for wider deployment.A significant component of O&M costs is the management and mitigation of degradation of components due to their impact on planning maintenance activities and staffing levels. Technologies that help characterize real-time risk of failure of key components are important in this context. Given the possibility of frequently changing AdvSMR plant configurations, approaches are needed to integrate three elements – advanced plant configuration information, equipment condition information, and risk monitors – to provide a measure of risk that is customized for each AdvSMR unit and support real-time decisions on O&M. This article describes an overview of ongoing research into diagnostics/prognostics and enhanced predictive risk monitors (ERM) for this purpose.

  8. Characterization of deoxyribonucleic acid from cells infected with Aleutian disease virus

    SciTech Connect

    Hahn, E.C.; Ramos, L.; Kenyon, A.J.

    1983-07-01

    Viral DNA was extracted from Crandell feline kidney (CRFK) cells infected with Aleutian disease virus (ADV) and labeled with (/sup 3/H)thymidine. The sedimentation coefficient in alkaline sucrose gradients was 16S corresponding to a molecular weight of 1.5 X 10(6). The buoyant densities of DNA from infected and control cells were determined by isopyknic sedimentation in CsCl and NaI gradients. Two additional peaks of (/sup 3/H)DNA were found in infected cells, but not in control cell extracts. Fractionation of this DNA on hydroxylapatite indicated that the new peaks represented a single-stranded component, density 1.728 g/cm3, and a double-stranded component, presumed to be a viral replicative intermediate, density 1.718 g/cm3. The target antigen formation in CRFK cells was measured by gamma-irradiation of ADV and assayed for focus formation. The calculated size of ADV based on these measurements was 1.1 X 10(6). The H-1 parvovirus also was shown to have a size of 1.5 X 10(6) daltons for both antigen and plaque formation. The data indicated similarities existed between ADV and other autonomously replicating parvoviruses in most properties, except that less-than-unit length genome of ADV may be transcribed.

  9. Localization of neutralization epitopes on adenovirus fiber knob from species C.

    PubMed

    Lang, Shuai; Wang, Lizheng; Wang, Zixuan; Zhu, Rui; Yan, Jingyi; Wang, Baoming; Wu, Jiaxin; Zhang, Haihong; Wu, Hui; Zhou, Yan; Kong, Wei; Yu, Bin; Yu, Xianghui

    2016-04-01

    Although potential neutralization epitopes on the fiber knob of adenovirus (AdV) serotype 2 (Ad2) and Ad5 have been revealed, few studies have been carried out to identify neutralization epitopes on the knob from a broader panel of AdV serotypes. In this study, based on sequence and structural analysis of knobs from Ad1, Ad2, Ad5 and Ad6 (all from species C), several trimeric chimeric knob proteins were expressed in Escherichia coli to identify the locations of neutralization epitopes on the knobs by analysing their reactivity with mouse and rabbit polyclonal sera raised against AdVs and human sera with natural AdV infection. The dominant neutralization epitopes were located mainly in the N-terminal part of knobs from Ad1, Ad2 and Ad5, but they seemed to be located in the C-terminal part of the Ad6 knob, with some individual differences in rabbit and human populations. Our study adds to our understanding of humoral immune responses to AdVs and will facilitate the construction of more desirable capsid-modified recombinant Ad5 vectors.

  10. The Evolution of Advanced Merger (U)LIRGs on the Color-Stellar Mass Diagram

    NASA Astrophysics Data System (ADS)

    Guo, Rui; Hao, Cai-Na; Xia, Xiao-Yang

    2016-08-01

    Based on a sample of 79 local advanced merger (adv-merger) (U)LIRGs, we search for evidence of quenching processes by investigating the distributions of star formation history indicators (EW(Hα), EW(HΔA) and Dn(4000)) on the NUV-r color-mass and SFR-M * diagrams. The distributions of EW(Hα) and Dn(4000) on the NUV-r color-mass diagram show clear trends that at a given stellar mass, galaxies with redder NUV-r colors have smaller EW(Hα) and larger D n (4000). The reddest adv-merger (U)LIRGs close to the green valley mostly have D n (4000)> 1.4. In addition, in the SFR-M * diagram, as the SFR decreases, the EW(Hα) decreases and the D n (4000) increases, implying that the adv-merger (U)LIRGs on the star formation main sequence have more evolved stellar populations than those above the main sequence. These results indicate that a fraction of the adv-merger (U)LIRGs have already exhibited signs of fading from the starburst phase and that the NUV-r reddest adv-merger (U)LIRGs are likely at the initial stage of post-starbursts with an age of ˜ 1 Gyr, which is consistent with the gas exhaustion time-scales. Therefore, our results offer additional support for the fast evolutionary track from the blue cloud to the red sequence.

  11. Molecular characterization, phylogeny analysis and pathogenicity of a Muscovy duck adenovirus strain isolated in China in 2014

    SciTech Connect

    Zhang, Xinheng; Zhong, Yangjin; Zhou, Zhenhai; Liu, Yang; Zhang, Huanmin; Chen, Feng; Chen, Weiguo; Xie, Qingmei

    2016-06-15

    This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The results of the analyses were in conformity with AdV properties. The full genome sequence was determined and analyzed. The new isolate (named CH-GD-12-2014) shared over 91% sequence identity with duck AdV-2 representing the species Duck aviadenovirus B. The most important distinguishing feature between the two DAdV strains was the presence of a second fiber gene in the Chinese isolate. Phylogeny reconstruction confirmed the affiliation of the virus with goose and duck AdVs in the genus Aviadenovirus. Experimental infection resulted in embryo death, and intramuscular inoculation provoked morbidity and mortality among ducks and chickens. - Highlights: • A duck adenovirus type 3 was isolated and the complete genome of DAdV-3 was obtained. • Physicochemical properties and electron microscopy were researched. • Pathogenicity of duck adenovirus type 3 was researched.

  12. High-Density Superconducting Cables for Advanced ACTPol

    NASA Technical Reports Server (NTRS)

    Pappas, C. G.; Austermann, J.; Beall, J. A.; Duff, S. M.; Gallardo, P. A.; Grace, E.; Henderson, S. W.; Ho, S. P.; Koopman, B. J.; Li, D.; hide

    2016-01-01

    Advanced ACTPol (AdvACT) is an upcoming Atacama Cosmology Telescope (ACT) receiver upgrade, scheduled to deploy in 2016, that will allow measure- ment of the cosmic microwave background polarization and temperature to the highest precision yet with ACT. The AdvACT increase in sensitivity is partly provided by an increase in the number of transition-edge sensors (TESes) per array by up to a factor of two over the current ACTPol receiver detector arrays. The high-density AdvACT TES arrays require 70 µ m pitch superconducting flexible cables (flex) to connect the detec- tor wafer to the first-stage readout electronics. Here, we present the flex fabrication process and test results. For the flex wiring layer, we use a 400-nm-thick sputtered alu- minum film. In the center of the cable, the wiring is supported by a polyimide substrate, which smoothly transitions to a bare (uncoated with polyimide) silicon substrate at the ends of the cable for a robust wedge wire-bonding interface. Tests on the first batch of flex made for the first AdvACT array show that the flex will meet the requirements for AdvACT, with a superconducting critical current above 1 mA at 500 mK, resilience to mechanical and cryogenic stress, and a room temperature yield of 97%.

  13. Mechanical Design and Development of TES Bolometer Detector Arrays for the Advanced ACTPol Experiment

    NASA Technical Reports Server (NTRS)

    Ward, Jonathan T.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Crowley, Kevin T.; Devlin, Mark J.; Duff, Shannon M.; Gallardo, Patricio M.; Henderson, Shawn W.; Ho, Shuay-Pwu Patty; hide

    2016-01-01

    The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling 5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150 mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline pro le leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modi ed to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.

  14. Monoclonal antibodies against Aleutian disease virus distinguish virus strains and differentiate sites of virus replication from sites of viral antigen sequestration.

    PubMed Central

    Race, R E; Chesebro, B; Bloom, M E; Aasted, B; Wolfinbarger, J

    1986-01-01

    Monoclonal antibodies (mAbs) were used to study antigenic differences among strains of Aleutian disease virus (ADV) and to characterize viral proteins in vitro and in vivo. A number of ADV field strains could be discriminated, and highly virulent Utah I ADV was clearly delineated from the tissue culture-adapted avirulent ADV-G strain. This specificity could be demonstrated by indirect immunofluorescence against infected cultures of Crandell feline kidney cells or against tissues of Utah I ADV-infected mink. Viral antigens were demonstrated in both the nuclei and the cytoplasm of infected tissue culture cells. However, in mink mesenteric lymph node, spleen, and liver, viral antigen was observed only in the cytoplasm. Absence of nuclear fluorescence suggested that the detected antigen represented phagocytized viral antigens rather than replicating virus. This conclusion was supported by the finding that mAbs reactive only against low-molecular-weight polypeptides derived from intact viral proteins gave the same pattern of in vivo fluorescence as mAbs with broad reactivity for large or small (or both) viral polypeptides. The distribution of infected cells was the same as that described for macrophages in these tissues and suggested that cells of the reticuloendothelial system had sequestered viral antigens. Images PMID:3001352

  15. Male predominance among Japanese adult patients with late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation.

    PubMed

    Asano, Y; Kanda, Y; Ogawa, N; Sakata-Yanagimoto, M; Nakagawa, M; Kawazu, M; Goyama, S; Kandabashi, K; Izutsu, K; Imai, Y; Hangaishi, A; Kurokawa, M; Tsujino, S; Ogawa, S; Aoki, K; Chiba, S; Motokura, T; Hirai, H

    2003-12-01

    Late-onset hemorrhagic cystitis (LHC) after hematopoietic stem cell transplantation (HSCT) is mainly caused by viral infections. We retrospectively analyzed the records of 141 Japanese adult patients who underwent a first allogeneic HSCT from 1995 to 2002. In all, 19 patients developed LHC a median of 51 days after HSCT. Adenovirus (AdV) was detected in the urine of 10 LHC patients, of whom eight had AdV type 11. Five of the six available serum samples from these patients were also positive for AdV type 11, but the detection of AdV in serum was not associated with a worse outcome. Male sex and the development of grade II-IV acute graft-versus-host disease were identified as independent significant risk factors for LHC. Male predominance was detected in LHC after HSCT, as has been previously shown in children with AdV-induced acute HC. The detection of AdV DNA in serum did not predict a poor outcome.

  16. Tenofovir alafenamide demonstrates broad cross-genotype activity against wild-type HBV clinical isolates and maintains susceptibility to drug-resistant HBV isolates in vitro.

    PubMed

    Liu, Yang; Miller, Michael D; Kitrinos, Kathryn M

    2017-03-01

    Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV). This study evaluated the antiviral activity of TAF against wild-type genotype A-H HBV clinical isolates as well as adefovir-resistant, lamivudine-resistant, and entecavir-resistant HBV isolates. Full length HBV genomes or the polymerase/reverse transcriptase (pol/RT) region from treatment-naïve patients infected with HBV genotypes A-H were amplified and cloned into an expression vector under the control of a CMV promoter. In addition, 11 drug resistant HBV constructs were created by site-directed mutagenesis of a full length genotype D construct. Activity of TAF was measured by transfection of each construct into HepG2 cells and assessment of HBV DNA levels following treatment across a range of TAF concentrations. TAF activity in vitro was similar against wild-type genotype A-H HBV clinical isolates. All lamivudine- and entecavir-resistant isolates and 4/5 adefovir-resistant isolates were found to be sensitive to inhibition by TAF in vitro as compared to the wild-type isolate. The adefovir-resistant isolate rtA181V + rtN236T exhibited low-level reduced susceptibility to TAF. TAF is similarly active in vitro against wild-type genotype A-H HBV clinical isolates. The TAF sensitivity results for all drug-resistant isolates are consistent with what has been observed with the parent drug TFV. The in vitro cell-based HBV phenotyping assay results support the use of TAF in treatment of HBV infected subjects with diverse HBV genotypes, in both treatment-naive and treatment-experienced HBV infected patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines.

    PubMed

    Balzarini, Jan; Schols, Dominique; Van Laethem, Kristel; De Clercq, Erik; Hocková, Dana; Masojidkova, Milina; Holý, Antonin

    2007-01-01

    To discover new potent and selective anti-human immunodeficiency virus (HIV) acyclic nucleoside phosphonate (ANP) drugs with in vivo antiretroviral activity. New acyclic pyrimidine nucleoside phosphonate derivatives that mimic the structure of the anti-HIV purine nucleoside phosphonates 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir) and (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA, tenofovir) were designed by linking the acyclic side chain of the ANPs through an ether bond to the C-6 position instead of the N-1 position of the pyrimidine ring. The compounds were evaluated against HIV and Moloney murine sarcoma virus (MSV) in cell culture, including a broad variety of HIV-1 clade clinical isolates and relevant mutant (drug-resistant) HIV-1 isolates. Their antiviral activities were correlated and investigated in an in vivo model consisting of MSV-infected newborn mice. MSV-induced tumour formation and associated death were recorded in drug-treated animals. Several 5-substituted 6-[2-(phosphonomethoxy)ethoxy]-2,4-diaminopyrimidine (PMEO-DAPy) analogues were found to inhibit a broad variety of HIV-1 clinical isolates. They showed a more favourable cross-resistance profile to mutant virus isolates than adefovir and tenofovir. There was a close correlation between inhibition of MSV in C3H/3T3 cells and inhibition of HIV-1 in CEM cells. The PMEO-DAPy derivatives potently inhibited MSV-induced tumour cell formation in newborn mice. The 5-methyl analogue PMEO-5-Me-DAPy proved markedly more inhibitory to MSV-induced tumour cell formation and associated animal death than its unsubstituted parent PMEO-DAPy derivative. When compared with adefovir, PMEO-5-Me-DAPy was less toxic and more antivirally active in MSV-infected mice. PMEO-5-Me-DAPy deserves further (pre)clinical investigations as a candidate anti-HIV drug.

  18. Cost-Effectiveness of Peg-Interferon, Interferon and Oral Nucleoside Analogues in the Treatment of Chronic Hepatitis B and D Infections in China.

    PubMed

    Goyal, Ashish; Murray, John M

    2016-08-01

    The cost-effectiveness of highly effective, but costly, peg-interferon (peg-IFN) treatment for chronic hepatitis B (CHB) infections in China is unknown. Endemic hepatitis D virus (HDV) may also modify the effectiveness of any HBV treatment option. The objective of this study is to determine the best antiviral treatment from a societal perspective in the Chinese population, which contains a mix of HBV and HDV infections. A Markov model is developed to simulate the clinical course of CHB and chronic hepatitis D (CHD) individuals. For a hypothetical Chinese cohort of 10,000 individuals aged 30-60 years, cost-utility analysis is performed for therapies with: lamivudine, adefovir, telbivudine, entecavir, IFN and Peg-IFN. Costs and quality-adjusted life-years (QALYs) are discounted at 3 % annually. A one-way sensitivity analysis is also conducted. Lamivudine, adefovir, telbivudine, and entecavir are all cost-effective treatments compared to palliative care at an incremental cost-effectiveness ratio (ICER) of -$418, -$197, -$443 and -$317 per QALY, respectively (2015 US dollars). Peg-IFN yields a maximum 156,000 QALYs with an ICER of $1149 per QALY while IFN results in the highest cumulative mortality of 48 % along with the lowest QALY gained. Probabilistic sensitivity analyses confirm that only Peg-IFN and ETV are the only two cost-effective options at the current willingness-to-pay (WTP) of $12,000 in China. However, entecavir has a higher probability of being cost-effective than Peg-IFN at current WTP for all age groups. Peg-IFN generates maximum QALYs compared to lamivudine, adefovir, telbivudine and interferon, and presents itself as a cost-effective option at current WTP. Alternatively entecavir can be used in China, generating 10 % lower QALYs than Peg-IFN but costing less than palliative care.

  19. [The ABC of viral hepatitis].

    PubMed

    Van Bambeke, F

    2008-03-01

    Viral hepatitis has long been under-diagnosed. Hepatitis A is an acute disease, while patients infected by hepatitis B and hepatitis C viruses are likely to develop chronical infections and severe complications (cancer, cirrhosis). The current treatment of hepatitis B and C consists in alpha interferon (preferably under its pegylated form), in combination with ribavirin for hepatitis C. The frequent and severe adverse effects of interferon-based therapy constitute, however, a major limiting factor (reactions at the injection site, flu-like syndrome, neurological disorders, ...). For hepatitis B, two alternatives are available so far, namely lamivudine and adefovir (used as a prodrug with highe oral bioavailability).

  20. Understanding and managing resistance.

    PubMed

    Berger, D S

    1998-01-01

    As many as 25 to 45 percent of patients using triple therapy with protease inhibitors will develop resistance due to a change in the genetic HIV code. However, patients who develop resistance may still benefit clinically when protease inhibitors are used in combination with other antiretrovirals. These patients may not have undetectable viral loads although they may have stable T4-cell counts. Resistance does not always lead to disease progression. Newer drugs under development or available through compassionate track programs may benefit people with resistance. DMP-266 (Sustiva) is a non-nucleoside reverse transcriptase inhibitor that shows promise for these patients. Other drugs in development include Compound 141, 1592, and adefovir.

  1. Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds.

    PubMed

    Hocková, Dana; Holý, Antonín; Masojídková, Milena; Andrei, Graciela; Snoeck, Robert; De Clercq, Erik; Balzarini, Jan

    2004-06-15

    Synthesis of 2,4-diamino-5-cyano-6-[[(diisopropoxyphosphoryl)methoxy]ethoxy]pyrimidine was based on the formation of the pyrimidine ring by cyclization followed by modification of the side chain by alkylation. The 5-cyano group was also transformed to a 5-formyl and 5-hydroxymethyl group by reduction. As a side product an unexpected dimer was formed. Resulting compounds were converted to the free phosphonic acids by treatment with bromotrimethylsilane followed by hydrolysis. The 5-cyano and 5-formyl derivatives showed pronounced antiretroviral activity, comparable to that of the reference drugs adefovir and tenofovir.

  2. [Entecavir--close perspective for using it].

    PubMed

    Halota, Waldemar; Pawłowska, Małgorzata

    2006-01-01

    There are 3 drugs registered to treatment of chronic hepatitis B: interferon, lamivudine and adefovir. Many other nucleoside and nucleotide analougs are examined. In experiments on the animals: woodchucks infected with WHBV and ducks infected with DHBV beneficial influence of entecavir on viral DNA and cccDNA supression. In these examination no resistance was present. In clinical studies resistanse to entecavir conserned only patients with resistance to lamivudine. Entecavir is safety and effective in the treatment of chronic hepatits B in patients HBeAg positive and negative and in patients with resistance to lamivudine.

  3. Assessment of Sensor Technologies for Advanced Reactors

    SciTech Connect

    Korsah, Kofi; Ramuhalli, Pradeep; Vlim, R.; Kisner, Roger A.; Britton, Jr, Charles L.; Wootan, D. W.; Anheier, Jr, N. C.; Diaz, A. A.; Hirt, E. H.; Chien, H. T.; Sheen, S.; Bakhtiari, Sasan; Gopalsami, S.; Heifetz, A.; Tam, S. W.; Park, Y.; Upadhyaya, B. R.; Stanford, A.

    2016-10-01

    Sensors and measurement technologies provide information on processes, support operations and provide indications of component health. They are therefore crucial to plant operations and to commercialization of advanced reactors (AdvRx). This report, developed by a three-laboratory team consisting of Argonne National Laboratory (ANL), Oak Ridge National Laboratory (ORNL) and Pacific Northwest National Laboratory (PNNL), provides an assessment of sensor technologies and a determination of measurement needs for AdvRx. It provides the technical basis for identifying and prioritizing research targets within the instrumentation and control (I&C) Technology Area under the Department of Energy’s (DOE’s) Advanced Reactor Technology (ART) program and contributes to the design and implementation of AdvRx concepts.

  4. Description of advanced third-stage larvae of Gnathostoma lamothei Bertoni-Ruiz et al. 2005 (Nematoda: Gnathostomatidae) from experimental hosts and contributions to its life cycle.

    PubMed

    Gaspar-Navarro, Jorge; Almeyda-Artigas, Roberto Javier; Sánchez-Miranda, Elizabeth; Carranza-Calderón, Laura; Mosqueda-Cabrera, Miguel Angel

    2013-01-01

    The advanced third-stage larvae (AdvL(3)) of Gnathostoma lamothei was obtained from experimental hosts. Frogs Lithobates heckscheri and snakes Nerodia fasciata pictiventris were compatible hosts allowing optimal larval development. AdvL(3) are 4,487.94 μm long, have two lateral cervical papillae between rows 10 and 16 and an excretory pore at row 23. The average counts of the cephalic bulb hooklets from the four rows are 39.3, 43.3, 44.2, and 47.3. Larvae show an esophagus that represents 40 % of the body width. These findings indicate that amphibians and reptiles could be involved as G. lamothei natural hosts; nevertheless, their role as etiological agents of human gnathostomiasis is uncertain. This paper reports for the first time the taxonomic description of G. lamothei AdvL(3) obtained from experimental hosts and contributes to the understanding of its life cycle.

  5. Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice

    PubMed Central

    Liu, Shan; Jackson, Andrew; Beloor, Jagadish; Kumar, Priti; Sutton, Richard E.

    2015-01-01

    Despite nearly three decades of research, a safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) has yet to be achieved. More recently, the discovery of highly potent anti-gp160 broadly neutralizing antibodies (bNAbs) has garnered renewed interest in using antibody-based prophylactic and therapeutic approaches. Here, we encoded bNAbs in first-generation adenoviral (ADV) vectors, which have the distinctive features of a large coding capacity and ease of propagation. A single intramuscular injection of ADV-vectorized bNAbs in humanized mice generated high serum levels of bNAbs that provided protection against multiple repeated challenges with a high dose of HIV-1, prevented depletion of peripheral CD4+ T cells, and reduced plasma viral loads to below detection limits. Our results suggest that ADV vectors may be a viable option for the prophylactic and perhaps therapeutic use of bNAbs in humans. PMID:25953321

  6. Comparative study of two extraction methods for enteric virus recovery from sewage sludge by molecular methods.

    PubMed

    Schlindwein, A D; Simões, C M O; Barardi, C R M

    2009-07-01

    The aim of this study was to compare two nucleic acid extraction methods for the recovery of enteric viruses from activated sludge. Test samples were inoculated with human adenovirus (AdV), hepatitis A virus (HAV), poliovirus (PV) and rotavirus (RV) and were then processed by an adsorption-elution-precipitation method. Two extraction methods were used: an organic solvent-based method and a silica method. The organic-based method was able to recoup 20% of the AdV, 90% of the RV and 100% of both the PV and HAV from seeded samples. The silica method was able to recoup 1.8% of the AdV and 90% of the RV. These results indicate that the organic-based method is more suitable for detecting viruses in sewage sludge.

