Sample records for reduction neutralization prn

  1. Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy.

    PubMed

    Abzug, Mark J; Qin, Min; Levin, Myron J; Fenton, Terence; Beeler, Judy A; Bellini, William J; Audet, Susette; Sowers, Sun Bae; Borkowsky, William; Nachman, Sharon A; Pelton, Stephen I; Rosenblatt, Howard M

    2012-08-15

    Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. NCT00013871 (www.clinicaltrials.gov).

  2. Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion

    PubMed Central

    Mir, Tahreem A.; Kherani, Saleema; Hafiz, Gulnar; Scott, Adrienne W.; Zimmer-Galler, Ingrid; Wenick, Adam S.; Solomon, Sharon; Han, Ian; Poon, David; He, Lingmin; Shah, Syed Mahmood; Brady, Christopher J.; Meyerle, Catherine; Sodhi, Akrit; Linz, Marguerite O.; Sophie, Raafay; Campochiaro, Peter A.

    2017-01-01

    Purpose To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab (RBZ) Design Secondary outcome measure in randomized double-masked controlled clinical trial Subjects Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO) Methods Subjects were randomized to 0.5mg or 2.0mg RBZ every month for 6 months and then re-randomized to pro re nata (prn) groups RBZ+scatter photocoagulation (laser) or RBZ alone for an additional 30 months. Main Outcome Measures Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5mg versus 2.0mg RBZ, during monthly injections versus prn RBZ, and in patients treated with prn RBZ versus prn RBZ+laser. Results In RVO patients given monthly injections of 0.5mg or 2.0mg RBZ for 6 months there was no significant difference in the percentage who showed reduction or increase in area of RNP. However, regardless of dose, during the 6 month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared to subsequent time periods of prn RBZ treatment. After the 6 month period of monthly injections, BRVO, but not CRVO patients randomized to prn RBZ+laser showed significantly less progression of RNP compared to patients treated with prn RBZ. Conclusions Regardless of dose of ranibizumab (0.5mg or 2.0mg), monthly injections promote improvement and reduce progression of RNP compared to prn injections. Addition of scatter photocoagulation to prn RBZ may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO. PMID:26712560

  3. High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

    PubMed Central

    Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

    2016-01-01

    In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

  4. Immunogenicity, Immunologic Memory, and Safety Following Measles Revaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Qin, Min; Levin, Myron J.; Fenton, Terence; Beeler, Judy A.; Bellini, William J.; Audet, Susette; Sowers, Sun Bae; Borkowsky, William; Nachman, Sharon A.; Pelton, Stephen I.; Rosenblatt, Howard M.

    2012-01-01

    Background. Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)–infected children in the absence of highly active antiretroviral therapy (HAART). Methods. HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30 000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4–5 years later, and PRN antibody was measured before and 7 and 28 days later. Results. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4–5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Conclusions. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. Clinical Trials Registration: NCT00013871 (www.clinicaltrials.gov). PMID:22693229

  5. Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

    PubMed

    Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane

    2014-01-01

    Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under ultrasound guidance after shoulder surgery, automated boluses of local anesthetic combined with PRN boluses did not provide any reduction in local anesthetic consumption or rescue analgesia, compared with continuous infusion combined with PRN boluses.

  6. Quantifying the combined effects of pronase and benzalkonium chloride in removing late-stage Listeria monocytogenes-Escherichia coli dual-species biofilms.

    PubMed

    Rodríguez-López, Pedro; Puga, Carmen H; Orgaz, Belén; Cabo, Marta L

    2017-09-01

    This work presents the assessment of the effectivity of a pronase (PRN)-benzalkonium chloride (BAC) sequential treatment in removing Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel (SS) using fluorescence microscopy and plate count assays. The effects of PRN-BAC on the occupied area (OA) by undamaged cells in 168 h dual-species samples were determined using a first-order factorial design. Empirical equations significantly (r 2 = 0.927) described a negative individual effect of BAC and a negative interactive effect of PRN-BAC achieving OA reductions up to 46%. After treatment, high numbers of remaining attached and released viable and cultivable E. coli cells were detected in PRN-BAC combinations when low BAC concentrations were used. Therefore, at appropriate BAC doses, in addition to biofilm removal, sequential application of PRN and BAC represents an appealing strategy for pathogen control on SS surfaces while hindering the dispersion of live cells into the environment.

  7. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study.

    PubMed

    Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Brown, David M; Vitti, Robert; Berliner, Alyson J; Kazmi, Husain; Ma, Yu; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert; Haller, Julia A

    2014-07-01

    To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). Randomized, double-masked, phase 3 trial. A total of 188 patients with macular edema secondary to CRVO. Patients received IAI 2 mg (IAI 2Q4) (n = 114) or sham injections (n = 74) every 4 weeks up to week 24. During weeks 24 to 52, patients from both arms were evaluated monthly and received IAI as needed, or pro re nata (PRN) (IAI 2Q4 + PRN and sham + IAI PRN). During weeks 52 to 100, patients were evaluated at least quarterly and received IAI PRN. The primary efficacy end point was the proportion of patients who gained ≥ 15 letters in best-corrected visual acuity (BCVA) from baseline to week 24. This study reports week 100 results. The proportion of patients gaining ≥ 15 letters was 56.1% versus 12.3% (P<0.001) at week 24, 55.3% versus 30.1% (P<0.001) at week 52, and 49.1% versus 23.3% (P<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean change from baseline BCVA was also significantly higher in the IAI 2Q4 + PRN group compared with the sham + IAI PRN group at week 24 (+17.3 vs. -4.0 letters; P<0.001), week 52 (+16.2 vs. +3.8 letters; P<0.001), and week 100 (+13.0 vs. +1.5 letters; P<0.0001). The mean reduction from baseline in central retinal thickness was 457.2 versus 144.8 μm (P<0.001) at week 24, 413.0 versus 381.8 μm at week 52 (P = 0.546), and 390.0 versus 343.3 μm at week 100 (P = 0.366) in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean number (standard deviation) of PRN injections in the IAI 2Q4 + PRN and sham + IAI PRN groups was 2.7 ± 1.7 versus 3.9 ± 2.0 during weeks 24 to 52 and 3.3 ± 2.1 versus 2.9 ± 2.0 during weeks 52 to 100, respectively. The most frequent ocular serious adverse event from baseline to week 100 was vitreous hemorrhage (0.9% vs. 6.8% in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively). The visual and anatomic improvements after fixed dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52 were diminished after continued PRN dosing, with a reduced monitoring frequency from weeks 52 to 100. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  8. Tolerance development in Listeria monocytogenes-Escherichia coli dual-species biofilms after sublethal exposures to pronase-benzalkonium chloride combined treatments.

    PubMed

    Rodríguez-López, Pedro; Cabo, Marta López

    2017-10-01

    This study was designed to assess the effects that sublethal exposures to pronase (PRN) and benzalkonium chloride (BAC) combined treatments have on Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel in terms of tolerance development (TD) to these compounds. Additionally, fluorescence microscopy was used to observe the changes of the biofilm structure. PRN-BAC exposure was carried out using three different approaches and TD was evaluated treating biofilms with a final 100 μg/ml PRN followed by 50 μg/ml BAC combined treatment. Results showed that exposure to PRN-BAC significantly decreased the number of adhered L. monocytogenes (P < 0.05), while E. coli counts remained generally unaltered. It was also demonstrated that the incorporation of recovery periods during sublethal exposures increased the tolerance of both species of the mixed biofilm to the final PRN-BAC treatment. Moreover, control biofilms became more resistant to PRN-BAC if longer incubation periods were used. Regardless of the treatment used, log reduction values were generally lower in L. monocytogenes compared to E. coli. Additionally, microscopy images showed an altered morphology produced by sublethal PRN-BAC in exposed L. monocytogenes-E. coli dual-species biofilms compared to control samples. Results also demonstrated that L. monocytogenes-E. coli dual-species biofilms are able to develop tolerance to PRN-BAC combined treatments depending on way they have been previously exposed. Moreover, they suggest that the generation of bacterial tolerance should be included as a parameter for sanitation procedures design. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Ecologically based targets for bioavailable (reactive) nitrogen discharge from the drainage basins of the Wet Tropics region, Great Barrier Reef.

    PubMed

    Wooldridge, Scott A; Brodie, Jon E; Kroon, Frederieke J; Turner, Ryan D R

    2015-08-15

    A modelling framework is developed for the Wet Tropics region of the Great Barrier Reef that links a quantitative river discharge parameter (viz. dissolved inorganic nitrogen concentration, DIN) with an eutrophication indicator within the marine environment (viz. chlorophyll-a concentration, chl-a). The model predicts catchment-specific levels of reduction (%) in end-of-river DIN concentrations (as a proxy for total potentially reactive nitrogen, PRN) needed to ensure compliance with chl-a 'trigger' guidelines for the ecologically distinct, but PRN-related issues of crown-of-thorns starfish (COTS) outbreaks, reef biodiversity loss, and thermal bleaching sensitivity. The results indicate that even for river basins dominated by agricultural land uses, quite modest reductions in end-of-river PRN concentrations (∼20-40%) may assist in mitigating the risk of primary COTS outbreaks from the mid-shelf reefs of the Wet Tropics. However, more significant reductions (∼60-80%) are required to halt and reverse declines in reef biodiversity, and loss of thermal bleaching resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Serologic Evidence of Jamestown Canyon and Keystone Virus Infection in Vertebrates of the Delmarva Peninsula

    DTIC Science & Technology

    1982-01-01

    as a potential tailed deer neutralized both JC and KEY viruses , amplifying host of this virus . Sika deer, and cot- Evidence based on PRN.,, titers...Bunyaviridae, Cali- fornia serogroup). Neutralizing (N) antibody to JC virus was most prevalent in white-tailed deer, sika deer, cottontail rabbits and... viruses also was found in raccoons, horses and humans. JC and/or KEY virus N antibodies were not demonstrable in sera of several other species of

  11. Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults.

    PubMed

    Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

    2017-01-02

    An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (P< 0.05). The anti-PRN IgG, anti-tetanus and anti-diphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel® and elicited significantly higher immune responses to PT and FHA.

  12. Spectral-Domain Optical Coherence Tomography-Driven Treat-and-Extend and Pro Re Nata Regimen in Patients with Macular Oedema due to Retinal Vein Occlusion: 24-Month Evaluation and Outcome Predictors.

    PubMed

    Guichard, Maria-Magdalena; Xavier, Anton R; Türksever, Cengiz; Pruente, Christian; Hatz, Katja

    2018-03-22

    To analyse the efficacy and outcome predictors of ranibizumab using a spectral-domain optical coherence tomography (SD-OCT)-driven treat-and-extend regimen (TER) versus SD-OCT-driven pro re nata regimen (PRN) in patients with cystoid macular oedema (CME) due to branch or central retinal vein occlusion (BRVO, CRVO). Retrospective, consecutive case series. Evaluation included best corrected visual acuity (BCVA), morphological parameters on SD-OCT, and treatment frequency. From baseline to months 12, 18, and 24, BCVA improved by 16.6 ± 13.1, 15.5 ± 14.4, and 16.6 ± 15.8 letters, respectively, in TER (n = 45), compared to 11.3 ± 17.0, 11.0 ± 15.0, and 10 ± 20.5 letters in PRN (n = 31) (p = 0.152, p = 0.237, p = 0.172). The mean reduction in central retinal thickness was -261 ± 189, -272 ± 188, and -264 ± 158 μm, respectively, in TER, compared to -130 ± 196, -140 ± 210, and -166 ± 207 μm in PRN (p = 0.006, p = 0.017, p = 0.064). 59% (53%) of TER and 22% (17%) of PRN patients showed no intra- or subretinal fluid on SD-OCT at 12 (24) months. Using TER, the maximum recurrence-free treatment interval increased from 8.9 ± 2.3 weeks at 12 months to 9.8 ± 2.3 and 10.5 ± 2.7 weeks at 18 and 24 months, respectively. The number of injections was significantly higher in the TER than in the PRN group. In CME, due to BRVO/CRVO, TER provides better morphological outcome using more injections than PRN. © 2018 The Author(s) Published by S. Karger AG, Basel.

  13. Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2015-11-17

    Whooping cough or pertussis is a highly infectious respiratory disease in humans caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been associated with the recent resurgence of pertussis in developed countries including Australia despite high vaccination coverage where B. pertussis strains that do not express pertactin (Prn), a key antigenic component of the ACV, have emerged and become prevalent. In this study, we used an in vivo competition assay in mice immunised with ACV and in naïve (control) mice to compare the proportion of colonisation with recent clinical Prn positive and Prn negative B. pertussis strains from Australia. The Prn negative strain colonised the respiratory tract more effectively than the Prn positive strain in immunised mice, out-competing the Prn positive strain by day 3 of infection. However, in control mice, the Prn positive strain out-competed the Prn negative strain. Our findings of greater ability of Prn negative strains to colonise ACV-immunised mice are consistent with reports of selective advantage for these strains in ACV-immunised humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Changing characteristics of a Psychiatric Emergency Care Centre. An eight year follow-up study.

    PubMed

    Seymour, Joanne; Chapman, Tristan; Starcevic, Vladan; Viswasam, Kirupamani; Brakoulias, Vlasios

    2018-05-01

    The objective of this study was to report changes in characteristics of admissions to an established Psychiatric Emergency Care Centre (PECC) eight years after its opening. Key clinical characteristics of admissions to the PECC were documented for 327 patients in 2015 and compared with the 477 patients in 2007, which is when the centre first opened. The characteristics of admission were evaluated using an audit of medical records from June to December in both 2007 and 2015. Statistically significant differences ( p<0.05) between 2007 and 2015 were: a reduction in the numbers of patients admitted with depression; a reduction in the numbers of patients diagnosed with adjustment disorder; an increase in the numbers of patients diagnosed with borderline personality disorder; a reduction in pro re nata (prn) use, including a reduction in the need for chemical restraint with midazolam and a decrease in the length of admission in the PECC. The significant reduction in aggression, the use of prn medication and the number of people with longer stays within the PECC support the usefulness of PECCs in relation to patient satisfaction and adherence to admission criteria policy. These factors may be considered as indicators of the efficiency of a PECC.

  15. Rapid increase in pertactin-deficient Bordetella pertussis isolates, Australia.

    PubMed

    Lam, Connie; Octavia, Sophie; Ricafort, Lawrence; Sintchenko, Vitali; Gilbert, Gwendolyn L; Wood, Nicholas; McIntyre, Peter; Marshall, Helen; Guiso, Nicole; Keil, Anthony D; Lawrence, Andrew; Robson, Jenny; Hogg, Geoff; Lan, Ruiting

    2014-04-01

    Acellular vaccines against Bordetella pertussis were introduced in Australia in 1997. By 2000, these vaccines had replaced whole-cell vaccines. During 2008-2012, a large outbreak of pertussis occurred. During this period, 30% (96/320) of B. pertussis isolates did not express the vaccine antigen pertactin (Prn). Multiple mechanisms of Prn inactivation were documented, including IS481 and IS1002 disruptions, a variation within a homopolymeric tract, and deletion of the prn gene. The mechanism of lack of expression of Prn in 16 (17%) isolates could not be determined at the sequence level. These findings suggest that B. pertussis not expressing Prn arose independently multiple times since 2008, rather than by expansion of a single Prn-negative clone. All but 1 isolate had ptxA1, prn2, and ptxP3, the alleles representative of currently circulating strains in Australia. This pattern is consistent with continuing evolution of B. pertussis in response to vaccine selection pressure.

  16. Discontinuing the Use of PRN Intramuscular Medication for Agitation in an Acute Psychiatric Hospital.

    PubMed

    Hayes, Ariel; Russ, Mark J

    2016-03-01

    This study examined the impact of eliminating intramuscular PRN medication for agitation on patient and staff safety in an acute psychiatric inpatient setting. The current retrospective chart review investigated the use of PRN medications (oral and intramuscular) to treat acute agitation, including aggression, and related outcomes before and after a mandated change in PRN practice that required real time physician input before administration of intramuscular medications. The use of both oral and intramuscular PRN medications dramatically decreased following implementation of the mandated change in practice. In particular, the use of intramuscular PRNs for agitation decreased by about half. Despite this decrease, the assault rate in the hospital was unchanged, and the utilization of restraint and seclusion continued to decrease. It is possible to reduce the utilization of PRN medications for agitation without broadly compromising safety on acute care psychiatric inpatient units.

  17. Responses of neurons in paramedian reticular nucleus to chemical stimulations and alteration of blood pressure in rats.

    PubMed

    Lin, A M; Wang, Y; Su, C K; Lee, E H; Kuo, J S; Chai, C Y

    1991-01-01

    Previous studies have shown that paramedian reticular nucleus (PRN) possessed sympathetic and parasympathetic inhibitions on autonomic nervous system. In the present study, the cardiovascular reactions of PRN by locally-applied DL-homocysteic acid (DLH), acetylcholine (ACh), monoamines and electrophysiological properties of PRN neurons responding to intravenous injection of ACh and NE were studied in adult Sprague-Dawley rats. In PRN, electrical stimulation caused hypotension and mild bradycardia while microinjection of DLH, which excites only cell body of the neurons but not passing fibers, evoked similar responses. Furthermore, direct application of ACh, norepinephrine (NE) or serotonin (5-HT) in PRN also produced hypotension, suggesting that these putative neurotransmitters may be involved in the cardiovascular responses in PRN. The electrophysiological properties of PRN neurons were studied: Neurons in PRN could be categorized into three types according to their neuronal activities in response to the changes of systemic arterial blood pressure (SAP) by ACh or NE given intravenously. Type I neurons (25/69) were activated in the same direction of SAP changes. Type II neurons (17/69) responded opposite to the direction of SAP changes. Type III neurons (27/69) responded inconsistently to the changes of SAP. All the three types of neurons were excited by locally-applied DLH and possessed a similar unfiltered action potential duration of greater than 0.5 msec.

  18. The impact of a good practice manual on professional practice associated with psychotropic PRN in acute mental health wards: an exploratory study.

    PubMed

    Baker, J A; Lovell, K; Harris, N

    2008-10-01

    As required or pro re nata (PRN) psychotropic medicines are frequently used in acute mental health wards. PRN is known to contribute to polypharmacy and high doses of antipsychotic medication. Few studies have attempted to improve clinician's use of these potentially harmful drugs. The objectives of the study were to determine the impact and acceptability of a good practice manual on prescribing and administration practices of PRN psychotropic medication in acute mental health wards. The study used a pre-post exploratory design with two acute mental health wards in the NW of England. Over the total trial period of 10 weeks, 28 of 35 patients received 484 doses of PRN. Patients had a mean of 3.6 prescriptions of 14 different PRN medications in 34 different dose combinations prescribed. Medication errors beyond poor quality of prescribing occurred in 23 of the 35 patients (65.7%). Prescription quality improved following the introduction of the intervention but quality of nursing notes reduced. Acceptability of the manual to both nursing and medical staff was high. The introduction of the manual appeared to influence some of the practices associated with the prescribing and administration of PRN psychotropic medications. Further, larger, more robust studies are required in this area. In particular research is required to identify the reasons why professionals continue to rely so heavily on using PRN medication.

  19. PRN 95-3: Reduction of Worker protection Standard (WPS) Interim Restricted Entry Intervals (REIS) for Certain Low Risk Pesticides

    EPA Pesticide Factsheets

    On January 11, 1995, EPA published a draft policy on Reduced Restricted Entry Intervals for Certain Pesticides, in the Federal Register. The final policy was published in the Federal Register on May 3, 1995. This Notice contains the final policy.

  20. High-Speed Digital Interferometry

    NASA Technical Reports Server (NTRS)

    De Vine, Glenn; Shaddock, Daniel A.; Ware, Brent; Spero, Robert E.; Wuchenich, Danielle M.; Klipstein, William M.; McKenzie, Kirk

    2012-01-01

    Digitally enhanced heterodyne interferometry (DI) is a laser metrology technique employing pseudo-random noise (PRN) codes phase-modulated onto an optical carrier. Combined with heterodyne interferometry, the PRN code is used to select individual signals, returning the inherent interferometric sensitivity determined by the optical wavelength. The signal isolation arises from the autocorrelation properties of the PRN code, enabling both rejection of spurious signals (e.g., from scattered light) and multiplexing capability using a single metrology system. The minimum separation of optical components is determined by the wavelength of the PRN code.

  1. Construction of a β-galactosidase-gene-based fusion is convenient for screening candidate genes involved in regulation of pyrrolnitrin biosynthesis in Pseudomonas chlororaphis G05.

    PubMed

    Luo, Wangtai; Miao, Jing; Feng, Zhibin; Lu, Ruiyang; Sun, Xiaoqiang; Zhang, Baoshen; Ding, Weiqiu; Lu, Yang; Wang, Yanhua; Chi, Xiaoyan; Ge, Yihe

    2018-05-28

    In our recent work, we found that pyrrolnitrin, and not phenazines, pyrrolnitrin contributed to the suppression of the mycelia growth of Fusarium graminearum that causes heavy Fusarium head blight (FHB) disease in cereal crops. However, pyrrolnitrin production of Pseudomonas chlororaphis G05 in King's B medium was very low. Although a few regulatory genes mediating the prnABCD (the prn operon, pyrrolnitrin biosynthetic locus) expression have been identified, it is not enough for us to enhance pyrrolnitrin production by systematically constructing a genetically-engineered strain. To obtain new candidate genes involved in regulation of the prn operon expression, we successfully constructed a fusion mutant G05ΔphzΔprn::lacZ, in which most of the coding regions of the prn operon and the phzABCDEFG (the phz operon, phenazine biosynthetic locus) were deleted, and the promoter region plus the first thirty condons of the prnA was in-frame fused with the truncated lacZ gene on its chromosome. The expression of the fused lacZ reporter gene driven by the promoter of the prn operon made it easy for us to detect the level of the prn expression in terms of the color variation of colonies on LB agar plates supplemented with 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside (X-Gal). With this fusion mutant as a recipient strain, mini-Tn5-based random insertional mutagenesis was then conducted. By picking up colonies with color change, it is possible for us to screen and identify new candidate genes involved in regulation of the prn expression. Identification of additional regulatory genes in further work could reasonably be expected to increase pyrrolnitrin production in G05 and to improve its biological control function.

  2. Structure and polymorphism of the mouse prion protein gene.

    PubMed Central

    Westaway, D; Cooper, C; Turner, S; Da Costa, M; Carlson, G A; Prusiner, S B

    1994-01-01

    Missense mutations in the prion protein (PrP) gene, overexpression of the cellular isoform of PrP (PrPC), and infection with prions containing the scrapie isoform of PrP (PrPSc) all cause neurodegenerative disease. To understand better the physiology and expression of PrPC, we retrieved mouse PrP gene (Prn-p) yeast artificial chromosome (YAC), cosmid, phage, and cDNA clones. Physical mapping positions Prn-p approximately 300 kb from ecotropic virus integration site number 4 (Evi-4), compatible with failure to detect recombination between Prn-p and Evi-4 in genetic crosses. The Prn-pa allele encompasses three exons, with exons 1 and 2 encoding the mRNA 5' untranslated region. Exon 2 has no equivalent in the Syrian hamster and human PrP genes. The Prn-pb gene shares this intron/exon structure but harbors an approximately 6-kb deletion within intron 2. While the Prn-pb open reading frame encodes two amino acid substitutions linked to prolonged scrapie incubation periods, a deletion of intron 2 sequences also characterizes inbred strains such as RIII/S and MOLF/Ei with shorter incubation periods, making a relationship between intron 2 size and scrapie pathogenesis unlikely. The promoter regions of a and b Prn-p alleles include consensus Sp1 and AP-1 sites, as well as other conserved motifs which may represent binding sites for as yet unidentified transcription factors. Images PMID:7912827

  3. Contribution of Bordetella bronchiseptica Filamentous Hemagglutinin and Pertactin to Respiratory Disease in Swine▿ †

    PubMed Central

    Nicholson, Tracy L.; Brockmeier, Susan L.; Loving, Crystal L.

    2009-01-01

    Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Most studies addressing virulence factors of B. bronchiseptica are based on isolates derived from hosts other than pigs. Two well-studied virulence factors implicated in the adhesion process are filamentous hemagglutinin (FHA) and pertactin (PRN). We hypothesized that both FHA and PRN would serve critical roles in the adhesion process and be necessary for colonization of the swine respiratory tract. To investigate the role of FHA and PRN in Bordetella pathogenesis in swine, we constructed mutants containing an in-frame deletion of the FHA or the PRN structural gene in a virulent B. bronchiseptica swine isolate. Both mutants were compared to the wild-type swine isolate for their ability to colonize and cause disease in swine. Colonization of the FHA mutant was lower than that of the wild type at all respiratory tract sites and time points examined and caused limited to no disease. In contrast, the PRN mutant caused similar disease severity relative to the wild type; however, colonization of the PRN mutant was reduced relative to the wild type during early and late infection and induced higher anti-Bordetella antibody titers. Together, our results indicate that despite inducing different pathologies and antibody responses, both FHA and PRN are necessary for optimal colonization of the swine respiratory tract. PMID:19237531

  4. Digitally Enhanced Heterodyne Interferometry

    NASA Technical Reports Server (NTRS)

    Shaddock, Daniel; Ware, Brent; Lay, Oliver; Dubovitsky, Serge

    2010-01-01

    Spurious interference limits the performance of many interferometric measurements. Digitally enhanced interferometry (DEI) improves measurement sensitivity by augmenting conventional heterodyne interferometry with pseudo-random noise (PRN) code phase modulation. DEI effectively changes the measurement problem from one of hardware (optics, electronics), which may deteriorate over time, to one of software (modulation, digital signal processing), which does not. DEI isolates interferometric signals based on their delay. Interferometric signals are effectively time-tagged by phase-modulating the laser source with a PRN code. DEI improves measurement sensitivity by exploiting the autocorrelation properties of the PRN to isolate only the signal of interest and reject spurious interference. The properties of the PRN code determine the degree of isolation.

  5. Efficacy and safety of a fixed bimonthly ranibizumab treatment regimen in eyes with neovascular age-related macular degeneration: results from the RABIMO trial.

    PubMed

    Feltgen, Nicolas; Bertelmann, Thomas; Bretag, Mirko; Pfeiffer, Sebastian; Hilgers, Reinhard; Callizo, Josep; Goldammer, Lena; Bemme, Sebastian; Hoerauf, Hans

    2017-05-01

    To evaluate prospectively the efficacy and safety of a fixed bimonthly ranibizumab treatment regimen (RABIMO) in eyes with neovascular age-related macular degeneration (nAMD) and to compare these results with a pro re nata (PRN) treatment scheme. This was a 12-month, phase IV, single center, randomised, non-inferiority study. Following three initial monthly injections, patients were randomised to receive either ranibizumab bimonthly (RABIMO group) or ranibizumab PRN (PRN group) (n = 20 each). Main outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of injections, and adverse events (AEs). BCVA [median (interquartile range, IQR)] increased significantly in both groups after 12 months [RABIMO group +8.5 (14); PRN group +6.5 (16) ETDRS letters] when compared to baseline (p < 0.0001; p = 0.0085). At month 12, the RABIMO treatment regimen was non-inferior to the PRN scheme (∆BCVA = 3.5 ETDRS letters; p < 0.0001). CRT was significantly reduced in both groups after the 12-month study period (p < 0.0001 each), with no significant difference between groups (p = 0.6772). Number of overall injections [median (IQR)] was 8 (0) in the RABIMO versus 4 (5) in the PRN group (p = 0.0037). Three patients in the RABIMO group received one additional unscheduled injection. We observed no significant differences between groups in the number of patients with reported SAEs/AEs (RABIMO group n = 6/15; PRN group n = 7/13) (p = 0.7357/p = 0.4902). We found no evidence of significant functional or anatomical differences between the RABIMO and PRN treatment regimens. However, the RABIMO group's number of injections was twice as high as the PRN group's (protocol-driven). In light of potential side effects, the fixed bimonthly treatment regimen might not be advisable for routine clinical care, but it might be a worthwhile treatment option if monthly monitoring is not possible. Eudra-CT number: 2009-017324-11.

  6. Two-year antibody persistence in children vaccinated at 12-15 months with a measles-mumps-rubella virus vaccine without human serum albumin.

    PubMed

    Berry, Andrea A; Abu-Elyazeed, Remon; Diaz-Perez, Clemente; Mufson, Maurice A; Harrison, Christopher J; Leonardi, Michael; Twiggs, Jerry D; Peltier, Christopher; Grogg, Stanley; Carbayo, Antonio; Shapiro, Steven; Povey, Michael; Baccarini, Carmen; Innis, Bruce L; Henry, Ouzama

    2017-07-03

    One combined measles-mumps-rubella (MMR) vaccine without Human Serum Albumin (HSA) is currently licensed in the USA (M-M-R II; Merck, USA) and another has been developed (Priorix™ [MMR-RIT, GSK, Belgium]). In this follow-up study, children from USA or Puerto Rico, who had received one dose of M-M-R II or MMR-RIT at 12-15 months of age in the primary study (NCT00861744), were followed-up for 2 y post-vaccination. Anti-measles and anti-rubella antibodies were measured using Enzyme-Linked Immunosorbent Assay (ELISA), and anti-mumps antibodies using ELISA and plaque reduction neutralization (PRN) assays. Serious adverse events (SAEs) were recorded during the entire follow-up. The according-to-protocol (ATP) persistence cohort included 752 children (M-M-R II = 186, MMR-RIT = 566), who received primary vaccination at a mean age of 12.3 ( ± 0.67) months. 104 children were revaccinated with MMR-containing vaccines; therefore, serology results for timepoints after revaccination were excluded from the analysis. Seropositivity for measles (Year 1≥ 98.3%; Year 2≥ 99.4%) and rubella (Year 1≥ 98.9%; Year 2 = 100%) remained as high at Year 2 as at Day 42. Similarly, seropositivity for mumps determined by ELISA (Year 1≥ 90.1%; Year 2≥ 94.1%) and PRN assays (Year 1≥ 87.5%; Year 2≥ 91.7%) persisted. Thirty-three SAEs were recorded in 23 children; 2 SAEs (inguinal adenitis and idiopathic thrombocytopenic purpura) and one SAE (febrile convulsion) were considered as potentially related to MMR-RIT and M-M-R II, respectively. This study showed that antibodies against measles, mumps and rubella persisted for up to 2 y post-vaccination with either MMR vaccine in children aged 12-15 months, and that both vaccines were well-tolerated during the follow-up period.

  7. Electronic Clinical Trial Protocol Distribution via the World-Wide Web

    PubMed Central

    Afrin, Lawrence B.; Kuppuswamy, Valarmathi; Slater, Barbara; Stuart, Robert K.

    1997-01-01

    Clinical trials today typically are inefficient, paper-based operations. Poor community physician awareness of available trials and difficult referral mechanisms also contribute to poor accrual. The Physicians Research Network (PRN) web was developed for more efficient trial protocol distribution and eligibility inquiries. The Medical University of South Carolina's Hollings Cancer Center trials program and two community oncology practices served as a testbed. In 581 man-hours over 18 months, 147 protocols were loaded into PRN. The trials program eliminated all protocol hardcopies except the masters, reduced photocopier use 59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage PRN. There were no known security breaches, downtime, or content-related problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method for distributing protocols and reducing distribution errors and delays because only a single copy of each protocol is maintained. Furthermore, PRN is being extended to serve other aspects of trial operations. PMID:8988471

  8. Documentation of psychotropic PRN medication administration: An evaluation of electronic health records compared with paper charts and verbal reports.

    PubMed

    Martin, Krystle; Ham, Elke; Hilton, Zoe

    2018-05-12

    To describe the documentation of pro re nata (PRN) medication for anxiety, and to compare documentation at two hospitals providing similar psychiatric services, one that used paper charts and another that used an electronic health record (EHR). We also assessed congruence between nursing documentation and verbal reports from staff about the PRN administration process. The ability to accurately document patients' symptoms and the care given is considered a core competency of the nursing profession (Wilkinson, 2007); however, researchers have found poor concordance between nursing notes and verbal reports or observations of events (e.g., De Marinis, Piredda, Pascarella et al., 2009) and considerable information missing (e.g., Marinis et al., 2010). Additionally, the administration of PRN medication has consistently been noted to be poorly documented (e.g., Baker, Lovell, & Harris, 2008). The project was a mixed method, two-phase study that collected data from two sites. In phase 1, nursing documentation of PRN medication administrations was reviewed in patient charts; phase 2 included verbal reports from staff about this practice. Nurses using EHR documented more information than those using paper charts, including the reason for PRN administration, who initiated the administration, and effectiveness. There were some differences between written and verbal reports, including whether potential side effects were explained to patients prior to PRN administration. We continue the calls for attention to be paid to improving the quality of nursing documentation. Our results support the shift to using EHR, yet not relying on this method completely to ensure comprehensiveness of documentation. Efforts to address the quality of documentation, particularly for PRN administration, are needed. This could be done through training, using structured report templates, and switching to electronic databases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.

    PubMed

    Kim, Edward; Seftel, Allen; Goldfischer, Evan; Baygani, Simin; Burns, Patrick

    2015-02-01

    Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. NCT01130532. International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

  10. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study.

    PubMed

    Brown, David M; Heier, Jeffrey S; Clark, W Lloyd; Boyer, David S; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Sandbrink, Rupert; Zhu, Xiaoping; Haller, Julia A

    2013-03-01

    To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO). Randomized controlled trial. This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52. At week 24, 56.1% of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3% of sham patients (P < .001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1% of sham + IAI PRN patients (P < .001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P < .001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure. Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Outcomes when Switching from a pro re nata Regimen to a Treat and Extend Regimen Using Aflibercept in Neovascular Age-Related Macular Degeneration.

    PubMed

    Giannakaki-Zimmermann, Helena; Ebneter, Andreas; Munk, Marion R; Wolf, Sebastian; Zinkernagel, Martin S

    2016-01-01

    To investigate outcomes in patients with neovascular age-related macular degeneration (AMD) switched from a pro re nata regimen (PRN) to a treat and extend regimen (TER) under aflibercept. Thirty-two patients were observed over 2 years: the first year on PRN and the second year on TER. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. Intra- and subretinal fluid as well as the number of visits and injections were assessed. Both regimens resulted in a stable BCVA. Patients in TER had a significant decrease of CRT after 1 year compared to 1 year of treatment on PRN (p < 0.0001). TER resulted in significantly less visits; however, significantly more injections were observed over the course of 1 year compared to PRN (10.25 vs. 7.5, p < 0.0001 and 5.97 vs. 7.5, p = 0.0002, respectively). A switch from PRN to TER in patients treated with aflibercept for AMD appears to be safe. © 2016 S. Karger AG, Basel.

  12. Monitoring of an antigen manufacturing process.

    PubMed

    Zavatti, Vanessa; Budman, Hector; Legge, Raymond; Tamer, Melih

    2016-06-01

    Fluorescence spectroscopy in combination with multivariate statistical methods was employed as a tool for monitoring the manufacturing process of pertactin (PRN), one of the virulence factors of Bordetella pertussis utilized in whopping cough vaccines. Fluorophores such as amino acids and co-enzymes were detected throughout the process. The fluorescence data collected at different stages of the fermentation and purification process were treated employing principal component analysis (PCA). Through PCA, it was feasible to identify sources of variability in PRN production. Then, partial least square (PLS) was employed to correlate the fluorescence spectra obtained from pure PRN samples and the final protein content measured by a Kjeldahl test from these samples. In view that a statistically significant correlation was found between fluorescence and PRN levels, this approach could be further used as a method to predict the final protein content.

  13. High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry.

    PubMed

    Manicke, Nicholas E; Kistler, Thomas; Ifa, Demian R; Cooks, R Graham; Ouyang, Zheng

    2009-02-01

    A newly developed high-throughput desorption electrospray ionization (DESI) source was characterized in terms of its performance in quantitative analysis. A 96-sample array, containing pharmaceuticals in various matrices, was analyzed in a single run with a total analysis time of 3 min. These solution-phase samples were examined from a hydrophobic PTFE ink printed on glass. The quantitative accuracy, precision, and limit of detection (LOD) were characterized. Chemical background-free samples of propranolol (PRN) with PRN-d(7) as internal standard (IS) and carbamazepine (CBZ) with CBZ-d(10) as IS were examined. So were two other sample sets consisting of PRN/PRN-d(7) at varying concentration in a biological milieu of 10% urine or porcine brain total lipid extract, total lipid concentration 250 ng/microL. The background-free samples, examined in a total analysis time of 1.5 s/sample, showed good quantitative accuracy and precision, with a relative error (RE) and relative standard deviation (RSD) generally less than 3% and 5%, respectively. The samples in urine and the lipid extract required a longer analysis time (2.5 s/sample) and showed RSD values of around 10% for the samples in urine and 4% for the lipid extract samples and RE values of less than 3% for both sets. The LOD for PRN and CBZ when analyzed without chemical background was 10 and 30 fmol, respectively. The LOD of PRN increased to 400 fmol analyzed in 10% urine, and 200 fmol when analyzed in the brain lipid extract.

  14. PRN: a preprint service for catalyzing R-fMRI and neuroscience related studies

    PubMed Central

    Yan, Chao-gan; Li, Qingyang; Gao, Lei

    2015-01-01

    Sharing drafts of scientific manuscripts on preprint hosting services for early exposure and pre-publication feedback is a well-accepted practice in fields such as physics, astronomy, or mathematics. The field of neuroscience, however, has yet to adopt the preprint model. A reason for this reluctance might partly be the lack of central preprint services for the field of neuroscience. To address this issue, we announce the launch of Preprints of the R-fMRI Network (PRN), a community funded preprint hosting service. PRN provides free-submission and free hosting of manuscripts for resting state functional magnetic resonance imaging (R-fMRI) and neuroscience related studies. Submitted articles are openly discussed and receive feedback from readers and a panel of invited consultants from the R-fMRI Network. All manuscripts and feedback are freely accessible online with citable permanent URL for open-access. The goal of PRN is to supplement the peer reviewed journal publication system – by more rapidly communicating the latest research achievements throughout the world. We hope PRN would help the field to embrace the preprint model and thus further accelerate R-fMRI and neuroscience related studies, eventually enhancing human mental health. PMID:25844159

  15. Clinical Outcomes of Fixed Versus As-Needed Use of Artificial Tears in Dry Eye Disease: A 6-Week, Observer-Masked Phase 4 Clinical Trial.

    PubMed

    Asbell, Penny; Vingrys, Algis J; Tan, Jacqueline; Ogundele, Abayomi; Downie, Laura E; Jerkins, Gary; Shettle, Lee

    2018-05-01

    To evaluate the clinical effects of using fixed (four times daily [QID]) versus as-needed (PRN) dosing of an artificial tear product (polyethylene glycol/propylene glycol [PEG/PG]; Systane Ultra) in individuals with dry eye disease. In this prospective, multicenter, observer-masked, active-control, parallel-group trial, participants were randomized (1:2 allocation) to receive 1 drop of PEG/PG QID (n = 34) or PRN (n = 63) for 28 days. The primary endpoint was change from baseline in the total ocular surface staining (TOSS) score (according to the Oxford scale) at day 28. At day 28, the change from baseline in least squares mean (LSM) TOSS scores for QID and PRN groups were -1.19 and -0.94, respectively (treatment difference [TD]: -0.26; 95% confidence interval [CI]: -∞ to 0.21; P = 0.184); superiority of QID versus PRN dosing was not established, as the upper limit of one-sided 95% CI for TD was not <0 (prespecified limit). At day 28, for QID and PRN groups, the LSM change from baseline in Impact of Dry Eye on Everyday Life (IDEEL) scores was symptom-bother, -7.0 and -2.94 (TD: -4.06, P = 0.037); treatment effectiveness, 2.43 and 0.16 (TD: 2.28, P = 0.278); and treatment-related inconvenience, -11.56 and -2.77 (TD: -8.8, P = 0.996), respectively. Incidence of adverse events was low (≤3.2%) in both the groups; no serious adverse events were reported. QID dosing of PEG/PG was not superior to PRN dosing in terms of ocular staining. The IDEEL symptom-bother score favored QID dosing, suggesting that regular use of artificial tears may provide better symptomatic relief than PRN use. (ClinicalTrials.gov number, NCT02446015.).

  16. Space Derived Health Aids (PRN, Neuropacemaker)

    NASA Technical Reports Server (NTRS)

    1981-01-01

    St. Jude Medical's (formerly known as Pacesetter Systems, Inc.) Programmable Rechargeable Neuropacemaker (PRN) is an implantable human tissue stimulator designed to provide relief to patients with disorders treatable by electrical stimulation. Examples are back, leg, and arm pain, cancer pain and multiple sclerosis.

  17. The video head impulse test during post-rotatory nystagmus: physiology and clinical implications.

    PubMed

    Mantokoudis, Georgios; Tehrani, Ali S Saber; Xie, Li; Eibenberger, Karin; Eibenberger, Bernhard; Roberts, Dale; Newman-Toker, David E; Zee, David S

    2016-01-01

    The aim of this study was to test the effects of a sustained nystagmus on the head impulse response of the vestibulo-ocular reflex (VOR) in healthy subjects. VOR gain (slow-phase eye velocity/head velocity) was measured using video head impulse test goggles. Acting as a surrogate for a spontaneous nystagmus (SN), a post-rotatory nystagmus (PRN) was elicited after a sustained, constant-velocity rotation, and then head impulses were applied. 'Raw' VOR gain, uncorrected for PRN, in healthy subjects in response to head impulses with peak velocities in the range of 150°/s-250°/s was significantly increased (as reflected in an increase in the slope of the gain versus head velocity relationship) after inducing PRN with slow phases of nystagmus of high intensity (>30°/s) in the same but not in the opposite direction as the slow-phase response induced by the head impulses. The values of VOR gain themselves, however, remained in the normal range with slow-phase velocities of PRN < 30°/s. Finally, quick phases of PRN were suppressed during the first 20-160 ms of a head impulse; the time frame of suppression depended on the direction of PRN but not on the duration of the head impulse. Our results in normal subjects suggest that VOR gains measured using head impulses may have to be corrected for any superimposed SN when the slow-phase velocity of nystagmus is relatively high and the peak velocity of the head movements is relatively low. The suppression of quick phases during head impulses may help to improve steady fixation during rapid head movements.

  18. Removal of Listeria monocytogenes dual-species biofilms using combined enzyme-benzalkonium chloride treatments.

    PubMed

    Rodríguez-López, Pedro; Carballo-Justo, Alba; Draper, Lorraine A; Cabo, Marta L

    2017-01-01

    The effects of pronase (PRN), cellulase (CEL) or DNaseI alone or combined with benzalkonium chloride (BAC) against Listeria monocytogenes-carrying biofilms were assayed. The best removal activity against L. monocytogenes-Escherichia coli biofilms was obtained using DNaseI followed by PRN and CEL. Subsequently, a modified logistic model was used to quantify the combined effects of PRN or DNaseI with BAC. A better BAC performance after PRN compared to DNaseI eradicating L. monocytogenes was observed. In E. coli the effects were the opposite. Finally, effects of DNaseI and DNaseI-BAC treatments were compared against two different L. monocytogenes-carrying biofilms. DNaseI-BAC was more effective against L. monocytogenes when co-cultured with E. coli. Nonetheless, comparing the removal effects after BAC addition, these were higher in mixed-biofilms with Pseudomonas fluorescens. However, a high number of released viable cells was observed after combined treatments. These results open new perspectives of enzymes as an anti-biofilm strategy for environmental pathogen control.

  19. Efficacy of Continuous Dosing of Tadalafil Once Daily vs Tadalafil On Demand in Clinical Subgroups of Men With Erectile Dysfunction: A Descriptive Comparison Using the Integrated Tadalafil Databases.

    PubMed

    Brock, Gerald; Ni, Xiao; Oelke, Matthias; Mulhall, John; Rosenberg, Matt; Seftel, Allen; D'Souza, Deborah; Barry, Jane

    2016-05-01

    Various factors play a role in the development of erectile dysfunction (ED). To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m(2), and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m(2) for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Staff and patient accounts of PRN medication administration and non-pharmacological interventions for anxiety.

    PubMed

    Martin, Krystle; Ham, Elke; Hilton, N Zoe

    2018-05-31

    Most psychiatric inpatients will receive psychotropic PRN medication during their hospital stay for agitation, anxiety, and/or insomnia. While helpful in some cases, caution is warranted with regard to PRN use due to inherent risks of additional medication; therefore, experts advise that non-pharmacological interventions should be attempted first where indicated. However, research to date highlights that, in practice, non-pharmaceutical approaches are attempted in a minority of cases. While some information is known about the practice of PRN administration and the use of and barriers to implementing non-pharmacological interventions for treating acute psychiatric symptoms, full understanding of this practice is hampered by poor or altogether missing documentation of the process. This study used interviews with patients and staff from two psychiatric hospitals to collect first-person accounts of administering PRN medication for anxiety, thereby addressing the limitations of relying on documented notation found in previous research. Our results indicate that nurses are engaging in non-pharmacological interventions more often than had previously been captured in research. However, the types of strategies suggested are not typically evidence based and further, only happening approximately half the time. The barriers to providing such care are centred on two main beliefs about client choice and efficacy of these non-medical strategies. Implications for research and practice are discussed. © 2018 Australian College of Mental Health Nurses Inc.

  1. PRN 2012-1: Material Safety Data Sheets as Pesticide Labeling

    EPA Pesticide Factsheets

    This Notice updates and clarifies EPA’s determination in PRN 92-4 that a Material Safety Data Sheet that accompanies a pesticide product is considered part of the pesticide’s labeling but does not need EPA approval if it is consistent with 40CFR Part 156.

  2. Resistance to changing practice from pro re nata prescriptions to patient group directions in acute mental health settings.

    PubMed

    Price, O; Baker, J A

    2013-09-01

    Poor practice associated with pro re nata (PRN) prescriptions in mental health is known to be common and can increase the risk of serious and potentially fatal side effects. A contributing factor to poor practice is the lack of a clear chain of accountability between the decision to prescribe and administer PRN prescriptions. To address this problem, a patient group direction (PGD) for acute behavioural disturbance (lorazepam 0.5-2 mg) and staff training materials were developed. The intention was to replace PRN prescriptions with the PGD in two mental health trusts. One of the potential benefits of this would be the removal of the contribution of PRN to high and combined dose antipsychotic prescriptions. This proposal, however, was met with significant resistance in both trusts and did not replace PRN as a result. A series of interviews and focus groups were conducted with 16 RMNs working in the two trusts, to explore the reasons why the PGD was met with resistance. Senior nurses perceived resistance to be associated with anxieties over increased responsibility for decision making. Junior nurses reported concerns regarding the medicalization of the nursing role, the paperwork associated with the PGD and the training approach used. Future efforts to implement PGDs in mental health settings must carefully consider the methods for engaging effectively with participating organizations, in terms of managing change and completing the necessary groundwork for successful implementation. © 2012 John Wiley & Sons Ltd.

  3. Genetic Variation of Bordetella pertussis in Austria.

    PubMed

    Wagner, Birgit; Melzer, Helen; Freymüller, Georg; Stumvoll, Sabine; Rendi-Wagner, Pamela; Paulke-Korinek, Maria; Repa, Andreas; Mooi, Frits R; Kollaritsch, Herwig; Mittermayer, Helmut; Kessler, Harald H; Stanek, Gerold; Steinborn, Ralf; Duchêne, Michael; Wiedermann, Ursula

    2015-01-01

    In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.

  4. The treat-and-extend injection regimen versus alternate dosing strategies in age-related macular degeneration: a systematic review and meta-analysis.

    PubMed

    Okada, Mali; Kandasamy, Rathika; Chong, Elaine W; McGuiness, Myra; Guymer, Robyn H

    2018-06-06

    To assess outcomes of the treat-and-extend (T&E) injection regimen for neovascular age related macular degeneration (AMD) as compared to either a monthly or a pro-re-nata (PRN) treatment strategy. Systematic review and meta-analysis METHODS: Studies that compared the T&E regimen with either monthly or PRN dosing for treatment-naïve AMD were included. Trial eligibility, data extraction and risk of bias were assessed according to Cochrane review methods. Estimates were pooled using random effects meta-analysis. Four eligible studies were identified, all using ranibizumab (total n=940 eyes), including two randomized controlled trials comparing T&E to monthly and two retrospective reviews comparing T&E to PRN. No studies evaluating aflibercept were identified. Improvements in vision and central retinal thickness were similar between T&E and monthly at 12 months, with a mean difference of -1.79 letters (95% CI: 3.70, 0.13) and 3.76μm (95% CI: -13.78, 21.30) in favour of monthly injections. In contrast, visual gains were higher in the T&E compared to PRN group (difference of +6.18 letters, 95% CI: 3.28, 9.08). Fewer injections were required using the T&E regimen when compared to monthly (mean of -1.6 and -6.9 injections less at 12 and 24 months respectively). A mean of 1.44 more injections was required for the T&E compared to PRN regimen at 12 months, however this was achieved with fewer visits. Despite the growing preference for the T&E regimen, there is limited head-to-head evidence comparing dosing strategies. The evidence available however, suggests that at 12 months, T&E is comparable to monthly and superior to PRN dosing for both efficacy and safety outcomes when using ranibizumab. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Social Workers in the Substance Abuse Treatment Field: A Snapshot of Service Activities

    ERIC Educational Resources Information Center

    Smith, Mickey J. W.; Whitaker, Tracy; Weismiller, Toby

    2006-01-01

    This article describes the results of the first Practice Research Network (PRN) survey conducted by the National Association of Social Workers, a collaborative project funded by the Center for Substance Abuse Treatment. The objectives of the PRN survey were to develop broad knowledge about social work practices and more specific knowledge about…

  6. Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma.