  7. Development of an Acoustic Droplet Vaporization, Ultrasound Drug Delivery Emulsion

    NASA Astrophysics Data System (ADS)

    Fabiilli, Mario L.; Sebastian, Ian E.; Fowlkes, J. Brian

    2010-03-01

    Many therapeutic applications of ultrasound (US) include the use of pefluorocarbon (PFC) microbubbles or emulsions. These colloidal systems can be activated in the presence of US, which in the case of emulsions, results in the production of bubbles—a process known as acoustic droplet vaporization (ADV). ADV can be used as a drug delivery mechanism, thereby yielding the localized release of toxic agents such a chemotherapeutics. In this work, emulsions that contain PFC and chlorambucil, a chemotherapy drug, are formulated using albumin or lipid shells. For albumin droplets, the oil phase—which contained CHL—clearly enveloped the PFC phase. The albumin emulsion also displayed better retention of CHL in the absence of US, which was evaluated by incubating Chinese hamster ovary cells with the various formulations. Thus, the developed emulsions are suitable for further testing in ADV-induced release of CHL.

  8. Discovery of natural perchlorate in the Antarctic Dry Valleys and its global implications.

    PubMed

    Kounaves, Samuel P; Stroble, Shannon T; Anderson, Rachel M; Moore, Quincy; Catling, David C; Douglas, Susanne; McKay, Christopher P; Ming, Douglas W; Smith, Peter H; Tamppari, Leslie K; Zent, Aaron P

    2010-04-01

    In the past few years, it has become increasingly apparent that perchlorate (ClO(4)(-)) is present on all continents, except the polar regions where it had not yet been assessed, and that it may have a significant natural source. Here, we report on the discovery of perchlorate in soil and ice from several Antarctic Dry Valleys (ADVs) where concentrations reach up to 1100 microg/kg. In the driest ADV, perchlorate correlates with atmospherically deposited nitrate. Far from anthropogenic activity, ADV perchlorate provides unambiguous evidence that natural perchlorate is ubiquitous on Earth. The discovery has significant implications for the origin of perchlorate, its global biogeochemical interactions, and possible interactions with the polar ice sheets. The results support the hypotheses that perchlorate is produced globally and continuously in the Earth's atmosphere, that it typically accumulates in hyperarid areas, and that it does not build up in oceans or other wet environments most likely because of microbial reduction on a global scale.

  9. Contribution of viruses, Chlamydia spp. and Mycoplasma pneumoniae to acute respiratory infections in Iranian children.

    PubMed

    Naghipour, Mohammadreza; Cuevas, Luis E; Bakhshinejad, Tahereh; Mansour-Ghanaei, Fariborz; Noursalehi, Smaeil; Alavy, Ali; Dove, Winifred; Hart, Charles Anthony

    2007-06-01

    The study reports the frequency and clinical presentation of respiratory syncytial virus (RSV), human metapneumovirus, influenza (Inf V), parainfluenza, adenovirus (Adv), Chlamydia spp. and Mycoplasma pneumoniae in children with acute respiratory infections (ARI) in Rasht, Iran. Nasopharyngeal aspirates and swabs were collected from 261 children in 2003 and 2004. Pathogens were detected using polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR), confirmed with sequence analysis. Ninety-three pathogens were detected in 83 children. RSV was present in 39 (15%), Adv in 37 (14%), Inf A in 11 (4%), C. trachomatis in 4 (2%) and M. pneumoniae, in 2 (1%) children. Neither parainfluenza nor metapneumovirus were detected. RSV, Inf A and C. trachomatis were more frequent in children with lower respiratory infections. Adv presented more frequently as upper respiratory infection. All pathogens, except M. pneumoniae, were detected in children with severe pneumonia. Viruses play a significant role in Iranian children with community-acquired ARI.

  10. Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells

    PubMed Central

    Wan, Li; Yao, Xinglei; Faiola, Francesco; Liu, Bojun; Zhang, Tianyuan; Tabata, Yasuhiko; Mizuguchi, Hiroyuki; Nakagawa, Shinsaku; Gao, Jian-Qing; Zhao, Robert Chunhua

    2016-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with multilineage potential, which makes them attractive tools for regenerative medicine applications. Efficient gene transfer into MSCs is essential not only for basic research in developmental biology but also for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors, but not into MSCs, which are deficient in coxsackievirus and adenovirus receptors expression. To overcome this problem, we developed an Adv coated with a spermine-pullulan (SP) cationic polymer and investigated its physicochemical properties and internalization mechanisms. We demonstrated that the SP coating could enhance adenoviral transduction of MSCs without detectable cytotoxicity or effects on differentiation. Our results argue in favor of the potentiality of the SP-coated Adv as a prototype vector for efficient and safe transduction of MSCs. PMID:28008251

  11. Role of coxsackievirus and adenovirus receptor (CAR) expression and viral load of adenovirus and enterovirus in patients with dilated cardiomyopathy.

    PubMed

    Sharma, Mirnalini; Mishra, Baijayantimala; Saikia, Uma Nahar; Bahl, Ajay; Ratho, Radha Kanta; Talwar, Kewal Kishan

    2016-01-01

    Enteroviruses (EVs) and adenoviruses (AdVs) are two important etiological agents of viral myocarditis and dilated cardiomyopathy (DCM). Both these viruses share a common receptor, the coxsackievirus and adenovirus receptor (CAR), for their infection. However, the role of viral load and CAR expression in disease severity has not yet been completely elucidated. The present study aimed to determine viral load of EV and AdV in DCM patients and correlate them with the level of CAR expression in these patients. Sixty-three DCM cases and 30 controls, each of whom died of heart disease other than DCM and non-cardiac disease respectively, were included. Viral load was determined by TaqMan real-time PCR using primers and probes specific for the AdV hexon gene and the 5'UTR region of EV. The CAR mRNA level was semi-quantitated by RT-PCR, and antigen expression was studied by immunohistochemistry. A significantly high AdV load (p < 0.05) and CAR expression (p < 0.05) were observed in DCM cases versus controls, whereas the EV load showed no significant difference. The data suggests a clinical threshold of 128 AdV copies/500 ng of DNA for DCM, with 66.7 % sensitivity and 65 % specificity. A positive correlation between AdV load and CAR expression (p < 0.001) was also observed in DCM cases. The high adenoviral load and increased CAR expression in DCM and their association with adverse disease outcome indicates role of both virus and receptor in disease pathogenesis. Thus, the need for targeting both the virus and the receptor for treatment of viral myocarditis and early DCM requires further confirmation with larger studies.

  12. Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B: A pilot study

    PubMed Central

    Srivastava, Manjita; Singh, Neha; Dixit, Vinod Kumar; Nath, Gopal; Jain, Ashok Kumar

    2016-01-01

    Background & objectives: Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients. Methods: A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed. Results: Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations: rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations. Interpretation & conclusions: LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice

  13. Effects of an advanced temperature cycle on smolt development and endocrinology indicate that temperature is not a zeitgeber for smolting in Atlantic salmon

    USGS Publications Warehouse

    McCormick, S.D.; Shrimpton, J.M.; Moriyama, S.; Bjornsson, Bjorn Thrandur

    2002-01-01

    Atlantic salmon (Salmo salar) juveniles were reared under simulated conditions of normal photoperiod (LDN) or short days (LD 9:15) and ambient temperature (AMB: normal temperature increases in April) or an advanced temperature cycle (ADV: temperature increases in February). Under both photoperiod conditions, the timing of increased and peak levels of gill Na+,K+-ATPase activity were not altered by temperature, although the rate of increase was initially greater under ADV. ADV/LD 9:15 resulted in peak gill Na+,K+-ATPase activity that was half of that seen under normal photoperiod and temperature conditions. Plasma growth hormone (GH) levels increased threefold in late March under ADV/LDN, but not under ADV/LD 9:15, indicating that there is a photoperiod-dependent effect of temperature on levels of this hormone. Plasma insulin-like growth factor I (IGF-I) increased in spring in all groups, with increases occurring significantly earlier in the ADV/LDN group. In each photoperiod condition, the advanced temperature cycle resulted in large decreases in plasma thyroxine (T4) levels in March, which subsequently recovered, whereas plasma 3,5,3???-triiodo-L-thyronine (T3) levels were not substantially affected by either photoperiod or temperature. There was no consistent pattern of change in plasma cortisol levels. The results do not provide support for the role of temperature as a zeitgeber, but do indicate that temperature has a role in the timing of smolting by affecting the rate of development and interacting with the photoperiod.

  14. An oral Aujeszky's disease vaccine (YS-400) induces neutralizing antibody in pigs

    PubMed Central

    2016-01-01

    Purpose Aujeszky's disease (AD) is an economically important disease affecting both wild and domestic pigs of the species Sus scrofa. A previous study yielded serological evidence of AD in Korean wild boars, which could spread AD to other animals. A new Aujeszky's disease virus (ADV) bait vaccine is required to prevent AD outbreaks in swine. In the present study, we investigated the safety and immunogenicity of a gE-deleted marker vaccine, strain YS-400, in young domestic pigs. Materials and Methods The YS-400 strain was propagated in Vero cells, and the trial ADV bait vaccine (a vaccine blister in a matrix including an attractant) was prepared. Pigs were orally immunized with the vaccine (2 mL, 107.5 TCID50/mL) delivered using a syringe or in the bait vaccine. The animals were observed for 9 weeks after vaccination, and immunogenicity was assessed using a virus neutralization (VN) test and enzyme linked immunosorbent assay. Results The YS-400 strain was non-pathogenic to pigs when given orally and induced high VN titers (1:32-1:128) 6 weeks post-administration. Of the pigs given the ADV bait vaccine twice or three times, 40% were seropositive by 2 weeks, and 100% were seropositive by 7 weeks after the first dose. Pigs that consumed the AD bait vaccine three times developed VN titers that were slightly higher than those of pigs given the vaccine twice. Conclusion Domestic pigs given the trial ADV bait vaccine exhibited no adverse effects and developed high VN titers against ADV, indicating that the YS-400 strain is safe and can prevent ADV infection in domestic pigs. PMID:27489803

  15. Functional characterization of a PEI-CyD-FA-coated adenovirus as delivery vector for gene therapy.

    PubMed

    Yao, Hong; Chen, Shih-Chi; Shen, Zan; Huang, Yun-Chao; Zhu, Xiao; Wang, Xiao-mei; Jiang, Wenqi; Wang, Zi-Feng; Bian, Xiu-Wu; Ling, Eng-Ang; Kung, Hsiang-fu; Lin, Marie C

    2013-01-01

    The recombinant adenovirus is evolving as a promising gene delivery vector for gene therapy due to its efficiency in transducing different genes into most types of cells. However, the host-immune response elicited by primary inoculation of an adenovirus can cause rapid clearance of the vector, impairing the efficacy of the adenovirus and hence obstructing its clinical application. We have previously synthesized a biodegradable co-polymer consisting of a low molecular weight PEI (MW 600 Da), cross-linked with β-cyclodextrin, and conjugated with folic acid (PEI-CyD-FA, named H1). Here we report that coating the adenovirus vector (Adv) with H1 (H1/rAdv) could significantly improve both the efficacy and biosafety of Adv. Enhanced transfection efficiency as well as prolonged duration of gene expression were clearly demonstrated either by intratumoral or systemic injection of a single dose of H1/rAdv in immunocompetent mice. Importantly, repeated injections of H1/rAdv did not reduce the transfection efficiency in immunocompetent mice. Furthermore, H1 transformed the surface charge of the adenovirus capsomers from negative to positive in physiological solution, suggesting that H1 coated the capsid protein of the adenovirus. This could shelter the epitopes of capsid proteins of the adenovirus, resulting in a reduced host-immune response and enhanced transfection efficiency. Taken together, these findings suggest that H1/rAdv is an effective gene delivery system superior to the adenovirus alone and that it could be considered as a preferred vehicle for gene therapy.

  16. Testing FlowTracker2 Performance and Wading Rod Flow Disturbance in Laboratory Tow Tanks

    NASA Astrophysics Data System (ADS)

    Fan, X.; Wagenaar, D.

    2016-12-01

    The FlowTracker2 was released in February 2016 by SonTek (Xylem) to be a more feature-rich and technologically advanced replacement to the Original FlowTracker ADV. These instruments are Acoustic Doppler Velocimeters (ADVs) used for taking high-precision wading discharge and velocity measurements. The accuracy of the FlowTracker2 probe was tested in tow tanks at three different facilities: the USGS Hydrologic Instrumentation Facility (HIF), the Swiss Federal Institute for Metrology (METAS), and at the SonTek Research and Development facility. Multiple mounting configurations were examined, including mounting the ADV probe directly to the tow carts, and incorporating the two most-used wading rods for the FlowTracker (round and hex). Tow speeds ranged from 5cm/s to 1.5m/s, and different tow tank seeding schemes and wait times were examined. In addition, the performance of the FlowTracker2 probe in low Signal-to-Noise Ratio (SNR) environments was compared to the Original FlowTracker ADV. Results confirmed that the FlowTracker2 probe itself performed well within the 1%+0.25cm/s accuracy specification advertised. Tows using the wading rods created a reduced measured velocity by 1.3% of the expected velocity due to flow disturbance, a result similar to the Original FlowTracker ADV despite the change in the FlowTracker2 probe design. Finally, due to improvements in its electronics, the FlowTracker2's performance in low SNR tests exceeded that of the Original FlowTracker ADV, showing less standard error in these conditions compared to its predecessor.

  17. Investigation of the pathogenesis of transplacental transmission of Aleutian mink disease parvovirus in experimentally infected mink.

    PubMed Central

    Broll, S; Alexandersen, S

    1996-01-01

    The transplacental transmission of Aleutian mink disease parvovirus (ADV) was studied in experimental infection of 1-year-old female non-Aleutian mink. The ADV-seronegative female mink were inoculated with ADV prior to mating or after the expected implantation of the embryos during pregnancy. A group of uninfected females served as a control group. Animals from each group were killed prior to or shortly after parturition. The in situ hybridization technique with radiolabeled strand-specific RNA probes was used to determine target cells of virus infection and virus replication. In both infected groups, ADV crossed the endotheliochorial placental barrier, although animals infected before mating already had high antibody titers against ADV at the time of implantation. The percentage of dead and resorbed fetuses was much higher in dams infected before mating. In the placentae of these mink, virus DNA and viral mRNA were detected in cells in the mesenchymal stroma of the placental labyrinth and hematoma but only occasionally in the cytotrophoblast of the placental hematoma. Placentae of animals infected during pregnancy showed in addition very high levels of virus and also viral replication in a large number of cytotrophoblast cells in the placental hematoma, which exhibited distinct inclusion bodies. In both groups, neither virus nor virus replication could be detected in maternal endothelial cells or fetal syncytiotrophoblast of the placental labyrinth. Fetuses were positive for virus and viral replication at high levels in a wide range of tissues. Possible routes of transplacental transmission of ADV and the role of trophoblast cells as targets for viral replication are discussed. PMID:8627663

  18. Correction of chromosomal mutation and random integration in embryonic stem cells with helper-dependent adenoviral vectors.

    PubMed

    Ohbayashi, Fumi; Balamotis, Michael A; Kishimoto, Atsuhiro; Aizawa, Emi; Diaz, Arturo; Hasty, Paul; Graham, Frank L; Caskey, C Thomas; Mitani, Kohnosuke

    2005-09-20

    For gene therapy of inherited diseases, targeted integration/gene repair through homologous recombination (HR) between exogenous and chromosomal DNA would be an ideal strategy to avoid potentially serious problems of random integration such as cellular transformation and gene silencing. Efficient sequence-specific modification of chromosomes by HR would also advance both biological studies and therapeutic applications of a variety of stem cells. Toward these goals, we developed an improved strategy of adenoviral vector (AdV)-mediated HR and examined its ability to correct an insertional mutation in the hypoxanthine phosphoribosyl transferase (Hprt) locus in male mouse ES cells. The efficiency of HR was compared between four types of AdVs that contained various lengths of homologies at the Hprt locus and with various multiplicities of infections. The frequency of HR with helper-dependent AdVs (HD AdVs) with an 18.6-kb homology reached 0.2% per transduced cell at a multiplicity of infection of 10 genomes per cell. Detection of random integration at DNA levels by PCR revealed extremely high efficiency of 5% per cell. We also isolated and characterized chromosomal sites where HD AdVs integrated in a random manner. In contrast to retroviral, lentiviral, and adeno-associated viral vectors, which tend to integrate into genes, the integration sites of AdV was distributed randomly inside and outside genes. These findings suggest that HR mediated by HD AdVs is efficient and relatively safe and might be a new viable option for ex vivo gene therapy as well as a tool for chromosomal manipulation of a variety of stem cells.

  19. The Role of Major Gas-rich Mergers on the Evolution of Galaxies from the Blue Cloud to the Red Sequence

    NASA Astrophysics Data System (ADS)

    Guo, Rui; Hao, Cai-Na; Xia, X. Y.; Mao, Shude; Shi, Yong

    2016-07-01

    With the aim of exploring the fast evolutionary path from the blue cloud of star-forming galaxies to the red sequence of quiescent galaxies in the local universe, we select a local advanced merging infrared luminous and ultraluminous galaxy (adv-merger (U)LIRGs) sample and perform careful dust extinction corrections to investigate their positions in the star formation rate-M *, u - r, and NUV - r color-mass diagrams. The sample consists of 89 (U)LIRGs at the late merger stage, obtained from cross-correlating the Infrared Astronomical Satellite Point Source Catalog Redshift Survey and 1 Jy ULIRGs samples with the Sloan Digital Sky Survey DR7 database. Our results show that 74 % +/- 5 % of adv-merger (U)LIRGs are localized above the 1σ line of the local star-forming galaxy main sequence. We also find that all adv-merger (U)LIRGs are more massive than and as blue as the blue cloud galaxies after corrections for Galactic and internal dust extinctions, with 95 % +/- 2 % and 81 % +/- 4 % of them outside the blue cloud on the u - r and NUV - r color-mass diagrams, respectively. These results, combined with the short timescale for exhausting the molecular gas reservoir in adv-merger (U)LIRGs (3× {10}7 to 3× {10}8 years), imply that the adv-merger (U)LIRGs are likely at the starting point of the fast evolutionary track previously proposed by several groups. While the number density of adv-merger (U)LIRGs is only ˜ 0.1 % of the blue cloud star-forming galaxies in the local universe, this evolutionary track may play a more important role at high redshift.

  20. Detection of enteric viruses in sewage sludge and treated wastewater effluent.

    PubMed

    Schlindwein, A D; Rigotto, C; Simões, C M O; Barardi, C R M

    2010-01-01

    Sewage sludge and treated wastewater when contaminated with enteric virus and discharged into the environment, could pose a human health risk. The aim of study was to verify the presence and viability of enteric viruses in sewage sludge and treated wastewater at a local sewage plant in Florianopolis city, Brazil. Sewage sludge was concentrated by organic flocculation and polyethylene glycol precipitation and wastewater by electronegative membrane filtration and ultrafiltration by Centriprep Concentrator. Adenovirus (AdV), hepatitis A virus (HAV), and Rotavirus (RV) were examined for all samples for 12 months and Poliovirus (PV) was also tested for in sewage sludge samples. AdV was the most prevalent in both kind of samples, followed by RV, PV (in sludge) and HAV. Viral viability by cell culture (ICC-PCR) was: AdV: 100%, HAV: 16.7%, PV: 91.7%, RV: 25% in sludge and AdV: 66.6%, HAV: 66.6% and RV: 0% in wastewater. IFA for AdV in sludge ranged from 70 to 300 FFU/ml. QPCR for AdV ranged from 4.6 x 10(4) to 1.2 x 10(6) and from 50 to 1.3 x 10(4) gc/ml in sludge and wastewater, respectively. HAV quantification in sludge ranged from 3.1 x 10(2) to 5.4 x 10(2) gc/ml. In conclusion, it was possible to correlate presence and viability of enteric viruses in the environmental samples analyzed.

  1. Detection of known and novel adenoviruses in cattle wastes via broad-spectrum primers.

    PubMed

    Sibley, Samuel D; Goldberg, Tony L; Pedersen, Joel A

    2011-07-01

    The critical assessment of bovine adenoviruses (BAdV) as indicators of environmental fecal contamination requires improved knowledge of their prevalence, shedding dynamics, and genetic diversity. We examined DNA extracted from bovine and other animal waste samples collected in Wisconsin for atadenoviruses and mastadenoviruses using novel, broad-spectrum PCR primer sets. BAdV were detected in 13% of cattle fecal samples, 90% of cattle urine samples, and 100% of cattle manure samples; 44 percent of BAdV-positive samples contained both Atadenovirus and Mastadenovirus DNA. Additionally, BAdV were detected in soil, runoff water from a cattle feedlot, and residential well water. Overall, we detected 8 of 11 prototype BAdV, plus bovine, rabbit, and porcine mastadenoviruses that diverged significantly from previously reported genotypes. The prevalence of BAdV shedding by cattle supports targeting AdV broadly as indicators of the presence of fecal contamination in aqueous environments. Conversely, several factors complicate the use of AdV for fecal source attribution. Animal AdV infecting a given livestock host were not monophyletic, recombination among livestock mastadenoviruses was detected, and the genetic diversity of animal AdV is still underreported. These caveats highlight the need for continuing genetic surveillance for animal AdV and for supporting data when BAdV detection is invoked for fecal source attribution in environmental samples. To our knowledge, this is the first study to report natural BAdV excretion in urine, BAdV detection in groundwater, and recombination in AdV of livestock origin.