    PubMed

    Nairismägi, M -L; Gerritsen, M E; Li, Z M; Wijaya, G C; Chia, B K H; Laurensia, Y; Lim, J Q; Yeoh, K W; Yao, X S; Pang, W L; Bisconte, A; Hill, R J; Bradshaw, J M; Huang, D; Song, T L L; Ng, C C Y; Rajasegaran, V; Tang, T; Tang, Q Q; Xia, X J; Kang, T B; Teh, B T; Lim, S T; Ong, C K; Tan, J

    2018-05-01

    Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.

  7. Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation.

    PubMed

    Spyres, Meghan B; Skolnik, Aaron B; Moore, Elizabeth C; Gerkin, Richard D; Padilla-Jones, Angela; Ruha, Anne-Michelle

    2018-06-01

    This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation. This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies. A single regional toxicology center PATIENTS:: Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA). This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing. One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6-12] vs 16 [interquartile range, 12-18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20-44 hr] vs 34 hr [interquartile range, 24-43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications. Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation.

  8. Psychosocial outcomes after initial treatment of erectile dysfunction with tadalafil once daily, tadalafil on demand or sildenafil citrate on demand: results from a randomized, open-label study.

    PubMed

    Hatzimouratidis, K; Buvat, J; Büttner, H; Vendeira, P A S; Moncada, I; Boehmer, M; Henneges, C; Boess, F G

    2014-01-01

    Initiation of ED treatment with a particular PDE5I may influence treatment-adherence and other outcomes. In this multicenter, open-label study, men with ED, naïve to PDE5I, were randomized to tadalafil 5 mg once-a-day (OaD; N=257), 10 mg on demand (PRN; N = 252) or sildenafil-citrate (sildenafil) 50 mg PRN (N = 261) for 8 weeks (dose adjustments allowed), followed by 16 weeks of pragmatic treatment (switching between PDE5I allowed). Primary outcomes (treatment-adherence) were reported previously. Here, we report effects on: Psychological and Interpersonal Relationship Scales, Self-Esteem and Relationship (SEAR) questionnaire, ED Inventory of Treatment Satisfaction (EDITS), International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) and Global Assessment Questions (GAQ). Mixed-model for repeated measures and analysis of covariance were used to analyze changes from baseline; GAQ-responses were evaluated by logistic regression. Analyses were adjusted for treatment, country, ED-severity, baseline and baseline-by-treatment interaction. Patients randomized to tadalafil OaD or PRN reported greater improvement (least-square mean (s.e.) change) in Sexual Self-Confidence (OaD +0.90 (0.048), PRN +0.93 (0.050), vs +0.73 (0.049); P=0.006 and P=0.001) and Spontaneity (OaD +0.11 (0.035), PRN +0.13 (0.035), vs +0.02 (0.035); P = 0.044 and P = 0.010) compared with sildenafil. Improvements in GAQ and SEP responses, IIEF-EF, orgasmic function, sexual desire, overall satisfaction domains, SEAR and EDITS scores did not differ significantly between treatment groups.

  9. Inhibition of spinal reflexes by paramedian reticular nucleus.

    PubMed

    Chai, C Y; Lin, Y F; Wang, H Y; Wu, W C; Yen, C T; Kuo, J S; Wayner, M J

    1990-10-01

    The inhibitory actions of the paramedian reticular nucleus (PRN), and its neighbouring structures, i.e., midline raphe nuclei (MRN) and dorsal medullary depressor area (DMD) on the knee jerk (KnJ) and crossed extension movement (CEM) induced by central sciatic stimulation and on the L5 ventral root response (EVRR) evoked by central tibial stimulation, were studied in cats under urethane (400 mg/kg) and alpha-chloralose (40 mg/kg) anesthesia alone, IP or further paralyzed with atracurium besylate (0.5 mg/kg/30 min), IV. Electrical stimulation of the above areas with rectangular pulses (80 Hz, 1.0 msec, 100-200 microA) decreased systemic arterial blood pressure (SAP) in an average value of: 36 +/- 3 mmHg for PRN; 19 +/- 2 mmHg for MRN; and 23 +/- 3 mmHg for DMD. The KnJ and CEM were almost completely suppressed by simultaneous PRN stimulation. The EVRR, including mono- and polysynaptic spinal reflexes with transmission velocity from 10 to 60 m/sec or above, were also suppressed. MRN stimulation only inhibited the KnJ, CEM and polysynaptic spinal reflexes with transmission velocities between 25 and 60 m/sec, but facilitated spinal reflexes with conduction velocities below 10 m/sec. On the other hand, DMD stimulation resulted in small suppression of KnJ, CEM and inhibition of polysynaptic spinal reflexes with conduction velocities between 25 and 60 m/sec. Even though MRN and DMD partially inhibited polysynaptic spinal reflexes, the magnitude of such inhibition was much smaller than that produced by PRN (-20% and -22% vs. -48%). The above-mentioned PRN effects on SAP and EVRR persisted in chronic animals decerebellated 9-12 days before.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. [Pro re nata anti-VEGF treatment results for neovascular age-related macular degeneration in routine clinical treatment: comparison of single with triple injections].

    PubMed

    Wintergerst, M W M; Larsen, P P; Heimes, B; Pauleikhoff, D; Holz, F G; Finger, R P

    2018-06-19

    Different injection regimens from continuous to pro re nata (PRN) have been proposed for treatment of neovascular age-related macular degeneration (nAMD). So far the PRN single injection on reactivation regimen has not been compared to the PRN triple injection on reactivation regimen (IVAN scheme). Comparison of the two nAMD PRN injection regimens with single and triple injections on reactivation in a real-world setting in a retrospective case series in two German treatment centers. Naïve nAMD patients, who started treatment according to either the single or triple injection regimen were included. Endpoints were best corrected visual acuity (LogMAR), central retinal thickness on optical coherence tomography (μm) and number of injections, all at 3, 6, 12, 18 and 24 months after treatment initiation. A total of 146 patients with single injection and 148 patients with triple injection regimens were included. There were no significant differences between the two treatment regimens in best corrected visual acuity (single vs. triple injection scheme: 0.50 ± 0.42 vs. 0.56 ± 0.42, p = 0.14), central retinal thickness (303 ± 76.2 vs. 306 ± 110, p = 0.79) and number of injections (13 ± 4.4 vs. 12 ± 5.4, p = 0.31). This was the case for all analyzed time points. There were no significant functional or morphological differences between the two PRN injection regimens with single and triple injections on reactivation after 24 months. For evaluation of long-term therapy results further studies are warranted.

  11. Evaluation of Emergency Department Management of Opioid-Tolerant Cancer Patients With Acute Pain.

    PubMed

    Patel, Pina M; Goodman, Lauren F; Knepel, Sheri A; Miller, Charles C; Azimi, Asma; Phillips, Gary; Gustin, Jillian L; Hartman, Amber

    2017-10-01

    There are no previously published studies examining opioid doses administered to opioid-tolerant cancer patients during emergency department (ED) encounters. To determine if opioid-tolerant cancer patients presenting with acute pain exacerbations receive adequate initial doses of as needed (PRN) opioids during ED encounters based on home oral morphine equivalent (OME) use. We performed a retrospective cohort study of opioid-tolerant cancer patients who received opioids in our ED over a two-year period. The percentage of patients who received an adequate initial dose of PRN opioid (defined as ≥10% of total 24-hour ambulatory OME) was evaluated. Logistic regression was used to establish the relationship between 24-hour ambulatory OME and initial ED OME to assess whether higher home usage was associated with higher likelihood of being undertreated. Out of 216 patients, 61.1% of patients received an adequate initial PRN dose of opioids in the ED. Of patients taking <200 OMEs per day at home, 77.4% received an adequate initial dose; however, only 3.2% of patients taking >400 OMEs per day at home received an adequate dose. Patients with ambulatory 24-hour OME greater than 400 had 99% lower odds of receiving an adequate initial dose of PRN opioid in the ED compared to patients with ambulatory 24-hour OME less than 100 (OR <0.01, CI 0.00-0.02, P < 0.001). Patients with daily home use less than 200 OMEs generally received adequate initial PRN opioid doses during their ED visit. However, patients with higher home opioid usage were at increased likelihood of being undertreated. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  12. Switching from pro re nata to treat-and-extend regimen improves visual acuity in patients with neovascular age-related macular degeneration.

    PubMed

    Kvannli, Line; Krohn, Jørgen

    2017-11-01

    To evaluate the visual outcome after transitioning from a pro re nata (PRN) intravitreal injection regimen to a treat-and-extend (TAE) regimen for patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients who were switched from a PRN regimen with intravitreal injections of bevacizumab, ranibizumab or aflibercept to a TAE regimen. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and type of medication used at baseline, at the time of changing treatment regimen and at the end of the study were analysed. Twenty-one eyes of 21 patients met the inclusion criteria. Prior to the switch, the patients received a mean of 13.8 injections (median, 10; range, 3-39 injections) with the PRN regimen for 44 months (range, 3-100 months), which improved the visual acuity in five patients (24%). After a mean of 6.1 injections (median, 5; range, 3-14 injections) with the TAE regimen over 8 months (range, 2-16 months), the visual acuity improved in 12 patients (57%). The improvement in visual acuity during treatment with the TAE regimen was statistically significant (p = 0.005). The proportion of patients with a visual acuity of 0.2 or better was significantly higher after treatment with the TAE regimen than after treatment with the PRN regimen (p = 0.048). No significant differences in CRT were found between the two treatment regimens. Even after prolonged treatment and a high number of intravitreal injections, switching AMD patients from a PRN regimen to a strict TAE regimen significantly improves visual acuity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Use of Modified Positive Behavioral Interventions and Supports in a Psychiatric Inpatient Unit for High-Risk Youths.

    PubMed

    Reynolds, Elizabeth K; Grados, Marco A; Praglowski, Nancy; Hankinson, Jessica C; Deboard-Lucas, Renee; Goldstein, Laura; Perry-Parrish, Carisa K; Specht, Matthew W; Ostrander, Rick

    2016-05-01

    Despite a call for the reduction and ultimate elimination of the use of seclusion and restraint, research on reduction of these practices in behavioral programs has been limited. This study sought to examine the effectiveness of a modified version of the Positive Behavioral Interventions and Supports (M-PBIS) implemented in a youth psychiatric inpatient unit to reduce use of seclusion and restraint. This naturalistic, prospective study covered a four-year period (1,485 admissions). The number of seclusion and restraint events, mean duration of events, and percentage of patients placed in seclusion or restraint were reduced, as was the overall seclusion rate for the unit. Furthermore, there was a significant reduction in the use of pro re nata (PRN) medications for agitation. These findings suggest that M-PBIS is a promising intervention to use in youth psychiatric inpatient units to reduce seclusion and restraint and PRNs.

  14. Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B).

    PubMed

    Hattenbach, Lars-Olof; Feltgen, Nicolas; Bertelmann, Thomas; Schmitz-Valckenberg, Steffen; Berk, Hüsnü; Eter, Nicole; Lang, Gabriele E; Rehak, Matus; Taylor, Simon R; Wolf, Armin; Weiss, Claudia; Paulus, Eva-Maria; Pielen, Amelie; Hoerauf, Hans

    2018-02-01

    To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Patients received either monthly ranibizumab for 3 months followed by Pro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followed by PRN sham injections (n = 118). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean changes in BCVA and foveal centre point thickness (FCPT), and adverse events (AEs). There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 (±11) letters versus +9.3 (±10.1) letters]. At month 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

    PubMed

    O'Connell, Oisin J; Almeida, Francisco A; Simoff, Michael J; Yarmus, Lonny; Lazarus, Ray; Young, Benjamin; Chen, Yu; Semaan, Roy; Saettele, Timothy M; Cicenia, Joseph; Bedi, Harmeet; Kliment, Corrine; Li, Liang; Sethi, Sonali; Diaz-Mendoza, Javier; Feller-Kopman, David; Song, Juhee; Gildea, Thomas; Lee, Hans; Grosu, Horiana B; Machuzak, Michael; Rodriguez-Vial, Macarena; Eapen, George A; Jimenez, Carlos A; Casal, Roberto F; Ost, David E

    2017-06-15

    Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. To develop a clinical prediction model for estimating the prN2/3. We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

  16. [BRAVO and CRUISE: ranibizumab for the treatment of macular edema secondary to retinal vein occlusion].

    PubMed

    Figueroa, M S; Ruiz Moreno, J M

    2012-12-01

    This article summarizes the results of the BRAVO and CRUISE trials, two randomized multicenter studies in patients with macular edema secondary to branch and central retinal vein occlusion, respectively. Randomization was 1:1:1 to 0.3 mg of ranibizumab, 0.5 mg of ranibizumab or placebo. Monthly injections were administered for 6 months followed by a 6-month observation period in which treatment on an on-demand (PRN) basis was applied with 0.5 mg ranibizumab. Patients in the control group were also eligible for 0.5 mg ranibizumab treatment in the observation period. The results showed a significant anatomical and visual improvement in both treatment groups 7 days after the intravitreal injection. PRN treatment with monthly follow-up maintained the visual improvements achieved after the first 6 months of treatment. Patients in the control group who received PRN treatment after the first 6 months showed an anatomical improvement similar to that in the treatment groups but less visual improvement.

  17. Temporal Trends in Analgesic Use in Long-Term Care Facilities: A Systematic Review of International Prescribing.

    PubMed

    La Frenais, Francesca L; Bedder, Rachel; Vickerstaff, Victoria; Stone, Patrick; Sampson, Elizabeth L

    2018-02-01

    To explore global changes in the prescription of analgesic drugs over time in the international long-term care (LTC) population. Systematic review. We included original research articles in English, published and unpublished, that included number of participants, country and year(s) of data collection, and prescription of analgesics (analgesics not otherwise specified, opioids, acetaminophen; scheduled only, or scheduled plus as needed (PRN)). LTC residents. We searched PubMed, EMBASE, CINAHL, International Pharmaceutical Abstracts, PsycINFO, Cochrane, Web of Science, Google Scholar, using keywords for LTC facilities and analgesic medication; hand-searched references of eligible papers; correspondence. Studies were quality rated using an adapted Newcastle-Ottawa scale. Pearson correlation coefficients were generated between percentage of residents prescribed an analgesic and year of data collection. If available, we investigated changes in acetaminophen and opioid prescriptions. Forty studies met inclusion criteria. A moderate correlation (0.59) suggested that scheduled prescription rates for analgesics have increased over time. Similar findings were reflected in scheduled prescriptions for acetaminophen and opioids. No increase was seen when analyzing scheduled plus PRN analgesics. Use of opioids (scheduled plus PRN) appears to have increased over time. Worldwide, use of opioids and acetaminophen has increased in LTC residents. Research is needed to explore whether this reflects appropriate pain management for LTC residents and if PRN medication is used effectively. © 2017 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  18. Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

    PubMed

    Stoller, Glenn L; Kokame, Gregg T; Dreyer, Richard F; Shapiro, Howard; Tuomi, Lisa L

    2016-05-12

    Understanding the range of temporal responses to ranibizumab is critical for the assessment of individualized treatment regimens for neovascular age-related macular degeneration. To examine patterns of visual and anatomical response to ranibizumab treatment. This study is a retrospective subanalysis of HARBOR (a phase 3, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (PRN) in patients with subfoveal neovascular age-related macular degeneration). A total of 1097 patients with neovascular age-related macular degeneration were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (PRN) with monthly monitoring. Of the 1097 patients, 1057 were included in the analysis for early responders (best-corrected visual acuity [BCVA] obtained at baseline and month 3), and 988 patients were included in the analysis for delayed responders (BCVA obtained at baseline, month 3, and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015. Patients were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month 3) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month 3 but did so at month 12). Changes from baseline in BCVA and central foveal thickness (CFT). In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 0.5-mg PRN, 2.0-mg monthly, and 2.0-mg PRN treatment groups, 63 (24.0%) of 263, 65 (24.6%) of 264, 68 (25.7%) of 265, and 70 (26.4%) of 265 patients were early responders, respectively, and 40 (16.3%) of 246, 31 (12.6%) of 247, 35 (14.1%) of 248, and 29 (11.7%) of 247 patients were delayed responders, respectively. By month 12, early vs delayed responders in the PRN treatment groups received 7.5 vs 7.4 ranibizumab injections, respectively (P = .84). More than 80% of early responders receiving PRN treatment maintained 15-letter or greater gains at month 24. At baseline, early vs delayed responders had worse BCVA (49.8 vs 55.4 letters; P < .001) and greater CFT (374.9 vs 339.0 µm; P = .02), although anatomical results were comparable by month 3 (CFT, 187.7 vs 188.9 µm). Improvement of 15 letters or more from baseline occurred in 266 (25.2%) of 1057 patients within 3 months of beginning ranibizumab treatment, whereas an additional 135 (13.7%) of 988 patients achieved this gain by 12 months. The 2 cohorts had similar anatomical temporal response patterns. PRN treatment with monthly monitoring was effective in maintaining early vision gains and allowing delayed vision gains. These results suggest that vision improvement can continue in some patients after macular edema resolves and CFT decreases stabilize.

  19. A systematic review on the quality, validity and usefulness of current cost-effectiveness studies for treatments of neovascular age-related macular degeneration.

    PubMed

    Elshout, Mari; Webers, Carroll A B; van der Reis, Margriet I; Schouten, Jan S A G

    2018-06-04

    Ophthalmologists increasingly depend on new drugs to advance their treatment options. These options are limited by restraints on reimbursements for new and expensive drugs. These restraints are put in place through health policy decisions based on cost-effectiveness analyses (CEA). Cost-effectiveness analyses need to be valid and of good quality to support correct decisions to create new treatment opportunities. In this study, we report the quality, validity and usefulness of CEAs for therapies for nAMD. A systematic review in PubMed, EMBASE and Cochrane was performed to include CEAs. Quality and validity assessment was based on current general quality criteria and on elements that are specific to the field of ophthalmology. Forty-eight CEAs were included in the review. Forty-four CEAs did not meet four basic model quality and validity criteria specific to CEAs in the field of ophthalmology (both eyes analysed instead of one; a time horizon extending beyond 4 years; extrapolating VA and treatment intervals beyond trial data realistically; and including the costs of low-vision). Four CEAs aligned with the quality and validity criteria. In two of these CEAs bevacizumab as-needed (PRN) was more cost-effective than bevacizumab monthly; aflibercept (VIEW); or ranibizumab monthly or PRN. In two CEAs, ranibizumab (PRN or treat and extent) was dominant over aflibercept. In two other CEAs, aflibercept was either more cost-effective or dominant over ranibizumab monthly or PRN. Two of the CEAs of sufficient quality and validity show that bevacizumab PRN is the most cost-effective treatment. Comparing ranibizumab and aflibercept, either treatment can be more cost-effective depending on the assumptions used for drug prices and treatment frequencies. The majority of the published CEAs are of insufficient quality and validity. They wrongly inform decision-makers at the cost of opportunities for ophthalmologists to treat patients. As such, they may negatively influence overall patient outcomes and societal costs. For future ophthalmic treatments, CEAs need to be improved and only published when they are of sufficient quality and validity. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  20. Characterizing primary refractory neuroblastoma: prediction of outcome by microscopic image analysis

    NASA Astrophysics Data System (ADS)

    Niazi, M. Khalid Khan; Weiser, Daniel A.; Pawel, Bruce R.; Gurcan, Metin N.

    2015-03-01

    Neuroblastoma is a childhood cancer that starts in very early forms of nerve cells found in an embryo or fetus. It is a highly lethal cancer of sympathetic nervous system that commonly affects children of age five or younger. It accounts for a disproportionate number of childhood cancer deaths and remains a difficult cancer to eradicate despite intensive treatment that includes chemotherapy, surgery, hematopoietic stem cell transplantation, radiation therapy and immunotherapy. A poorly characterized group of patients are the 15% with primary refractory neuroblastoma (PRN) which is uniformly lethal due to de novo chemotherapy resistance. The lack of response to therapy is currently assessed after multiple months of cytotoxic therapy, driving the critical need to develop pretreatment clinic-biological biomarkers that can guide precise and effective therapeutic strategies. Therefore, our guiding hypothesis is that PRN has distinct biological features present at diagnosis that can be identified for prediction modeling. During a visual analysis of PRN slides, stained with hematoxylin and eosin, we observed that patients who survived for less than three years contained large eosin-stained structures as compared to those who survived for greater than three years. So, our hypothesis is that the size of eosin stained structures can be used as a differentiating feature to characterize recurrence in neuroblastoma. To test this hypothesis, we developed an image analysis method that performs stain separation, followed by the detection of large structures stained with Eosin. On a set of 21 PRN slides, stained with hematoxylin and eosin, our image analysis method predicted the outcome with 85.7% accuracy.

  1. Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration.

    PubMed

    Mori, Ryusaburo; Tanaka, Koji; Haruyama, Miho; Kawamura, Akiyuki; Furuya, Koichi; Yuzawa, Mitsuko

    2017-01-01

    The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months. © 2017 S. Karger AG, Basel.

  2. Implementation of Trauma-Informed Care and Brief Solution-Focused Therapy: A Quality Improvement Project Aimed at Increasing Engagement on an Inpatient Psychiatric Unit.

    PubMed

    Aremu, Babatunde; Hill, Pamela D; McNeal, Joanne M; Petersen, Mary A; Swanberg, Debbie; Delaney, Kathleen R

    2018-03-14

    Addressing tense and escalating situations with noncoercive measures is an important element of inpatient psychiatric treatment. Although restraint rates are frequently monitored, the use of pro re nata (PRN) intramuscular (IM) injections to address agitation is also an important indicator. In 2015, at the current study site, a significant increase was noted in PRN IM medication use despite unit leadership's efforts to build a culture of trauma-informed care (TIC). The purpose of the current quality improvement project was to educate staff on methods to incorporate TIC into daily practice and the use of brief solution-focused therapy techniques in escalating situations. Measurement of attitudes toward patient aggression and engagement with patients followed two waves of staff education. Upon completion of the project, a decrease in PRN IM medications, improvement in staff attitudes toward patient aggression, and improved sense of staff competency in handling tense situations were noted. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.]. Copyright 2018, SLACK Incorporated.

  3. PCR-based identification and characterization of Burkholderia cepacia complex bacteria from clinical and environmental sources.

    PubMed

    Seo, S-T; Tsuchiya, K

    2004-01-01

    To study the genotypic identification and characterization of the 119 Burkholderia cepacia complex (Bcc) strains recovered from clinical and environmental sources in Japan and Thailand. Based on the results of analysis by 16S rDNA RFLP generated after digestion with DdeI, the Bcc strains were differentiated into two patterns: pattern 1 (including Burkholderia vietnamiensis) and pattern 2 (including B. cepacia genomovar I, Burkholderia cenocepacia and Burkholderia stabilis). All strains belonged to pattern 2 except for one strain. In the RFLP analysis of the recA gene using HaeIII, strains were separated into eight patterns designated as A, D, E, G, H, I, J and K, of which pattern K was new. Burkholderia cepacia epidemic strain marker (BCESM) encoded by esmR [corrected] and the pyrrolnitrin biosynthetic locus encoded by prnC were present in 22 strains (18%) and 88 strains (74%) from all sources, respectively. All esmR-positive [corrected] strains belonged to B. cenocepacia, whereas most prnC-positive strains belonged to B. cepacia genomovar I. Strains derived from clinical sources were assigned to B. cepacia genomovar I, B. cenocepacia, B. stabilis and B. vietnamiensis. The majority of Bcc strains from environmental sources (77 of a total 95 strains) belonged to B. cepacia genomovar I, whereas the rest belonged to B. cenocepacia. On the basis of genomovar-specific PCR and prnC RFLP analysis, strains belonging to recA pattern K were identified as B. cepacia genomovar I. This work provides the genotypic identification of a collection of the Bcc strains from Japan and Thailand. RFLP analysis of the prnC gene promises to be a useful method for differentiating Burkholderia pyrrocinia from B. cepacia genomovar I strains.

  4. Theory of Planned Behavior Constructs Associated with Nurses' Pain Assessment and Pro Re Nata (PRN) Opioid Analgesic Administration: A Cross-sectional Study.

    PubMed

    Youngcharoen, Phichpraorn; Vincent, Catherine; Park, Chang G

    2017-06-01

    Little theory-based research has been performed to better understand nurses' perceptions of pain management. Framed by the theory of planned behavior, the aims of the study were to describe nurses' beliefs (behavioral, normative, and control) about pain management for hospitalized elderly patients with postoperative pain; to present an item analysis for beliefs, attitudes, perceived norms, perceived behavioral control, intentions, and behaviors (measured in case study vignettes) for nurses (a) with different durations of nursing experience, (b) working in university, public health, and military hospitals, and (c) who either had or had not received pain management training in the past six months; and to compare differences in the constructs across these three groups. A comparative descriptive cross-sectional design was used with a convenience sample of 140 Thai nurses working in three Bangkok hospitals. Participants responded to pain assessment and management questionnaires. Most nurses expressed fairly strong beliefs about pain assessment and pro re nata (PRN) opioid analgesic administration. Nurses with more than 10 years of experience had the highest scores for attitudes toward pain assessment and perceptions of others' expectations about PRN opioid analgesic administration. Responses of nurses working in different types of hospitals indicated significantly different pain assessment and PRN opioid analgesic administration behaviors. No significant differences were found for nurses who did and did not receive pain management training. The study highlighted the need for improved pain management education for nurses to enhance the quality of patient care. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  5. Characterization of the key antigenic components of pertussis vaccine based on outer membrane vesicles.

    PubMed

    Ormazábal, Maximiliano; Bartel, Erika; Gaillard, María Emilia; Bottero, Daniela; Errea, Agustina; Zurita, M Eugenia; Moreno, Griselda; Rumbo, Martin; Castuma, Celina; Flores, Dario; Martín, María Julia; Hozbor, Daniela

    2014-10-21

    Pertussis has resurged during the last two decades in different countries. In particular in the 2010-2013 period large outbreaks were detected in US, Australia, UK and The Netherlands with significant mortality in infants. The epidemiological situation of pertussis points out the need to develop new vaccines and in this regard we previously developed a new vaccine based on outer membrane vesicles (OMVs) which have been shown to be safe and to induce protection in mice. Here we have further investigated the properties of OMVs vaccines; in particular we studied the contribution of pertussis toxin (PTx) and pertactin (Prn) in OMVs-mediated protection against pertussis. PTx-deficient OMVs and Prn-deficient OMVs were obtained from defective Bordetella pertussis mutants. The absence of PTx or Prn did compromise the protective capacity of the OMVs formulated as Tdap vaccine. Whereas the protective efficacy of the PTx-deficient OMVs in mice was comparable to Prn-deficient OMVs, the protective capacity of both of them was significantly impaired when it was compared with the wild type OMVs. Interestingly, using OMVs obtained from a B. pertussis strain which does not express any of the virulence factors but expresses the avirulent phenotype; we observed that the protective ability of such OMVs was lower than that of OMVs obtained from virulent B. pertussis phase. However, it was surprising that although the protective capacity of avirulent OMVs was lower, they were still protective in the used mice model. These results allow us to hypothesize that OMVs from avirulent phase shares protective components with all OMVs assayed. Using an immune proteomic strategy we identified some common components that could play an important role in protection against pertussis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. A 650-year record of past summer temperatures from Pirin, Bulgaria tree-ring density

    NASA Astrophysics Data System (ADS)

    Meko, M. D.; Trouet, V.; Panayotov, M.; Frank, D. C.

    2017-12-01

    New proxy records of past climate provide valuable data essential to enhance spatial and temporal coverage of the global paleoclimate record - the context against which ongoing climate change and climate-model forcing is examined and evaluated. We present a new 650-year record of past summer temperatures in southeastern (SE) Europe derived from tree-ring maximum-latewood-density (MXD) data measured from Bosnian pine (Pinus heldreichii) growing at high elevations in the Pirin Mountains, Bulgaria (PRN). The PRN collection is well-replicated, with 64 trees contributing MXD series ranging in length from 113 to 865 years (median series length = 480 years) spanning the years 1143-2009. The PRN chronology shows a significant (p < 0.05) relationship with summer (JAS) temperatures across a broad geographical area of SE Europe, including the entire Balkan peninsula, southern Italy, and southwestern Anatolia. Our temperature reconstruction, produced by multiple regression utilizing lagged predictors and calibrated against Sofia, Bulgaria meteorological observations, explains nearly 60% of target variance and reveals variability across decadal, centennial, and longer timescales over the 1350-2009 reconstruction interval. Relative to the instrumental 1900-1980 mean, our record shows multidecadal cool anomalies spanning the first half of the 19th century and the late 17th century, and warm periods spanning the 18th century, 16th and early-to-mid 17th centuries, and late 14th to early 15th century. A comparison of the PRN reconstruction with existing reconstructions of Northern Hemisphere temperatures reveal intervals of asynchrony between local and hemisphere-scale decadal temperature variability, with marked asynchrony in the late 16th-early 17th centuries, and unprecedented asynchrony in the late 20th-to early 21st century.

  7. The NuRD complex component p66 suppresses photoreceptor neuron regeneration in planarians.

    PubMed

    Vásquez-Doorman, Constanza; Petersen, Christian P

    2016-06-01

    Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin-modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA-binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians. This suppressive effect appeared restricted to PRNs because p66 inhibition did not influence numbers of eye pigment cup cells (PCCs) and decreased numbers of brain neurons and epidermal progenitors. PRNs from p66(RNAi) animals differentiated with some abnormalities but nonetheless produced arrestin+ projections to the brain. p66 inhibition produced excess ovo+otxA+ PRN progenitors without affecting numbers of ovo+otxA- PCC progenitors, and ovo and otxA were each required for the p66(RNAi) excess PRN phenotype. Together these results suggest that p66 acts through the NuRD complex to suppress PRN production by limiting expression of lineage-specific transcription factors.

  8. Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for Neovascular Age-Related Macular Degeneration in the UK: Interim Results from TERRA.

    PubMed

    Yang, Yit; Downey, Louise; Mehta, Hemal; Mushtaq, Bushra; Narendran, Niro; Patel, Nishal; Patel, Praveen J; Ayan, Filis; Gibson, Kara; Igwe, Franklin; Jeffery, Pete

    2017-06-01

    Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study. Two cohorts, those switching from a PRN to a T&E regimen ('prior PRN') and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy ('anti-VEGF-naïve') were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site. At the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and -67.7 μm (95% CI -106.5, -28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics. This is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. Novartis Pharmaceuticals UK Limited.

  9. A Retrospective Study of Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration (nAMD) in Australia and the United Kingdom.

    PubMed

    Johnston, Robert L; Carius, Hans-Joachim; Skelly, Adrian; Ferreira, Alberto; Milnes, Fran; Mitchell, Paul

    2017-03-01

    Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss among persons aged 65 years and older. Anti-vascular endothelial growth factor (anti-VEGF) treatment is the recommended standard of care. The current study compares the effectiveness of ranibizumab in routine clinical practice in two countries that generally apply two different treatment regimens, treat-and-extend (T&E) in Australia or pro re nata (PRN) in the UK. This retrospective, comparative, non-randomised cohort study is based on patients' data from electronic medical record (EMR) databases in Australia and the UK. Treatment regimens were defined based on location, with Australia as a proxy for analysing T&E and UK as a proxy for analysing PRN. The study included patients with a diagnosis of nAMD who started treatment with ranibizumab between January 2009 and July 2014. A total of 647 eyes of 570 patients in Australia and 3187 eyes of 2755 patients in the UK with complete 12-months follow-up were analysed. Baseline patient characteristics were comparable between the two cohorts. After 1 year of treatment, T&E-treated eyes achieved higher mean (±SE) visual acuity (VA) gains (5.00 ± 0.54 letters [95% confidence interval (CI) 3.93-6.06]) than PRN-treated eyes [3.04 ± 0.24 letters (95% CI 2.57-3.51); difference in means 2.07 ± 0.69 (95% CI 0.73-3.41), p < 0.001]. Non-inferiority of T&E compared to PRN was concluded based on the change in mean visual acuity gains at 12 months. Over the 12-month follow-up, T&E-treated eyes received a higher mean [±standard deviation (SD)] number of injections (9.29 ± 2.43) than PRN-treated eyes (6.04 ± 2.19) (p < 0.0001). Australian patients had a lower mean (±SD) number of total clinic visits (10.29 ± 2.90) than UK patients (11.47 ± 2.93) (p < 0.0001). The higher injection frequency in the T&E cohort may account for the trend toward improved vision. Novartis Pharma AG, Basel, Switzerland.

  10. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times.

    PubMed

    Fauser, Sascha; Muether, Philipp S

    2016-11-01

    To determine clinical correlations to intraocular vascular endothelial growth factor A (VEGF-A) suppression times (VSTs) on the treatment of neovascular age-related macular degeneration (nAMD) with ranibizumab (Lucentis) or aflibercept (Eylea). Seven of 89 treatment-naïve nAMD eyes showed persistent choroidal neovascular membrane (CNV) activity throughout a spectral domain optical coherence tomography (SD-OCT)-driven pro re nata (PRN) regimen of intravitreal ranibizumab injections over 28±4 months. The treatment was switched to PRN aflibercept injections and patients were followed for another 15±2 months. A total of 160 aqueous humour specimens were collected before the intravitreal injections, and their VEGF-A concentrations were assayed by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Intraocular VEGF-A concentrations were correlated to CNV activity shown by SD-OCT. The mean duration of suppression of VEGF-A concentrations in aqueous humour below the lower limit of quantification of our assay was 34±5 (26-69) days for ranibizumab and 67±14 (49-89) days for aflibercept (p<0.001). The percentual reduction of central retinal volume (CRV) 6 weeks after injection was higher for aflibercept compared with ranibizumab (p=0.009). The time point of clinical re-activity occurred about 50% earlier than the respective VST for each ranibizumab and aflibercept. The VST under aflibercept treatment exceeded that under ranibizumab treatment by a factor of 2. This difference correlated with differential clinical CRV reduction 6 weeks after the respective injection. For both medications, clinical activity was found at a time point as early as 50% of the individual VST. NCT01213667, post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Experiences of mental health professionals and patients in the use of pro re nata medication in acute adult mental healthcare settings: a systematic review.

    PubMed

    Morkunas, Bernadette; Porritt, Kylie; Stephenson, Matthew

    2016-10-01

    The use of pro re nata (PRN) medication, a medication that is given when needed, as opposed to medication that is given at a regular time, is surrounded by claims of misuse and poor accountability within the mental health setting. Gaining insight into and understanding of the experiences of health professionals' and patients' use of PRN medication will assist in contributing to improving education and safety around this common intervention. To analyze and synthesize the best available evidence on the perspectives of patients and mental health professionals (MHPs) with their experiences of PRN medication in mental health settings. Participants considered for inclusion in this review include MHPs working in, and adult patients admitted to, an acute adult mental healthcare setting. This review will consider studies that investigated the experience of MHPs' and patients' use of PRN medication in acute adult mental healthcare settings. The current review will consider studies that focused on qualitative data including, but not limited to, designs such as phenomenology, grounded theory, ethnography, action research and feminist research. The context of the review is acute adult mental healthcare settings with no restriction on geographical location. The search strategy aims to find both published and unpublished studies. The databases searched include CINAHL, PubMed, Scopus, PsycINFO and Embase. A gray literature search included ProQuest Dissertations and Theses, Mednar and Google Scholar. Papers selected for retrieval were assessed by two independent reviewers for methodological validity before inclusion in the review using the standardized critical appraisal instrument from the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI). The standardized data extraction tool from the JBI-QARI was used to extract data from the papers. Qualitative research findings were pooled using the JBI-QARI. This involved the aggregation of findings to generate a set of statements that represented that aggregation, through assembling the findings rated according to their quality and categorizing these findings by similarity in meaning. These categories were then subjected to a meta-synthesis to produce a single comprehensive set of synthesized findings that can be used as a basis for evidence-based practice. Four studies were included in the systematic review. Two studies each from both groups' perspective. These experiences were combined in one synthesis to look at the issues from mutual perspectives. A total of 40 findings were extracted from these four studies. The findings were grouped into 10 categories and five synthesized findings were developed. Pro re nata medication use among MHPs and service users is subject to many variables from individual decision making to organizational policies. There are many factors that contribute to MHPs prescribing and administering PRN medications and patients had views and opinions on their use of PRN medication in the acute mental health setting.

  12. Cancelable biometrics realization with multispace random projections.

    PubMed

    Teoh, Andrew Beng Jin; Yuang, Chong Tze

    2007-10-01

    Biometric characteristics cannot be changed; therefore, the loss of privacy is permanent if they are ever compromised. This paper presents a two-factor cancelable formulation, where the biometric data are distorted in a revocable but non-reversible manner by first transforming the raw biometric data into a fixed-length feature vector and then projecting the feature vector onto a sequence of random subspaces that were derived from a user-specific pseudorandom number (PRN). This process is revocable and makes replacing biometrics as easy as replacing PRNs. The formulation has been verified under a number of scenarios (normal, stolen PRN, and compromised biometrics scenarios) using 2400 Facial Recognition Technology face images. The diversity property is also examined.

  13. [New perspectives in the approach to central retinal vein occlusion].

    PubMed

    Figueroa, M S

    2015-03-01

    The COPERNICUS and GALILEO trials were designed to evaluate the safety and efficacy of intravitreal injection of 2mg of aflibercept in the treatment of macular edema secondary to central retinal vein occlusion. Two phase III randomized, double-masked trials: COPERNICUS in North America (188 patients) and galileo in Europe and Asia (177 patients). In COPERNICUS, the patients in the treatment group received monthly injections of 2mg aflibercept for 6 months and later continued with strict PRN treatment with monthly follow-up every 6 months and with a minimum of 3-monthly follow up for 1 year. Patients in the placebo group could receive treatment after the sixth month, with similar treatment regimens and follow-up to the treatment group. In contrast, in galileo, the placebo group received no PRN treatment until 1 year of follow-up and during the first 6 months, followup visits were bi-monthly. The treatment group in COPERNICUS showed a mean improvement of 13 letters versus the placebo group (1.5 letters) at week 100 of follow-up. In galileo, the mean best corrected visual acuity at 76 weeks were 13.7 and 6.6 in the treatment and placebo groups, respectively. Early treatment with intravitreal afliberceptin achieves better results than when treatment is delayed by 6 months or 1 year. The visual benefits obtained with the drug are affected by the reduction in the frequency of monitoring during follow-up. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Optical Coherence Tomography Monitoring Strategies for A-VEGF—Treated Age-Related Macular Degeneration: An Evidence-Based Analysis

    PubMed Central

    Pron, G

    2014-01-01

    Background New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti–vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals’ AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. Objectives To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF–treated neovascular AMD (n-AMD) patients. Data Sources Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF–treated n-AMD patients monitored in longitudinal follow-up. Review Methods Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. Results A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF–treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and PRN re-treatment; and monthly monitoring with either VA-guided re-treatment or quantitative-only VA/OCT- (central retinal thickness [CRT] > 100 μm) guided re-treatment. PRN re-treatment strategies with A-VEGF on the basis of monthly follow-up and rigorous reviews of OCT qualitative and quantitative measures of disease activity did decrease injection burden while maintaining visual gains. Gains in VA obtained with PRN re-treatment in usual clinical practice, however, were not as high as gains in clinical trials. Conclusions To reduce treatment burden and provide a more individualized treatment strategy for n-AMD patients, OCT/VA-guided PRN treatment strategies have become the preferred and the dominant maintenance strategy. Success of these strategies, however, is dependent on close monitoring and adherence to tightly defined re-treatment criteria. PMID:26316918

  15. Optical Coherence Tomography Monitoring Strategies for A-VEGF-Treated Age-Related Macular Degeneration: An Evidence-Based Analysis.

    PubMed

    Pron, G

    2014-01-01

    New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals' AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients. Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored in longitudinal follow-up. Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and PRN re-treatment; and monthly monitoring with either VA-guided re-treatment or quantitative-only VA/OCT- (central retinal thickness [CRT] > 100 μm) guided re-treatment. PRN re-treatment strategies with A-VEGF on the basis of monthly follow-up and rigorous reviews of OCT qualitative and quantitative measures of disease activity did decrease injection burden while maintaining visual gains. Gains in VA obtained with PRN re-treatment in usual clinical practice, however, were not as high as gains in clinical trials. To reduce treatment burden and provide a more individualized treatment strategy for n-AMD patients, OCT/VA-guided PRN treatment strategies have become the preferred and the dominant maintenance strategy. Success of these strategies, however, is dependent on close monitoring and adherence to tightly defined re-treatment criteria.

  16. Automated image-based assay for evaluation of HIV neutralization and cell-to-cell fusion inhibition.

    PubMed

    Sheik-Khalil, Enas; Bray, Mark-Anthony; Özkaya Şahin, Gülsen; Scarlatti, Gabriella; Jansson, Marianne; Carpenter, Anne E; Fenyö, Eva Maria

    2014-08-30

    Standardized techniques to detect HIV-neutralizing antibody responses are of great importance in the search for an HIV vaccine. Here, we present a high-throughput, high-content automated plaque reduction (APR) assay based on automated microscopy and image analysis that allows evaluation of neutralization and inhibition of cell-cell fusion within the same assay. Neutralization of virus particles is measured as a reduction in the number of fluorescent plaques, and inhibition of cell-cell fusion as a reduction in plaque area. We found neutralization strength to be a significant factor in the ability of virus to form syncytia. Further, we introduce the inhibitory concentration of plaque area reduction (ICpar) as an additional measure of antiviral activity, i.e. fusion inhibition. We present an automated image based high-throughput, high-content HIV plaque reduction assay. This allows, for the first time, simultaneous evaluation of neutralization and inhibition of cell-cell fusion within the same assay, by quantifying the reduction in number of plaques and mean plaque area, respectively. Inhibition of cell-to-cell fusion requires higher quantities of inhibitory reagent than inhibition of virus neutralization.

  17. Influence of the Vitreoretinal Interface on the Treatment with Anti-VEGF for Exudative Age-Related Macular Degeneration.

    PubMed

    Gil, Pedro; Gil, João; Oliveira, Nuno; Laíns, Inês; Camilo, Eduardo Nery Rossi; Fonseca, Cristina; Raimundo, Miguel; Cachulo, Maria da Luz; Silva, Rufino

    2018-05-07

    To investigate the influence of the vitreoretinal interface on the outcomes of different ranibizumab regimens for exudative age-related macular degeneration. We conducted a retrospective subanalysis of 2 prospective clinical trials. Patients were treated with ranibizumab for 12 months according to 3 different regimens: pro-re-nata (PRN), treat and extend (T&E), and monthly. Vitreoretinal interface was assessed for absence (group ON) or presence (group OFF) of posterior vitreous detachment (PVD). We included 64 eyes from 64 patients. Visual improvement was poorer for group ON (0.3 ± 10.7 letters) than for group OFF (9.2 ± 13.3; p = 0.007). A significant difference in letters of improvement between groups was observed in the PRN cohort (ON: -5.0 ± 12.9; OFF: 11.4 ± 11.9; p = 0.003), but not in the cohorts with monthly (ON: 5.7 ± 7.8; OFF: 7.9 ± 15.2; p = 0.735) or T&E (ON: 4.3 ± 4.3; OFF: 7.8 ± 11.1; p = 0.424) treatment. The negative impact of absence of PVD is regimen dependent, with monthly dosing providing similar outcomes to PVD patients. In the absence of PVD (group ON), PRN should be avoided, and T&E might be an alternative. © 2018 S. Karger AG, Basel.

  18. Effect of visual art on patient anxiety and agitation in a mental health facility and implications for the business case.

    PubMed

    Nanda, U; Eisen, S; Zadeh, R S; Owen, D

    2011-06-01

    There is a growing body of evidence on the impact of the environment on health and well-being. This study focuses on the impact of visual artworks on the well-being of psychiatric patients in a multi-purpose lounge of an acute care psychiatric unit. Well-being was measured by the rate of pro re nata (PRN) medication issued by nurses in response to visible signs of patient anxiety and agitation. Nurses were interviewed to get qualitative feedback on the patient response. Findings revealed that the ratio of PRN/patient census was significantly lower on the days when a realistic nature photograph was displayed, compared to the control condition (no art) and abstract art. Nurses reported that some patients displayed agitated behaviour in response to the abstract image. This study makes a case for the impact of visual art on mental well-being. The research findings were also translated into the time and money invested on PRN incidents, and annual cost savings of almost $US30,000 a year was projected. This research makes a case that simple environmental interventions like visual art can save the hospital costs of medication, and staff and pharmacy time, by providing a visual distraction that can alleviate anxiety and agitation in patients. © 2010 Blackwell Publishing.

  19. Two way time transfer results at NRL and USNO

    NASA Technical Reports Server (NTRS)

    Galysh, Ivan J.; Landis, G. Paul

    1993-01-01

    The Naval Research Laboratory (NRL) has developed a two way time transfer modem system for the United States Naval Observatory (USNO). Two modems in conjunction with a pair of Very Small Aperture Terminal (VSAT) and a communication satellite can achieve sub nanosecond time transfer. This performance is demonstrated by the results of testing at and between NRL and USNO. The modems use Code Division Multiple Access (CDMA) methods to separate their signals through a single path in the satellite. Each modem transmitted a different Pseudo Random Noise (PRN) code and received the others PRN code. High precision time transfer is possible with two way methods because of reciprocity of many of the terms of the path and hardware delay between the two modems. The hardware description was given in a previous paper.

  20. ''As-Needed'' Range Orders for Opioid Analgesics in the Management of Pain: A Consensus Statement of the American Society for Pain Management Nursing and the American Pain Society.

    PubMed

    Drew, Debra J; Gordon, Debra B; Morgan, Bonnie; Manworren, Renee C B

    2018-06-01

    Effective pain management requires careful titration of analgesics and evaluation of individual patient's responses to treatment using valid and reliable pain and pain relief assessment tools, and evidence-based patient monitoring for adverse treatment effects. A registered nurse, competent in pain assessment and analgesic administration, can safely interpret and implement properly written ''as-needed'' or ''PRN'' range orders for analgesic medications. The American Society for Pain Management Nursing (ASPMN) and the American Pain Society (APS) support safe medication practices and the appropriate use of PRN range orders for opioid analgesics in the management of pain. Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  1. PRN 93-10: Effluent Discharge Labeling Statements

    EPA Pesticide Factsheets

    This notice describes revised effluent discharge labeling statements required on all manufacturing use products and end use products that may be discharged to waters of the United States ormunicipal sewer systems.

  2. Comparison of early dexamethasone retreatment versus standard dexamethasone regimen combined with PRN ranibizumab in diabetic macular edema.

    PubMed

    Arıkan Yorgun, Mücella; Toklu, Yasin; Mutlu, Melek

    2017-02-01

    The purpose of the study is to evaluate the efficacy and safety of as-needed dexamethasone (DEX) retreatment compared with standard DEX retreatment combined with PRN ranibizumab injections among patients with persistent diabetic macular edema (DME). Twenty-eight patients with persistent macular edema having recurrence earlier than 6 months after initial DEX implantation were included in this retrospective study. Group I consisted of 13 patients retreated using monthly PRN ranibizumab injections combined with standard 6-monthly DEX implantation; Group II consisted of 15 patients retreated with DEX implantation earlier than 6 months on an "as-needed" basis. There was no significant difference between the groups with regarding to age, gender, HbA1C levels, duration of diabetes, duration of macular edema, baseline central macular thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) values (p > 0.05). The mean follow-up time of the whole study population was 10.13 ± 1.75 months (range 9-15). The mean CMT values were significantly decreased in both groups compared to baseline values except for the 6th-month CMT in Group I (p < 0.05). The mean logMAR BCVA values were not statistically different between groups during the follow-up compared to baseline BCVA values (p > 0.05). However, a significant change in mean BCVA from baseline was seen at 4th, 6th, and 9th months in Group II (p ≤ 0.05). The mean number of total intravitreal treatments was 3.50 ± 0.77 in Group I and 2.53 ± 0.51 in Group II (p = 0.001). During the follow-up period, one patient in Group I and five patients in Group II had increased IOP (≥25 mmHg). Early DEX retreatment improved vision with superior anatomical improvement at 6th month and with fewer intravitreal treatments in eyes with DME. However, improvement in visual acuity is similar with standard DEX retreatment combined with PRN ranibizumab group.

  3. PRN 2000-7: Non-Dietary Exposure Task Force

    EPA Pesticide Factsheets

    This PR Notice announces an industry-wide task force to jointly develop residential indoor exposure data for pesticides containing one or more of the active ingredients synthetic pyrethroids, pyrethrum and synergists.

  4. PRN 66 Federal Registration of Economic Poisons

    EPA Pesticide Factsheets

    The Federal Insecticide, Fungicide, and Rodenticide Act, and the regulations promulgated thereunder, provide that an economic poison is misbranded if its labeling bears any statement, graphic representation, or design which is false or misleading.

  5. PRN 2011-1: Residential Exposure Joint Venture

    EPA Pesticide Factsheets

    This PR Notice is to advise registrants of an industry-wide joint venture, titled the Residential Exposure Joint Venture (REJV), which has developed a national survey regarding residential consumer use/usage data for pesticides.

  6. PRN 84-5: Label Improvement Program for Fumigants

    EPA Pesticide Factsheets

    This notice required registrants of fumigant products to revise the labeling of products registered under FIFRA section 3 or 24(c) to include additional precautionary statements and other statements described in the notice.