  2. Optimization of adenovirus 40 and 41 recovery from tap water using small disk filters.

    PubMed

    McMinn, Brian R

    2013-11-01

    Currently, the U.S. Environmental Protection Agency's Information Collection Rule (ICR) for the primary concentration of viruses from drinking and surface waters uses the 1MDS filter, but a more cost effective option, the NanoCeram® filter, has been shown to recover comparable levels of enterovirus and norovirus from both matrices. In order to achieve the highest viral recoveries, filtration methods require the identification of optimal concentration conditions that are unique for each virus type. This study evaluated the effectiveness of 1MDS and NanoCeram filters in recovering adenovirus (AdV) 40 and 41 from tap water, and optimized two secondary concentration procedures the celite and organic flocculation method. Adjustments in pH were made to both virus elution solutions and sample matrices to determine which resulted in higher virus recovery. Samples were analyzed by quantitative PCR (qPCR) and Most Probable Number (MPN) techniques and AdV recoveries were determined by comparing levels of virus in sample concentrates to that in the initial input. The recovery of adenovirus was highest for samples in unconditioned tap water (pH 8) using the 1MDS filter and celite for secondary concentration. Elution buffer containing 0.1% sodium polyphosphate at pH 10.0 was determined to be most effective overall for both AdV types. Under these conditions, the average recovery for AdV40 and 41 was 49% and 60%, respectively. By optimizing secondary elution steps, AdV recovery from tap water could be improved at least two-fold compared to the currently used methodology. Identification of the optimal concentration conditions for human AdV (HAdV) is important for timely and sensitive detection of these viruses from both surface and drinking waters. Published by Elsevier B.V.

  3. Random sampling of the Central European bat fauna reveals the existence of numerous hitherto unknown adenoviruses.

    PubMed

    Vidovszky, Márton; Kohl, Claudia; Boldogh, Sándor; Görföl, Tamás; Wibbelt, Gudrun; Kurth, Andreas; Harrach, Balázs

    2015-12-01

    From over 1250 extant species of the order Chiroptera, 25 and 28 are known to occur in Germany and Hungary, respectively. Close to 350 samples originating from 28 bat species (17 from Germany, 27 from Hungary) were screened for the presence of adenoviruses (AdVs) using a nested PCR that targets the DNA polymerase gene of AdVs. An additional PCR was designed and applied to amplify a fragment from the gene encoding the IVa2 protein of mastadenoviruses. All German samples originated from organs of bats found moribund or dead. The Hungarian samples were excrements collected from colonies of known bat species, throat or rectal swab samples, taken from live individuals that had been captured for faunistic surveys and migration studies, as well as internal organs of dead specimens. Overall, 51 samples (14.73%) were found positive. We detected 28 seemingly novel and six previously described bat AdVs by sequencing the PCR products. The positivity rate was the highest among the guano samples of bat colonies. In phylogeny reconstructions, the AdVs detected in bats clustered roughly, but not perfectly, according to the hosts' families (Vespertilionidae, Rhinolophidae, Hipposideridae, Phyllostomidae and Pteropodidae). In a few cases, identical sequences were derived from animals of closely related species. On the other hand, some bat species proved to harbour more than one type of AdV. The high prevalence of infection and the large number of chiropteran species worldwide make us hypothesise that hundreds of different yet unknown AdV types might circulate in bats.

  4. Assessing Photocatalytic Oxidation Using Modified TiO 2 Nanomaterials for Virus Inactivation in Drinking Water: Mechanisms and Application

    NASA Astrophysics Data System (ADS)

    Liga, Michael Vincent

    Photocatalytic oxidation is an alternative water treatment method under consideration for disinfecting water. Chlorine disinfection can form harmful byproducts, and some viruses (e.g. adenoviruses) are resistant to other alternative disinfection methods. Photocatalytic oxidation using nano-sized photocatalytic particles (e.g. TiO2, fullerene) holds promise; however, it is limited by its low efficiency and long required treatment times. This research focuses on improving virus inactivation by photocatalytic oxidation by modifying catalysts for improved activity, by analyzing virus inactivation kinetics, and by elucidating the inactivation mechanisms of adenovirus serotype 2 (AdV2) and bacteriophage MS2. Modifying TiO2 with silver (nAg/TiO2) or silica (SiO2-TiO2) improves the inactivation kinetics of bacteriophage MS2 by a factor of 3-10. nAg/ TiO2 increases hydroxyl radical (HO·) production while SiO2 increases the adsorption of MS2 to TiO 2. These results suggest that modifying the photocatalyst surface to increase contaminant adsorption is an important improvement strategy along with increasing HO· production. The inactivation kinetics of AdV2 by P25 TiO2 is much slower than the MS2 inactivation kinetics and displays a strong shoulder, which is not present in the MS2 kinetics. nAg/TiO2 initially improves the inactivation rate of AdV2. SiO2-TiO2 reduces the AdV2 inactivation kinetics since adsorption is not significantly enhanced, as it is with MS2. Amino-C60 is highly effective for AdV2 inactivation under visible light irradiation, making it a good material for use in solar disinfection systems. The efficacy of amino-fullerene also demonstrates that singlet oxygen is effective for AdV2 inactivation. When exposed to irradiated TiO2, AdV2 hexon proteins are heavily damaged resulting in the release of DNA. DNA damage is also present but may occur after capsids break. With MS2, the host interaction protein is rapidly damaged, but not the coat protein. The kinetics

  5. High-level recombinant protein production in CHO cells using an adenoviral vector and the cumate gene-switch.

    PubMed

    Gaillet, Bruno; Gilbert, Rénald; Amziani, Rachid; Guilbault, Claire; Gadoury, Christine; Caron, Antoine W; Mullick, Alaka; Garnier, Alain; Massie, Bernard

    2007-01-01

    To facilitate and accelerate the production of eukaryotic proteins with correct post-translational modifications, we have developed a protein production system based on the transduction of Chinese hamster ovary (CHO) cells using adenovirus vectors (AdVs). We have engineered a CHO cell line (CHO-cTA) that stably expresses the transactivator (cTA) of our newly developed cumate gene-switch transcription system. This cell line is adapted to suspension culture and can grow in serum-free and protein-free medium. To increase the transduction level of AdVs, we have also generated a cell line (CHO-cTA-CAR) that expresses additional amounts of the coxackievirus and adenovirus receptor (CAR) on its surface. Recombinant protein production was tested using an AdV carrying the secreted alkaline phosphatase (SEAP) under the control of the CR5 promoter, which is strongly and specifically activated by binding to cTA. The SEAP expression was linked to the expression of the green fluorescent protein (GFP) through an internal ribosome entry site (IRES) to facilitate titration of the AdV. We monitored SEAP expression on a daily basis for 9 days after transduction of CHO-cTA and CHO-cTA-CAR using different quantities of AdVs at 37 and 30 degrees C. Incubation at the latter temperature increased the production of SEAP at least 10-fold, and the presence of CAR increased the transduction level of the AdV. Maximum SEAP production (63 mg/L) was achieved at 6-7 days post-infection at 30 degrees C by transducing CHO-cTA-CAR with 500 infectious particles/cell. Because numerous AdVs can now be generated within a few weeks and large-scale production of AdVs is now a routine procedure, this system could be used to produce rapidly milligram quantities of a battery of recombinant proteins as well as for large-scale protein production.

  6. Effect of ammonia production on intracellular pH: Consequent effect on adenovirus vector production.

    PubMed

    Ferreira, T B; Carrondo, M J T; Alves, P M

    2007-05-01

    Recombinant adenoviral vectors (AdV) have proven to be highly efficient for the delivery and expression of foreign genes in a broad spectrum of cell types and species both for vaccination and gene therapy in a number of specific applications. In this study, the effect of ammonia production on intracellular pH (pH(i)) and consequently inhibition of AdV production at high cell densities is assessed. Different specific ammonia production rates were obtained for 293 cells adapted to grow in glutamate supplemented medium (non-ammoniagenic medium) as compared with 293 cells growing in glutamine supplemented medium (ammoniagenic medium); pH(i) was observed to be lower during cell growth and AdV production at both high and low CCI in the ammoniagenic medium, where the specific ammonia production rate is higher. In addition, after infection at CCI of 3x10(6)cell/ml, the cell viability decreased significantly in the ammoniagenic medium, attributed to the activation of an acidic pathway of apoptosis. Furthermore, AdV DNA was observed to be degraded at the observed pH(i) in the ammoniagenic medium, decreasing significantly the amount of AdV DNA available for encapsulation. To elucidate the pH(i) effect upon AdV production, 293 cells were infected at a CCI of 1 x 10(6)cell/ml in the non-ammoniagenic medium with a manipulated pH(i) as observed at the time of infection at CCI of 3 x 10(6)cell/ml in the ammoniagenic (pH(i) 7.0) and non-ammoniagenic (pH(i) 7.3) media; AdV volumetric productivities were observed to be lower when the cells were exposed to the lower pH(i). Thus, the importance of controlling all the factors contributing to pH(i) on AdV production, such as ammonia production, has been established.

  7. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial.

    PubMed

    Qian, Chongsheng; Campidelli, Arnaud; Wang, Yingying; Cai, Huili; Venard, Véronique; Jeulin, Hélène; Dalle, Jean Hugues; Pochon, Cécile; D'aveni, Maud; Bruno, Benedicte; Paillard, Catherine; Vigouroux, Stéphane; Jubert, Charlotte; Ceballos, Patrice; Marie-Cardine, Aude; Galambrun, Claire; Cholle, Clément; Clerc Urmes, Isabelle; Petitpain, Nadine; De Carvalho Bittencourt, Marcelo; Decot, Véronique; Reppel, Loïc; Salmon, Alexandra; Clement, Laurence; Bensoussan, Danièle

    2017-05-08

    Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 10(3) CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo

  8. Arctic decadal variability in a warming world

    NASA Astrophysics Data System (ADS)

    van der Linden, Eveline C.; Bintanja, Richard; Hazeleger, Wilco

    2017-04-01

    The Arctic is currently warming much faster than other parts of the world, and sea ice is rapidly diminishing. Superimposed on these temperature and sea ice trends is a strong decadal variability, which can reinforce or oppose the trends, depending on its phase. It is therefore imperative to know not only the characteristics of current variability but also how (patterns of) Arctic decadal variability (ADV) might change as the climate warms. We evaluated the ADV characteristics in three long, equilibrium climate simulations for present-day, doubled, and quadrupled atmospheric CO2 forcing. These simulations show that ADV changes non-linearly with increasing CO2 concentrations, with maximum variability occurring in the CO2 doubling climate when sea ice becomes more vulnerable to melt over vast stretches of the Arctic. The dominant region of variability, which is located over the Barents Sea and the Greenland Sea in the current climate, shifts to the central Arctic and Siberian regions as the climate warms. Furthermore, the links between dominant atmospheric circulation modes and Arctic climate characteristics vary strongly with climate change. For instance, a positive Arctic Oscillation (AO) index is associated with a colder Arctic region in warmer climates, instead of a warmer Arctic at present. Such changing relationships are partly related to the retreat of sea ice because altered wind patterns influence the sea ice distribution and hence the associated local surface fluxes. The atmospheric pressure distributions governing ADV also change with climate warming. The Aleutian and Icelandic Lows both play a key role in the changing mean state and the associated variability of the large-scale circulation. Whereas ocean heat transport is firmly associated with ADV in the current and the CO2 doubling climate, the importance of the atmospheric heat transport increases in even warmer climates, suggesting that the large-scale dynamics associated with ADV change as well. The

  9. A Newborn with an Alternative Porto-Caval Shunt

    PubMed Central

    Damar, Çağrı; Alımlı, Ayşe Gül; Derinkuyu, Betül Emine; Özcan, Kudret Ebru; Olgaç, Asburçe; Koç, Ali Murat

    2017-01-01

    Summary Background Absent ductus venosus (ADV) is a rare condition, but it should be known that this embryonic anomaly may be detected by fetal echocardiographic or newborn ultrasound examinations. Case Report We present a baby with an ADV and an accompanying alternative porto-caval shunt between the right portal vein and inferior vena cava detected on postnatal ultrasound examination. Conclusions Variations in the fetal umbilical or porto-systemic circulations should be detected by fetal or newborn ultrasound examinations and kept in mind before common interventions such as UV catheterizations. PMID:28685004

  10. A Newborn with an Alternative Porto-Caval Shunt.

    PubMed

    Damar, Çağrı; Alımlı, Ayşe Gül; Derinkuyu, Betül Emine; Özcan, Kudret Ebru; Olgaç, Asburçe; Koç, Ali Murat

    2017-01-01

    Absent ductus venosus (ADV) is a rare condition, but it should be known that this embryonic anomaly may be detected by fetal echocardiographic or newborn ultrasound examinations. We present a baby with an ADV and an accompanying alternative porto-caval shunt between the right portal vein and inferior vena cava detected on postnatal ultrasound examination. Variations in the fetal umbilical or porto-systemic circulations should be detected by fetal or newborn ultrasound examinations and kept in mind before common interventions such as UV catheterizations.

  11. Novel adenovirus detected in kowari (Dasyuroides byrnei) with pneumonia.

    PubMed

    Gál, János; Mándoki, Míra; Sós, Endre; Kertész, Péter; Koroknai, Viktória; Bányai, Krisztián; Farkas, Szilvia L

    2017-02-15

    A male kowari (Dasyuroides byrnei) originating from a zoo facility was delivered for post mortem evaluation in Hungary. Acute lobar pneumonia with histopathologic changes resembling an adenovirus (AdV) infection was detected by light microscopic examination. The presence of an AdV was confirmed by obtaining partial sequence data from the adenoviral DNA-dependent DNA-polymerase. Although the exact taxonomic position of this novel marsupial origin virus could not be determined, pairwise identity analyses and phylogenetic calculations revealed that it is distantly related to other members in the family Adenoviridae.

  12. Advection of NH3 over a pasture field, and its effect on gradient flux measurements

    NASA Astrophysics Data System (ADS)

    Loubet, B.; Milford, C.; Hensen, A.; Daemmgen, U.; Erisman, J.-W.; Cellier, P.; Sutton, M. A.

    2009-01-01

    Deposition of atmospheric ammonia (NH3) to semi-natural ecosystems leads to serious adverse effects, such as acidification and eutrophication. A step in this quantification is the measurement of NH3 fluxes over semi-natural and agricultural land. However, measurement of NH3 fluxes over vegetation in the vicinity of strong NH3 sources is difficult, since NH3 emissions are highly heterogeneous. Indeed, under such conditions, local advection errors may alter the measured fluxes. In this study, local advection errors (Δ Fz,adv) were estimated over a 14 ha grassland field, which was successively cut and fertilised, as part of the GRAMINAE integrated Braunschweig experiment. The magnitude of Δ Fz,adv was determined up to 810 m downwind from farm buildings emitting between 6 and 12 kg NH3 day-1. The GRAMINAE experiment provided a unique opportunity to compare two methods of estimating Δ Fz,adv: (1) based on direct measurements of horizontal concentration gradients, and (2) based on inverse dispersion modelling. Two sources of local advection were clearly identified: the farm NH3 emissions leading to positive Δ Fz,adv, and field NH3 emissions, after cutting and fertilisation, which led to a negative Δ Fz,adv. The local advection flux from the farm was in the range 0 to 27 ng m-2 s-1 NH3 at 610 m from the farm, whereas Δ Fz,adv due to field emission was proportional to the local flux, and ranged between -209 and 13 ng m-2 s-1 NH3. The local advection flux Δ Fz,adv was either positive or negative depending on the magnitude of these two contributions. The modelled and measured advection errors agreed well, provided the modelled Δ Fz,adv was estimated at 2 m height. This study constitutes the first attempt to validate the inverse modelling approach to determine advection errors for NH3. The measured advection errors, relative to the vertical flux at 1 m height, were 121% on average, before the field was cut (when downwind of the farm), and less than 7% when the field

  13. Dimethylamino acid esters as biodegradable and reversible transdermal permeation enhancers: effects of linking chain length, chirality and polyfluorination.

    PubMed

    Novotný, Jakub; Kovaríková, Petra; Novotný, Michal; Janůsová, Barbora; Hrabálek, Alexandr; Vávrová, Katerina

    2009-04-01

    Series of N,N-dimethylamino acid esters was synthesized to study their transdermal permeation-enhancing potency, biodegradability and reversibility of action. Effects of chirality, linking chain length and polyfluorination were investigated. In vitro activities were evaluated using porcine skin and four model drugs-theophylline, hydrocortisone, adefovir and indomethacin. Biodegradability was determined using porcine esterase, reversibility was measured using electrical resistance. No differences in activity were found between (R), (S) and racemic dodecyl 2-(dimethylamino)propanoate (DDAIP). Substitution of hydrocarbon tail by fluorocarbon one resulted in loss of activity. Replacement of branched linking chain between nitrogen and ester of DDAIP by linear one markedly improved penetration-enhancing activity with optimum in 4-6C acid derivatives. Dodecyl 6-(dimethylamino)hexanoate (DDAK) was more potent than clinically used skin absorption enhancer DDAIP for theophylline (enhancement ratio of DDAK and DDAIP was 17.3 and 5.9, respectively), hydrocortisone (43.2 and 11.5) and adefovir (13.6 and 2.8), while DDAIP was better enhancer for indomethacin (8.7 and 22.8). DDAK was rapidly metabolized by porcine esterase, and displayed low acute toxicity. Electrical resistance of DDAK-treated skin barrier promptly recovered to control values. DDAK, highly effective, broad-spectrum, biodegradable and reversible transdermal permeation enhancer, is promising candidate for future research.

  14. New drugs on the horizon.

    PubMed

    1998-04-01

    Since many new anti-HIV drugs are variations of currently available drugs, they may be more effective for people who are beginning treatment. One study shows favorable results when using efavirenz in triple combination therapy; however, it is recommended that this therapy be reserved for people who are treatment-naive and symptom-free. It is still unclear if all non-nucleoside RT inhibitors (NNRTIs) are as potent as efavirenz and whether the long-term potential for them is as promising as standard combinations. Researchers caution against pairing an NNRTI with a protease inhibitor in the event that resistance to the combination develops. That resistance may eliminate the option of using any other protease inhibitor or NNRTI in future therapies. Conversely, abacavir, an NARTI, has been effective in combination with many protease inhibitors. Amprenavir shows good antiviral activity; although studies show that it may not be successful as a salvage therapy with protease inhibitors. Nucleotide analogue reverse transcriptase inhibitors, such as adefovir and bis-poc PMPA, showed moderate anti-HIV potency. A study evaluating FTC alone showed a good reduction in viral load. FTC also fights hepatitis B and requires only one dose daily. Information is included about expanded access programs for abacavir, adefovir, and efavirenz.

  15. Hepatitis B virus related cryoglobulinemic vasculitis: A multicentre open label study from the Gruppo Italiano di Studio delle Crioglobulinemie - GISC.

    PubMed

    Mazzaro, Cesare; Dal Maso, Luigino; Urraro, Teresa; Mauro, Endri; Castelnovo, Laura; Casarin, Pietro; Monti, Giuseppe; Gattei, Valter; Zignego, Anna Linda; Pozzato, Gabriele

    2016-07-01

    Cryoglobulinemic vasculitis (CV) related to Hepatitis-B Virus (HBV) is rare and its treatment is ill-defined. To describe clinical and treatment characteristics of HBV-related CV patients. In addition, the efficacy of treatment with antiviral agent nucleotide (NUC), including Entecavir, Adefovir, and Lamivudine, was explored. In four Italian centres, 17 HBV-positive CV patients (median age 56 years, range 45-70) were enrolled. The extrahepatic manifestations were: purpura (100%), arthralgias (71%), peripheral neuropathy (29%), chronic hepatitis (47%), liver cirrhosis (29%), and glomerulonephritis (18%). Mixed cryoglobulinemias were type II (88%) and type III (12%). The median cryocrit was 3% (range 1-14), rheumatoid factor was 200U/L (range 20-5850), C4 was 12mg/dl (range 2-31), ALT 71U/L (range 36-114). All patients were HBsAg-positive and 80% anti-HbeAg-positive. At enrollment, they were treated with steroids (eight), Entecavir (five), Alpha-IFN (two), Adefovir and Lamivudine (one each). After NUC treatment, no disease progression was observed and, in all patients, HBV-DNA became undetectable. Moreover, a regression of purpura and a reduction of cryocrit were observed. Four patients died during therapy, two of kidney failure and two of liver cirrhosis. NUC therapy appeared to be safe and effective in CV-related HBV. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Results of a retrospective database analysis of drug utilization and costs for treatment of chronic hepatitis B virus infection in the northern Netherlands between 2000 and 2006.

    PubMed

    Tu, Hong Anh T; Bos, Jens H J; Woerdenbag, Herman J; Visser, Sipke T; Wilschut, Jan C; van Assen, Sander; de Jong-van den Berg, Lolkje T W; Postma, Maarten J

    2010-01-01

    The main aims of this work were to describe patterns of medication use in the treatment of chronic hepatitis B virus (HBV) infection in patients in the northern part of the Netherlands and to compare these practices with established guidelines. In addition, the duration of use and the costs of these treatments were investigated. We selected subjects from the University of Groningen's IADB.nl database; by 2006, the database provided information about drug utilization from 55 community pharmacies in the northern Netherlands and included a population of 528,911 individuals, of which 49% were male. Eligible subjects had received >or=1 prescription for drugs used to treat chronic HBV infection (ie, lamivudine, pegylated interferon-alpha2a, pegylated interferon-alpha2b, adefovir, tenofovir, and entecavir) between the years 2000 and 2006. The annual prevalence and cumulative incidence of HBV treatment per 1000 people covered in the database were calculated and stratified by sex. Kaplan-Meier survival analysis was used to analyze the duration of use. Drug costs in the treatment were calculated for all patients or per patient, and by drugs used per subperiod (2000-2003 and 2004-2006). Treatments for hepatitis C virus and HIV were excluded from the analyses. From the database, we identified 59 patients (46 male, 13 female), aged 25 to 60 years, who received >or=1 prescription for a medication to treat chronic HBV infection between 2000 and 2006. The overall prevalence of people using chronic treatments for HBV was between 0.03 and 0.06 per 1000 during the years of the study. The cumulative incidence of treatment was approximately 0.01 per 1000 per year (ranging from a high of 0.021 in 2000 to a low of 0.009 in 2006). When stratified by sex, there were more male than female subjects who received medications for HBV. Lamivudine was the most commonly prescribed drug, followed by adefovir and pegylated interferon-alpha2b. In 2000 and 2001, lamivudine was the only medication

  17. CONCENTRATION AND PROCESSING OF WATERBORNE VIRUSES BY POSITIVE CHARGE 1MDS CARTRIDGE FILTERS AND ORGANIC FLOCCULATION

    EPA Science Inventory

    This chapter describes the most widely used virus adsorption-elution (VIRADEL) method for recovering human enteric viruses from water matrices (Fout et al., 1996). The method takes advantage of postively charged cartridge filters to concentrate viruses from water. The major adv...

  18. 77 FR 24239 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-23

    ... meet the 10% ADV requirement, and use of specified SLP mnemonics. In addition, the business unit of the... unique mnemonics specifically dedicated to SLMM activity. Use of these unique mnemonics will enable SLMMs... to the Exchange. As proposed, such mnemonics may not be used for trading in securities other than...

  19. 77 FR 7634 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... Trust'') and United States Oil Fund (``USO'' or ``USO Fund'') at $0.50 strike price intervals where the... are known on the Exchange as Exchange-Traded Fund Shares, underlie SLV and USO options.\\6\\ SLV and USO... (``ADV'') over the previous three calendar months was 60,087,539 for SLV and 13,881,380 for USO. \\7...

  20. DEVELOPING AZO AND FORMAZAN DYES BASED ON ENVIRONMENTAL CONSIDERATIONS: SALMONELLA MUTAGENICITY

    EPA Science Inventory

    Abstract
    In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. In this regard, it was shown that in certain cases iron could be substituted for the traditionally used metals, chromium and cobalt, without having an adve...

  1. Molecular Identification of Human Fungal Pathogens

    DTIC Science & Technology

    2007-03-01

    to analysis of morphological and biochemical characteristics (7). Although this is the first reported case of C. thermophila causing candidemia in a...candidal infections. Adv. Pediatr. 43:209–230. 3. Kossoff, E. H., E. S. Buescher, and M. G. Karlowicz. 1998. Candidemia in a neonatal intensive care unit

  2. 77 FR 74536 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-14

    ...\\ These rebates will replace the current 25% MDR paid to ETP Holders that meet the ADV requirements under... data product. Order Delivery Mode is a unique market structure that costs more to operate and regulate... model and technology, the Exchange maintains this high cost structure to foster competition...

  3. High Speed Imaging using Nanoprobe Arrays

    DTIC Science & Technology

    2010-06-23

    6774 2006. 13 B. Gotsmann, U. Dürig, J. Frommer , and C. J. Hawker, Adv. Funct. Mater. 16, 1499 2006. 14 S. Bakbak, P. J. Leech, B. E. Carson, S...2006. [36] B. Gotsmann, U. Dürig, J. Frommer , and C. J. Hawker, “Exploiting chemical switching in a Diels-Alder polymer for nanoscale probe litho

  4. Printed Biopolymer-Based Electro-Optic Device Components

    DTIC Science & Technology

    2013-07-01

    with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...S. Sariciftci, J. G. Grote, Adv Polym Sci. DOI:10.1007/12 2009 6 [6] J. G. Grote, D. E. Diggs, R. L. Nelson, J. S. Zetts, F. K. Hopkins, N. Ogata

  5. How I treat adenovirus in hematopoietic stem cell transplant recipients

    PubMed Central

    Lindemans, Caroline A.; Leen, Ann M.

    2010-01-01

    Adenovirus (AdV) infections are very common in the general pediatric population. The delayed clearance in young persons imposes a threat to immunocompromised patients after hematopoietic stem cell transplantation (HSCT), who can reactivate the virus, resulting in life-threatening disseminated disease. Although a definitive cure requires adequate immune reconstitution, 2 approaches appear to be feasible and effective to improve the outcomes of AdV infections. Strict monitoring with AdV quantitative polymerase chain reaction followed by preemptive treatment with low-dose (1 mg/kg) cidofovir 3 times a week, is effective in most cases to bridge the severely immunocompromised period shortly after HSCT, with acceptable toxicity rates. For centers who have the access, AdV-specific cytotoxic T cells can be the other important cornerstone of anti-AdV therapy with promising results so far. Methods to positively influence the reconstitution of the immune system after HSCT and optimizing new and currently available cellular immunotherapies will make HSCT safer against the threat of AdV infection/reactivation and associated disease. PMID:20837781

  6. [Development of immunoenzyme methods for detecting antibodies to Aujeszky's disease virus gB glycoprotein in swine serum].

    PubMed

    Morenkov, O S

    2000-01-01

    Four ELISA methods have been developed for detecting antibodies to Aujeszky's disease virus (ADV) glycoprotein gB. Indirect ELISA is based on affinity-purified gB (affi-gB-ELISA); three blocking ELISAs: indirect blocking ELISA (lbgB-ELISA), direct blocking ELISA (db-gB-ELISA), and two-site "sandwich" ELISA (sb-gB-ELISA) are based on monoclonal antibodies to conservative immunodominant epitopes of gB. The specificities and sensitivities of ELISAs were compared with each other and with indirect ELISA based on purified ADV virions (vir-ELISA). Affi-gB ELISA, db-gB-ELISA, and sb-gB-ELISA possess 100% sensitivity, ib-gB-ELISA 98% sensitivity, and vir-ELISA 93% sensitivity. Affi-gB ELISA, ib-gB-ELISA, db-gB-ELISA, and sb-gB-ELISA possess 100% specificity and vir-ELISA 92% specificity. The efficiency of detection of ADV-specific antibodies by affi-gB ELISA, db-gB-ELISA, and sb-gB-ELISA was comparable to that of analogous commercial test. Since db-gB-ELISA is easier to perform than affi-gB-ELISA or sb-gB-ELISA, it is concluded to be the most appropriate test for detecting pigs infected with ADV among non-vaccinated animals.

  7. MICRO DOSE ASESSMENT OF INHALED PARTICLES IN HUMAN LUNGS: A STEP CLOSER TOWARDS THE TARGET TISSUE DOSE

    EPA Science Inventory

    Rationale: Inhaled particles deposit inhomogeneously in the lung and this may result in excessive deposition dose at local regions of the lung, particularly at the anatomic sites of bifurcations and junctions of the airways, which in turn leads to injuries to the tissues and adve...

  8. MICRO DOSE ASESSMENT OF INHALED PARTICLES IN HUMAN LUNGS: A STEP CLOSER TOWARDS THE TARGET TISSUE DOSE

    EPA Science Inventory

    Rationale: Inhaled particles deposit inhomogeneously in the lung and this may result in excessive deposition dose at local regions of the lung, particularly at the anatomic sites of bifurcations and junctions of the airways, which in turn leads to injuries to the tissues and adve...

  9. Effects of viscosity on endothelial cell damage under acoustic droplet vaporization

    NASA Astrophysics Data System (ADS)

    Seda, Robinson; Singh, Rahul; Li, David; Pitre, John; Putnam, Andrew; Fowlkes, J. Brian; Bull, Joseph

    2014-11-01

    Acoustic droplet vaporization (ADV) is a process by which stabilized superheated microdroplets are able to undergo phase transition with the aid of focused ultrasound. Gas bubbles resulting from ADV can provide local occlusion of the blood vessels supplying diseased tissue, such as tumors. The ADV process can also induce bioeffects that increase vessel permeability, which is beneficial for localized drug delivery. Previous in vitro studies have demonstrated that vaporization at the endothelial layer will affect cell attachment and viability. Several hypotheses have been proposed to elucidate the mechanism of damage including the generation of normal and shear stresses during bubble expansion. A single 3.5 MHz ultrasound pulse consisting of 8 cycles (~2.3 μs) and a 6 MPa peak rarefactional pressure was used to induce ADV on endothelial cells in media of different viscosities. Carboxylmethyl cellulose was added to the cell media to increase the viscosity up to 300 cP to and aid in the reduction of stresses during bubble expansion. The likelihood of cell damage was decreased when compared to our control (~1 cP), but it was still present in some cases indicating that the mechanism of damage does not depend entirely on viscous stresses associated with bubble expansion. This work was supported by NIH Grant R01EB006476.

  10. Biomimetic Nanosensor Arrays for Selective Small Molecule Detection

    DTIC Science & Technology

    2012-02-21

    Tooth Enamel .” Nat. Commun. Under Revision (2012). 6. H. Tao, M. A. Brenckle, M. Yang, J. Zhang, M. Liu, S. M. Siebert, R. D. Averitt, M. S. Mannoor...M. C. McAlpine, J. A. Rogers, D. L. Kaplan, F. G. Omenetto. “Silk-based Conformal, Adhesive , Edible Food Sensors.” Adv. Mater. In Press (2012). 5

  11. Bionanomaterials and Bioinspired Nanostructures for Selective Vapor Sensing

    DTIC Science & Technology

    2013-04-03

    Clayton JD, Sengupta A,KaplanDL, et al. 2012.Graphene-basedwireless bacteria detection on tooth enamel . Nat. Commun. 3:1767 115. Khamis SM, Jones RA...Silk-based conformal, adhesive , edible food sensors. Adv. Mater. 24:1067–72 159. Potyrailo RA,Nagraj N, Tang Z,Mondello FJ, SurmanC,MorrisW. 2012

  12. Induction of Olefin Metathesis by Acetylenes.

    DTIC Science & Technology

    1980-11-20

    essentially that of 2. The acetylene is thus an activator, but unlike the organometallic co- catalysts like C2 H5A1C1 2 , which it replaces, it is unique in...J.C.; Moulijn, J.A. Adv. Catal. 1975, 24, 131. (4) Some of the results were discussed at the 3rd NSF Workshop on Organo - metallic Chemistry, Pingree

  13. Mineralogy of Antarctica Dry Valley Soils: Implications for Pedogenic Processes on Mars

    NASA Technical Reports Server (NTRS)

    Quinn, J. E.; Ming, D. W.; Morris, R. V.; Douglas, S.; Kounaves, S. P.; McKay, C. P.; Tamppari, L, K.; Smith, P. H.; Zent, A. P.; Archer, P. D., Jr.

    2010-01-01

    The Antarctic Dry Valleys (ADVs) located in the Transantarctic Mountains are the coldest and driest locations on Earth. The mean annual air temperature is -20 C or less and the ADVs receive 100mm or less of precipitation annually in the form of snow. The cold and dry climate in the ADVs is one of the best terrestrial analogs for the climatic conditions on Mars [2]. The soils in the ADVs have been categorized into three soil moisture zones: subxerous, xerous and ultraxerous. The subxerous zone is a coastal region in which soils have ice-cemented permafrost relatively close to the surface. Moisture is available in relatively large amounts and soil temperatures are above freezing throughout the soil profile (above ice permafrost) in summer months. The xerous zone, the most widespread of the three zones, is an inland region with a climate midway between the subxerous and ultraxerous. The soils from this zone have dry permafrost at moderate depths (30-75cm) but have sufficient water in the upper soil horizons to allow leaching of soluble materials. The ultraxerous zone is a high elevation zone, where both temperature and precipitation amounts are very low resulting in dry permafrost throughout the soil profile. The three moisture regime regions are similar to the three microclimatic zones (coastal thaw, inland mixed, stable upland) defined by Marchant and Head.

  14. Animal Studies of Life Shortening and Cancer Risk from Space Radiation

    DTIC Science & Technology

    1986-01-01

    105 REM 52 REM 18 REM YEARLY 75 REM 225 REM 112 REM 38 REM CAN99R 400 am 1200 REM 600 WPI 200 REM Recently, the NCRP has Suggested that the reference...Sinclair, Adv. Space Res. 3, #8, 151 (1983) 15. National Research Council, Report of the Committee on the Biological Effects of Ionizing Radiation

  15. Peer Influences on the Dating Aggression Process among Brazilian Street Youth: A Brief Report

    ERIC Educational Resources Information Center

    Antonio, Tiago; Koller, Silvia H.; Hokoda, Audrey

    2012-01-01

    This study explored risk factors for adolescent dating aggression (ADA) among Brazilian street youth. Forty-three adolescents, between the ages of 13 and 17 years, were recruited at services centers in Porto Alegre, Brazil. Simultaneous multiple regression revealed that ADA was significantly predicted by adolescent dating victimization (ADV), and…

  16. Experimental Design for Evaluating Selected Nondestructive Measurement Technologies - Advanced Reactor Technology Milestone: M3AT-16PN2301043

    SciTech Connect

    Ramuhalli, Pradeep; Hirt, Evelyn H.; Pitman, Stan G.; Dib, Gerges; Roy, Surajit; Good, Morris S.; Walker, Cody M.

    2016-07-16

    The harsh environments in advanced reactors (AdvRx) increase the possibility of degradation of safety-critical passive components, and therefore pose a particular challenge for deployment and extended operation of these concepts. Nondestructive evaluation technologies are an essential element for obtaining information on passive component condition in AdvRx, with the development of sensor technologies for nondestructively inspecting AdvRx passive components identified as a key need. Given the challenges posed by AdvRx environments and the potential needs for reducing the burden posed by periodic in-service inspection of hard-to-access and hard-to-replace components, a viable solution may be provided by online condition monitoring of components. This report identifies the key challenges that will need to be overcome for sensor development in this context, and documents an experimental plan for sensor development, test, and evaluation. The focus of initial research and development is on sodium fast reactors, with the eventual goal of the research being developing the necessary sensor technology, quantifying sensor survivability and long-term measurement reliability for nondestructively inspecting critical components. Materials for sensor development that are likely to withstand the harsh environments are described, along with a status on the fabrication of reference specimens, and the planned approach for design and evaluation of the sensor and measurement technology.

  17. 17 CFR 275.203-1 - Application for investment adviser registration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... registration after January 1, 2011, you must file a brochure(s) that satisfies the requirements of Part 2A of...)) on July 20, 2011, you are exempt from registration with the Commission as an investment adviser until...: For Federal Register citations affecting Form ADV, see the List of CFR Sections Affected, which...

  18. Operator identities involving the bivariate Rogers-Szegö polynomials and their applications to the multiple q-series identities

    NASA Astrophysics Data System (ADS)

    Zhang, Zhizheng; Wang, Tianze

    2008-07-01

    In this paper, we first give several operator identities involving the bivariate Rogers-Szegö polynomials. By applying the technique of parameter augmentation to the multiple q-binomial theorems given by Milne [S.C. Milne, Balanced summation theorems for U(n) basic hypergeometric series, AdvE Math. 131 (1997) 93-187], we obtain several new multiple q-series identities involving the bivariate Rogers-Szegö polynomials. These include multiple extensions of Mehler's formula and Rogers's formula. Our U(n+1) generalizations are quite natural as they are also a direct and immediate consequence of their (often classical) known one-variable cases and Milne's fundamental theorem for An or U(n+1) basic hypergeometric series in Theorem 1E49 of [S.C. Milne, An elementary proof of the Macdonald identities for , Adv. Math. 57 (1985) 34-70], as rewritten in Lemma 7.3 on p. 163 of [S.C. Milne, Balanced summation theorems for U(n) basic hypergeometric series, Adv. Math. 131 (1997) 93-187] or Corollary 4.4 on pp. 768-769 of [S.C. Milne, M. Schlosser, A new An extension of Ramanujan's summation with applications to multilateral An series, Rocky Mountain J. Math. 32 (2002) 759-792].

  19. Information Processing, Specificity of Practice, and the Transfer of Learning: Considerations for Reconsidering Fidelity

    ERIC Educational Resources Information Center

    Grierson, Lawrence E. M.

    2014-01-01

    Much has been made in the recent medical education literature of the incorrect characterization of simulation along a continuum of low to high fidelity (Cook et al. "JAMA" 306(9): 978-988, 2011; Norman et al. "Med Educ" 46(7): 636-647, 2012; Teteris et al. "Adv Health Sci Educ" 17(1): 137-144, 2012). For the most…

  20. Polyfluoroalkyl Chemicals in the Serum and Milk of Breastfeeding Women.

    EPA Science Inventory

    Polyfluoroalkyl chemicals (PFCs) comprise a group of man-made organic compounds, some of which are persistent contaminants with developmental toxicity shown in laboratory animals. There is a paucity of human perinatal exposure data. The US EPA conducted a pilot study (Methods Adv...

  1. The Kidney and Acid-Base Regulation

    ERIC Educational Resources Information Center

    Koeppen, Bruce M.

    2009-01-01

    Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these…

  2. Realization of New and Enhanced Materials Properties Through Nanostructural Control

    DTIC Science & Technology

    2006-05-15

    Fifield, L. R. Dalton, A. Mazzoldi, D. De-Rossi, I. I. Khayrullin , and R. H. Baughman, "Pneumatic Carbon Nanotube Actuators," Adv. Mater., 14, 1728-32 (2002... Khayrullin , and B. H. Baughman, "Pneumatic Actuator Response from Carbon Nanotube Sheets," Materials Research Society Symposium Proceedings, v. 706

  3. The transduction of Coxsackie and Adenovirus Receptor-negative cells and protection against neutralizing antibodies by HPMA-co-oligolysine copolymer-coated adenovirus

    PubMed Central

    Wang, Chung-Huei K.; Chan, Leslie W.; Johnson, Russell N.; Chu, David S.H.; Shi, Julie; Schellinger, Joan G.; Lieber, Andre; Pun, Suzie H.

    2011-01-01

    Adenoviral (AdV) gene vectors offer efficient nucleic acid transfer into both dividing and non-dividing cells. However issues such as vector immunogenicity, toxicity and restricted transduction to receptor-expressing cells have prevented broad clinical translation of these constructs. To address this issue, engineered AdV have been prepared by both genetic and chemical manipulation. In this work, a polymer-coated Ad5 formulation is optimized by evaluating a series of N-(2-hydroxypropyl) methacrylamide (HPMA)-co-oligolysine copolymers synthesized by living polymerization techniques. This synthesis approach was used to generate highly controlled and well-defined polymers with varying peptide length (K5, K10 and K15), polymer molecular weight, and degradability to coat the viral capsid. The optimal formulation was not affected by the presence of serum during transduction and significantly increased Ad5 transduction of several cell types that lack the Coxsackie and Adenovirus Receptor (CAR) by up to 6-fold compared to unmodified AdV. Polymer-coated Ad5 also retained high transduction capability in the presence of Ad5 neutralizing antibodies. The critical role of heparan sulfate proteoglycans (HSPGs) in mediating cell binding and internalization of polymer-coated AdV was also demonstrated by evaluating transduction in HSPG-defective recombinant CHO cells. The formulations developed here are attractive vectors for ex vivo gene transfer in applications such as cell therapy. In addition, this platform for adenoviral modification allows for facile introduction of alternative targeting ligands. PMID:21959008

  4. Peer Influences on the Dating Aggression Process among Brazilian Street Youth: A Brief Report

    ERIC Educational Resources Information Center

    Antonio, Tiago; Koller, Silvia H.; Hokoda, Audrey

    2012-01-01

    This study explored risk factors for adolescent dating aggression (ADA) among Brazilian street youth. Forty-three adolescents, between the ages of 13 and 17 years, were recruited at services centers in Porto Alegre, Brazil. Simultaneous multiple regression revealed that ADA was significantly predicted by adolescent dating victimization (ADV), and…

  5. Enhanced Oxidation and Solvolysis Reactions in Chemically Inert Microheterogeneous Systems.

    DTIC Science & Technology

    1987-01-13

    Mackay, Adv.Coll.Interf.Sc{. 15, 131 (1981) 11 C. Bodea and J. Silberg, "Recent Advances in the Chemistry of Phenothiazines" in "Advances in Heterocyclic ... Chemistry ", A.R. Katritzky and A.J. Boulton, , eds., Vol. 9, Academic Press, New York, 1968, p. 321 12 A.M. Braun, M.-A. Gilson, M. Krieg, M.-T

  6. 78 FR 25101 - Proposal Review Panel for Physics, Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ... Proposal Review Panel for Physics, Notice of Meeting In accordance with the Federal Advisory Committee Act...: AdvLIGO Construction Review Site Visit at Livingston Observatory for Physics, 1208 Date and Time.... Contact Person: Mark Coles, Director of Large Facilities, Division of Physics, National Science Foundation...

  7. 76 FR 20412 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-12

    ... daily volume (as such term is defined in Endnote 3 of the Fee Schedule, ``Liquidity Adding ADV'') is less than 20 basis points of Total Consolidated Average Daily Volume (as defined in Endnote 13 of the... with Endnote 8), and NSX Rule 16.4 would be deleted in its entirety. \\5\\ NSX Rule 16.4(b). To...

  8. ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

    EPA Science Inventory

    Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

  9. AGARD Engine Disc Cooperative Test Programme, Addendum, (Rapport sur le Programme d’Essais Commun des DIsques Moteur (Supplement)

    DTIC Science & Technology

    1993-04-01

    DTC aims to exploit in scriice.Apart from economic adv-antages, the DTC approach offers a practical. method for usinge modern high-strength disc...Engine Disc Cooperative Test Programme 1-1 1w- .N. Raienne Cnhaper 2 Part I Fractograpliic and Microstructural Anal)sis of Fatigue Crack 2-1 Grouth in Ti

  10. Enhancing Active Learning in the Student Laboratory

    ERIC Educational Resources Information Center

    Modell, Harold I.; Michael, Joel A.; Adamson, Tom; Horwitz, Barbara

    2004-01-01

    We previously examined how three approaches to directing students in a laboratory setting impacted their ability to repair a faulty mental model in respiratory physiology (Modell, HI, Michael JA, Adamson T, Goldberg J, Horwitz BA, Bruce DS, Hudson ML, Whitescarver SA, and Williams S. Adv Physiol Educ 23: 82?90, 2000). This study addresses issues…

  11. Visualization of dietary patterns and their associations with age-related macular degeneration

    USDA-ARS?s Scientific Manuscript database

    PURPOSE: We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. METHODS: A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n=2739), early AMD (n=4599), and adv...