  7. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Psiaki, Mark L. (Inventor); Kintner, Jr., Paul M. (Inventor); Ledvina, Brent M. (Inventor); Powell, Steven P. (Inventor)

    2007-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  8. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Psiaki, Mark L. (Inventor); Ledvina, Brent M. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2006-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  9. PRN 93-5: Labeling Requirements of the Clean Air Act

    EPA Pesticide Factsheets

    A regulation under the Clean Air Act requires a warning statement on products (including pesticide products) manufactured with or containing Class I ozone-depleting substances, including chlorofluorocarbons, methyl chloroform and carbon tetrachloride.

  10. PRN 98-1: Self-Certification of Product Chemistry Data with Attachments

    EPA Pesticide Factsheets

    The Office of Pesticide Programs has established a self-certification program for certain product chemistry data of manufacturing-use products and end-use products produced by a non-integrated formulation system.

  11. PRN 96-3: Pesticide Products Used to Disinsect Aircraft

    EPA Pesticide Factsheets

    This Notice specifies labeling changes for any pesticide product (insecticide) used for disinsecting aircraft. EPA required these changes based on incident information associated with the use of insecticide spray products occupied aircraft cabins.

  12. Microwave-based navigation of femtosatellites using on-off keying

    NASA Astrophysics Data System (ADS)

    Kamte, Namrata Jagdish

    The objective of this research is to validate that a custom-built microchip-scale satellite transmitting a signal modulated with a Pseudo Random Noise code using On-Off Keying, can be tracked. The weak GPS satellite signal is modulated with a Pseudo Random Noise (PRN) code that provides a mathematical gain. Our signal is modulated with the same PRN code using On-Off Keying (OOK) unlike Phase Shift Keying used in GPS satellites. Our goal is to obtain timing and positioning information from the microchip-scale satellite via a ground station using the concepts of PRN encoding and the OOK modulation technique. Decimeter scale satellites, with a mass of 2--6 kilograms, referred to as picosatellites, have been tracked successfully by ground stations. The microchip-scale satellite, called the femtosatellite is smaller with even less mass, at most 100 grams. At this size the satellite can take advantage of small-scale physics to perform maneuver, such as solar pressure, which only slightly perturb large spacecraft. Additionally, the reduced size decreases the cost of launch as compared to the picosatellites. A swarm of such femtosatellites can serve as environmental probes, interplanetary chemists or in-orbit inspectors of the parent spacecraft. In May 2011, NASA's last space shuttle mission STS-134 carried femtosatellites developed by Cornell researchers called "Sprites". The sprites were deployed from the International Space Station but ground stations on Earth failed to track them. In an effort to develop an alternative femtosatellite design, we have built our own femtosatellite prototype. Our femtosatellite prototype contains the AVR microcontroller on an Arduino board. This assembly is connected to a radio transmitter and a custom antenna transmitting a 433 Mhz radio frequency signal. The prototype transmits a PRN code modulated onto the signal using OOK. Our ground station consists of a Universal Software Radio Peripheral (USRP) with a custom antenna for reception of the 433 MHz signal. The USRP is driven by an open source software-defined radio application called GNU Radio. The required components of the signal are extracted from GNU Radio and processed in order to plot the received data. Benchtop testing of these OOK signals has yielded a reception sensitivity of upto 1 microsecond, which translates into a ranging capability similar to that of GPS satellites. We have correlated the received and replica PRN sequences and demonstrated that they match. The correlation can be used to obtain the identity and position of the femtosatellite prototype. This demonstrates the ability to track a femtosatellite signal that is lower than ambient noise, just like the signals broadcast from GPS satellites. Further, we have performed a system analysis and recognized key system behavioral problems. Thus we have determinately developed an optimum femtosatellite prototype and designed a novel positioning signal, providing a stepping- stone in the journey of successful femtosatellite communication.

  13. PRN 2001-1: First Aid Statements on Pesticide Product Labels

    EPA Pesticide Factsheets

    This PR notice is intended to provide guidance for what the Agency believes is the most updated appropriate first aid language for pesticide product labels to ensure that they continue to adequately protect the public.

  14. PRN 88-2: Clustering of Quaternary Ammonium Compounds

    EPA Pesticide Factsheets

    This Notice announces that EPA has clustered the Quaternary Ammonium Compounds into four groups for the purpose of testing chemicals to build a database that will support continued registration of the entire family of quaternary ammonium compounds

  15. PRN 96-8: Toxicologically Significant Levels of Pesticide Active Ingredients

    EPA Pesticide Factsheets

    This notice sets out EPA's interpretation of the term toxicologically significant as it applies to contaminants in pesticide products that are also pesticide active ingredients. It provides risk-based concentration levels of such contaminants.

  16. PRN 93-4: Ban on Aerosol Products Containing CFCs and HCFCs under the Clean Air Act

    EPA Pesticide Factsheets

    This notice alerts pesticide registrants to a rule under the Clean Air Act banning distribution and sale of aerosol and pressurized products, including pesticide products, that contain chlorofluorocarbons (CFCs).

  17. PRN 94-2: Recycling Empty Aerosol Pesticide Containers

    EPA Pesticide Factsheets

    This notice offers registrants use of an optional label statement permitting recycling as an alternative to instructions to dispose of aerosol pesticide containers. Registrants may add a label reference to recycling the empty aerosol pesticide container.

  18. PRN 2001-2: Acute Toxicity Data Requirements For Granular Pesticide Products, Including Those With Granular Fertilizers in the Product.

    EPA Pesticide Factsheets

    This PR Notice announces guidance intended to streamline the acute toxicity review and classification process for certain granular pesticide products, including those products that contain granular fertilizers.

  19. PRN 96-1: Tolerance Enforcement Methods - Independent Laboratory Validation by Petitioner

    EPA Pesticide Factsheets

    This notice is intended to clarify the requirements for submission of an Independent Laboratory Validation to accompany new pesticide analytical methods and does not contain additional data requirements.This notice supersedes PR Notice 88-5.

  20. PRN 93-3: Labeling Statement Prohibiting Application to Water

    EPA Pesticide Factsheets

    This notice explaining the policy on label statement prohibiting pesticide application to water pertains only to the labeling statement on pesticide products. It does not address the term wetlands as defined with respect to the Clean Water Act.

  1. PRN 2000-5: Guidance for Mandatory and Advisory Labeling Statements

    EPA Pesticide Factsheets

    This notice provides guidance for improving the clarity of labeling statements in order to avoid confusing directions and precautions and to prevent the misuse of pesticides. It includes definitions and examples for mandatory and advisory label statements.

  2. PRN 2002-X Draft: False or Misleading Pesticide Product Brand Name

    EPA Pesticide Factsheets

    This notice provides guidance to registrants and distributors on pesticide product brand names that may be false or misleading, either by themselves or in association with particular company names or trademarks. It is a draft.

  3. PRN 2008-1: Notice to Manufacturers, Producers, Formulators, and Registrants of Pesticide Products

    EPA Pesticide Factsheets

    This Notice presents EPA's guidance on optional environmental hazard label language for certain non-restricted use pesticide products intended for outdoor residential use. It clarifies language on how the user can avoid environmental contamination.

  4. PRN 2009-1: Establishment of Antimicrobial Exposure Assessment Task Force II

    EPA Pesticide Factsheets

    This PR notice announces the establishment of the Antimicrobial Exposure Assessment Task Force II, an industry-wide task force to develop mixer, loader, applicator and post-application exposure data for antimicrobial pesticides used in various settings.

  5. PRN 96-4: Label Statements Involving Product Efficacy and Potential for Harm to Property

    EPA Pesticide Factsheets

    This notice explains EPA procedures in approving pesticide labels that include claims relating to the efficacy of agricultural pesticides and provides a warning to growers regarding reliance on label statements regarding pesticide efficacy.

  6. Information Placement and Retrieval Through NHIN (InfoPRN)

    DTIC Science & Technology

    2011-05-01

    and FISMA.  Dr. Steffensen will contact NMDS (Captain Bensic), JTF CapMed , and perhaps Kaiser Permanente to ascertain their interest in...activities, project stakeholders, critical project deliverables and milestones were defined and agreed upon. Therefore, the Integrated Master

  7. PRN 97-4: Consumer Access Numbers on Pesticide Labels

    EPA Pesticide Factsheets

    This notice describes EPA policy on including telephone numbers and other access numbers or internet addresses, on pesticide product labeling. It also explains how the telephone number of the National Pesticide Information Center hotline may be used.

  8. PRN 87-1: Label Improvement Program for Pesticides Applied through Irrigation Systems (Chemigation)

    EPA Pesticide Factsheets

    This Notice requires registrants of pesticide products registered under FIFRA and applied through irrigation systems to revise the labeling for such products to include additional use directions and other statements described in this Notice.

  9. On becoming neutral: effects of experimental neutralizing reconsidered.

    PubMed

    van den Hout, M; van Pol, M; Peters, M

    2001-12-01

    Behaviour Research and Therapy 34 (1996) 889-898 found that writing out a negative thought produced anxiety and an urge to neutralize the thought, that instructing participants to neutralize the thought reduced anxiety/neutralization urge in the short run (i.e. within 2 min), but that in the control group 20 min without instruction was attended by the same reduction in anxiety/urge to neutralize ("natural decay"). The observations were made with pariticipants who scored high on "thought action fusion" and the experiment was set up as exerimental model of obsessions. We repeated the study with participants that were not selected on thought action fusion. All the findings reported by Behaviour Research and Therapy 34 (1996) 889-898 were replicated. Correlational analysis indicated that the strength of the effect was not related to scores on scales measuring "thought action fusion". Behaviour Research and Therapy 34 (1996) 889-898 did not assess whether non-neutralizing was followed by immediate reductions in distress. We did assess this and found that the larger part of the immediate reduction of distress after neutralization also occurs when no neutralization instruction is given. The effects of neutralization instructions in the present type of experiment are considerably less powerful than suggested earlier.

  10. One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema.

    PubMed

    Do, Diana V; Nguyen, Quan Dong; Boyer, David; Schmidt-Erfurth, Ursula; Brown, David M; Vitti, Robert; Berliner, Alyson J; Gao, Bo; Zeitz, Oliver; Ruckert, Rene; Schmelter, Thomas; Sandbrink, Rupert; Heier, Jeff S

    2012-08-01

    To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME). Randomized, double-masked, multicenter, phase 2 clinical trial. Diabetic patients (n = 221) with center-involved DME. Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation. The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline. As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus -1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were -165.4 μm, -227.4 μm, -187.8 μm, and -180.3 μm versus -58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure. Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  11. Neutralizing Monoclonal Antibodies against Ricin’s Enzymatic Subunit Interfere with Protein Disulfide Isomerase-Mediated Reduction of Ricin Holotoxin In Vitro

    PubMed Central

    O’Hara, Joanne M.; Mantis, Nicholas J.

    2013-01-01

    The penultimate event in the intoxication of mammalian cells by ricin toxin is the reduction, in the endoplasmic reticulum (ER), of the intermolecular disulfide bond that links ricin’s enzymatic (RTA) and binding (RTB) subunits. In this report we adapted an in vitro protein disulfide isomerase (PDI)-mediated reduction assay to test the hypothesis that the RTA-specific neutralizing monoclonal antibody (mAb) IB2 interferes with the liberation of RTA from RTB. IB2 recognizes an epitope located near the interface between RTA and RTB and, like a number of other RTA-specific neutralizing mAbs, is proposed to neutralize ricin intracellularly. In this study, we found that IB2 virtually eliminated the reduction of ricin holotoxin into RTA and RTB in vitro. Surprisingly, three other neutralizing mAbs (GD12, R70 and SyH7) that bind epitopes at considerable distance from ricin’s disulfide bond were as effective (or nearly as effective) as IB2 in interfering with PDI-mediated liberation of RTA from RTB. By contrast, two non-neutralizing RTA-specific mAbs, FGA12 and SB1, did not affect PDI-mediated reduction of ricin. These data reveal a possible mechanism by which RTA-specific antibodies may neutralize ricin intracellularly, provided they are capable of trafficking in association with ricin from the cell surface to the ER. PMID:23774033

  12. PRN 97-8: Time Extension of PR Notice 96-7 - Termiticide Labeling

    EPA Pesticide Factsheets

    EPA intends to grant a 90-day extension to permit the distribution or sale of products not bearing labeling consistent with PR Notice 96-7. View the reasons for this extension and what products are affected.

  13. PRN 93-8: Labeling Statement Prohibiting Application to Water; Amendment to PR Notice 93-3

    EPA Pesticide Factsheets

    This notice adds one paragraph to P.R. Notice 93-3, which requested registrants to amend product labeling to include a new labeling statement prohibiting application of a pesticide to water for certain products.

  14. PRN 95-1: Effluent Discharge Labeling Statements

    EPA Pesticide Factsheets

    This notice exempts certain pesticide products from bearing effluent discharge labeling statements specified by P.R. Notice 93-10 for manufacturing use products and end use products that may be discharged to waters of the U.S. or municipal sewer systems.

  15. PRN 2001-X Draft: Spray and Dust Drift Label Statements for Pesticide Products

    EPA Pesticide Factsheets

    This Notice sets forth the U.S. Environmental Protection Agency's (EPA or Agency) draft guidance for labeling statements for controlling spray drift and dust drift from application sites and for implementing these statements for risk mitigation.

  16. PRN 2007-3: The Agricultural Handlers Exposure Task Force, L.L.C

    EPA Pesticide Factsheets

    This PR Notice discusses the Agricultural Handlers Exposure Task Force, an industry-wide task force formed to develop mixer, loader, and applicator exposure data for pesticides used in agricultural settings. It includes contacts for more information.

  17. PRN 94-6: Pesticide Products Registered for Use on Humans to Control Lice (Pediculicides)

    EPA Pesticide Factsheets

    This notice alerts pesticide registrants to a rule issued by Food and Drug Administration (FDA) under the Federal Food, Drug and Cosmetic Act (FFDCA) establishing conditions for safe and effective use of pediculicide drug products.

  18. PRN 98-6: Flammability Labeling Requirements for Total Release Fogger Pesticides

    EPA Pesticide Factsheets

    This notice describes new labeling requirements for total release foggers and provides the procedures and time frame for compliance. It ONLY affects total release foggers containing a propellant with a flash point at or below 20 degrees Fahrenheit.

  19. PRN 83-3: Label Improvement Program - Storage and Disposal Label Statements

    EPA Pesticide Factsheets

    This Notice is to inform all registrants that the label of all pesticide products must include updated storage and disposal statements. No application for amended registration is required if you use the exact wording contained in this Notice.

  20. PRN 84-1: Clarification of Label Improvement Program for Farmworker Safety and Pesticide Storage and Disposal Instructions

    EPA Pesticide Factsheets

    This PR notice clarifies EPA's intentions regarding the Pesticide Label Improvement Program for Farmworker Safety (PR Notice 83-2) and Pesticide Storage and Disposal Instructions (PR Notice 83-3) issued on March 26, 1983.

  1. PRN 99-1: Import of Unregistered Pesticides Intended for Export

    EPA Pesticide Factsheets

    This PR notice clarifies EPA's interpretation of the scope of the FIFRA Section 17 (a)(1) for import of unregistered pesticides, devices or pesticide active ingredients when the importation is solely for the purpose of formulation or packaging for export.

  2. PRN 2000-1: Applicability of the Treated Articles Exemption to Antimicrobial Pesticides

    EPA Pesticide Factsheets

    This notice clarifies EPA policy with respect to the scope of the treated articles exemption in 40 CFR 152.25(a). This exemption covers qualifying treated articles and substances bearing claims to protect the article or substance itself.

  3. PRN 2002-1: Lists of Pests of Significant Public Health Importance

    EPA Pesticide Factsheets

    This notice identifies pests of significant public health importance. This list does not, by itself, determine whether a pesticide product might be considered a public health pesticide“ as that term is used in FIFRA. See Appendix A for the list.

  4. PRN 97-5: Use of Common Names for Active Ingredients on Pesticide Labeling

    EPA Pesticide Factsheets

    This notice announces EPA policy to expand the use of common names on pesticide labeling. EPA will permit the use of common names approved by ANSI in the label ingredients statement without the accompanying scientific chemical name.

  5. PRN Notice 96-6: Pet Pesticide Product Label Statements

    EPA Pesticide Factsheets

    This notice specifies statements that should be added to the labels of pesticide products registered for use on dogs and/or cats. These label statements will help to ensure that products bear labeling to reduce the potential for misuse of pet products.

  6. Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium

    PubMed Central

    Caboré, Raïssa Nadège; Maertens, Kirsten; Dobly, Alexandre; Leuridan, Elke; Van Damme, Pierre; Huygen, Kris

    2017-01-01

    ABSTRACT Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent. In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation. PMID:28277900

  7. How is agitation and restlessness managed in the last 24 h of life in patients whose care is supported by the Liverpool care pathway for the dying patient?

    PubMed

    Gambles, M; McGlinchey, T; Latten, R; Dickman, A; Lowe, D; Ellershaw, J E

    2011-12-01

    Guidance regarding the patient centred management of agitation and restlessness reinforces the importance of considering underlying causes, non-pharmacological approaches to treatment and judicious use of medications titrated to patient need. In contrast, recent reports in the literature suggest that the practice of continuous deep sedation until death is prevalent in the UK. To use data from the National Care of the Dying Audit-Hospitals (NCDAH) to explore the administration of medication for management of agitation and restlessness in the last 24 h of life. Hospitals submitted data from up to 30 consecutive adult patients whose care in the final hours/days of life was supported by the Liverpool Care Pathway for the Dying Patient (LCP). Data on the total dose received in the last 24 h of life PRN and the last dose prescribed for administration via continuous subcutaneous infusion (CSCI) for agitation and restlessness were submitted. 155 hospitals provided data from 3893 patients. Median total doses in the last 24 h for midazolam, haloperidol and levomepromazine, respectively, were: PRN only, 2.5, 1.5 and 6.25 mg; CSCI only, 10, 3 and 6.25 mg; PRN+CSCI, 15, 3 and 12.5 mg. Only 51% of patients received medication to alleviate agitation and restlessness in the last 24 h of life. Median doses were low in comparison to doses recommended for continuous deep sedation, suggesting that there is no 'blanket' policy for continuous deep sedation at the end of life for patients whose care is supported by the LCP.

  8. Resurgence of Pertussis and Emergence of the Ptxp3 Toxin Promoter Allele in South Italy.

    PubMed

    Loconsole, Daniela; De Robertis, Anna Lisa; Morea, Anna; Metallo, Angela; Lopalco, Pier Luigi; Chironna, Maria

    2018-05-01

    Despite universal immunization programs, pertussis remains a major public health concern. This study aimed to describe the pertussis epidemiology in the Puglia region in 2006-2015 and to identify recent polymorphisms in Bordetella pertussis virulence-associated genes. The pertussis cases in 2006-2015 were identified from the National Hospital Discharge Database and the Information System of Infectious Diseases. Samples of pertussis cases in 2014-2016 that were confirmed by the Regional Reference Laboratory were subjected to ptxA, ptxP and prn gene sequencing and, in 10 cases, multiple-locus variable-number tandem repeat analysis. In Puglia in 2006-2015, the pertussis incidence rose from an average of 1.39/100,000 inhabitants in 2006-2013 to 2.56-2.54/100,000 in 2014-2015. In infants <1 year of age, the incidence rose from an average of 60.4/100,000 infants in 2006-2013 to 149.9/100,000 in 2015. Of the 661 cases recorded in 2006-2015, 80.3% required hospitalization; of these, 45.4% were <1 year of age. Of the 80 sequenced samples, the allelic profile ptxA1-ptxP3-prn2 was detected in 74. This variant was detected in both vaccinated and unvaccinated people. Six Bordetella pertussis samples were prn deficient. The multiple-locus variable-number tandem repeat analysis cases exhibited multiple-locus variable-number tandem repeat analysis-type 27. The pertussis incidence in Puglia has risen. The hypervirulent strain was also found in vaccinated people. This suggests bacterial adaptation to the vaccine and raises questions about acellular vaccine effectiveness. Prevention of infant pertussis cases is best achieved by immunizing the pregnant mother. Enhanced surveillance and systematic laboratory confirmation of pertussis should be improved in Italy.

  9. Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium.

    PubMed

    Caboré, Raïssa Nadège; Maertens, Kirsten; Dobly, Alexandre; Leuridan, Elke; Van Damme, Pierre; Huygen, Kris

    2017-10-03

    Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent. In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation.

  10. Reliability of reference distances used in photogrammetry.

    PubMed

    Aksu, Muge; Kaya, Demet; Kocadereli, Ilken

    2010-07-01

    To determine the reliability of the reference distances used for photogrammetric assessment. The sample consisted of 100 subjects with mean ages of 22.97 +/- 2.98 years. Five lateral and four frontal parameters were measured directly on the subjects' faces. For photogrammetric assessment, two reference distances for the profile view and three reference distances for the frontal view were established. Standardized photographs were taken and all the parameters that had been measured directly on the face were measured on the photographs. The reliability of the reference distances was checked by comparing direct and indirect values of the parameters obtained from the subjects' faces and photographs. Repeated measure analysis of variance (ANOVA) and Bland-Altman analyses were used for statistical assessment. For profile measurements, the indirect values measured were statistically different from the direct values except for Sn-Sto in male subjects and Prn-Sn and Sn-Sto in female subjects. The indirect values of Prn-Sn and Sn-Sto were reliable in both sexes. The poorest results were obtained in the indirect values of the N-Sn parameter for female subjects and the Sn-Me parameter for male subjects according to the Sa-Sba reference distance. For frontal measurements, the indirect values were statistically different from the direct values in both sexes except for one in male subjects. The indirect values measured were not statistically different from the direct values for Go-Go. The indirect values of Ch-Ch were reliable in male subjects. The poorest results were obtained according to the P-P reference distance. For profile assessment, the T-Ex reference distance was reliable for Prn-Sn and Sn-Sto in both sexes. For frontal assessment, Ex-Ex and En-En reference distances were reliable for Ch-Ch in male subjects.

  11. Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fractures.

    PubMed

    Tidermark, Jan; Ponzer, Sari; Carlsson, Pronoti; Söderqvist, Anita; Brismar, Kerstin; Tengstrand, Birgitta; Cederholm, Tommy

    2004-08-01

    To evaluate the effects of a protein-rich liquid supplementation, alone or in combination with the anabolic steroid nandrolone decanoate, on body composition, activities of daily living (ADL) status and the health-related quality of life (HRQoL) after a femoral neck fracture. Sixty women, aged 83 +/- 5 years (mean +/- SD), BMI < 24 kg/m2 (20.4 +/- 2 kg/m2 ) and capable of co-operating, with a femoral neck fracture treated with internal fixation, were randomised to open treatment during 6 months with a protein-rich liquid formula alone (PR, Fortimel, 200 ml/day, 20 g protein/day) or in combination with nandrolone decanoate (PR/N, Deca-Durabol 25 mg i.m./3 weeks) or to a control group (C). The patients were re-examined after 6 and 12 months regarding body weight (BW), lean body mass (LBM, DXA), ADL status according to Katz, HRQoL according to EQ 5-D and fracture healing. LBM decreased in the C (-1.2 +/- 2 kg) and PR groups (-1.2 +/- 1 kg) but remained the same in the PR/N group (0.3 +/- 1 kg) (P < 0.05 between groups). ADL remained at a high level in the two intervention groups but declined significantly in the C group (P < 0.005 between groups). The decline in HRQoL was least pronounced in the PR/N group at 6 months (P < 0.05 between groups). Patients with fracture healing complications lost more BW (P < 0.05) and LBM (P < 0.01) than patients with uneventful fracture healing. Protein-rich liquid supplementation in combination with nandrolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM, ADL and HRQoL. Copyright 2003 Elsevier Ltd.

  12. Neutralizing monoclonal antibodies against ricin's enzymatic subunit interfere with protein disulfide isomerase-mediated reduction of ricin holotoxin in vitro.

    PubMed

    O'Hara, Joanne M; Mantis, Nicholas J

    2013-09-30

    The penultimate event in the intoxication of mammalian cells by ricin toxin is the reduction, in the endoplasmic reticulum (ER), of the intermolecular disulfide bond that links ricin's enzymatic (RTA) and binding (RTB) subunits. In this report we adapted an in vitro protein disulfide isomerase (PDI)-mediated reduction assay to test the hypothesis that the RTA-specific neutralizing monoclonal antibody (mAb) IB2 interferes with the liberation of RTA from RTB. IB2 recognizes an epitope located near the interface between RTA and RTB and, like a number of other RTA-specific neutralizing mAbs, is proposed to neutralize ricin intracellularly. In this study, we found that IB2 virtually eliminated the reduction of ricin holotoxin into RTA and RTB in vitro. Surprisingly, three other neutralizing mAbs (GD12, R70 and SyH7) that bind epitopes at considerable distance from ricin's disulfide bond were as effective (or nearly as effective) as IB2 in interfering with PDI-mediated liberation of RTA from RTB. By contrast, two non-neutralizing RTA-specific mAbs, FGA12 and SB1, did not affect PDI-mediated reduction of ricin. These data reveal a possible mechanism by which RTA-specific antibodies may neutralize ricin intracellularly, provided they are capable of trafficking in association with ricin from the cell surface to the ER. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. PRN 93-11: Supplemental Guidance for PR Notice 93-7 - Labeling Revisions Required by the WPS

    EPA Pesticide Factsheets

    This pesticide registration notice augments the guidance provided by PR notice 97-3 to provide options that you may choose to allow efficient production and distribution of products that comply with PR Notice 93-7.