  12. ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

    EPA Science Inventory

    Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

  13. DEVELOPING AZO AND FORMAZAN DYES BASED ON ENVIRONMENTAL CONSIDERATIONS: SALMONELLA MUTAGENICITY

    EPA Science Inventory

    Abstract
    In previous papers, the synthesis and chemical properties of iron-complexed azo and formazan dyes were reported. In this regard, it was shown that in certain cases iron could be substituted for the traditionally used metals, chromium and cobalt, without having an adve...

  14. Random Sampling of Squamate Reptiles in Spanish Natural Reserves Reveals the Presence of Novel Adenoviruses in Lacertids (Family Lacertidae) and Worm Lizards (Amphisbaenia)

    PubMed Central

    Szirovicza, Leonóra; López, Pilar; Kopena, Renáta; Benkő, Mária; Martín, José; Pénzes, Judit J.

    2016-01-01

    Here, we report the results of a large-scale PCR survey on the prevalence and diversity of adenoviruses (AdVs) in samples collected randomly from free-living reptiles. On the territories of the Guadarrama Mountains National Park in Central Spain and of the Chafarinas Islands in North Africa, cloacal swabs were taken from 318 specimens of eight native species representing five squamate reptilian families. The healthy-looking animals had been captured temporarily for physiological and ethological examinations, after which they were released. We found 22 AdV-positive samples in representatives of three species, all from Central Spain. Sequence analysis of the PCR products revealed the existence of three hitherto unknown AdVs in 11 Carpetane rock lizards (Iberolacerta cyreni), nine Iberian worm lizards (Blanus cinereus), and two Iberian green lizards (Lacerta schreiberi), respectively. Phylogeny inference showed every novel putative virus to be a member of the genus Atadenovirus. This is the very first description of the occurrence of AdVs in amphisbaenian and lacertid hosts. Unlike all squamate atadenoviruses examined previously, two of the novel putative AdVs had A+T rich DNA, a feature generally deemed to mirror previous host switch events. Our results shed new light on the diversity and evolution of atadenoviruses. PMID:27399970

  15. Department of Defense Chemical and Biological Defense Programs: DoD Advance Planning Briefing for Industry

    DTIC Science & Technology

    2013-05-16

    Tech Development - Adv Dev for CB Prep at Univ of Med & Dentistry of NJ - Miniaturization of CB Detectors - Biodefense Statewide Med Response - Bio...aerobiolgoical research, forensic genomics and certified forensic biological threat agent capability 28 Biological Defense Homeland Security Support Program

  16. Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

    PubMed Central

    Fabiilli, Mario L.; Wilson, Christopher G.; Padilla, Frédéric; Martín-Saavedra, Francisco M.; Fowlkes, J. Brian; Franceschi, Renny T.

    2013-01-01

    Wound healing is regulated by temporally and spatially restricted patterns of growth factor signaling, but there are few delivery vehicles capable of the “on-demand” release necessary for recapitulating these patterns. Recently we described a perfluorocarbon double emulsion that selectively releases a protein payload upon exposure to ultrasound through a process known as acoustic droplet vaporization (ADV). In this study, we describe a delivery system composed of fibrin hydrogels doped with growth factor-loaded double emulsion for applications in tissue regeneration. Release of immunoreactive basic fibroblast growth factor (bFGF) from the composites increased up to 5-fold following ADV and delayed release was achieved by delaying exposure to ultrasound. Releasates of ultrasound-treated materials significantly increased the proliferation of endothelial cells compared to sham controls, indicating that the released bFGF was bioactive. ADV also triggered changes in the ultrastructure and mechanical properties of the fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated composites were accompanied by up to a 22-fold increase in shear stiffness. ADV did not reduce the viability of cells suspended in composite scaffolds. These results demonstrate that an acoustic droplet–hydrogel composite could have broad utility in promoting wound healing through on-demand control of growth factor release and/or scaffold architecture. PMID:23535233

  17. The Relationship between Preservice Early Childhood Teachers' Cultural Values and Their Perceptions of Scientists' Cultural Values

    ERIC Educational Resources Information Center

    Akerson, Valarie L.; Buzzelli, Cary A.; Eastwood, Jennifer

    2010-01-01

    This paper describes research that compares preservice early childhood teachers' cultural values and the values they believe are held by scientists. Using the Schwartz Values Inventory (SVI) (Schwartz (1992) "Adv Exp Soc Psychol" 25:331-351) preservice early childhood teachers cultural values were assessed, followed by an assessment of…

  18. The Phagocyte Function during Multifactorial Military Stress and Neuroendocrine Interactions with Phagocytes

    DTIC Science & Technology

    2001-03-01

    to the effects of catecholamines and cortisol (Loeper and Crouzon 1904, Bishop et al. 1968, Weicker and Werle 1991, Hack et al. 1992, Gabriel et al...prolonged physical exercise. Adv Exper Med Biol 240: 57-63 Loeper M, Crouzon 0 (1904) L’action de l’adrdnaline sur le sang. Arch Med Exp Anat Path 18

  19. The Effects of Elevated pCO2, Hypoxia and Temperature on Larval Sheepshead minnow, Cyprinodon variegatus: How much stress is too much?

    EPA Science Inventory

    Estuarine fish are acclimated to living in an environment with rapid and frequent changes in temperature, salinity, pH, and dissolved oxygen (DO) levels; the physiology of these organisms is well suited to cope with extreme thermal, hypercapnic, and hypoxic stress. While the adve...

  20. Comparative Evaluation of Viability Assays for Storage of Ornamental Giner (Hedychium spp.) Pollen

    USDA-ARS?s Scientific Manuscript database

    In the United States, Hedychium plants are mostly grown in the southern part of the country where they generally flower in the summer and fall, but some species bloom in winter and spring times. This asynchronous flowering could constitute an impediment for breeders of that region to fully take adv...

  1. High Performance Biocomputation

    DTIC Science & Technology

    2005-03-01

    13] R. Elber, A. Ghosh, A. Cardenas , and H. Stern. Bridging the gap between reaction pathways, long time dynamics and calculation of rates. Adv. Chem...Research Ms. Nancy Forbes Code 31 Homeland Security Institute 800 North Quincy Street Threats Division Arlington, VA 22217-5660 2900 N. Quincy St

  2. Logic Nanocells Within 3-Terminal Ordered Arrays

    DTIC Science & Technology

    2007-02-28

    Seminario , J. M.; Araujo, R. A.; Yan, L. J. Phys. Chem. B 2004, 108, 6915-6918. (3) Reed, M. A.; Lee, T. Molecular Nanoelectronics, American Scientific...Reliab. 2002, 42, 583-596. (31) Cahen, D.; Naaman, R.; Vager, Z. Adv. Funct. Mater. 2005, 15,1571-1578. (32) Seminario , J. M.; Yan, L.; Ma, Y. Proc. IEEE

  3. Providing Assistance to the Victims of Adolescent Dating Violence: A National Assessment of School Nurses' Practices

    ERIC Educational Resources Information Center

    Khubchandani, Jagdish; Telljohann, Susan K.; Price, James H.; Dake, Joseph A.; Hendershot, Candace

    2013-01-01

    Background: This study assessed the perceptions and practices of school nurses regarding adolescent dating violence (ADV). Methods: The membership list of the National Association of School Nurses was used to identify a national random cross-sectional sample of high school nurses in the United States (N?=?750). A valid and reliable survey…

  4. Solar Drivers of 11-yr and Long-Term Cosmic Ray Modulation (PostPrint)

    DTIC Science & Technology

    2012-03-06

    largely reproduce the observed GCR intensity for the past ∼35 years. The failure to do so during cycle 20 appears to be a relatively rare occurrence. Fig... Terr . Phys. 70, 207 (2008) M.S. Potgieter, Adv. Space Res. 46, 402 (2010) M.S. Potgieter, J.A. Le Roux, Astrophys. J. 423, 817 (1994) M.S. Potgieter

  5. MODELS-3 COMMUNITY MULTISCALE AIR QUALITY (CMAQ) MODEL AEROSOL COMPONENT 2. MODEL EVALUATION

    EPA Science Inventory

    Ambient air concentrations of particulate matter (atmospheric suspensions of solid of liquid materials, i.e., aerosols) continue to be a major concern for the U.S. Environmental Protection Agency (EPA). High particulate matter (PM) concentrations are associated not only with adv...

  6. PROCESS TRANSFER FUNCTIONS TO RELATE STREAM ECOLOGICAL CONDITION METRICS TO NITRATE RETENTION

    EPA Science Inventory

    Ecologists have developed hydrological metrics to characterize the nutrient processing capability of streams. In most cases these are used qualitatively to draw inferences on ecological function. In this work, several of these metrics have been integrated in a nonsteady state adv...

  7. 75 FR 3513 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-21

    ... impact. \\9\\ For the $1 Strike Program delisting policy, see Securities Exchange Act Release No. 59588... effectiveness). The $1 Strike Program delisting policy includes a provision stating that the Exchange may grant... program); and Chapter IV Section 4(l) (low ADV delisting policy) and Securities Exchange Act Release No...

  8. The Relationship between Preservice Early Childhood Teachers' Cultural Values and Their Perceptions of Scientists' Cultural Values

    ERIC Educational Resources Information Center

    Akerson, Valarie L.; Buzzelli, Cary A.; Eastwood, Jennifer

    2010-01-01

    This paper describes research that compares preservice early childhood teachers' cultural values and the values they believe are held by scientists. Using the Schwartz Values Inventory (SVI) (Schwartz (1992) "Adv Exp Soc Psychol" 25:331-351) preservice early childhood teachers cultural values were assessed, followed by an assessment of…

  9. Occurrence of Bacterial and Viral Pathogens in Common and Noninvasive Diagnostic Sampling from Parrots and Racing Pigeons in Slovenia.

    PubMed

    Dovč, Alenka; Jereb, Gregor; Krapež, Uroš; Gregurić-Gračner, Gordana; Pintarič, Štefan; Slavec, Brigita; Knific, Renata Lindtner; Kastelic, Marjan; Kvapil, Pavel; Mićunović, Jasna; Vadnjal, Stanka; Ocepek, Matjaž; Zadravec, Marko; Zorman-Rojs, Olga

    2016-06-01

    Airborne pathogens can cause infections within parrot (Psittaciformes) and pigeon (Columbiformes) holdings and, in the case of zoonoses, can even spread to humans. Air sampling is a useful, noninvasive method which can enhance the common sampling methods for detection of microorganisms in bird flocks. In this study, fecal and air samples were taken from four parrot holdings. Additionally, cloacal and oropharyngeal swabs as well as air samples were taken from 15 racing pigeon holdings. Parrots were examined for psittacine beak and feather disease virus (PBFDV), proventricular dilatation disease virus (PDDV), adenoviruses (AdVs), avian paramyxovirus type-1 (APMV-1), avian influenza virus (AIV), Chlamydia psittaci (CP), and Mycobacterium avium complex (MAC). MAC and AdVs were detected in three parrot holdings, CP was detected in two parrot holdings, and PBFDV and PDDV were each detected in one parrot holding. Pigeons were examined for the pigeon circovirus (PiCV), AdVs, and CP; PiCV and AdVs were detected in all investigated pigeon holdings and CP was detected in five pigeon holdings.

  10. MODELS-3 COMMUNITY MULTISCALE AIR QUALITY (CMAQ) MODEL AEROSOL COMPONENT 2. MODEL EVALUATION

    EPA Science Inventory

    Ambient air concentrations of particulate matter (atmospheric suspensions of solid of liquid materials, i.e., aerosols) continue to be a major concern for the U.S. Environmental Protection Agency (EPA). High particulate matter (PM) concentrations are associated not only with adv...

  11. 10. PHOTOCOPY OF PHOTOGRAPH: WEST FRONT AT NIGHT, Date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. PHOTOCOPY OF PHOTOGRAPH: WEST FRONT AT NIGHT, Date unknown. from FOURTH CHURCH OF CHRIST, SCIENTIST ARCHIVE (used with permission) E. S. Cheney and R. B. Bird, Photographers Cheney Photo Adv. Co., Oakland, California - Fourth Church of Christ, Scientist, 1330 Lakeshore Avenue, Oakland, Alameda County, CA

  12. 14. PHOTOCOPY OF PHOTOGRAPH: DOMED CEILING OF AUDITORIUM, Date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. PHOTOCOPY OF PHOTOGRAPH: DOMED CEILING OF AUDITORIUM, Date unknown. from FOURTH CHURCH OF CHRIST, SCIENTIST ARCHIVE (used with permission) E. S. Cheney and R. B. Bird, Photographers, Cheney Photo Adv. Co., Oakland, California. - Fourth Church of Christ, Scientist, 1330 Lakeshore Avenue, Oakland, Alameda County, CA

  13. 13. PHOTOCOPY OF PHOTOGRAPH: AUDITORIUM, LOOKING WEST TOWARD BALCONY AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. PHOTOCOPY OF PHOTOGRAPH: AUDITORIUM, LOOKING WEST TOWARD BALCONY AND FOYER, Date unknown. from FOURTH CHURCH OF CHRIST, SCIENTIST ARCHIVE (used with permission) E. S. Cheney and R. B. Bird, Photographers, Cheney Photo Adv. Co., Oakland, California - Fourth Church of Christ, Scientist, 1330 Lakeshore Avenue, Oakland, Alameda County, CA

  14. Practical Photonic Bandgap Calculations using MPB

    DTIC Science & Technology

    2013-02-22

    R. Soc. Interface, doi: 10.1098/ rsif.2011.0730, 2011. Distribution A 19 14. Galusha, J.W., Richey, L.R., Gardner, J.S., Cha, J.N. and Bartl ...J.W., Jorgensen, M.R. and Bartl , M.H., “Diamond-structured titania photonic- bandgap crystals from biological templates”, Adv. Materials, Vol. 22

  15. The Kidney and Acid-Base Regulation

    ERIC Educational Resources Information Center

    Koeppen, Bruce M.

    2009-01-01

    Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these…

  16. Complete Genome Sequence of Human Adenovirus 7 Associated with Fatal Adult Pneumonia.

    PubMed

    Yatsyshina, Svetlana B; Ageeva, Margarita R; Deviatkin, Andrey A; Pimkina, Ekaterina V; Markelov, Mikhail L; Dedkov, Vladimir G; Safonova, Marina V; Shumilina, Elena Y; Lukashev, Alexander N; Shipulin, German A

    2016-10-27

    Human adenovirus 7 (hAdv7) 19BOVLB/Volgograd/Rus/2014 was isolated from the autopsy material from an adult with fatal pneumonia in Volgograd, Russia, in March 2014. Whole-genome sequencing of the virus isolate was performed.

  17. Are endothelial cell bioeffects from acoustic droplet vaporization proximity dependent?

    NASA Astrophysics Data System (ADS)

    Seda, Robinson; Li, David; Fowlkes, J. Brian; Bull, Joseph

    2013-11-01

    Acoustic droplet vaporization (ADV) produces gas microbubbles that provide a means of selective occlusion in gas embolotherapy. Vaporization and subsequent occlusion occur inside blood vessels supplying the targeted tissue, such as tumors. Theoretical and computational studies showed that ADV within a vessel can impart high fluid mechanical stresses on the vessel wall. Previous in vitro studies have demonstrated that vaporization at an endothelial layer may affect cell attachment and viability. The current study is aimed at investigating the role of vaporization distance away from the endothelial layer. HUVECs were cultured in OptiCell™ chambers until reaching confluence. Dodecafluoropentane microdroplets were added, attaining a 10:1 droplet to cell ratio. A single ultrasound pulse (7.5 MHz) consisting of 16 cycles (~ 2 μs) and a 5 MPa peak rarefactional pressure was used to produce ADV while varying the vaporization distance from the endothelial layer (0 μm, 500 μm, 1000 μm). Results indicated that cell attachment and viability was significantly different if the distance was 0 μm (at the endothelial layer). Other distances were not significantly different from the control. ADV will significantly affect the endothelium if droplets are in direct contact with the cells. Droplet concentration and flow conditions inside blood vessels may play an important role. This work was supported by NIH grant R01EB006476.

  18. The Effects of Elevated pCO2, Hypoxia and Temperature on Larval Sheepshead minnow, Cyprinodon variegatus: How much stress is too much?

    EPA Science Inventory

    Estuarine fish are acclimated to living in an environment with rapid and frequent changes in temperature, salinity, pH, and dissolved oxygen (DO) levels; the physiology of these organisms is well suited to cope with extreme thermal, hypercapnic, and hypoxic stress. While the adve...

  19. DESTRUCTION OF PCBS USING SULFATE RADICAL-BASED ADVANCED OXIDATION PROCESSES

    EPA Science Inventory

    Polychlorinated biphenyls (PCBs) are a class of 209 congeners that were extensively used in industrial applications during 1929 to early 1970s, The presence of PCBs in the environment poses long-term risk to public health and wildlife due to their persistent and toxic nature. Adv...

  20. Transfected Cell Microarrays for the Expression of Membrane-Displayed Single-Chain Antibodies

    DTIC Science & Technology

    2011-01-01

    Appli- cations of single-chain variable fragment antibodies in therapeutics and diagnostics. Biotechnology Adv 27, 502–520. 6. Denzin , L. K...4-20. J Biol Chem 266, 14095–14103. Transfected Cell Microarrays 137 7. Denzin , L. K., Gulliver, G. A., Voss, E. W., Jr. (1993) Mutational analysis of

  1. Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-hour glucose and insulin excursions

    USDA-ARS?s Scientific Manuscript database

    It has been proposed that the adverse metabolic effects of chronic consumption of sugar-sweetened beverages which contain both glucose and fructose are a consequence of increased circulating glucose and insulin excursions, i.e dietary glycemic index (GI). Objective: We determined if the greater adv...

  2. Enhancing Active Learning in the Student Laboratory

    ERIC Educational Resources Information Center

    Modell, Harold I.; Michael, Joel A.; Adamson, Tom; Horwitz, Barbara

    2004-01-01

    We previously examined how three approaches to directing students in a laboratory setting impacted their ability to repair a faulty mental model in respiratory physiology (Modell, HI, Michael JA, Adamson T, Goldberg J, Horwitz BA, Bruce DS, Hudson ML, Whitescarver SA, and Williams S. Adv Physiol Educ 23: 82?90, 2000). This study addresses issues…

  3. EM Properties of High Tc Superconductors

    DTIC Science & Technology

    1992-06-01

    those calculated by Kes and van den Berg’ 9 for pinning 12A. M. CamDbell and J. Evetts, Adv. Phys. 21. 199 (1972). by twin boundaries . Our...consstet wih dnsey poulaed pnni 9~nter. ao ’J. Clem, in Proceedings of the International Conf’erence on pinning due to twin boundaries is Unlikely to be the

  4. DESTRUCTION OF PCBS USING SULFATE RADICAL-BASED ADVANCED OXIDATION PROCESSES

    EPA Science Inventory

    Polychlorinated biphenyls (PCBs) are a class of 209 congeners that were extensively used in industrial applications during 1929 to early 1970s, The presence of PCBs in the environment poses long-term risk to public health and wildlife due to their persistent and toxic nature. Adv...

  5. Polyfluoroalkyl Chemicals in the Serum and Milk of Breastfeeding Women.

    EPA Science Inventory

    Polyfluoroalkyl chemicals (PFCs) comprise a group of man-made organic compounds, some of which are persistent contaminants with developmental toxicity shown in laboratory animals. There is a paucity of human perinatal exposure data. The US EPA conducted a pilot study (Methods Adv...

  6. Quantum Model of Dephasing-Enhanced Laser Desorption: Master Equation Approach.

    DTIC Science & Technology

    1985-04-01

    York, 1973), Chapt. 6. 1B. S. H. Lin and H. Eyring , Proc. Natl. Acad. Sci. U.S.A. 78, 2013 (1978). 19. E. W. Montroll and K. E. Shuler, Adv. Chem. Phys...Department of Chemistry Thomas J. Watson Research Center Janes Franck Institute P.O. Box 218 5640 Ellis Avenue Yorktown Heights, New York 10598 Chicago

  7. 75 FR 28083 - Self-Regulatory Organizations; The Chicago Stock Exchange, Inc.; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... Effectiveness of Proposed Rule Change To Establish a Fixed Provide Credit for CHX-Registered Institutional... Schedule''), effective May 3, 2010, to establish a fixed provide credit for CHX-registered institutional... entitled to a fixed provide credit irrespective of its ADV for orders subject to the Agency Execution fees...

  8. Steric Control of Complex Chemical Reactions - 1

    DTIC Science & Technology

    2011-12-26

    their contrasting behaviors upon vibrational and translational excitations can serve as benchmark for gaining deeper insights into polyatomic reaction...equipped with a uniquely designed ion velocity map imaging detector capable of measuring the product pair correlation. The ultrafast femtosecond laser...From A + BC to Polyatomic Systems” K. Liu, Adv. in Chem. Phys. 149, (in press). Invited Review Invited talks at Conferences (* denoting

  9. PROCESS TRANSFER FUNCTIONS TO RELATE STREAM ECOLOGICAL CONDITION METRICS TO NITRATE RETENTION

    EPA Science Inventory

    Ecologists have developed hydrological metrics to characterize the nutrient processing capability of streams. In most cases these are used qualitatively to draw inferences on ecological function. In this work, several of these metrics have been integrated in a nonsteady state adv...

  10. Modeling of Finite Depth Wind Wave Dissipation

    DTIC Science & Technology

    2001-09-30

    source-sink energy balance. At Lake George, two different devices, the standard SonTek ADV and the Dopbeam ( Veron and Melville, 1999), were used to...for deep water waves. Part 1: Unforced irrotational wave groups. Submitted to JPO. Veron , F. and W.K. Melville, 1999. Pulse-to-pulse coherent

  11. Serology and protein electrophoresis for evidence of exposure to 12 mink pathogens in free-ranging American mink (Neovison vison) in Argentina.

    PubMed

    Martino, Pablo Eduardo; Samartino, Luis Ernesto; Stanchi, Néstor Oscar; Radman, Nilda Esther; Parrado, Eduardo Joaquín

    2017-12-01

    Basic pathologic characteristics for farmed minks were previously reported worldwide. However, its status in the wild has not been studied in detail. Serology and electrophoresis were carried out for evidence of exposure to 12 mink pathogens on two different locations. Serology was done in 87 wild minks by reference techniques against Toxoplasma gondii, Encephalitozoon cuniculi, Neospora caninum, Brucella abortus, Mycobacterium bovis, Leptospira interrogans, canine distemper virus (CDV), canine adenovirus (CAV), canine parvovirus (CPV), rabies virus (RV), Influenza A virus (FLUAV) and Aleutian disease virus (ADV). Hypergammaglobulinemia, the ADV main clinical feature, was determined by conventional electrophoresis. Seventy-one percent of the 87 sera had antibodies against one or more pathogens. ADV accounted for the highest seroprevalence (29%), followed by T. gondii (26%), L. interrogans (14%), M. bovis (12%), B. abortus (9%), N. caninum (3%), CPV (3%) and CDV (2%). Seroprevalence was influenced by location but not sex or age. Additionally, 16% of the seropositive samples for ADV had gammaglobulin levels >40.0 g/L. Antibody titers for CDV and CPV were low and difficult to interpret as almost all these cases had borderline concentrations. A cautious interpretation of the results is urged as the epidemiological role of the wild mink is largely unexplored for most of these agents. Nevertheless, the information may be clinically relevant..

  12. Likert and Guttman scaling of visual function rating scale questionnaires.

    PubMed

    Massof, Robert W

    2004-12-01

    To test the assumptions underlying Likert scoring of visual function questionnaires. Questionnaires were administered to 284 low-vision subjects by telephone. Each subject was administered two of four questionnaires: ADVS, NEI VFQ-25 plus supplement, expanded VAQ, and VF-14. Z-scores for cumulative frequency of using each rating category across subjects are not linear with rating category rank and items are not the same difficulty for any of the questionnaires. Guttmann coefficients of reproducibility ranged from 57% for the ADVS to 51% for the NEI VFQ-25. Cronbach alphas ranged from 0.92 for the VF-14 to 0.96 for the NEI VFQ; however, inter-item consistency coefficients ranged from 0.24 for the VAQ to 0.45 for the NEI VFQ. Likert scores were significantly correlated between instruments, ranging from 0.66 for NEI VFQ vs ADVS to 0.90 for the VF-14 vs. ADVS. The rating scales of all four questionnaires fail to satisfy Likert's assumptions. Also, ratings are probabilistic, rather than deterministic, which means that the Likert model is not valid for these questionnaires. However, Likert scores for all four instruments are intercorrelated, suggesting that they are monotonic with the latent subject trait distributed in the low vision sample.

  13. [Adenovirus infections in children: experience in the field of the allogeneic stem cell transplantation].

    PubMed

    Le Henaff, G; Corradini, N; Gras, C; Méchinaud, F

    2007-07-01

    Adenovirus (Adv) infections are frequent in pediatric patients, sometimes serious, above all in immunocompromised children. We report the cases of 2 children who presented an Adv infection after allogeneic stem cell transplantation (SCT). Case n(o) 1 concerns a boy who received SCT at the age of 6 years. He had a hemorragic cystitis, which resolved after antiviral treatment and successful engraftment. Case n(o) 2 concerns a boy who received SCT at the age of 2. He shortly presented a disseminated infection, and died in spite of antiviral treatment and re-infusion of an autologous transplant. T-cell depletion (mainly carried out in vivo at present) is the major risk factor of Adv infection after allogeneic SCT. It is important to be recognized, in order to proceed to a routine screening among transplanted patients. Moreover, the detection of viral genoma by molecular biology is a predictive factor of disseminated disease development, with mortality rates higher than 50%. Early treatment is thus crucial. Immunotherapy is to be developed, by tapering of immunosuppression, or by manipulating grafts and donor lymphocyte infusions, in order to improve Adv specific responses. The possibility of a prophylaxis is still to be investigated.

  14. Flex Biohybrid Nanomembranes as a Platform for Multifunctional Sensors

    DTIC Science & Technology

    2007-10-10

    central sensing layer via principles of biomineralization and exploring their ability to assemble into organized arrays in a fashion suitable for...fabricated and outstanding strength has been measured Examples of studies conducted Design on new functional materials for biomineralization of central...Singamaneni, V. V Tsukruk, Trilayered ceramic- metal -polymer microcantilevers with dramatically enhanced thermal sensitivity, Adv. Mater. 2006, 18

  15. A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by dsDNA Viruses

    ClinicalTrials.gov

    2013-08-28

    Male or Female Patients With a Serious or Immediately Life-threatening; Disease or Condition Caused by CMV, ADV, HSV, VAVC, VARV or; Monkeypox Viruses(s) Who Have a Life Expectancy of ≥ 2 Weeks and for; Whom no Comparable or Satisfactory Alternative Therapy is Available

  16. Controlled Stochastic Dynamical Systems

    DTIC Science & Technology

    2007-04-18

    the existence of value functions of two-player zero-sum stochastic differential games Indiana Univ. Math. Journal, 38 (1989), pp 293-314. [6] George ...control problems, Adv. Appl. Prob., 15, (1983) pp 225-254. [10] Karatzas, I. Ocone, D., Wang, H. and Zervos , M., Finite fuel singular control with

  17. Decontamination of a drinking water pipeline system contaminated with adenovirus and Escherichia coli utilizing peracetic acid and chlorine.

    PubMed

    Kauppinen, Ari; Ikonen, Jenni; Pursiainen, Anna; Pitkänen, Tarja; Miettinen, Ilkka T

    2012-09-01

    A contaminated drinking water distribution network can be responsible for major outbreaks of infections. In this study, two chemical decontaminants, peracetic acid (PAA) and chlorine, were used to test how a laboratory-scale pipeline system can be cleaned after simultaneous contamination with human adenovirus 40 (AdV40) and Escherichia coli. In addition, the effect of the decontaminants on biofilms was followed as heterotrophic plate counts (HPC) and total cell counts (TCC). Real-time quantitative polymerase chain reaction (qPCR) was used to determine AdV40 and plate counting was used to enumerate E. coli. PAA and chlorine proved to be effective decontaminants since they decreased the levels of AdV40 and E. coli to below method detection limits in both water and biofilms. However, without decontamination, AdV40 remained present in the pipelines for up to 4 days. In contrast, the concentration of cultivable E. coli decreased rapidly in the control pipelines, implying that E. coli may be an inadequate indicator for the presence of viral pathogens. Biofilms responded to the decontaminants by decreased HPCs while TCC remained stable. This indicates that the mechanism of pipeline decontamination by chlorine and PAA is inactivation rather than physical removal of microbes.

  18. Angiotensin type I receptor blockade in conjunction with enhanced Akt activation restores coronary collateral growth in the metabolic syndrome

    PubMed Central

    Jadhav, Rashmi; Dodd, Tracy; Smith, Erika; Bailey, Erin; DeLucia, Angelo L.; Russell, James C.; Madison, Rowan; Potter, Barry; Walsh, Kenneth; Jo, Hanjoong

    2011-01-01

    We have previously demonstrated that Akt was required for repetitive ischemia (RI)-induced coronary collateral growth (CCG) in healthy rats but was not activated by RI in the metabolic syndrome (JCR:LA-cp rats) where CCG was impaired. Here we hypothesized that failure of angiotensin type I receptor (AT1R) blockers to restore Akt activation is a key determinant of their inability to completely restore CCG in the metabolic syndrome. Therefore, we investigated whether adenovirus-mediated delivery of constitutively active Akt (MyrAkt-Adv) in conjunction with AT1R blockade (candesartan) was able to restore RI-induced CCG in JCR:LA-cp rats. Successful myocardial MyrAkt-Adv delivery was confirmed by a >80% transduction efficiency and an approximately fourfold increase in Akt expression and activation. CCG was assessed by myocardial blood flow measurements in the normal and collateral-dependent zones. MyrAkt-Adv alone significantly increased RI-induced CCG in JCR:LA-cp rats (∼30%), but it completely restored CCG in conjunction with administration of candesartan. In contrast, dominant negative Akt (DN-Akt-Adv) reversed the beneficial effect of candesartan on CCG in JCR:LA-cp rats. We conclude that optimal restoration of coronary collateral growth in JCR:LA-cp rats requires a combination of AT1R blockade with constitutive Akt activation. These findings may carry implications for metabolic syndrome patients in need of coronary revascularization. PMID:21335466

  19. Selecting a Benchmark Suite to Profile High-Performance Computing (HPC) Machines

    DTIC Science & Technology

    2014-11-01

    Performance Evaluation Corporation . Gainesville (VA): SPEC; c1995 [accessed 2014 Jun 2]. http://www.spec.org/. 16. Woo SC, Ohara M, Torrie E, Singh JP... communicatons systems. In Proceedings of the 30th Annual ACM/IEEE International Symposium on Microarchitecture; 1997, p. 330–335. 20. Li ML, Sasanka R, Adve

  20. Comparison between Sendai virus and adenovirus vectors to transduce HIV-1 genes into human dendritic cells.

    PubMed

    Hosoya, Noriaki; Miura, Toshiyuki; Kawana-Tachikawa, Ai; Koibuchi, Tomohiko; Shioda, Tatsuo; Odawara, Takashi; Nakamura, Tetsuya; Kitamura, Yoshihiro; Kano, Munehide; Kato, Atsushi; Hasegawa, Mamoru; Nagai, Yoshiyuki; Iwamoto, Aikichi

    2008-03-01

    Immuno-genetherapy using dendritic cells (DCs) can be applied to human immunodeficiency virus type 1 (HIV-1) infection. Sendai virus (SeV) has unique features such as cytoplasmic replication and high protein expression as a vector for genetic manipulation. In this study, we compared the efficiency of inducing green fluorescent protein (GFP) and HIV-1 gene expression in human monocyte-derived DCs between SeV and adenovirus (AdV). Human monocyte-derived DCs infected with SeV showed the maximum gene expression 24 hr after infection at a multiplicity of infection (MOI) of 2. Although SeV vector showed higher cytopathic effect on DCs than AdV, SeV vector induced maximum gene expression earlier and at much lower MOI. In terms of cell surface phenotype, both SeV and AdV vectors induced DC maturation. DCs infected with SeV as well as AdV elicited HIV-1 specific T-cell responses detected by interferon gamma (IFN-gamma) enzyme-linked immunospot (Elispot). Our data suggest that SeV could be one of the reliable vectors for immuno-genetherapy for HIV-1 infected patients.

  1. New Applications of Ionization and Fluorescence Techniques for Detection and Characterization of Open-Shell Organometallics in the Gas Phase

    DTIC Science & Technology

    1992-06-01

    112, 3668. 20. Poliakoff , M.; Weitz, E. Adv Organomet. Chem. 19 86, 25,277. 21. (a) Graham, M. A.; Perutz, R. N.; Poliakoff , M.; Turner, J. J. J...Perutz, R. N.; Turner, J. J. J. Am. Chem. Soc. 1975,97,4800. (e) Burdett, J. K.; Graham, M. A.; Perutz, R. N.; Poliakoff , M.; Turner, J. J.; Turner

  2. New Applications of Ionization and Fluorescence Techniques for Detecting and Characterization of Open-Shell Organometallics in the Gas Phase

    DTIC Science & Technology

    1992-06-01

    Poliakoff , M.; Weitz, E. Adv~ Organomet Chem. 19 86,25,277. 21. (a) Graham, M. A.; Perutz, R. N.; Poliakoff , M.; Turner, J. J. J. Organomet Chem. 1972,34...Turner, J. J. J. Am. Chem. Soc. 1975,97,4800. (e) Burdett, J. K.; Graham, M. A.; Perutz, R. N.; Poliakoff , M.; Turner, J. J.; Turner, R. F. J. Am. Chem

  3. Yes-No Question Patterns in Southern Min: Variation Across Some Dialects in Fujian.

    ERIC Educational Resources Information Center

    Crosland, Jeff

    1998-01-01

    Suggests that, in some Fujian Southern Min dialects, the patterns VP-neg and Adv-VP are mutually exclusive, presenting data from Xiamen to show recent innovations in the yes-no question pattern. Describes this innovation, explaining how the origin of the innovative patterns and limitations on their further development are influenced by…

  4. Information Processing, Specificity of Practice, and the Transfer of Learning: Considerations for Reconsidering Fidelity

    ERIC Educational Resources Information Center

    Grierson, Lawrence E. M.

    2014-01-01

    Much has been made in the recent medical education literature of the incorrect characterization of simulation along a continuum of low to high fidelity (Cook et al. "JAMA" 306(9): 978-988, 2011; Norman et al. "Med Educ" 46(7): 636-647, 2012; Teteris et al. "Adv Health Sci Educ" 17(1): 137-144, 2012). For the most…

  5. Deflections of Fast Coronal Mass Ejections and the Properties of Associated Solar Energetic Particle Events (POSTPRINT)

    DTIC Science & Technology

    2012-09-20

    36 flare sources lying outside a 15◦ radius of the sub-Earth point. The source flare PA (fPA) correlates with the observed MPA at CC = 0.47, well above...Univ. Press), 401 Cliver, E. W., et al. 2005, Proc. 29th Int. Cosmic Ray Conf., 1, 121 Cremades, H., Bothmer, V., & Tripathi, D. 2006, Adv. Space Res

  6. Providing Assistance to the Victims of Adolescent Dating Violence: A National Assessment of School Nurses' Practices

    ERIC Educational Resources Information Center

    Khubchandani, Jagdish; Telljohann, Susan K.; Price, James H.; Dake, Joseph A.; Hendershot, Candace

    2013-01-01

    Background: This study assessed the perceptions and practices of school nurses regarding adolescent dating violence (ADV). Methods: The membership list of the National Association of School Nurses was used to identify a national random cross-sectional sample of high school nurses in the United States (N?=?750). A valid and reliable survey…

  7. Event-Related Potentials Index Subclinical Neurological Differences in HIV Patients During Rapid Decision-Making

    DTIC Science & Technology

    1994-06-01

    Pashler H: Atentional limitations In doing two tasks at the same time. Current Directions in Psychological Science 1992, 1:44-48. 13. Donchin E...clinically evident CNS deficits . In P.M. Rossini and F. Mauguibre (Eds.), New Trends and Adv~anced Techniques in Clinical Neurophysiology 1990, EEG Suppl

  8. Electrostatic Effects on the Free-Energy Balance in Folding a Ribosome-Inactivating Protein

    DTIC Science & Technology

    2001-01-01

    Tidor , M. Karplus, Science 244 (1989) 1069. [24] B. Tidor , M. Karplus, Biochemistry 30 (1991) 3217. [25] T. Simonson, AT. Briinger...775. [30] Z.S. Hendsch, B. Tidor , Protein Sei. 3 (1994) 211. [31] B. Honig, A.S. Yang, Adv. Protein Chem. 46 (1995) 27. [32] J.K. Myers

  9. Tropical Cyclone Intensity and Structure: Improved Understanding and Prediction. Evaluation of Existing and Development of New Techniques for Global and Mesoscale NWP Model Assessment

    DTIC Science & Technology

    2003-09-30

    published, refereed] 6 Leslie, LM, MS Speer,and L Qi, (2003) Prediction of Extreme Rainfall for the Coffs Harbour Catchment. Aust. Meteor. Mag...Adv. Space Res.,30, 2479-2486. [published, refereed] Shao, Y, E Jung and LM Leslie (2002): Numerical prediction of northeast Asian dust storms using

  10. 77 FR 1769 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... because they are open to all SLPs on an equal basis and provide incentives that are reasonably related to... liquidity requirement to the percent of consolidated ADV for each individual security will reward SLPs for... incentive to add liquidity across more securities, including less active securities where there may be fewer...

  11. An Energy Gap for Complex Yang-Mills Equations

    NASA Astrophysics Data System (ADS)

    Huang, Teng

    2017-08-01

    We use the energy gap result of pure Yang-Mills equation [Feehan P.M.N., Adv. Math. 312 (2017), 547-587] to prove another energy gap result of complex Yang-Mills equations [Gagliardo M., Uhlenbeck K., J. Fixed Point Theory Appl. 11 (2012), 185-198], when Riemannian manifold X of dimension n≥ 2 satisfies certain conditions.

  12. 78 FR 75644 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... Average Daily Volume Calculations Any Trading Day on Which the Exchange Is Closed for Trading Due To an... the average daily volume calculation for any trading day on which the Exchange is closed for trading... daily volume (``ADV'') calculation for any trading day on which the Exchange is closed for trading...

  13. Comparison of the Phoenix Mars Lander WCL soil analyses with Antarctic Dry Valley soils, Mars meteorite EETA79001 sawdust, and a Mars simulant

    NASA Astrophysics Data System (ADS)

    Stroble, Shannon T.; McElhoney, Kyle M.; Kounaves, Samuel P.

    2013-08-01

    The results of the Mars Phoenix Lander's Wet Chemistry Laboratory (WCL) for the analyses of the soluble ionic species present in the soil at the northern polar plains of Mars are compared to soil from the Antarctic Dry Valleys (ADVs), martian meteorite EETA79001 sawdust, and a Mars simulant. The ADV soil was compared to the Phoenix site by averaging the samples at analogous 0-5 cm depths and also all the samples from the pavement to the ice-table. Results from each analysis reveal similar ion concentrations ranging plus or minus one order-of-magnitude for all ions except perchlorate (ClO4-), which was three orders-of-magnitude greater in the Phoenix soil. The pH and solution electrical conductivity were also found to be similar for the ADV and Mars soils. The ADV profiles confirm that ClO4- gradients are sensitive indicators for the presence and form of liquid H2O on both Earth and Mars. The Phoenix and meteorite samples contained similar species and ratios but the meteorite concentrations were on average ˜4% of those for the Phoenix soil. The only exception was the ˜16% higher level of Ca2+ in the meteorite due to the CaCO3 druse. The ADV results imply that the Phoenix site is significantly more arid than University Valley, and has been for a greater period of time, as evidenced by the lack of salt gradients and the age of the soils. A Mars simulant was also formulated according to a MINEQL equilibrium model of the WCL results, and its analysis provides confidence that the soluble composition and parent salts at the Phoenix site are reasonably constrained. Overall, comparison of these samples of soil and sawdust indicates that not only does the martian meteorite EETA79001 contain similar soluble ionic species as the martian soil from the northern polar plains, but also that the soils from the ADV are similar to both, thus strengthening the argument for the ADV as a suitable terrestrial Mars analog environment.

  14. Anti-adenovirus activity, antioxidant potential, and phenolic content of black tea (Camellia sinensis Kuntze) extract.

    PubMed

    Karimi, Ali; Moradi, Mohammad-Taghi; Alidadi, Somayeh; Hashemi, Leila

    2016-12-01

    BackgroundAdenovirus (ADV) causes a number of diseases in human, and to date, no specific antiviral therapy is approved against this virus. Thus, searching for effective anti-ADV agents seems to be an urgent requirement. Many studies have shown that components derived from medicinal plants have antiviral activity. Therefore, the present study was aimed to evaluate in vitro anti-ADV activity and also antioxidant potential and total phenolic compounds of black tea (Camellia sinensis) crude extract. MethodsIn this study, the hydroalchoholic extract of black tea was prepared and its anti-ADV activity was evaluated on HEp2 cell line using MTT [3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. The 50 % inhibitory concentration (IC50) and 50 % cytotoxicity concentration (CC50) of the extract were determined using regression analysis. Its inhibitory effect on adsorption and/or post-adsorption stages of the virus replication cycle was evaluated. To determine antioxidant activity, total phenol content, and flavonoids content of the extract, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method were used, respectively. ResultsThe CC50 and the IC50 of the extract were 165.95±12.7 and 6.62±1.4 µg/mL, respectively, with the selectivity index (SI) of 25.06. This extract inhibited ADV replication in post-adsorption stage. The IC50 of DPPH radical was 8±1.41 μg/mL, compared with butylated hydroxytoluene, with IC50 of 25.41±1.89 μg/mL. The total phenol and flavonoid contents of the extract were 341.8±4.41 mg gallic acid equivalent per gram and 21.1±2.11 mg/g, respectively. ConclusionsHaving SI value of 25.06 with inhibitory effect on ADV replication, particularly during the post-adsorption period, black tea extract could be considered as a potential anti-ADV agent. The antiviral activity of this extract could be attributed to its phenolic compounds.