  14. PRN 2003-1: Labeling of Pesticide Products under the National Organic Program

    EPA Pesticide Factsheets

    This notice describes how registrants can obtain EPA approval of label language indicating that all ingredients (active and inert) in a pesticide product and all uses of that pesticide meet the criteria defined in the USDA's National Organic Program Rule.

  15. PRN 75-5: Unacceptable Use of the Word Chlorine in the Name and Labeling of Pesticides

    EPA Pesticide Factsheets

    Use of the word CHLORINE on labels other than in products containing liquified chlorine under pressure has been determined to be in violation of Section 2(q)(l)(A) of the Federal Insecticide, Fungicide, and Rodenticide Act.

  16. PRN 97-7: Existing Stocks for Labeling Changes in PR Notices

    EPA Pesticide Factsheets

    EPA intends to establish October 1 as the annual compliance date for most EPA-initiated label changes specified by a PR Notice, FR Notice or similar mechanism. We will allow at least one year for an action to become effective. Other dates may apply.

  17. PRN 91-1: Procedures for Voluntarily Requesting Deletion of Approved Uses from Registered Labels

    EPA Pesticide Factsheets

    This pesticide registration notice defines procedures for registrants to use when they with to request an amendment to delete one or more uses from an approved registration, and it summarizes the actions the Agency will take in response to such requests.

  18. PRN 2000-8: Reportability of Attorneys’ Opinions and Conclusions Under 40 CFR Part 159 and FIFRA Section 6(a)(2)

    EPA Pesticide Factsheets

    EPA is issuing this pesticide registration notice to inform registrants of EPA’s opinion that an attorney’s professional legal judgment is not an opinion or conclusion that is reportable under 40 CFR part 159.

  19. PRN 98-5: New Forms for the Certification with Respect to Citation of Data

    EPA Pesticide Factsheets

    In 1998, EPA established new forms for citation of data to support the registration or reregistration of pesticide products. These forms are EPA Form 8570-34 (“Certification with Respect to Citation of Data”) and 8570-35 (“Data Matrix”).

  20. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results.

    PubMed

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo; Wolf, Sebastian; Simader, Christian; Tokaji, Erika; Pilz, Stefan; Weisberger, Annemarie

    2012-05-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration. Prospective, multicenter, double-masked, randomized, active-controlled trial. We included 255 patients with all types of active subfoveal choroidal neovascularization. Patients were randomized 1:1 to as-needed (pro re nata; PRN) combination (standard-fluence verteporfin 6 mg/m(2) PDT and ranibizumab 0.5 mg) or PRN ranibizumab monotherapy (sham infusion [5% dextrose] PDT and ranibizumab 0.5 mg). Patients received 3 consecutive monthly injections followed by PRN retreatments based on protocol-specific retreatment criteria. Mean change in best-corrected visual acuity (BCVA) from baseline to month 12, and the proportion of patients with treatment-free interval ≥3 months at any timepoint after month 2. The mean change in BCVA at month 12 was +2.5 and +4.4 letters in the combination and monotherapy groups, respectively (P = 0.0048; difference: -1.9 letters [95% confidence interval, -5.76 to 1.86], for having achieved noninferiority with a margin of 7 letters). The proportion of patients with a treatment-free interval of ≥3 months at any timepoint after month 2 was high, but did not show a clinically relevant difference between the treatment groups. Secondary efficacy endpoints included the mean number of ranibizumab retreatments after month 2 (1.9 and 2.2 with combination and monotherapy, respectively [P = 0.1373]). The time to first ranibizumab retreatment after month 2 was delayed by 34 days (about 1 monthly visit) with combination (month 6) versus monotherapy (month 5). At month 12, mean ± standard error central retinal thickness decreased by 115.3±9.04 μm in the combination group and 107.7±11.02 μm in the monotherapy group. The mean number of verteporfin/sham PDT treatments was comparable in the 2 groups (combination, 1.7; monotherapy, 1.9). The safety profiles of the 2 groups were comparable, with a low incidence of ocular serious adverse events. The combination PRN treatment regimen with verteporfin PDT and ranibizumab was effective in achieving BCVA gain comparable with ranibizumab monotherapy; however, the study did not show benefits with respect to reducing the number of ranibizumab retreatment over 12 months. The combination therapy was well tolerated. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  1. Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy--Results from a Randomized Controlled Trial (REACTT).

    PubMed

    Mulhall, John P; Brock, Gerald; Oelke, Matthias; Fode, Mikkel; Probst, Kai A; Henneges, Carsten; d'Anzeo, Gianluca; Rossi, Andrea; Büttner, Hartwig

    2016-04-01

    The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function (EF)-recovery, which was predefined as achieving an International Index of Erectile Function (IIEF)-EF score ≥22. Here, we report descriptive post-hoc analyses, using the more strict definition for EF-recovery of returning back to the pre-surgery IIEF-EF-level ("back-to-baseline analysis"). REACTT included 422 men <68 years with adenocarcinoma of the prostate and preoperative IIEF-EF ≥22 who underwent nsRP at 50 centers from 9 European countries and Canada. Patients were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on-demand (pro-re-nata, PRN; n = 142), or placebo (n = 141), followed by 6-week drug-free washout (DFW) and 3-month open-label tadalafil OaD treatment (OLT). Proportion of patients returning to their preoperative IIEF-EF category (22-25 or ≥26) at the end of DBT, DFW, and OLT. Overall, 92.4% of patients had pre-surgery (baseline) IIEF-EF scores ≥26 (tadalafil OaD 94.2%, PRN 91.6%, placebo 91.5%), 7.4% had IIEF-EF 22-25. At the end of DBT, 22.3% of patients on tadalafil OaD had achieved "back-to-baseline" IIEF-EF, compared with 11.3% on tadalafil PRN and 7.8% on placebo. Of all 58 patients "back-to-baseline" at the end of DBT, only 1 PRN-group patient had started from a baseline IIEF-EF <26. The treatment-group difference at the end of DBT was not maintained after DFW. After 3 months of OLT with tadalafil OaD, the proportion of patients with "back-to-baseline" IIEF-EF had almost doubled in all 3 groups. Changing the definition for EF-recovery from IIEF-EF ≥22 to the more strict definition of "returning back-to-baseline IIEF-EF" had no major impact. Tadalafil OaD started early after nsRP improved drug-assisted EF, but had no effect on unassisted EF following treatment cessation after 9 months. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  2. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides

    EPA Pesticide Factsheets

    EPA encourages the development, registration and use of lower-risk pesticide products which would result in reduced risks to human health and the environment. This Pesticide Registration notice and the related web page explain the process and criteria.

  3. PRN 90-3: Announcing the Formation of an Industry-Wide Spray Drift Task Force

    EPA Pesticide Factsheets

    A Spray Drift Task Force has been organized pursuant to provisions of FIFRA section 3 (c)(2)(B)(ii) to share the cost of developing a generic spray drift data base capable of satisfying spray drift data requirements for pesticide product registrations.

  4. Draft PRN 2006-A: Use of Antimicrobial Pesticide Products in Heating, Ventilation, Air Conditioning and Refrigeration Systems (HVAC&R)

    EPA Pesticide Factsheets

    This draft notice provides guidance to registrants of EPA-registered antimicrobial products whose labels bear general directions related to hard, non-porous or porous surfaces, but which are not but which are not specifically registered for HVAC uses.

  5. High degree of correlation between Ebola virus BSL-4 neutralization assays and pseudotyped VSV BSL-2 fluorescence reduction neutralization test.

    PubMed

    Konduru, Krishnamurthy; Shurtleff, Amy C; Bavari, Sina; Kaplan, Gerardo

    2018-04-01

    Ebola virus (EBOV), classified as a category A agent by the CDC and NIH, requires BSL-4 containment and induces high morbidity and mortality in humans. The 2013-2015 epidemic in West Africa underscored the urgent need to develop vaccines and therapeutics to prevent and treat EBOV disease. Neutralization assays are needed to evaluate the efficacy of EBOV vaccines and antibody therapies. Pseudotyped viruses based on nonpathogenic or attenuated vectors reduce the risks involved in the evaluation of neutralizing antibodies against highly pathogenic viruses. Selectable markers, fluorescent proteins, and luciferase have been introduced into pseudotyped viruses for detection and quantitation purposes. The current study describes the development of a BSL-2 fluorescence reduction neutralization test (FRNT) using a recombinant vesicular stomatitis virus (VSV) in which the VSV-G envelope gene was replaced with the EBOV glycoprotein (GP) and green fluorescent protein (GFP) genes (rVSV-EBOVgp-GFP). Cells infected with rVSV-EBOVgp-GFP express GFP. Anti-GP neutralizing monoclonal and polyclonal antibodies blocked rVSV-EBOVgp-GFP infection preventing or reducing GFP fluorescence. The high degree of correlation between the EBOV BSL-2 FRNT and the BSL-4 plaque reduction neutralization test (PRNT), the accepted standard of EBOV neutralization tests, supports the use of the EBOV BSL-2 FRNT to evaluate neutralizing antibodies in clinical trials. Published by Elsevier B.V.

  6. Application of behavior-based ergonomics therapies to improve quality of life and reduce medication usage for Alzheimer's/dementia residents.

    PubMed

    Mowrey, Corinne; Parikh, Pratik J; Bharwani, Govind; Bharwani, Meena

    2013-02-01

    Behavior-based ergonomics therapy (BBET) has been proposed in the past as a viable individualized non-pharmacological intervention to manage challenging behaviors and promote engagement among long-term care residents diagnosed with Alzheimer's/dementia. We evaluate the effect of BBET on quality of life and behavioral medication usage in an 18-bed dementia care unit at a not-for-profit continuing care retirement community in West Central Ohio. Comparing a target cohort during the 6-month pre-implementation period with the 6-month post-implementation period, our study indicates that BBET appears to have a positive impact on the resident's quality of life and also appears to correlate with behavioral medical reduction. For instance, the number of days with behavioral episodes decreased by 53%, the total Minimum Data Set (MDS) mood counts decreased by 70%, and the total MDS behavior counts decreased by 65%. From a medication usage standpoint, the number of pro re nata (PRN) Ativan doses decreased by 57%.

  7. PRN 94-7: Label Improvement Program for the Revision of Use Directions for Commensal Rodenticides and Statement of the Agency's Policies on the Use of Rodenticide Bait Stations

    EPA Pesticide Factsheets

    This Notice requires registrants of certain pesticide products claimed to control commensal rodents and registered under FIFRA to revise the labeling of such products to bear certain statements concerning tamper-resistant bait stations.

  8. PRN 94-9: Announcing the Formation of Two Industry-Wide Task Forces: Agricultural Reentry Task Force and Outdoor Residential Exposure Task Force

    EPA Pesticide Factsheets

    This Notice announces two industry-wide Task Forces being formed in response to generic exposure data requirements. It contains EPA's policy on a registrant's options for, and responsibilities when joining Task Force as a way to satisfy data requirements.

  9. PRN 2007-2: Guidance on Small-Scale Field Testing and Low-level Presence in Food of Plant-Incorporated Protectants (PIPs)

    EPA Pesticide Factsheets

    This notice clarifies how EPA ensures the safety of residues of PIPs possibly present in food or feed and when a tolerance or tolerance exemption would be required for field tests for biotechnology-derived food and feed crop plants containing PIPs.

  10. Transforming Equity-Oriented Leaders: Principal Residency Network Program Evaluation

    ERIC Educational Resources Information Center

    Braun, Donna; Billups, Felice D.; Gable, Robert K.

    2013-01-01

    After 12 years focused on developing school leaders who act as change agents for educational equity, the Principal Residency Network (PRN) partnered with Johnson and Wales University's Center for Research and Evaluation to conduct a utilization-focused (Patton, 2002) program evaluation funded by a grant from the Rhode Island Foundation. The PRN…

  11. Predictors of Nurses' Intentions to Administer As-Needed Opioid Analgesics for Pain Relief to Postoperative Orthopaedic Patients in the Acute Care Setting.

    PubMed

    Taylor, Colleen Y; Sheu, Jiunn-Jye; Chen, Huey-Shys; Glassman, Tavis; Dake, Joseph

    Patients undergoing orthopaedic surgery experience severe postoperative pain that is frequently undertreated. No study was found that examined the predictors of nurses' intentions to administer as needed (PRN) opioid analgesics for postoperative pain relief. The purpose of this study was to determine what constructs from the Integrated Behavioral Model (IBM) can predict nurses' intentions to administer PRN opioid analgesics for pain relief to hospitalized postoperative orthopaedic patients. A nonexperimental, cross-sectional quantitative format was used. The sample consisted of 800 nurses. Data collection was done by survey. Path analysis revealed the significant predictors of nurses' intention to administer opioid analgesics to be self-efficacy (β= 0.15), normative beliefs (β= 0.21), and salience (importance) of the behavior (β= 0.25). The study showed that the IBM constructs are useful for predicting intentions toward performance of a professional behavior. The inclusion of self-efficacy, underlying beliefs, and salience of the behavior was new and unique contributions to the existing body of knowledge.

  12. The archaeo-eukaryotic primase of plasmid pRN1 requires a helix bundle domain for faithful primer synthesis

    PubMed Central

    Beck, Kirsten; Vannini, Alessandro; Cramer, Patrick; Lipps, Georg

    2010-01-01

    The plasmid pRN1 encodes for a multifunctional replication protein with primase, DNA polymerase and helicase activity. The minimal region required for primase activity encompasses amino-acid residues 40–370. While the N-terminal part of that minimal region (residues 47–247) folds into the prim/pol domain and bears the active site, the structure and function of the C-terminal part (residues 248–370) is unknown. Here we show that the C-terminal part of the minimal region folds into a compact domain with six helices and is stabilized by a disulfide bond. Three helices superimpose well with the C-terminal domain of the primase of the bacterial broad host range plasmid RSF1010. Structure-based site-directed mutagenesis shows that the C-terminal helix of the helix bundle domain is required for primase activity although it is distant to the active site in the crystallized conformation. Furthermore, we identified mutants of the C-terminal domain, which are defective in template binding, dinucleotide formation and conformation change prior to DNA extension. PMID:20511586

  13. The mechanism of neutral red-mediated microbial electrosynthesis in Escherichia coli: menaquinone reduction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harrington, Timothy D.; Tran, Vi N.; Mohamed, Abdelrhman

    The aim of this work was to elucidate the mechanism of mediated microbial electrosynthesis via neutral red from an electrode to fermenting Escherichia coli cultures in a bioelectrochemical system. Chemical reduction of NAD+ by reduced neutral red did not occur as predicted. Instead, neutral red was shown to reduce the menaquinone pool in the inner bacterial membrane. The reduced menaquinone pool altered fermentative metabolite production via the arcB redox-sensing cascade in the absence of terminal electron acceptors. When the acceptors DMSO, fumarate, or nitrate were provided, as many as 19% of the electrons trapped in the reduced acceptors were derivedmore » from the electrode. These results demonstrate the mechanism of neutral red-mediated microbial electrosynthesis during fermentation as well as how neutral red enables microbial electrosynthesis of reduced terminal electron acceptors.« less

  14. Pseudo-plaque reduction neutralization test (PPRNT) for the measurement of neutralizing antibodies to Crimean-Congo hemorrhagic fever virus.

    PubMed

    Canakoglu, Nurettin; Berber, Engin; Ertek, Mustafa; Yoruk, Mustafa D; Tonbak, Sukru; Bolat, Yusuf; Aktas, Munir; Kalkan, Ahmet; Ozdarendeli, Aykut

    2013-01-03

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus family Bunyaviridae, which are enveloped viruses containing tripartite, negative polarity, single-stranded RNA. CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Europe. Currently, there are no specific treatments or licensed vaccines available for CCHFV. Recently, two research groups have found adult mice with defective interferon responses allowed to lethal CCHFV infection. These mouse models could provide invaluable information for further studies. Efforts to develop a vaccine against CCHFV are being made. To determine the efficacy of vaccine candidates it is important to conduct serological studies that can accurately measure levels of protective antibodies. In the present study, a pseudo-plaque reduction neutralization test (PPRNT) based on enzyme-catalyzed color development of infected cells probed with anti-CCHFV antibodies was used to measure neutralization antibody of CCHFV. Sixty-nine human serum samples (20 acute and 49 convalescent) were tested. The presence of CCHFV antibodies was determined and confirmed by a commercial ELISA kit. CCHFV RNA was determined by RT-PCR. All the samples were analyzed by PPRNT and fluorescent focus reduction neutralization test (FFRNT) to measure of CCHFV-neutralizing antibodies. Pseudo-plaque reduction neutralization test showed a high sensitivity (98%), specificity (100%) and agreement (96,6%) in qualitative comparison with those of the FFRNT. There was a high correlation between the titers obtained in PPRNT and FFRNT (R2 = 0.92). The inter- and intra-assay variation of PPRNT revealed good reproducibility and positive cut-off of PPRNT was defined as 1:4 by the geometric mean titers for the individual samples distributed. The pseudo-plaque reduction neutralization test described in this study is a fast, reproducible and sensitive method for the measurement of CCHF neutralizing antibodies. This novel assay could serve as useful tools for CCHF research in epidemiology, vaccine development and other studies of immunity. It also provides an alternative to PRNT when viruses with no or poor CPE in cell culture.

  15. Pseudo-plaque reduction neutralization test (PPRNT) for the measurement of neutralizing antibodies to Crimean-Congo hemorrhagic fever virus

    PubMed Central

    2013-01-01

    Background Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus family Bunyaviridae, which are enveloped viruses containing tripartite, negative polarity, single-stranded RNA. CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Europe. Currently, there are no specific treatments or licensed vaccines available for CCHFV. Recently, two research groups have found adult mice with defective interferon responses allowed to lethal CCHFV infection. These mouse models could provide invaluable information for further studies. Efforts to develop a vaccine against CCHFV are being made. To determine the efficacy of vaccine candidates it is important to conduct serological studies that can accurately measure levels of protective antibodies. In the present study, a pseudo-plaque reduction neutralization test (PPRNT) based on enzyme-catalyzed color development of infected cells probed with anti-CCHFV antibodies was used to measure neutralization antibody of CCHFV. Methods Sixty-nine human serum samples (20 acute and 49 convalescent) were tested. The presence of CCHFV antibodies was determined and confirmed by a commercial ELISA kit. CCHFV RNA was determined by RT-PCR. All the samples were analyzed by PPRNT and fluorescent focus reduction neutralization test (FFRNT) to measure of CCHFV-neutralizing antibodies. Results Pseudo-plaque reduction neutralization test showed a high sensitivity (98%), specificity (100%) and agreement (96,6%) in qualitative comparison with those of the FFRNT. There was a high correlation between the titers obtained in PPRNT and FFRNT (R2 = 0.92). The inter- and intra-assay variation of PPRNT revealed good reproducibility and positive cut-off of PPRNT was defined as 1:4 by the geometric mean titers for the individual samples distributed. Conclusion The pseudo-plaque reduction neutralization test described in this study is a fast, reproducible and sensitive method for the measurement of CCHF neutralizing antibodies. This novel assay could serve as useful tools for CCHF research in epidemiology, vaccine development and other studies of immunity. It also provides an alternative to PRNT when viruses with no or poor CPE in cell culture. PMID:23282186

  16. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks.

    PubMed

    Martinez-Serrano, Maria Guadalupe; Rodriguez-Reyes, Abelardo; Guerrero-Naranjo, Jose Luis; Salcedo-Villanueva, Guillermo; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

    2017-01-01

    The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV), secondary to angioid streaks (AS), who were treated with antiangiogenic drugs in a pro re nata (PRN) regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of awareness and self-referral by the patients are believed to be the cause of the PRN regimen failure. To assess the long-term outcomes (>4 years) of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA) over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR ( P =0.9). Central macular thickness at baseline was: 360.85±173.82 μm; at the end of follow-up: 323.85±100.34 μm ( P =0.6). Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4-15). Mean time between injections was 3.8±2.7 months (range 1.9-5.8 months). Despite initial anatomical and functional improvement, patients at the end of the follow-up had no visual improvement after a pro re nata regimen of antiangiogenic drugs. The amount of retreatments, number of recurrences, and time between intravitreal injections were similar to previous reports with shorter follow-up.

  17. The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters*

    PubMed Central

    Gournas, Christos; Evangelidis, Thomas; Athanasopoulos, Alexandros; Mikros, Emmanuel; Sophianopoulou, Vicky

    2015-01-01

    Amino acid uptake in fungi is mediated by general and specialized members of the yeast amino acid transporter (YAT) family, a branch of the amino acid polyamine organocation (APC) transporter superfamily. PrnB, a highly specific l-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical approaches to investigate the molecular basis of this difference and identify residues governing substrate binding and specificity. We demonstrate that l-proline is recognized by PrnB via interactions with residues within TMS1 (Gly56, Thr57), TMS3 (Glu138), and TMS6 (Phe248), which are evolutionary conserved in YATs, whereas specificity is achieved by subtle amino acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently l-alanine, l-azetidine-2-carboxylic acid, and glycine without significantly affecting the apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas T414S, despite displaying reduced proline uptake, could transport l-alanine and glycine, a phenotype suppressed by the S130C mutation. A combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport l-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core, or affecting conformational changes of the transport cycle. PMID:25572393

  18. The role of Toll-like receptor-4 in pertussis vaccine-induced immunity

    PubMed Central

    Banus, Sander; Stenger, Rachel M; Gremmer, Eric R; Dormans, Jan AMA; Mooi, Frits R; Kimman, Tjeerd G; Vandebriel, Rob J

    2008-01-01

    Background The gram-negative bacterium Bordetella pertussis is an important causative agent of pertussis, an infectious disease of the respiratory tract. After introduction of whole-cell vaccines (wP) in the 1950's, pertussis incidence has decreased significantly. Because wP were found to be reactogenic, in most developed countries they have been replaced by acellular vaccines (aP). We have previously shown a role for Toll-like receptor 4 (Tlr4) in pertussis-infected mice and the pertussis toxin (Ptx)-IgG response in wP-vaccinated children, raising the issue of the relative importance of Tlr4 in wP vaccination of mice. Here we analyze the effects of wP and aP vaccination and B. pertussis challenge, in Tlr4-deficient C3H/HeJ and wild-type C3H/HeOuJ mice. aP consists of Ptx, filamentous hemagglutinin (FHA), and pertactin (Prn). Results We show an important role of Tlr4 in wP and (to a lesser extent) aP vaccination, induction of Th1 and Th17 cells by wP but not aP vaccination, and induction of Th17 cells by infection, confirming data by Higgins et al. (J Immunol 2006, 177:7980–9). Furthermore, in Tlr4-deficient mice, compared to wild-type controls (i) after vaccination only, Ptx-IgG (that was induced by aP but not wP vaccination), FHA-IgG, and Prn-IgG levels were similar, (ii) after infection (only), lung IL-1α and IL-1β expression were lower, (iii) after wP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while lung IL-1β, TNF-α, IFN-γ, IL-17, and IL-23 expression were lower, and lung pathology was absent, and (iv) after aP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while Ptx-IgG level was lower. Conclusion Tlr4 does not influence the humoral response to vaccination (without challenge), plays an important role in natural immunity, wP and aP efficacy, and induction of Th1 and Th17 responses, is critical for lung pathology and enhances pro-inflammatory cytokine production after wP vaccination and challenge, and diminishes Th2 responses after both wP and aP vaccination and challenge. wP vaccination does not induce Ptx-IgG. A role for LPS in the efficacy of wP underlines the usefulness of LPS analogs to improve bacterial subunit vaccines such as aP. PMID:18498620

  19. PRN Notice 94-4: Interim Measures for the Registration of Antimicrobial Products/Liquid Chemical Germicides with Medical Device Use Claims Under the Memorandum of Understanding Between EPA and FDA

    EPA Pesticide Factsheets

    This Notice is intended to provide the regulated community with detailed guidance on the interim EPA registration procedures for antimicrobial products affected by the June 4, 1993, Memorandum of Understanding (MOU) between EPA and FDA.

  20. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study.

    PubMed

    Korobelnik, Jean-François; Holz, Frank G; Roider, Johann; Ogura, Yuichiro; Simader, Christian; Schmidt-Erfurth, Ursula; Lorenz, Katrin; Honda, Miki; Vitti, Robert; Berliner, Alyson J; Hiemeyer, Florian; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert

    2014-01-01

    To evaluate the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO). A randomized, multicenter, double-masked phase 3 study. A total of 177 treatment-naive patients with macular edema secondary to CRVO were randomized in a 3:2 ratio. Patients received either 2-mg intravitreal aflibercept or sham injections every 4 weeks for 20 weeks. From week 24 to 48, the aflibercept group received aflibercept as needed (pro re nata [PRN]), and the sham group continued receiving sham injections. The primary efficacy end point was the proportion of patients who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24. This study reports week 52 results including the proportion of patients who gained 15 letters or more in BCVA and the mean change from baseline BCVA and central retinal thickness. Efficacy end points at week 52 were all exploratory. At week 52, the mean percentage of patients gaining 15 letters or more was 60.2% in the aflibercept group and 32.4% in the sham group (P = 0.0004). Aflibercept patients, compared with sham patients, had a significantly higher mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and reduction in central retinal thickness (-423.5 μm vs. -219.3 μm, respectively) at week 52 (P < 0.0001 for both). Aflibercept patients received a mean of 2.5 injections (standard deviation, 1.7 injections) during PRN dosing. The most common ocular adverse events in the aflibercept group were related to the injection procedure or the underlying disease, and included macular edema (33.7%), increased intraocular pressure (17.3%), and eye pain (14.4%). Treatment with intravitreal aflibercept provided significant functional and anatomic benefits after 52 weeks as compared with sham. The improvements achieved after 6 monthly doses at week 24 largely were maintained until week 52 with as-needed dosing. Intravitreal aflibercept generally was well tolerated. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  1. Aqueous Cr(VI) reduction by electrodeposited zero-valent iron at neutral pH: acceleration by organic matters.

    PubMed

    Liu, Junxi; Wang, Chuan; Shi, Jianying; Liu, Hong; Tong, Yexiang

    2009-04-15

    This work investigated the effect of co-existing organic matters on aqueous Cr(VI) reduction by electrodeposited zero-valent iron (ED Fe(0)) at neutral pH. The ED Fe(0) prepared in a solution containing mixture of saccharin, L-ascorbic acid and sodium dodecyl sulfate showed higher activity in reducing the aqueous Cr(VI) at neutral pH than that prepared without any organic presence. XRD and SEM indicated that the structure of ED Fe(0) was significantly improved to nano-scale by the presence of organic mixture in the preparation solution. Further, the ED Fe(0) activity in the Cr(VI) reduction at neutral pH was increased by the co-existence of citric acid or oxalic acid in the chromate solution. Electrochemical impedance spectroscopy (EIS) demonstrated that the corrosive current increased with the concentration of organic matter in the reaction solution. With the co-existing organic matters in the preparation solution, the ED Fe(0) corroded more rapidly due to its nano-size, thus the Cr(VI) reduction by the ferrous iron was accelerated. With the co-existing organic matters in the reaction solution, the Cr(VI) reduction was accelerated by a Fe(II) complex as the main electron donor, and a prevention of the passivation due to the Fe(III) and Cr(III) complexes also accelerated the Cr(VI) reduction.

  2. Labs21 Approach to Climate Neutral Campuses | Climate Neutral Research

    Science.gov Websites

    Campuses | NREL Labs21 Approach to Climate Neutral Campuses Labs21 Approach to Climate Neutral included a whole-building approach to energy efficiency in laboratory buildings. This website takes that approach a step further in carrying out campus-wide energy- and carbon-reduction strategies. The

  3. A novel approach in red mud neutralization using cow dung.

    PubMed

    Patel, Sucharita; Pal, Bhatu Kumar; Patel, Raj Kishore

    2018-05-01

    In this study, cow dung was identified as a neutralizing agent for red mud (RM). Present research estimated a significant reduction in pH value of red mud (10 g) from 10.28 to 8.15 and reduction in alkalinity of ~148 mg/L from ~488 mg/L by adding 80 g of cow dung in 40 days of anaerobic condition. XRD results exhibit a high intensity of quartz and found new compound, the calcium carbide. The acid neutralizing capacity (ANC) of NRM reduces to ~0.87 from ~1.506 mol H + /kg. Based on the resultant research, present study proposes cow dung as an efficient neutralizing agent for reducing the pH and alkalinity in the red mud.

  4. Comparison of the PRNT and an immune fluorescence assay in yellow fever vaccinees receiving immunosuppressive medication.

    PubMed

    Wieten, Rosanne W; Jonker, Emile F F; Pieren, Daan K J; Hodiamont, Caspar J; van Thiel, Pieter P A M; van Gorp, Eric C M; de Visser, Adriëtte W; Grobusch, Martin P; Visser, Leo G; Goorhuis, Abraham

    2016-03-04

    The 17D-yellow fever (YF) vaccination is considered contraindicated in immune-compromised patients; however, accidental vaccination occurs. In this population, measuring the immune response is useful in clinical practice. In this study we compare two antibody tests (the Immune Fluorescence Assay and the Plaque Reduction Neutralization Test) in a group of Dutch immune-compromised travellers with a median of 33 days (IQR [28-49]) after primary YF vaccination. We collected samples of 15 immune-compromised vaccinees vaccinated with the 17D yellow fever vaccine between 2004 and 2012. All samples measured in the plaque reduction neutralization test yielded positive results (>80% virus neutralization with a 1:10 serum dilution). Immune Fluorescence Assay sensitivity was 28% (95% CI [0.12-0.49]). No adverse events were reported. All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared to the plaque reduction neutralization test, the sensitivity of the Immune Fluorescence Assay test was low. Further research is needed to ascertain that 17D vaccination in immune-compromised patients is safe. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Seroprevalence of West Nile Virus in Wild Birds in Far Eastern Russia Using a Focus Reduction Neutralization Test

    PubMed Central

    Murata, Ryo; Hashiguchi, Kazuaki; Yoshii, Kentaro; Kariwa, Hiroaki; Nakajima, Kensuke; Ivanov, Leonid I.; Leonova, Galina N.; Takashima, Ikuo

    2011-01-01

    West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus. Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia. PMID:21363987

  6. Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High-Risk Age Groups in South Korea, 2010

    PubMed Central

    Ju, Young Ran; Han, Myung Guk; Lee, Won-Ja; Jeong, Young Eui

    2016-01-01

    After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (≥40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30–39, 40–49, 50–59, and 60–69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (2.2%) subjects were found to have been recently infected by the virus. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea. PMID:26807709

  7. Lokalisatie Maskergelaatslekkage (Localization of Face-Seal Leak Sites)

    DTIC Science & Technology

    2004-03-01

    2004-A 12 TNO Prins Maurits Laboratorium Lokallisatie Maskergellaatslekkage DISTRIBUTION STATEMENT A Approved for Public Release Lange Kleiweg 137 Datum...1 /- O 9 TNO Prins Maurits Laboratorium is onderdeel van de hoofdgroep TNO Defensieonderzoek waartoe verder b~ehoren: TNO Fysisct en Elektronisch... Laboratorium Nedertandse Organisatie voor toegepast- TNO Te~chnische Menakunde natuurwetenschaDpeliik onderzoek TNO TNO Prn Ma rt LA. mu * s gg 2

  8. Analysis, modeling, and simulation (AMS) testbed development and evaluation to support dynamic mobility applications (DMA) and active transportation and demand management (ATDM) programs — evaluation report for ATDM program. [supporting datasets - Pasadena Testbed

    DOT National Transportation Integrated Search

    2017-07-26

    This zip file contains POSTDATA.ATT (.ATT); Print to File (.PRN); Portable Document Format (.PDF); and document (.DOCX) files of data to support FHWA-JPO-16-385, Analysis, modeling, and simulation (AMS) testbed development and evaluation to support d...

  9. Things That Go Boom!: Noise and Toxic Exposures Associated with Weapon Systems

    DTIC Science & Technology

    2010-06-17

    Munitions Pyrotechnics Tracers Spot ing Charges Oxidizers Delay Elements Propellatl s Fuses De· onators Pr~n1ers Constituent of Concern BariL ...r11 chromate Potassium perchlorate lead oxide BariL m chromate P a tass ~L m perch I o r,ate l e ad chromate An1n1onil tll perch lara e P a

  10. Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

    PubMed

    Mantel, Irmela

    2015-06-01

    This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research, but a subsequent process after the pivotal clinical trials - represents an important translational step from the clinical proof of efficacy to optimization in terms of patients' and clinics' needs. The related scientific procedure includes the exploration of the concept, evaluation of security, and finally proof of efficacy.

  11. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks

    PubMed Central

    Martinez-Serrano, Maria Guadalupe; Rodriguez-Reyes, Abelardo; Guerrero-Naranjo, Jose Luis; Salcedo-Villanueva, Guillermo; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

    2017-01-01

    Background The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV), secondary to angioid streaks (AS), who were treated with antiangiogenic drugs in a pro re nata (PRN) regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of awareness and self-referral by the patients are believed to be the cause of the PRN regimen failure. Purpose To assess the long-term outcomes (>4 years) of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. Methods This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA) over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. Results The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR (P=0.9). Central macular thickness at baseline was: 360.85±173.82 μm; at the end of follow-up: 323.85±100.34 μm (P=0.6). Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4–15). Mean time between injections was 3.8±2.7 months (range 1.9–5.8 months). Conclusion Despite initial anatomical and functional improvement, patients at the end of the follow-up had no visual improvement after a pro re nata regimen of antiangiogenic drugs. The amount of retreatments, number of recurrences, and time between intravitreal injections were similar to previous reports with shorter follow-up. PMID:28031699

  12. Clover-Tagged Porcine Reproductive and Respiratory Syndrome Virus Infectious Clones for Rapid Detection of Virus Neutralizing Antibodies.

    PubMed

    Huang, Baicheng; Xiao, Xia; Xue, Biyun; Zhou, En-Min

    2018-06-24

    Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is a widespread disease that affects domestic pigs of all ages. Accurate and rapid detection of PRRSV specific neutralizing antibodies levels in a pig herd is beneficial for the evaluation of the herd's immunity to combat the specific viral infection. However, the current methods for viral detection, including fluorescent focus neutralization (FFN) and cytopathic effect (CPE) reduction neutralizing assays, are subjective and time-consuming. Therefore, a Clover-tagged PRRSV virus neutralization assay were developed that instrumentally measures the fluorescence signal of Clover stably expressing by a PRRSV infectious clone for at least 10 passages. Herein, the results showed that the proposed Clover-tagged PRRSV neutralization assay is reliable using instrumental measurements of the fluorescence signal of Clover and allows for rapid detection of neutralizing antibodies against PRRSV. The assay was evaluated by testing swine sera from experimental and field samples, and comparisons were made with the traditional FFN and CPE reduction assays. These results suggest that the Clover-tagged PRRSV infectious clone offers a fast and reliable testing method for neutralizing antibodies and could permit high-throughput screening of new antiviral agents. Copyright © 2018. Published by Elsevier B.V.

  13. 78 FR 28551 - Medicaid Program; State Disproportionate Share Hospital Allotment Reductions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-15

    ... budget neutrality calculation for a coverage expansion approved under section 1115 as of July 31, 2009... Factor. 8. Apply a section 1115 Budget Neutrality Factor for each qualifying state. 9. Identify the state... the DSH allotment for a state was included in part or in whole in the budget neutrality calculation...

  14. Extreme late-summer drought causes neutral annual carbon balance in southwestern ponderosa pine forests and grasslands

    NASA Astrophysics Data System (ADS)

    Kolb, Thomas; Dore, Sabina; Montes-Helu, Mario

    2013-03-01

    We assessed the impacts of extreme late-summer drought on carbon balance in a semi-arid forest region in Arizona. To understand drought impacts over extremes of forest cover, we measured net ecosystem production (NEP), gross primary production (GPP), and total ecosystem respiration (TER) with eddy covariance over five years (2006-10) at an undisturbed ponderosa pine (Pinus ponderosa) forest and at a former forest converted to grassland by intense burning. Drought shifted annual NEP from a weak source of carbon to the atmosphere to a neutral carbon balance at the burned site and from a carbon sink to neutral at the undisturbed site. Carbon fluxes were particularly sensitive to drought in August. Drought shifted August NEP at the undisturbed site from sink to source because the reduction of GPP (70%) exceeded the reduction of TER (35%). At the burned site drought shifted August NEP from weak source to neutral because the reduction of TER (40%) exceeded the reduction of GPP (20%). These results show that the lack of forest recovery after burning and the exposure of undisturbed forests to late-summer drought reduce carbon sink strength and illustrate the high vulnerability of forest carbon sink strength in the southwest US to predicted increases in intense burning and precipitation variability.

  15. Serological comparison of canine rotavirus with various simian and human rotaviruses by plaque reduction neutralization and hemagglutination inhibition tests.

    PubMed Central

    Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

    1983-01-01

    By the plaque reduction neutralization test, the CU-1 strain of canine rotavirus was similar, if not identical, to three strains (no. 14, no. 15, and P) of the tentatively designated third human rotavirus serotype. In addition, strain CU-1 demonstrated a one-way antigenic relationship with two other strains (M and B) of the third human rotavirus serotype. The CU-1 strain of canine rotavirus hemagglutinated human group O, rhesus monkey, dog, sheep, and guinea pig erythrocytes. A two-way antigenic relationship between canine (CU-1) and simian (MMU 18006 and SA11) rotaviruses demonstrated previously by the plaque reduction neutralization test was confirmed further with two additional isolates (A79-10 and LSU 79C-36) of canine rotavirus by the plaque reduction neutralization test and the hemagglutination inhibition test. The CU-1 strain of canine rotavirus, which is known to be distinct from two well-characterized human rotavirus serotypes (Wa and DS-1), was also found to be distinct from the St. Thomas no. 4 strain, which is a newly defined fourth human rotavirus serotype. Thus, this canine strain, which is related antigenically to one of four human rotavirus serotypes, is another example of an animal rotavirus which shares serotype specificity with a human rotavirus. Images PMID:6190752

  16. Virtual Genomes in Flux: An Interplay of Neutrality and Adaptability Explains Genome Expansion and Streamlining

    PubMed Central

    Cuypers, Thomas D.; Hogeweg, Paulien

    2012-01-01

    The picture that emerges from phylogenetic gene content reconstructions is that genomes evolve in a dynamic pattern of rapid expansion and gradual streamlining. Ancestral organisms have been estimated to possess remarkably rich gene complements, although gene loss is a driving force in subsequent lineage adaptation and diversification. Here, we study genome dynamics in a model of virtual cells evolving to maintain homeostasis. We observe a pattern of an initial rapid expansion of the genome and a prolonged phase of mutational load reduction. Generally, load reduction is achieved by the deletion of redundant genes, generating a streamlining pattern. Load reduction can also occur as a result of the generation of highly neutral genomic regions. These regions can expand and contract in a neutral fashion. Our study suggests that genome expansion and streamlining are generic patterns of evolving systems. We propose that the complex genotype to phenotype mapping in virtual cells as well as in their biological counterparts drives genome size dynamics, due to an emerging interplay between adaptation, neutrality, and evolvability. PMID:22234601

  17. Changes in EEG spectral power on perception of neutral and emotional words in patients with schizophrenia, their relatives, and healthy subjects from the general population.

    PubMed

    Alfimova, M V; Uvarova, L G

    2008-06-01

    EEG correlates of impairments in the processing of emotiogenic information which might reflect a genetic predisposition to schizophrenia were sought by studying the dynamics of EEG rhythm powers on presentation of neutral and emotional words in 36 patients with schizophrenia, 50 of their unaffected first-degree relatives, and 47 healthy subjects without any inherited predisposition to psychoses. In controls, passive hearing of neutral words produced minimal changes in cortical rhythms, predominantly in the form of increases in the power levels of slow and fast waves, while perception of emotional words was accompanied by generalized reductions in the power of the alpha and beta(1) rhythms and regionally specific suppression of theta and beta(2) activity. Patients and their relatives demonstrated reductions in power of alpha and beta(1) activity, with an increase in delta power on hearing both groups of words. Thus, differences in responses to neutral and emotional words in patients and their relatives were weaker, because of increased reactions to neutral words. These results may identify EEG reflections of pathology of involuntary attention, which is familial and, evidently, inherited in nature. No reduction in reactions to emotiogenic stimuli was seen in patients' families.

  18. Novel stimuli are negative stimuli: evidence that negative affect is reduced in the mere exposure effect.

    PubMed

    Robinson, Brent M; Elias, Lorin J

    2005-04-01

    Repeated exposure of a nonreinforced stimulus results in an increased preference for that stimulus, the mere exposure effect. The present study repeatedly presented positive, negative, and neutrally affective faces to 48 participants while they made judgments about the emotional expression. Participants then rated the likeability of novel neutrally expressive faces and some of these previously presented faces, this time in their neutral expression. Faces originally presented as happy were rated as the most likeable, followed by faces originally presented as neutral. Negative and novel faces were not rated significantly differently from each other. These findings support the notion that the increase in preference towards repeatedly presented stimuli is the result of the reduction in negative affect, consistent with the modified two-factor uncertainty-reduction model and classical conditioning model of the mere exposure effect.

  19. Tagging and Playback Studies to Toothed Whales

    DTIC Science & Technology

    2013-09-30

    different deep-diving species, long-finned pilot whales (Globicephala melas ). b) Compare responses of beaked whales vs other odontocetes to playbacks of...deployments Playbacks Globicephala melas 1 0 Med10 Tag deployments Playbacks Globicephala melas 16 0 Ziphius cavirostris Two days of attempts 0 Med11...Tag deployments Playbacks Globicephala melas 19 8 (4 animals, KW + PRN) 3 RESULTS Over the past three years, we have developed a powerful

  20. Results from the Evaluation of the Massachusetts Nursing Home Connection Program

    DTIC Science & Technology

    1989-10-01

    pn nDosage 2 f. Numberof Doses 193L II mg LI9I g, prn Dosage 3. h. Numberof Doses; Was the following medication admfnistered Haldol ( Haloperidol ) [Dse...Dosage 3 h. Number of Doses I F 9i W mg 58F[17 22 Was the lollowing medication administered Haldol ( Haloperidol )" [Dose range. 0.5 mg to 5 0 ri1g] 1 E YES

  1. Restraint, Seclusion and PRN Medication in English Services for People with Learning Disabilities Administered by the National Health Service: An Analysis of the 2007 National Audit Survey

    ERIC Educational Resources Information Center

    Sturmey, Peter

    2009-01-01

    Background: There is much interest in the use and prevention of unnecessary restrictive behavioural procedures; however, accurate estimates of their use are lacking. The Healthcare Commission and Commission for Social Care Inspection (2007) recently reported such data from a large sample of units administered by the National Health Service (NHS).…

  2. The ARMOUR Study: Anti-VEGF in Neovascular AMD--Our Understanding in a Real-World Indian Setting.

    PubMed

    Jain, Nimesh; Yadav, Naresh Kumar; Jayadev, Chaitra; Srinivasan, Priya; Mohan, Ashwin; Shetty, Bhujang K

    2017-01-01

    The aim of our study was to share our experience with anti-vascular endothelial growth factor (anti-VEGF) injections in the treatment of neovascular age-related macular degeneration (nAMD) in a real-world setting. A retrospective, observational study. Patients of Indian origin with nAMD receiving anti-VEGF with a minimum follow-up of 12 months were enrolled in this study. In group 1, patients were treated on a pro re nata (PRN) basis; in group 2, patients received a loading dose (3 injecti Results: Overall, we observed that 77.31% (92/119 eyes) of patients either maintained or had improved visual acuity at 12 months' follow-up. Similar visual outcome was observed in both groups. The average number of injections given in group 1 was 4.98 and in group 2 was 3.7. CDVA at 12 months was significantly correlated with type of drug molecule, CSFT at 3 and 12 months, baseline visual acuity, and CDVA at 3 months. PRN treatment with significantly fewer injections achieved similar anatomical and functional outcomes when compared with the loading dose group. The results of this study need to be validated with a larger study group and a longer follow-up. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  3. Complexes of a dianionic bis(diphosphinomethanide) with lithium, sodium, potassium and zirconium. Effect of substitution on the Schlenk dimerisation of vinylidene phosphines.

    PubMed

    Izod, Keith; McFarlane, William; Tyson, Brent V; Clegg, William; Harrington, Ross W

    2004-12-07

    The vinylidene phosphine (Pr(n)(2)P)(2)C=CH(2) (1) undergoes Schlenk dimerisation on treatment with an excess of any of the alkali metals Li, Na or K to give the butane-1,4-diide complexes [(L)M{(Pr(n)(2)P)(2)CCH(2)}](2)[(L)M =(THF)(2)Li (6), (THF)(3)Na (7b), (DME)(2)K (8b)], after recrystallisation. Whereas the reaction between the analogous phenyl derivative (Ph(2)P)(2)C=CH(2) and K results in cleavage of a P-C bond, 1 reacts smoothly with K to give 8, with no evidence for P-C cleavage. Compound 6 is an excellent ligand transfer reagent: metathesis reactions between either 6 or its phenyl analogue [(THF)(2)Li{(Ph(2)P)(2)CCH(2)}](2) (2) and two equivalents of Cp(2)ZrCl(2) in THF give the corresponding dinuclear zirconocene derivatives [Cp(2)Zr(Cl){(R(2)P)(2)CCH(2)}](2) in good yields [R = Ph (11), Pr(n)(12)]. Compounds 6, 7b, 8b, 11 and 12 have been characterised by multi-element NMR spectroscopy and, where possible, by elemental analysis; compounds 6, 7b, 11 and 12 have additionally been characterised by X-ray crystallography.

  4. Respiratory Syncytial Virus (RSV): Neutralizing Antibody, a Correlate of Immune Protection.

    PubMed

    Piedra, Pedro A; Hause, Anne M; Aideyan, Letisha

    2016-01-01

    Assays that measure RSV-specific neutralizing antibody activity are very useful for evaluating vaccine candidates, performing seroprevalence studies, and detecting infection. Neutralizing antibody activity is normally measured by a plaque reduction neutralization assay or by a microneutralization assay with or without complement. These assays measure the functional capacity of serum (or other fluids) to neutralize virus infectivity in cells as compared to ELISA assays that only measure the binding capacity against an antigen. This chapter discusses important elements in standardization of the RSV-specific microneutralization assay for use in the laboratory.

  5. Definition of human rotavirus serotypes by plaque reduction assay.

    PubMed Central

    Wyatt, R G; Greenberg, H B; James, W D; Pittman, A L; Kalica, A R; Flores, J; Chanock, R M; Kapikian, A Z

    1982-01-01

    Twenty different human rotavirus reassortants were characterized serologically by a plaque reduction assay as belonging to one of three distinct serotypes. Fourteen were similar if not identical to our prototype Wa strain; two were like the prototype DS-1 strain, and four belonged to a third serotype for which a prototype has not yet been selected. Hyperimmune sera raised against the three serotypes were required to distinguish among them, since postinfection sera had lower titers and were more cross-reactive than hyperimmune sera. These results confirmed the ability of a qualitative cytopathic neutralization test to predict correctly the Wa or DS-1 serotype. A strain of rhesus rotavirus (MMU 18006) was identified as belonging to the newly defined third serotype. Finally, an attempt was made to correlate previously published serotype analysis by neutralization of fluorescent cell-forming units with the results determined by the plaque reduction neutralization assay. PMID:6286487

  6. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies

    PubMed Central

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013–2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of Biologics Evaluation and Research, with plaque reduction neutralization test performed by Focus Diagnostics, and with hemaglutination inhibition assay performed in-house at Sanofi Pasteur. Taken together, fADI assay appears to be a useful high throughput functional immunoassay for assessment of antibody-related neutralization of the viral infections for which pre-attachment neutralization pathway is predominant, such as polio, influenza, yellow fever and dengue. PMID:26863313

  7. Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

    PubMed

    Phan, Jack; Pollard, Courtney; Brown, Paul D; Guha-Thakurta, Nandita; Garden, Adam S; Rosenthal, David I; Fuller, Clifton D; Frank, Steven J; Gunn, G Brandon; Morrison, William H; Ho, Jennifer C; Li, Jing; Ghia, Amol J; Yang, James N; Luo, Dershan; Wang, He C; Su, Shirley Y; Raza, Shaan M; Gidley, Paul W; Hanna, Ehab Y; DeMonte, Franco

    2018-04-27

    OBJECTIVE The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. METHODS From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. RESULTS Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention. CONCLUSIONS GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

  8. Protozoa Drive the Dynamics of Culturable Biocontrol Bacterial Communities.

    PubMed

    Müller, Maren Stella; Scheu, Stefan; Jousset, Alexandre

    2013-01-01

    Some soil bacteria protect plants against soil-borne diseases by producing toxic secondary metabolites. Such beneficial biocontrol bacteria can be used in agricultural systems as alternative to agrochemicals. The broad spectrum toxins responsible for plant protection also inhibit predation by protozoa and nematodes, the main consumers of bacteria in soil. Therefore, predation pressure may favour biocontrol bacteria and contribute to plant health. We analyzed the effect of Acanthamoeba castellanii on semi-natural soil bacterial communities in a microcosm experiment. We determined the frequency of culturable bacteria carrying genes responsible for the production of the antifungal compounds 2,4-diacetylphloroglucinol (DAPG), pyrrolnitrin (PRN) and hydrogen cyanide (HCN) in presence and absence of A. castellanii. We then measured if amoebae affected soil suppressiveness in a bioassay with sugar beet seedlings confronted to the fungal pathogen Rhizoctonia solani. Amoebae increased the frequency of both DAPG and HCN positive bacteria in later plant growth phases (2 and 3 weeks), as well as the average number of biocontrol genes per bacterium. The abundance of DAPG positive bacteria correlated with disease suppression, suggesting that their promotion by amoebae may enhance soil health. However, the net effect of amoebae on soil suppressiveness was neutral to slightly negative, possibly because amoebae slow down the establishment of biocontrol bacteria on the recently emerged seedlings used in the assay. The results indicate that microfaunal predators foster biocontrol bacterial communities. Understanding interactions between biocontrol bacteria and their predators may thus help developing environmentally friendly management practices of agricultural systems.