  15. Remnant amount and cleanup for 3 adhesives after debracketing.

    PubMed

    David, Valerie A; Staley, Robert N; Bigelow, Harold F; Jakobsen, Jane R

    2002-03-01

    The cleanup of remnant bonding adhesive from the enamel surface after debonding is an important factor for clinicians. The purposes of this study were to compare the weight, the surface area, and the cleanup times of remnant adhesive for a composite resin, Transbond (TB); a resin-modified glass ionomer, Fuji ORTHO LC bonded to enamel both conditioned (FOC) and nonconditioned (FONC); and a fluoride-releasing composite resin, Advance (ADV), bonded to nonetched enamel. In addition, 2 qualitative methods for scoring remnant adhesive were compared with the quantitative weight and area data. Forty extracted human incisors were weighed, bonded with brackets, debonded, weighed, and photographed. Area was measured from the photographs with a sonic digitizer. Mean adhesive remnant weights differed between groups (analysis of variance [ANOVA], P =.02): The remnants from ADV and FOC were equal and both significantly heavier than the remnants from FONC; the weights of the TB remnants were intermediate between the heavier ADV and FOC remnants and the lighter FONC remnants. Mean remnant areas differed between groups (ANOVA, P =.03): The remnants from ADV were significantly larger than the remnants from TB and FONC, which were equal; the areas of the FOC remnants were intermediate between the larger ADV remnants and the smaller remnants from TB and FONC. Mean cleanup times also differed between groups (ANOVA, P <.001): TB and FOC had equal times that were significantly longer than the times for ADV and FONC, which were equal. Adhesives bonded to acid-etched or conditioned enamel took about 1 and a half times longer to clean up than did those bonded to nonetched enamel. When bonded to conditioned enamel, the resin-modified glass ionomer had mean remnant adhesive weights, areas, and cleanup times statistically equivalent to TB. ADV had the fastest mean cleanup time per amount of remnant (ANOVA, P <.002). The graphs of scores for 2 qualitative methods used for scoring remnant amount

  16. Influence of wastewater treatment process and the population size on human virus profiles in wastewater.

    PubMed

    Hewitt, Joanne; Leonard, Margaret; Greening, Gail E; Lewis, Gillian D

    2011-11-15

    Human adenovirus (AdV and AdV species F), enterovirus (EV) and norovirus (NoV) concentrations entering wastewater treatment plants (WWTP) serving different-sized communities, and effectiveness of different treatment processes in reducing concentrations were established. Data was combined to create a characteristic and unique descriptor of the individual viral composition and termed as the sample virus profile. Virus profiles were generally independent of population size and treatment process (moving bed biofilm reactors, activated sludge, waste stabilisation ponds). AdV and EV concentrations in wastewater were more variable in small (<4000) and medium-sized (10,000-64,000) WWTP than in large-sized (>130,000 inhabitants) plants. AdV and EV concentrations were detected in influent of most WWTP (AdV range 1.00-4.08 log(10) infectious units (IU)/L, 3.25-8.62 log(10) genome copies/L; EV range 0.7-3.52 log(10) plaque forming units (PFU)/L; 2.84-6.67 log(10) genome copies/L) with a reduced median concentration in effluent (AdV range 0.70-3.26 log(10) IU/L, 2.97-6.95 log(10) genome copies/L; EV range 0.7-2.15 log(10)PFU/L, 1.54-5.28 log(10) genome copies/L). Highest culturable AdV and EV concentrations in effluent were from a medium-sized WWTP. NoV was sporadic in all WWTP with GI and GII concentrations being similar in influent (range 2.11-4.64 and 2.19-5.46 log(10) genome copies/L) as in effluent (range 2.18-5.06 and 2.88-5.46 log(10) genome copies/L). Effective management of WWTP requires recognition that virus concentration in influent will vary - particularly in small and medium plants. Irrespective of treatment type, culturable viruses and NoV are likely to be present in non-disinfected effluent, with associated human health risks dependent on concentration and receiving water usage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Terrestrial cold-desert analogs: Antarctic landforms and implications for regional glaciation on Mars

    NASA Astrophysics Data System (ADS)

    Head, J. W.; Marchant, D. R.; Dickson, J. L.; Baker, D. M.; Mackay, S.; Lamp, J.

    2011-12-01

    The Antarctic Dry Valleys (ADV) are generally classified as a hyper-arid, cold-polar desert. The region has long been considered an important terrestrial analog for Mars because of its cold and dry climate and because it contains a suite of landforms at macro-, meso-, and microscales that closely resemble those occurring on the martian surface. The extreme hyperaridity of both Mars and the ADV has focused attention on the importance of salts and brines on soil development, phase transitions from liquid water to ice, and ultimately, on process geomorphology and landscape evolution at a range of scales on both planets. The ADV can be subdivided into three microclimate zones: a coastal thaw zone, an inland mixed zone, and a stable upland zone; zones are defined on the basis of summertime measurements of atmospheric temperature, soil moisture, and relative humidity. Subtle variations in these climate parameters result in considerable differences in the distribution and morphology of: (1) macroscale features (e.g., slopes and gullies); (2) mesoscale features (e.g., polygons, including ice-wedge, sand-wedge, and sublimation-type polygons, as well as viscous-flow features, including solifluction lobes, gelifluction lobes, and debris-covered glaciers); and (3) microscale features (e.g., rock-weathering processes/features, including salt weathering, wind erosion, and surface pitting). Equilibrium landforms are those features that formed in balance with environmental conditions within fixed microclimate zones. We report on our multi-year field and instrument analysis of four important ADV landforms: 1) sublimation polygons and relation to buried ice, 2) gullies and the environmental controls responsible for their episodic activity, 3) slope streaks, the role of water and brines in their formation and the timing of their activity, and 4) debris-covered glaciers and their three-dimensional geometry, mode and rates of formation. The relative geomorphic and climate stability for

  18. Advection of NH3 over a pasture field and its effect on gradient flux measurements

    NASA Astrophysics Data System (ADS)

    Loubet, B.; Milford, C.; Hensen, A.; Daemmgen, U.; Erisman, J.-W.; Cellier, P.; Sutton, M. A.

    2009-07-01

    Deposition of atmospheric ammonia (NH3) to semi-natural ecosystems leads to serious adverse effects, such as acidification and eutrophication. A step in quantifying such effects is the measurement of NH3 fluxes over semi-natural and agricultural land. However, measurement of NH3 fluxes over vegetation in the vicinity of strong NH3 sources is challenging, since NH3 emissions are highly heterogeneous. Indeed, under such conditions, local advection errors may alter the measured fluxes. In this study, local advection errors (ΔFz,adv) were estimated over a 14 ha grassland field, which was successively cut and fertilised, as part of the GRAMINAE integrated Braunschweig experiment. The magnitude of ΔFz,adv was determined up to 810 m downwind from farm buildings emitting between 6.2 and 9.9 kg NH3 day-1. The GRAMINAE experiment provided a unique opportunity to compare two methods of estimating ΔFz,adv: one inference method based on measurements of horizontal concentration gradients, and one based on inverse dispersion modelling with a two-dimensional model. Two sources of local advection were clearly identified: the farm NH3 emissions leading to positive ΔFz,adv ("bias towards emissions") and field NH3 emissions, which led to a negative ΔFz,adv ("bias towards deposition"). The local advection flux from the farm was in the range 0 to 27 ng NH3 m-2 s-1 at 610 m from the farm, whereas ΔFz,adv due to field emission was proportional to the local flux, and ranged between -209 and 13 ng NH3 m-2 s-1. The local advection flux ΔFz,adv was either positive or negative depending on the magnitude of these two contributions. The modelled and inferred advection errors agreed well. The inferred advection errors, relative to the vertical flux at 1 m height, were 52% on average, before the field was cut, and less than 2.1% when the field was fertilised. The variability of the advection errors in response to changes in micrometeorological conditions is also studied. The limits of the 2

  19. Quantifying measurement uncertainties in ADCP measurements in non-steady, inhomogeneous flow

    NASA Astrophysics Data System (ADS)

    Schäfer, Stefan

    2017-04-01

    The author presents a laboratory study of fixed-platform four-beam ADCP and three-beam ADV measurements in the tailrace of a micro hydro power setup with a 35kW Kaplan-turbine and 2.5m head. The datasets discussed quantify measurement uncertainties of the ADCP measurement technique coming from non-steady, inhomogeneous flow. For constant discharge of 1.5m3/s, two different flow scenarios were investigated: one being the regular tailrace flow downstream the draft tube and the second being a straightened, less inhomogeneous flow, which was generated by the use of a flow straightening device: A rack of diameter 40mm pipe sections was mounted right behind the draft tube. ADCP measurements (sampling rate 1.35Hz) were conducted in three distances behind the draft tube and compared bin-wise to measurements of three simultaneously measuring ADV probes (sampling rate 64Hz). The ADV probes were aligned horizontally and the ADV bins were placed in the centers of two facing ADCP bins and in the vertical under the ADCP probe of the corresponding depth. Rotating the ADV probes by 90° allowed for measurements of the other two facing ADCP bins. For reasons of mutual probe interaction, ADCP and ADV measurements were not conducted at the same time. The datasets were evaluated by using mean and fluctuation velocities. Turbulence parameters were calculated and compared as far as applicable. Uncertainties coming from non-steady flow were estimated with the normalized mean square error und evaluated by comparing long-term measurements of 60 minutes to shorter measurement intervals. Uncertainties coming from inhomogeneous flow were evaluated by comparison of ADCP with ADV data along the ADCP beams where ADCP data were effectively measured and in the vertical under the ADCP probe where velocities of the ADCP measurements were displayed. Errors coming from non-steady flow could be compensated through sufficiently long measurement intervals with high enough sampling rates depending on the

  20. Etiology of maculopapular rash in measles and rubella suspected patients from Belarus.

    PubMed

    Yermalovich, Marina A; Semeiko, Galina V; Samoilovich, Elena O; Svirchevskaya, Ekaterina Y; Muller, Claude P; Hübschen, Judith M

    2014-01-01

    As a result of successful implementation of the measles/rubella elimination program, the etiology of more and more double negative cases remains elusive. The present study determined the role of different viruses as causative agents in measles or rubella suspected cases in Belarus. A total of 856 sera sent to the WHO National Laboratory between 2009 and 2011 were tested for specific IgM antibodies to measles virus (MV), rubella virus (RV) and human parvovirus B19 (B19V). The negatives were further investigated for antibodies to enterovirus (EV) and adenovirus (AdV). Children of up to 3 years were tested for IgM antibodies to human herpesvirus 6 (HHV6). A viral etiology was identified in 451 (52.7%) cases, with 6.1% of the samples being positive for MV; 2.6% for RV; 26.2% for B19V; 9.7% for EV; 4.6% for AdV; and 3.6% for HHV6. Almost all measles and rubella cases occurred during limited outbreaks in 2011 and nearly all patients were at least 15 years old. B19V, EV and AdV infections were prevalent both in children and adults and were found throughout the 3 years. B19V occurred mainly in 3-10 years old children and 20-29 years old adults. EV infection was most common in children up to 6 years of age and AdV was confirmed mainly in 3-6 years old children. HHV6 infection was mostly detected in 6-11 months old infants. Laboratory investigation of measles/rubella suspected cases also for B19V, EV, AdV and HHV6 allows diagnosing more than half of all cases, thus strengthening rash/fever disease surveillance in Belarus.

  1. Admiralty Inlet Advanced Turbulence Measurements: May 2015

    DOE Data Explorer

    Kilcher, Levi

    2015-05-18

    This data is from measurements at Admiralty Head, in Admiralty Inlet (Puget Sound) in May of 2015. The measurements were made using Inertial Motion Unit (IMU) equipped ADVs mounted on a 'StableMoor' (Manufacturer: DeepWater Buoyancy) buoy and a Tidal Turbulence Mooring (TTM). These platforms position ADV heads above the seafloor to make mid-depth turbulence measurements. The inertial measurements from the IMU allows for removal of mooring motion in post processing. The mooring and buoy motion has been removed from the stream-wise and vertical velocity signals (u, w). The lateral (v) velocity has some 'persistent motion contamination' due to mooring sway. The TTM was deployed with one ADV, it's position was: 48 09.145', -122 41.209' The StableMoor was deployed twice, the first time it was deployed in 'wing-mode' with two ADVs ('Port' and 'Star') at: 48 09.166', -122 41.173' The second StableMoor deployment was in 'Nose' mode with one ADV at: 48 09.166', -122 41.174' Units ----- - Velocity data (_u, urot, uacc) is in m/s. - Acceleration (Accel) data is in m/s^2. - Angular rate (AngRt) data is in rad/s. - The components of all vectors are in 'ENU' orientation. That is, the first index is True East, the second is True North, and the third is Up (vertical). - All other quantities are in the units defined in the Nortek Manual. Motion correction and rotation into the ENU earth reference frame was performed using the Python-based open source DOLfYN library (http://lkilcher.github.io/dolfyn/). Details on motion correction can be found there. Additional details on TTM measurements at this site can be found in the included Marine Energy Technology Symposium paper.

  2. Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway.

    PubMed

    Guzman, Efrain; Taylor, Geraldine; Hope, Jayne; Herbert, Rebecca; Cubillos-Zapata, Carolina; Charleston, Bryan

    2016-10-01

    Dendritic cells (DC) are central to the initiation of immune responses, and various approaches have been used to target vaccines to DC in order to improve immunogenicity. Cannulation of lymphatic vessels allows for the collection of DC that migrate from the skin. These migrating DC are involved in antigen uptake and presentation following vaccination. Human replication-deficient adenovirus (AdV) 5 is a promising vaccine vector for delivery of recombinant antigens. Although the mechanism of AdV attachment and penetration has been extensively studied in permissive cell lines, few studies have addressed the interaction of AdV with DC. In this study, we investigated the interaction of bovine skin-migrating DC and replication-deficient AdV-based vaccine vectors. We found that, despite lack of expression of Coxsackie B-Adenovirus Receptor and other known adenovirus receptors, AdV readily enters skin-draining DC via an actin-dependent endocytosis. Virus exit from endosomes was pH independent, and neutralizing antibodies did not prevent virus entry but did prevent virus translocation to the nucleus. We also show that combining adenovirus with adjuvant increases the absolute number of intracellular virus particles per DC but not the number of DC containing intracellular virus. This results in increased trans-gene expression and antigen presentation. We propose that, in the absence of Coxsackie B-Adenovirus Receptor and other known receptors, AdV5-based vectors enter skin-migrating DC using actin-dependent endocytosis which occurs in skin-migrating DC, and its relevance to vaccination strategies and vaccine vector targeting is discussed.

  3. Adenoviral L4 33K forms ring-like oligomers and stimulates ATPase activity of IVa2: implications in viral genome packaging

    PubMed Central

    Ahi, Yadvinder S.; Vemula, Sai V.; Hassan, Ahmed O.; Costakes, Greg; Stauffacher, Cynthia; Mittal, Suresh K.

    2015-01-01

    The mechanism of genome packaging in adenoviruses (AdVs) is presumed to be similar to that of dsDNA viruses including herpesviruses and dsDNA phages. First, the empty capsids are assembled after which the viral genome is pushed through a unique vertex by a motor which consists of three minimal components: an ATPase, a small terminase and a portal. Various components of this motor exist as ring-like structures forming a central channel through which the DNA travels during packaging. In AdV, the IVa2 protein is believed to function as a packaging ATPase, however, the equivalents of the small terminase and the portal have not been identified in AdVs. IVa2 interacts with another viral protein late region 4 (L4) 33K which is important for genome packaging. Both IVa2 and 33K are expressed at high levels during the late stage of virus infection. The oligomeric state of IVa2 and 33K was analyzed in virus-infected cells, IVa2 and 33K transfected cells, AdV particles, or as recombinant purified proteins. Electron microscopy of the purified proteins showed ring-like oligomers for both proteins which is consistent with their putative roles as a part of the packaging motor. We found that the ATPase activity of IVa2 is stimulated in the presence of 33K and the AdV genome. Our results suggest that the 33K functions analogous to the small terminase proteins and so will be part of the packaging motor complex. PMID:25954255

  4. Technical Report on Preliminary Methodology for Enhancing Risk Monitors with Integrated Equipment Condition Assessment

    SciTech Connect

    Ramuhalli, Pradeep; Coles, Garill A.; Coble, Jamie B.; Hirt, Evelyn H.

    2013-09-17

    Small modular reactors (SMRs) generally include reactors with electric output of ~350 MWe or less (this cutoff varies somewhat but is substantially less than full-size plant output of 700 MWe or more). Advanced SMRs (AdvSMRs) refer to a specific class of SMRs and are based on modularization of advanced reactor concepts. AdvSMRs may provide a longer-term alternative to traditional light-water reactors (LWRs) and SMRs based on integral pressurized water reactor concepts currently being considered. Enhancing affordability of AdvSMRs will be critical to ensuring wider deployment. AdvSMRs suffer from loss of economies of scale inherent in small reactors when compared to large (~greater than 600 MWe output) reactors. Some of this loss can be recovered through reduced capital costs through smaller size, fewer components, modular fabrication processes, and the opportunity for modular construction. However, the controllable day-to-day costs of AdvSMRs will be dominated by operation and maintenance (O&M) costs. Technologies that help characterize real-time risk are important for controlling O&M costs. Risk monitors are used in current nuclear power plants to provide a point-in-time estimate of the system risk given the current plant configuration (e.g., equipment availability, operational regime, and environmental conditions). However, current risk monitors are unable to support the capability requirements listed above as they do not take into account plant-specific normal, abnormal, and deteriorating states of active components and systems. This report documents technology developments that are a step towards enhancing risk monitors that, if integrated with supervisory plant control systems, can provide the capability requirements listed and meet the goals of controlling O&M costs. The report describes research results from an initial methodology for enhanced risk monitors by integrating real-time information about equipment condition and POF into risk monitors.

  5. Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival.

    PubMed

    Gong, N; Pleyer, U; Volk, H-D; Ritter, T

    2007-03-01

    In this study, we explored the immunomodulatory effects of viral interleukin (IL) IL-10 after ex vivo and in vivo gene transfer in experimental corneal transplantation. Wistar-Furth rats were used as donors and major histocompatibility complex class I/II-disparate Lewis rats served as recipients. For ex vivo gene therapy donor corneas were either transfected with liposome/vIL-10 plasmid DNA mixtures or transduced with a vIL-10 expressing adenovirus vector (AdvIL-10). For in vivo studies, recipients were treated with AdvIL-10 intraperitoneally 1 day before transplantation. Graft survival was analysed using the Kaplan-Meier survival method. To monitor the efficacy of the therapy messenger RNA (mRNA) cytokine expression profiles in grafts and draining lymph nodes were analysed by quantitative real-time reverse transcription-polymerase chain reaction. Moreover, anti-adenovirus immunity was also investigated. Neither ex vivo liposome-mediated vIL-10 gene transfer nor ex vivo AdvIL-10 gene transfer led to prolonged corneal allograft survival. In contrast, corneal allograft survival was significantly prolonged in animals receiving systemic AdvIL-10 gene transfer. Moreover, only systemic vIL-10 gene therapy modulated the cytokine mRNA expression profile in draining lymph nodes. Interestingly, systemic AdvIL-10 gene transfer could not inhibit the generation of anti-adenovirus antibodies. Our data indicate systemic expression of the vIL-10 gene is required to modulate the cytokine expression profile in the draining lymph nodes, which might be a pre-requisite for the success of cytokine gene therapy.

  6. Production of first generation adenoviral vectors for preclinical protocols: amplification, purification and functional titration.

    PubMed

    Armendáriz-Borunda, Juan; Bastidas-Ramírez, Blanca Estela; Sandoval-Rodríguez, Ana; González-Cuevas, Jaime; Gómez-Meda, Belinda; García-Bañuelos, Jesús

    2011-11-01

    Gene therapy represents a promising approach in the treatment of several diseases. Currently, the ideal vector has yet to be designed; though, adenoviral vectors (Ad-v) have provided the most utilized tool for gene transfer due principally to their simple production, among other specific characteristics. Ad-v viability represents a critical variable that may be affected by storage or shipping conditions and therefore it is advisable to be assessed previously to protocol performance. The present work is unique in this matter, as the complete detailed process to obtain Ad-v of preclinical grade is explained. Amplification in permissive HEK-293 cells, purification in CsCl gradients in a period of 10 h, spectrophotometric titration of viral particles (VP) and titration of infectious units (IU), yielding batches of AdβGal, AdGFP, AdHuPA and AdMMP8, of approximately 10¹³-10¹⁴ VP and 10¹²-10¹³ IU were carried out. In vivo functionality of therapeutic AdHuPA and AdMMP8 was evidenced in rats presenting CCl₄-induced fibrosis, as more than 60% of fibrosis was eliminated in livers after systemic delivery through iliac vein in comparison with irrelevant AdβGal. Time required to accomplish the whole Ad-v production steps, including IU titration was 20 to 30 days. We conclude that production of Ad-v following standard operating procedures assuring vector functionality and the possibility to effectively evaluate experimental gene therapy results, leaving aside the use of high-cost commercial kits or sophisticated instrumentation, can be performed in a conventional laboratory of cell culture.

  7. Nanomodified vermiculite NMV - a new material for recycling ammonium nitrogen

    NASA Astrophysics Data System (ADS)

    Rama, Miradije; Laiho, Taina; Eklund, Olav; Lehto, Kirsi; Shebanov, Alex; Smått, Jan-Henrik

    2016-04-01

    Vermiculites ((Mg,Fe,Al)3(Al,Si)4O10(OH)24H2O) are naturally occurring minerals from hydromica group with a high cation exchange capacity and large surface area. Since vermiculite is a hydrated mineral, its structure can be changed with heat. In this study vermiculite samples were heated in an oven until the interlayer distance of them diminished from 14 Å to 11.7 Å. This method for improving vermiculites intake of ammonium ions by heating, is an invention made at the University of Turku. Nanomodified vermiculite (NMV) is able to absorb up to 4.7 wt% of ammonium. NMV can be used as an efficient filter and immobilizer of ammonium in different environments. NMV has been efficiently tested on waste water from a biogas plant, human urine, combustion experiments, industrial chimneys, excrements from farms etc. Ammonium doped vermiculite (ADV) is further developed for fertilizer use. Performed experiments have testified the usability of ADV as a fertilizer. At first step the NMV was processed with the reject water from a biogas plant, were it absorbed NH4+ into the lattice. At second, the ADV was used as nutrient source for garden plants. Geraniums and begonias were used as test plants of the work. Plant growth rate was evaluated based on plant weight. Results showed that significant increase of the growth of geraniums and of begonias were observed when comparing to those cultivations where plants have got normal fertilization. Moreover, ADV has been tested as a fertilizer in greenhouse experiments with spruces and pines. After five months, the weight of the plants that had grown in a substrate containing ADV was 10 times the weight of plants growing in the reference substrate.

  8. Clinical and epidemiological aspects related to the detection of adenovirus or respiratory syncytial virus in infants hospitalized for acute lower respiratory tract infection.

    PubMed

    Ferone, Eduardo A; Berezin, Eitan N; Durigon, Giuliana S; Finelli, Cristiane; Felício, Maria C C; Storni, Juliana G; Durigon, Edison L; Oliveira, Danielle B L de

    2014-01-01

    To characterize and compare clinical, epidemiological, and laboratory aspects of infants with acute lower respiratory infection (ALRI) associated with the detection of adenovirus (ADV) or respiratory syncytial virus (RSV). A preliminary respiratory infection surveillance study collected samples of nasopharyngeal aspirate (NPA) for viral research, linked to the completion of a standard protocol, from children younger than two years admitted to a university hospital with ALRI, between March of 2008 and August of 2011. Polymerase chain reaction (PCR) was used for eight viruses: ADV, RSV, metapneumovirus, Parainfluenza 1, 2, and 3, and Influenza A and B. Cases with NPA collected during the first 24 hours of admission, negative results of blood culture, and exclusive detection of ADV (Gadv group) or RSV (Grsv group) were selected for comparisons. The preliminary study included collection of 1,121 samples of NPA, 813 collected in the first 24 hours of admission, of which 50.3% were positive for at least one virus; RSV was identified in 27.3% of cases surveyed, and ADV was identified in 15.8%. Among the aspects analyzed in the Gadv (n = 58) and Grsv (n = 134) groups, the following are noteworthy: the higher mean age, more frequent prescription of antibiotics, and the highest median of total white blood cell count and C-reactive protein values in Gadv. PCR can detect persistent/latent forms of ADV, an aspect to be considered when interpreting results. Additional studies with quantitative diagnostic techniques could elucidate the importance of the high frequency observed. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. Use of cidofovir in pediatric patients with adenovirus infection

    PubMed Central

    Ganapathi, Lakshmi; Arnold, Alana; Jones, Sarah; Patterson, Al; Graham, Dionne; Harper, Marvin; Levy, Ofer

    2016-01-01

    Background: Adenoviruses contribute to morbidity and mortality among immunocompromised pediatric patients including stem cell and solid organ transplant recipients. Cidofovir (CDV), an antiviral compound approved by the FDA in 1996, is used for treatment of adenoviral (ADV) infections in immunocompromised patients despite concern of potential nephrotoxicity.   Methods: We conducted a retrospective 5-year review at Boston Children’s Hospital of 16 patients (mean age = 6.5 years) receiving 19 courses of CDV. During therapy all pertinent data elements were reviewed to characterize potential response to therapy and incidence of renal dysfunction.   Results: Of the 19 CDV courses prescribed, 16 courses (84%) were in patients who had a positive blood ADV Polymerase chain reaction (PCR) alone or in combination with positive ADV PCR/ Direct Immunofluorescence Assay (DFA) at another site. Respiratory symptoms with or without pneumonia were the most common presentation (10/19, 53%). In the majority of blood positive courses (10/16, 63%), viral clearance was also accompanied by clinical response. This was not the case in four courses where patients expired despite viral clearance, including one in which death was directly attributable to adenovirus. There was reversible renal dysfunction observed during the use of CDV. Conclusions:  CDV appeared safe and reasonably tolerated for treatment of ADV in this pediatric population and was associated with viral response and clinical improvement in the majority of patients but reversible renal dysfunction was a side effect. Further studies of the efficacy of CDV for immunocompromised children with ADV infection are warranted. PMID:27239277

  10. Self-reported assessment of visual function in a population-based study: the SEE project. Salisbury Eye Evaluation.

    PubMed

    Valbuena, M; Bandeen-Roche, K; Rubin, G S; Munoz, B; West, S K

    1999-02-01

    To report on the usefulness of the Activities of Daily Vision Scale (ADVS) questionnaire for assessing visual functioning, a population-based sample of elderly Americans. The ADVS questionnaire was administered to a population-based sample of 2520 community-dwelling individuals 65 to 84 years of age in Salisbury, MD. Items and subscales were evaluated for internal consistency, item discrimination, and content validity. Published subscale groupings and item associations in our population were compared for coherence using correlation, factor, and cluster analyses. Whole-sample and race- and gender-specific analyses were conducted. External validity was explored by regressing ADVS scores on standard psychophysical vision measures. ADVS scores were skewed to high visual functioning levels; approximately 60% of the population had function scores of 95 or better (of a possible 100). The overall, night driving, and near vision scales were internally consistent and had strong item-subscale associations; the day driving and glare subscales were not acceptable regarding these properties. The far vision subscale was acceptably scalable but only weakly differentiated from the other subscales. Overall, night driving, near vision, and far vision scores were all statistically and independently associated with multiple psychophysical vision measures. Findings were consistent across race and gender subgroups. As assessed by the ADVS, reported visual functioning is high in our representative older population. The overall scale and selected subscales effectively distinguish persons along a spectrum of ability. They correlate with measures of visual impairment in a reasonable way and thus hold promise for risk factor investigations. The published day driving and glare subscales should be examined for relevance and consistency before being applied in population-based settings. Methods specific to population-based settings should be investigated for their ability to better elicit

  11. Admiralty Inlet Advanced Turbulence Measurements: June 2014

    DOE Data Explorer

    Kilcher, Levi

    2014-06-30

    This data is from measurements at Admiralty Head, in Admiralty Inlet (Puget Sound) in June of 2014. The measurements were made using Inertial Motion Unit (IMU) equipped ADVs mounted on Tidal Turbulence Mooring's (TTMs). The TTM positions the ADV head above the seafloor to make mid-depth turbulence measurements. The inertial measurements from the IMU allows for removal of mooring motion in post processing. The mooring motion has been removed from the stream-wise and vertical velocity signals (u, w). The lateral (v) velocity has some 'persistent motion contamination' due to mooring sway. Each ttm was deployed with two ADVs. The 'top' ADV head was positioned 0.5m above the 'bottom' ADV head. The TTMs were placed in 58m of water. The position of the TTMs were: ttm01 : (48.1525, -122.6867) ttm01b : (48.15256666, -122.68678333) ttm02b : (48.152783333, -122.686316666) Deployments TTM01b and TTM02b occurred simultaneously and were spaced approximately 50m apart in the cross-stream direction. Units ----- - Velocity data (_u, urot, uacc) is in m/s. - Acceleration (Accel) data is in m/s^2. - Angular rate (AngRt) data is in rad/s. - The components of all vectors are in 'ENU' orientation. That is, the first index is True East, the second is True North, and the third is Up (vertical). - All other quantities are in the units defined in the Nortek Manual. Motion correction and rotation into the ENU earth reference frame was performed using the Python-based open source DOLfYN library (http://lkilcher.github.io/dolfyn/). Details on motion correction can be found there. Additional details on TTM measurements at this site can be found in the included Marine Energy Technology Symposium paper.

  12. Mechanical Designs and Developement of Advanced ACT: A Transfomative Upgrade to the ACTPol Receiver on the Atacama Cosmology Telescope.

    NASA Astrophysics Data System (ADS)

    Ward, Jonathan; Advanced ACT Collaboration, NASA Space Technology Research Fellowship

    2017-06-01

    The Atacama Cosmology Telescope is a six-meter diameter telescope located at 17,000 feet (5,200 meters) on Cerro Toco in the Andes Mountains of northern Chile. The next generation Advanced ACT (AdvACT) experiment is currently underway and will consist of three multichroic TES bolometer arrays operating together, totaling 5800 detectors on the sky. Each array will be sensitive to two frequency bands: a high frequency (HF) array at 150 and 230 GHz, two middle frequency (MF) arrays at 90 and 150 GHz, and a low frequency (LF) array at 28 and 41 GHz. The AdACT detector arrays will feature a revamped design when compared to ACTPol, including a transition to 150mm wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors consists of a feedhorn array of stacked silicon wafers which form a corrugated profile leading to each pixel. This is then followed by a four-piece detector stack assembly of silicon wafers which includes a waveguide interface plate, detector wafer, backshort cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured out of gold-plated, high purity copper. In addition to the detector array assembly, the array package also encloses the majority of our readout electronics. We present the full mechanical design of the AdvACT HF and MF detector array packages along with a detailed look at the detector array assemblies. We also highlight the use of continuously rotating warm half-wave plates (HWPs) at the front of the AdvACT receiver. We review the design of the rotation system and also early pipeline data analysis results. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT instruments with pre-existing ACTPol infrastructure.

  13. Evaluation of a virucidal quantitative carrier test for surface disinfectants.

    PubMed

    Rabenau, Holger F; Steinmann, Jochen; Rapp, Ingrid; Schwebke, Ingeborg; Eggers, Maren

    2014-01-01

    Surface disinfectants are part of broader preventive strategies preventing the transmission of bacteria, fungi and viruses in medical institutions. To evaluate their virucidal efficacy, these products must be tested with appropriate model viruses with different physico-chemical properties under conditions representing practical application in hospitals. The aim of this study was to evaluate a quantitative carrier assay. Furthermore, different putative model viruses like adenovirus type 5 (AdV-5) and different animal parvoviruses were evaluated with respect to their tenacity and practicability in laboratory handling. To evaluate the robustness of the method, some of the viruses were tested in parallel in different laboratories in a multi-center study. Different biocides, which are common active ingredients of surface disinfectants, were used in the test. After drying on stainless steel discs as the carrier, model viruses were exposed to different concentrations of three alcohols, peracetic acid (PAA) or glutaraldehyde (GDA), with a fixed exposure time of 5 minutes. Residual virus was determined after treatment by endpoint titration. All parvoviruses exhibited a similar stability with respect to GDA, while AdV-5 was more susceptible. For PAA, the porcine parvovirus was more sensitive than the other parvoviruses, and again, AdV-5 presented a higher susceptibility than the parvoviruses. All parvoviruses were resistant to alcohols, while AdV-5 was only stable when treated with 2-propanol. The analysis of the results of the multi-center study showed a high reproducibility of this test system. In conclusion, two viruses with different physico-chemical properties can be recommended as appropriate model viruses for the evaluation of the virucidal efficacy of surface disinfectants: AdV-5, which has a high clinical impact, and murine parvovirus (MVM) with the highest practicability among the parvoviruses tested.

  14. Evaluation of a Virucidal Quantitative Carrier Test for Surface Disinfectants

    PubMed Central

    Rabenau, Holger F.; Steinmann, Jochen; Rapp, Ingrid; Schwebke, Ingeborg; Eggers, Maren

    2014-01-01

    Surface disinfectants are part of broader preventive strategies preventing the transmission of bacteria, fungi and viruses in medical institutions. To evaluate their virucidal efficacy, these products must be tested with appropriate model viruses with different physico-chemical properties under conditions representing practical application in hospitals. The aim of this study was to evaluate a quantitative carrier assay. Furthermore, different putative model viruses like adenovirus type 5 (AdV-5) and different animal parvoviruses were evaluated with respect to their tenacity and practicability in laboratory handling. To evaluate the robustness of the method, some of the viruses were tested in parallel in different laboratories in a multi-center study. Different biocides, which are common active ingredients of surface disinfectants, were used in the test. After drying on stainless steel discs as the carrier, model viruses were exposed to different concentrations of three alcohols, peracetic acid (PAA) or glutaraldehyde (GDA), with a fixed exposure time of 5 minutes. Residual virus was determined after treatment by endpoint titration. All parvoviruses exhibited a similar stability with respect to GDA, while AdV-5 was more susceptible. For PAA, the porcine parvovirus was more sensitive than the other parvoviruses, and again, AdV-5 presented a higher susceptibility than the parvoviruses. All parvoviruses were resistant to alcohols, while AdV-5 was only stable when treated with 2-propanol. The analysis of the results of the multi-center study showed a high reproducibility of this test system. In conclusion, two viruses with different physico-chemical properties can be recommended as appropriate model viruses for the evaluation of the virucidal efficacy of surface disinfectants: AdV-5, which has a high clinical impact, and murine parvovirus (MVM) with the highest practicability among the parvoviruses tested. PMID:24475079

  15. Estimation of suspended sediment concentration in rivers using acoustic methods.

    PubMed

    Elçi, Sebnem; Aydin, Ramazan; Work, Paul A

    2009-12-01

    Acoustic Doppler current meters (ADV, ADCP, and ADP) are widely used in water systems to measure flow velocities and velocity profiles. Although these meters are designed for flow velocity measurements, they can also provide information defining the quantity of particulate matter in the water, after appropriate calibration. When an acoustic instrument is calibrated for a water system, no additional sensor is needed to measure suspended sediment concentration (SSC). This provides the simultaneous measurements of velocity and concentration required for most sediment transport studies. The performance of acoustic Doppler current meters for measuring SSC was investigated in different studies where signal-to-noise ratio (SNR) and suspended sediment concentration were related using different formulations. However, these studies were each limited to a single study site where neither the effect of particle size nor the effect of temperature was investigated. In this study, different parameters that affect the performance of an ADV for the prediction of SSC are investigated. In order to investigate the reliability of an ADV for SSC measurements in different environments, flow and SSC measurements were made in different streams located in the Aegean region of Turkey having different soil types. Soil samples were collected from all measuring stations and particle size analysis was conducted by mechanical means. Multivariate analysis was utilized to investigate the effect of soil type and water temperature on the measurements. Statistical analysis indicates that SNR readings ob tained from the ADV are affected by water temperature and particle size distribution of the soil, as expected, and a prediction model is presented relating SNR readings to SSC mea surements where both water temperature and sediment characteristics type are incorporated into the model. The coefficients of the suggested model were obtained using the multivariate anal ysis. Effect of high turbidity

  16. Acoustic droplet vaporization for diagnostic and therapeutic applications

    NASA Astrophysics Data System (ADS)

    Kripfgans, Oliver Daniel

    A technology, termed Acoustic Droplet Vaporization (ADV), is developed whereby superheated droplets are caused to vaporize by application of an ultrasonic field. The droplet emulsion (90% <6 um diameter) is made by mixing saline, albumin, and perfluorocarbon at high speed. It has been observed that an acoustic pressure threshold exists above which the droplets vaporize into bubbles approximately 25-times the original droplet diameter. For frequencies between 1.5 and 8 MHz, the threshold decreases from 4.5 to 0.75 MPa peak rarefactional pressure. The single pulse efficiency of ADV has been measured as 26%. This technology might be useful for tissue occlusion in cancer treatment as well as for aberration correction in acoustic imaging. To demonstrate these potential applications, gas bubbles were made in vivo in animal models by ADV. It was found that ADV could be used to temporarily form large gas bubbles (>30 um) in vivo, which at large number density occluded targeted tissues and reduced the blood flow by 34%. Alternatively, for a very sparse droplet population, gas bubbles could serve as potential point beacons for phase aberration correction given their backscatter amplitudes of 24 dB above tissue background. Other possible applications include drug delivery, indicator for cryo therapy, pressure/radiation beacons, hyperthermia, and cavitation nuclei. ADV of individual droplets showed that during acoustic irradiation, droplets perform dipole-type oscillations and that such oscillations increased in amplitude with acoustic intensity. Smaller droplets required more acoustic intensity for vaporization than larger droplets; however, independent of droplet diameter, a maximum oscillation amplitude of 1.3 um, was required. This threshold corresponds to a Reynolds number of ˜5 x 104. Vaporization started either as a spot on the axis of oscillation close to a pole of the droplet, or homogeneously throughout the droplet's imaged cross-section. It is concluded that

  17. Summary of the Preliminary Optical ICHMI Design Study: A Preliminary Engineering Design Study for a Standpipe Viewport

    SciTech Connect

    Anheier, Norman C.; Qiao, Hong; Berglin, Eric J.; Hatchell, Brian K.

    2013-12-26

    This summary report examines an in-vessel optical access concept intended to support standoff optical instrumentation, control and human-machine interface (ICHMI) systems for future advanced small modular reactor (AdvSMR) applications. Optical-based measurement and sensing systems for AdvSMR applications have several key benefits over traditional instrumentation and control systems used to monitor reactor process parameters, such as temperature, flow rate, pressure, and coolant chemistry (Anheier et al. 2013). Direct and continuous visualization of the in-vessel components can be maintained using external cameras. Many optical sensing techniques can be performed remotely using open optical beam path configurations. Not only are in-vessel cables eliminated by these configurations, but also sensitive optical monitoring components (e.g., electronics, lasers, detectors, and cameras) can be placed outside the reactor vessel in the instrument vault, containment building, or other locations where temperatures and radiation levels are much lower. However, the extreme AdvSMR environment present challenges for optical access designs and optical materials. Optical access is not provided in any commercial nuclear power plant or featured in any reactor design, although successful implementation of optical access has been demonstrated in test reactors (Arkani and Gharib 2009). This report outlines the key engineering considerations for an AdvSMR optical access concept. Strict American Society of Mechanical Engineers (ASME) construction codes must be followed for any U.S. nuclear facility component (ASME 2013); however, the scope of this study is to evaluate the preliminary engineering issues for this concept, rather than developing a nuclear-qualified design. In addition, this study does not consider accident design requirements. In-vessel optical access using a standpipe viewport concept serves as a test case to explore the engineering challenges and performance requirements

  18. INITIATORS AND TRIGGERING CONDITIONS FOR ADAPTIVE AUTOMATION IN ADVANCED SMALL MODULAR REACTORS

    SciTech Connect

    Katya L Le Blanc; Johanna h Oxstrand

    2014-04-01

    It is anticipated that Advanced Small Modular Reactors (AdvSMRs) will employ high degrees of automation. High levels of automation can enhance system performance, but often at the cost of reduced human performance. Automation can lead to human out-of the loop issues, unbalanced workload, complacency, and other problems if it is not designed properly. Researchers have proposed adaptive automation (defined as dynamic or flexible allocation of functions) as a way to get the benefits of higher levels of automation without the human performance costs. Adaptive automation has the potential to balance operator workload and enhance operator situation awareness by allocating functions to the operators in a way that is sensitive to overall workload and capabilities at the time of operation. However, there still a number of questions regarding how to effectively design adaptive automation to achieve that potential. One of those questions is related to how to initiate (or trigger) a shift in automation in order to provide maximal sensitivity to operator needs without introducing undesirable consequences (such as unpredictable mode changes). Several triggering mechanisms for shifts in adaptive automation have been proposed including: operator initiated, critical events, performance-based, physiological measurement, model-based, and hybrid methods. As part of a larger project to develop design guidance for human-automation collaboration in AdvSMRs, researchers at Idaho National Laboratory have investigated the effectiveness and applicability of each of these triggering mechanisms in the context of AdvSMR. Researchers reviewed the empirical literature on adaptive automation and assessed each triggering mechanism based on the human-system performance consequences of employing that mechanism. Researchers also assessed the practicality and feasibility of using the mechanism in the context of an AdvSMR control room. Results indicate that there are tradeoffs associated with each

  19. Impact of cataract surgery on self-reported visual difficulties: comparison with a no-surgery reference group.

    PubMed

    McGwin, Gerald; Scilley, Kay; Brown, Jay; Owsley, Cynthia

    2003-05-01

    To examine the impact of cataract surgery on older adults' self-reported visual difficulties and compare them with those of patients with cataract who declined surgery over the same period. Twelve area practices. This was a consecutive chart review over a 6-month period. Primary inclusion criteria were 55 years or older, cataract in 1 or both eyes with 20/40 visual acuity or worse (best corrected, distance), and no previous cataract surgery in either eye. The Activities of Daily Vision Scale (ADVS) and visual acuity, contrast sensitivity, and disability glare tests were administered at baseline and at a 1-year follow-up visit. This study comprised 245 patients, 156 of whom elected to have cataract surgery and 89 of whom declined. Those electing surgery were more likely to be white, female, and have worse visual acuity and no ocular comorbidities. At baseline, ADVS subscale scores ranged from 53 to 76 in the surgery group and from 72 to 89 in the no-surgery group. In the surgery group, subscale scores improved by 15 to 21 points on average at the 1-year follow-up; scores were unchanged or worse in the no-surgery group over this period. This difference between the groups remained statistically significant after adjustment for group baseline differences in demographics, vision, and ADVS score. In the surgery group, visual acuity improvement in the first eye was an independent predictor of increases in the ADVS overall score and night driving and glare disability subscales; contrast sensitivity was an independent predictor of improvement in the night driving subscale. A reduction in disability glare in the second eye was independently linked to increases in the overall ADVS score and the night driving, near vision, and glare disability subscales. Baseline findings suggest that cataract patients who have surgery have more difficulty in visual tasks than those who decline surgery. After surgery, patients reported less difficulty with visual tasks. In the no-surgery group

  20. Protein kinase C-alpha-induced hypertrophy of neonatal rat ventricular myocytes.

    PubMed

    Vijayan, Kalpana; Szotek, Erika L; Martin, Jody L; Samarel, Allen M

    2004-12-01

    Protein kinase C (PKC) isoenzymes play a critical role in cardiomyocyte hypertrophy. At least three different phorbol ester-sensitive PKC isoenzymes are expressed in neonatal rat ventricular myocytes (NRVMs): PKC-alpha, -delta, and -epsilon. Using replication-defective adenoviruses (AdVs) that express wild-type (WT) and dominant-negative (DN) PKC-alpha together with phorbol myristate acetate (PMA), which is a hypertrophic agonist and activator of all three PKC isoenzymes, we studied the role of PKC-alpha in signaling-specific aspects of the hypertrophic phenotype. PMA induced nuclear translocation of endogenous and AdV-WT PKC-alpha in NRVMs. WT PKC-alpha overexpression increased protein synthesis and the protein-to-DNA (P/D) ratio but did not affect cell surface area (CSA) or cell shape compared with uninfected or control AdV beta-galactosidase (AdV betagal)-infected cells. PMA-treated uninfected cells displayed increased protein synthesis, P/D ratio, and CSA and elongated morphology. PMA did not further enhance protein synthesis or P/D ratio in AdV-WT PKC-alpha-infected cells. To assess the requirement of PKC-alpha for these PMA-induced changes, AdV-DN PKC-alpha or AdV betagal-infected NRVMs were stimulated with PMA. Without PMA, AdV-DN PKC-alpha had no effects on protein synthesis, P/D ratio, CSA, or shape vs. AdV betagal-infected NRVMs. PMA increased protein synthesis, P/D ratio, and CSA in AdV betagal-infected cells, but these parameters were significantly reduced in PMA-stimulated AdV-DN PKC-alpha-infected NRVMs. Overexpression of DN PKC-alpha enhanced PMA-induced cell elongation. Neither WT PKC-alpha nor DN PKC-alpha affected atrial natriuretic factor gene expression. Insulin-like growth factor-1 also induced nuclear translocation of endogenous PKC-alpha. PMA but not WT PKC-alpha overexpression induced ERK1/2 activation. However, AdV-DN PKC-alpha partially blocked PMA-induced ERK activation. Thus PKC-alpha is necessary for certain aspects of PMA-induced NRVM