  9. Protozoa Drive the Dynamics of Culturable Biocontrol Bacterial Communities

    PubMed Central

    Müller, Maren Stella; Scheu, Stefan; Jousset, Alexandre

    2013-01-01

    Some soil bacteria protect plants against soil-borne diseases by producing toxic secondary metabolites. Such beneficial biocontrol bacteria can be used in agricultural systems as alternative to agrochemicals. The broad spectrum toxins responsible for plant protection also inhibit predation by protozoa and nematodes, the main consumers of bacteria in soil. Therefore, predation pressure may favour biocontrol bacteria and contribute to plant health. We analyzed the effect of Acanthamoeba castellanii on semi-natural soil bacterial communities in a microcosm experiment. We determined the frequency of culturable bacteria carrying genes responsible for the production of the antifungal compounds 2,4-diacetylphloroglucinol (DAPG), pyrrolnitrin (PRN) and hydrogen cyanide (HCN) in presence and absence of A. castellanii. We then measured if amoebae affected soil suppressiveness in a bioassay with sugar beet seedlings confronted to the fungal pathogen Rhizoctonia solani. Amoebae increased the frequency of both DAPG and HCN positive bacteria in later plant growth phases (2 and 3 weeks), as well as the average number of biocontrol genes per bacterium. The abundance of DAPG positive bacteria correlated with disease suppression, suggesting that their promotion by amoebae may enhance soil health. However, the net effect of amoebae on soil suppressiveness was neutral to slightly negative, possibly because amoebae slow down the establishment of biocontrol bacteria on the recently emerged seedlings used in the assay. The results indicate that microfaunal predators foster biocontrol bacterial communities. Understanding interactions between biocontrol bacteria and their predators may thus help developing environmentally friendly management practices of agricultural systems. PMID:23840423

  10. Neutral source and particle balance in the HSX edge

    NASA Astrophysics Data System (ADS)

    Stephey, Laurie; Kumar, Santhosh; Bader, Aaron; Akerson, Adrian; Schmitz, Oliver; Anderson, David; A, Simon; Talmadge, Joseph; Hegna, Chris

    2015-11-01

    The ability to control the neutral particle and impurity source in fusion devices is critical to obtaining high purity, high confinement plasmas. The neutral particle source defines the edge density gradients and plasma flows. To understand the relationship between the neutral particle source, plasma density gradients and plasma edge and core transport in HSX, a single reservoir particle balance is being used to provide a complete particle inventory. Detailed spectroscopic measurements of hydrogen and helium emission have yielded neutral and plasma profiles and ionization length estimations. The plasma puff source rate has been directly measured. To determine the recycling source rate, two specially designed limiters will be inserted to intercept 99% of the field lines, resulting in a well-defined LCFS and plasma interaction zone. Single limiter insertion resulted in a 50% reduction in global line emission, implying a reduction in wall recycling. Future camera and probe measurements will provide a recycling source rate. HSX neutral physics is also being investigated using EMC3-EIRENE. All results are discussed along with complementary plans for the Wendelstein 7-X startup phase. This work supported by US DOE Grant DE-FG02-93ER54222 and DE-SC0006103.

  11. Interpretation modification training reduces social anxiety in clinically anxious children.

    PubMed

    Klein, Anke M; Rapee, Ronald M; Hudson, Jennifer L; Schniering, Carolyn A; Wuthrich, Viviana M; Kangas, Maria; Lyneham, Heidi J; Souren, Pierre M; Rinck, Mike

    2015-12-01

    The present study was designed to examine the effects of training in positive interpretations in clinically anxious children. A total of 87 children between 7 and 12 years of age were randomly assigned to either a positive cognitive bias modification training for interpretation (CMB-I) or a neutral training. Training included 15 sessions in a two-week period. Children with an interpretation bias prior to training in the positive training group showed a significant reduction in interpretation bias on the social threat scenarios after training, but not children in the neutral training group. No effects on interpretation biases were found for the general threat scenarios or the non-threat scenarios. Furthermore, children in the positive training did not self-report lower anxiety than children in the neutral training group. However, mothers and fathers reported a significant reduction in social anxiety in their children after positive training, but not after neutral training. This study demonstrated that clinically anxious children with a prior interpretation bias can be trained away from negative social interpretation biases and there is some evidence that this corresponds to reductions in social anxiety. This study also highlights the importance of using specific training stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Rheological characterization of neutral and anionic polysaccharides with reduced mucociliary transport rates.

    PubMed

    Shah, Ankur J; Donovan, Maureen D

    2007-04-20

    The purpose of this research was to compare the viscoelastic properties of several neutral and anionic polysaccharide polymers with their mucociliary transport rates (MTR) across explants of ciliated bovine tracheal tissue to identify rheologic parameters capable of predicting the extent of reduction in mucociliary transport. The viscoelastic properties of the polymer gels and gels mixed with mucus were quantified using controlled stress rheometry. In general, the anionic polysaccharides were more efficient at decreasing the mucociliary transport rate than were the neutral polymers, and a concentration threshold, where no further decreases in mucociliary transport occurred with increasing polymer concentration, was observed for several of the neutral polysaccharides. No single rheologic parameter (eta, G', G'', tan delta, G*) was a good predictor of the extent of mucociliary transport reduction, but a combination of the apparent viscosity (eta), tangent to the phase angle (tan delta), and complex modulus (G*) was found to be useful in the identification of formulations capable of decreasing MTR. The relative values of each of the rheologic parameters were unique for each polymer, yet once the relationships between the rheologic parameters and mucociliary transport rate reduction were determined, formulations capable of resisting mucociliary clearance could be rapidly optimized.

  13. Some Complexity Results About Packet Radio Networks

    DTIC Science & Technology

    1983-03-01

    divsio-muti-cces)schemes foP TD ^12A 1 660 SECURITY CLASSIFICATION OF THIS PAGE (ft* 60 IAD SZCURTY CLASSIFICATION Of THIS PAGE(Whan Data Entoted) -other...8217-21-. bbd bd a aK (a) (b) b-d b 0~~ C C (c) (d) Fig. 1. Situations in a PRN for which (c,d) conflicts with (a,b). -22- 12 3 3m 3m+1- 3m+2 Fig. 2. A

  14. Carbon-neutral energy cycles using alcohols.

    PubMed

    Fukushima, Takashi; Kitano, Sho; Hata, Shinichi; Yamauchi, Miho

    2018-01-01

    We demonstrated carbon-neutral (CN) energy circulation using glycolic acid ( GC )/oxalic acid ( OX ) redox couple. Here, we report fundamental studies on both catalyst search for power generation process, i.e. GC oxidation, and elemental steps for fuel generation process, i.e. OX reduction, in CN cycle. The catalytic activity test on various transition metals revealed that Rh, Pd, Ir, and Pt have preferable features as a catalyst for electrochemical oxidation of GC . A carbon-supported Pt catalyst in alkaline conditions exhibited higher activity, durability, and product selectivity for electrooxidation of GC rather than those in acidic media. The kinetic study on OX reduction clearly indicated that OX reduction undergoes successive two-electron reductions to form GC . Furthermore, application of TiO 2 catalysts with large specific area for electrochemical reduction of OX facilitates the selective formation of GC .

  15. Carbon-neutral energy cycles using alcohols

    PubMed Central

    Fukushima, Takashi; Kitano, Sho; Hata, Shinichi; Yamauchi, Miho

    2018-01-01

    Abstract We demonstrated carbon-neutral (CN) energy circulation using glycolic acid (GC)/oxalic acid (OX) redox couple. Here, we report fundamental studies on both catalyst search for power generation process, i.e. GC oxidation, and elemental steps for fuel generation process, i.e. OX reduction, in CN cycle. The catalytic activity test on various transition metals revealed that Rh, Pd, Ir, and Pt have preferable features as a catalyst for electrochemical oxidation of GC. A carbon-supported Pt catalyst in alkaline conditions exhibited higher activity, durability, and product selectivity for electrooxidation of GC rather than those in acidic media. The kinetic study on OX reduction clearly indicated that OX reduction undergoes successive two-electron reductions to form GC. Furthermore, application of TiO2 catalysts with large specific area for electrochemical reduction of OX facilitates the selective formation of GC. PMID:29511392

  16. Optimization and Validation of a Plaque Reduction Neutralization Test for the Detection of Neutralizing Antibodies to Four Serotypes of Dengue Virus Used in Support of Dengue Vaccine Development

    PubMed Central

    Timiryasova, Tatyana M.; Bonaparte, Matthew I.; Luo, Ping; Zedar, Rebecca; Hu, Branda T.; Hildreth, Stephen W.

    2013-01-01

    A dengue plaque reduction neutralization test (PRNT) to measure dengue serotype–specific neutralizing antibodies for all four virus serotypes was developed, optimized, and validated in accordance with guidelines for validation of bioanalytical test methods using human serum samples from dengue-infected persons and persons receiving a dengue vaccine candidate. Production and characterization of dengue challenge viruses used in the assay was standardized. Once virus stocks were characterized, the dengue PRNT50 for each of the four serotypes was optimized according to a factorial design of experiments approach for critical test parameters, including days of cell seeding before testing, percentage of overlay carboxymethylcellulose medium, and days of incubation post-infection to generate a robust assay. The PRNT50 was then validated and demonstrated to be suitable to detect and measure dengue serotype-specific neutralizing antibodies in human serum samples with acceptable intra-assay and inter-assay precision, accuracy/dilutability, specificity, and with a lower limit of quantitation of 10. PMID:23458954

  17. Vaccinia virus-free rescue of fluorescent replication-defective vesicular stomatitis virus and pseudotyping with Puumala virus glycoproteins for use in neutralization tests.

    PubMed

    Paneth Iheozor-Ejiofor, Rommel; Levanov, Lev; Hepojoki, Jussi; Strandin, Tomas; Lundkvist, Åke; Plyusnin, Alexander; Vapalahti, Olli

    2016-05-01

    Puumala virus (PUUV) grows slowly in cell culture. To study antigenic properties of PUUV, an amenable method for their expression would be beneficial. To achieve this, a replication-defective recombinant vesicular stomatitis virus, rVSVΔG*EGFP, was rescued using BSRT7/5 and encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES)-enabled rescue plasmids. Using these particles, pseudotypes bearing PUUV Sotkamo strain glycoproteins were produced, with titres in the range 105-108, and were used in pseudotype focus reduction neutralization tests (pFRNTs) with neutralizing monoclonal antibodies and patient sera. The results were compared with those from orthodox focus reduction neutralization tests (oFRNTs) using native PUUV with the same samples and showed a strong positive correlation (rs = 0.82) between the methods. While developing the system we identified three amino acids which were mutated in the Vero E6 cell culture adapted PUUV prototype Sotkamo strain sequence, and changing these residues was critical for expression and neutralizing antibody binding of PUUV glycoproteins.

  18. Scheduled versus Pro Re Nata Dosing in the VIEW Trials.

    PubMed

    Richard, Gisbert; Monés, Jordi; Wolf, Sebastian; Korobelnik, Jean François; Guymer, Robyn; Goldstein, Michaella; Norenberg, Christiane; Sandbrink, Rupert; Zeitz, Oliver

    2015-12-01

    To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52). Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials. Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients. Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks. Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits. After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96. These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  19. Zika Virus and the World Health Organization Criteria for Determining Recent Infection Using Plaque Reduction Neutralization Testing.

    PubMed

    Ward, Matthew J; Alger, Jackeline; Berrueta, Mabel; Bock, Harry; Buekens, Pierre; Cafferata, Maria Luisa; Ciganda, Alvaro; García, Jorge; García, Kimberly; Lorenzana, Ivette; Lopez, Wendy; Parham, Leda; Wesson, Dawn M

    2018-06-25

    The recent Zika virus (ZIKV) epidemic swept across Latin America and the Caribbean, where dengue virus (DENV) is endemic. The antigenic similarities of these closely related flaviviruses left researchers and clinicians with challenges to interpret serological tests. Thirty-six women attending a prenatal clinic in Honduras and with positive DENV IgM enzyme-linked immunoabsorbent assays (ELISAs) were screened with a ZIKV IgM ELISA, RT-PCR for ZIKV and DENV 1-4, and plaque reduction neutralization tests (PRNTs) for ZIKV and DENV-2. Plaque reduction neutralization test results were interpreted using the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Using the WHO criteria of a PRNT90 titer ≥ 20 and a 4-fold difference between ZIKV and DENV titers, we determined that 69.4% of samples had a recent ZIKV infection, compared with 5.6% using CDC criteria. The interpretation of ZIKV PRNTs in a DENV-endemic region is highly dependent on the choice of interpretation criteria.

  20. Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    situ RNA hybridization staining of a TMA set and tissue sections from Roswell Park Cancer Institute (RPCI) and PCaP, respectively; 2) completion of...Facility at Roswell Park Cancer Institute (RPCI). Three Subtasks were proposed: Subtask 1 (months 1-3): Obtain approval for IRB protocol and request...Resource Network (PRN) at Roswell Park Cancer Institute (RPCI). The predominantly expressed SLCO transporters in AA or EA, and the transporters with

  1. Packet Radio Temporary Note Index.

    DTIC Science & Technology

    1984-05-07

    Dynamic Control in Carrier Sense Multiple Access 180 Cross-Radio Debugger Beeler 06/76 BBN 179 New Capabilities of the PR Gitman 05/76 NAC Simulation...Program 178 An Approximate Analytical Model for Gitman 05/76 NAC Initialization of Single Hop PRNETs 177 SPP Definition Beeler 04/76 BBN 176 PR Protocol...Sussman 03/79 BBN Labeling Process (Revision 7) 173 Interfacing Terminals to the PRN Fralick 04/76 BBN 172 Connectivity Issues in Mobile PR Gitman 03/76

  2. A Real-Time Robust Method to Detect BeiDou GEO/IGSO Orbital Maneuvers

    PubMed Central

    Huang, Guanwen; Qin, Zhiwei; Zhang, Qin; Wang, Le; Yan, Xingyuan; Fan, Lihong; Wang, Xiaolei

    2017-01-01

    The frequent maneuvering of BeiDou Geostationary Orbit (GEO) and Inclined Geosynchronous Orbit (IGSO) satellites affects the availability of real-time orbit, and decreases the accuracy and performance of positioning, navigation and time (PNT) services. BeiDou satellite maneuver information cannot be obtained by common users. BeiDou broadcast ephemeris is the only indicator of the health status of satellites, which are broadcast on an hourly basis, easily leading to ineffective observations. Sometimes, identification errors of satellite abnormity also appear in the broadcast ephemeris. This study presents a real-time robust detection method for a satellite orbital maneuver with high frequency and high reliability. By using the broadcast ephemeris and pseudo-range observations, the time discrimination factor and the satellite identification factor were defined and used for the real-time detection of start time and the pseudo-random noise code (PRN) of satellites was used for orbital maneuvers. Data from a Multi-GNSS Experiment (MGEX) was collected and analyzed. The results show that the start time and the PRN of the satellite orbital maneuver could be detected accurately in real time. In addition, abnormal start times and satellite abnormities caused by non-maneuver factors also could be detected using the proposed method. The new method not only improves the utilization of observations for users with the data effective for about 92 min, but also promotes the reliability of real-time PNT services. PMID:29186058

  3. A Real-Time Robust Method to Detect BeiDou GEO/IGSO Orbital Maneuvers.

    PubMed

    Huang, Guanwen; Qin, Zhiwei; Zhang, Qin; Wang, Le; Yan, Xingyuan; Fan, Lihong; Wang, Xiaolei

    2017-11-29

    The frequent maneuvering of BeiDou Geostationary Orbit (GEO) and Inclined Geosynchronous Orbit (IGSO) satellites affects the availability of real-time orbit, and decreases the accuracy and performance of positioning, navigation and time (PNT) services. BeiDou satellite maneuver information cannot be obtained by common users. BeiDou broadcast ephemeris is the only indicator of the health status of satellites, which are broadcast on an hourly basis, easily leading to ineffective observations. Sometimes, identification errors of satellite abnormity also appear in the broadcast ephemeris. This study presents a real-time robust detection method for a satellite orbital maneuver with high frequency and high reliability. By using the broadcast ephemeris and pseudo-range observations, the time discrimination factor and the satellite identification factor were defined and used for the real-time detection of start time and the pseudo-random noise code (PRN) of satellites was used for orbital maneuvers. Data from a Multi-GNSS Experiment (MGEX) was collected and analyzed. The results show that the start time and the PRN of the satellite orbital maneuver could be detected accurately in real time. In addition, abnormal start times and satellite abnormities caused by non-maneuver factors also could be detected using the proposed method. The new method not only improves the utilization of observations for users with the data effective for about 92 min, but also promotes the reliability of real-time PNT services.

  4. [Endocrine differences between patients with luteal phase deficiency and inadequate endometrial response].

    PubMed

    Xu, M; Zhang, Z; Jiang, S

    1997-03-01

    To study the difference of endocrine characteristics between patients with luteal phase deficiency (LPD) and inadequate endometrial response (IER). Serum estradiol (E2), progesterone (P), follicle-stimulating hormone, luteinizing hormone and prolactin levels were determined by radioimmunoassay in cycles of LPD, IER and normal controls. Contents of endometrial cytoplasmic estradiol receptors (ERc), nuclear estradiol receptors (ERn), cytoplasmic progesterone receptors (PRc) and nuclear progesterone receptors (PRn) were determined by dextran coated charcoal assay in the same cycle. Serum E2 and P levels in the luteal phase of patients with LPD were significantly lower than those of normal group (P < 0.001), no significant difference of endometrial estrogen receptor and progesterone receptor contents was found between the two groups (P > 0.1). Serum E2 levels in both follicular and luteal phase of IER patients were significantly lower than those of normal groups (P < 0.001), but serum P levels in luteal phase of the two groups showed no difference (P > 0.1). The contents of ERc and PRn in proliferative phase and PRc contents throughout the menstrual cycle were also lower than those of the normal group (P < 0.001, < 0.001 and < 0.05 respectively). These results indicate that LPD and IER are two distinct entities in terms of endocrine characteristics. To distinguish underdeveloped endometrium caused by either LPD or IER is the key to choose appropriate treatment.

  5. Efficient solar-assisted O2 reduction by a cofacial iron porphyrin dimer integrated to a p-CuBi2O4 photocathode prepared by a simple novel method.

    PubMed

    Zahran, Zaki N; Mohamed, Eman A; Naruta, Yoshinori; Haleem, Ashraf

    2017-10-04

    A cofacial iron porphyrin hetero-dimer, Fe2TPFPP-TMP showed high electro-catalytic activity, selectivity, and stability for the O2 reduction to H2O both in homogeneous non-aqueous and heterogeneous neutral aqueous solutions. Moreover, when it is integrated to FTO/p-CuBi2O4 (FTO = fluorine doped tin oxide) photocathode prepared by a simple novel method, a remarkable efficient solar-assisted O2 reduction is achieved in neutral potassium phosphate (KPi) or basic NaOH solutions saturated with O2. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Durability and Kinetics of Maternal Pertussis Antibodies in Infants of Mothers Immunized with Tdap During Pregnancy

    PubMed Central

    Healy, C Mary; Rench, Marcia; Swaim, Laurie; Timmins, Audra; Vyas, Anuja; Ng, Nancy; Paulos, Simon; Park, So Hee; Jeyachandran, Amilia; Rajam, Gorisankar; Schiffer, Jarad; Baker, Carol J

    2017-01-01

    Abstract Background Infant protection against severe pertussis requires sufficient maternal pertussis antibodies until infant immunization begins. The kinetics of maternally-derived Tdap-induced antibodies in infants is poorly understood. Methods 34 healthy mother-infant pairs were followed prospectively from maternal Tdap immunization to infant age 6 weeks. Blood was collected from women pre-Tdap, 4 weeks post Tdap and at delivery, and from infants at birth, and age 3 and 6 weeks. IgG to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by luminex assay (IU/mL). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) for pertussis-specific IgG and half-life of IgG to PT were calculated. Results Mean maternal age was 31.1 years (range 22.7–39.7); 47% were white, 32% Hispanic and 21% Black. Tdap was administered at a mean gestation of 30.7 weeks (28–32.7). Infants had a mean gestation of 39.1 weeks (36–41.1) and birthweight of 3379g (2580–4584). GMCs (95%C.I.) for maternal pertussis-specific IgG increased significantly 4 weeks post-Tdap (4-fold higher in 59%, 41%, 29% and 44% for PT, FHA, FIM and PRN, respectively) and waned before delivery. Placental transfer was 135% for PT, 141% for FHA, 131% for FIM and 136% for PRN. Maternal antibodies in infants decayed quickly, but at age 6 weeks GMC of infant PT-specific IgG was 21.1IU/mL (14.7–30.2) and 91% had PT ≥ 10 IU/mL. Estimated half-life of PT-specific IgG in infants was 30.9 days. Time PT (IU/mL) FHA (IU/mL) FIM (IU/mL) PRN (IU/mL) Pre-Tdap 9.85 (6.71–14.45) 32.81 (21.79–49.42) 131.55 (81.98–211.15) 55.67 (35.75–86.68) Post-Tdap 46.8 (34.4–63.68) 116.82 (88.9–153.5) 440.35 (327.57–591.97) 233.02 (179.14–303.04) Maternal Delivery 40.78 (29.4–56.53) 104.81 (78.27–140.35) 384.5 (287.41–514.28) 204.41 (155.42–268.84) Infant Cord 55.12 (38.65–78.6) 147.81 (113.47–192.49) 505.36 (366.44–696.95) 278.55 (216.57–358.26) Infant 3w 30.73 (21.57–43.79) 82.49 (63.65–106.93) 292.87 (221.11–388.06) 167.72 (129.57–217.07) Infant 6w 21.1 (14.72–30.23) 54.98 (41.97–72.03) 210.52 (153.74–288.27) 113.03 (86.94–146.99) Conclusion Although the half-life of maternal PT- specific antibodies induced by Tdap immunization during the third trimester of pregnancy is shorter than previously thought, this strategy results in levels likely sufficient to protect infants through the start of the immunization series. Disclosures All authors: No reported disclosures.

  7. Development of a High-Content Orthopoxvirus Infectivity and Neutralization Assays

    PubMed Central

    Gates, Irina; Olson, Victoria; Smith, Scott; Patel, Nishi; Damon, Inger; Karem, Kevin

    2015-01-01

    Currently, a number of assays measure Orthopoxvirus neutralization with serum from individuals, vaccinated against smallpox. In addition to the traditional plaque reduction neutralization test (PRNT), newer higher throughput assays are based on neutralization of recombinant vaccinia virus, expressing reporter genes such as β-galactosidase or green fluorescent protein. These methods could not be used to evaluate neutralization of variola virus, since genetic manipulations of this virus are prohibited by international agreements. Currently, PRNT is the assay of choice to measure neutralization of variola virus. However, PRNT assays are time consuming, labor intensive, and require considerable volume of serum sample for testing. Here, we describe the development of a high-throughput, cell-based imaging assay that can be used to measure neutralization, and characterize replication kinetics of various Orthopoxviruses, including variola, vaccinia, monkeypox, and cowpox. PMID:26426117

  8. Importance Sampling Variance Reduction in GRESS ATMOSIM

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wakeford, Daniel Tyler

    This document is intended to introduce the importance sampling method of variance reduction to a Geant4 user for application to neutral particle Monte Carlo transport through the atmosphere, as implemented in GRESS ATMOSIM.

  9. Defining harm reduction.

    PubMed

    Single, E

    1995-01-01

    Harm reduction attempts to reduce the adverse consequences of drug use among persons who continue to use drugs. It developed in response to the excesses of a "zero tolerance approach". Harm reduction emphasizes practical rather than idealized goals. It has been expanded from illicit drugs to legal drugs and is grounded in the evolving public health and advocacy movements. Harm reduction has proved to be effective and it has gained increasing official acceptance; for example, it is now the basis of Canada's Drug Strategy. However, the concept is still poorly defined, as virtually any drug policy or programme, even abstinence-oriented programmes, attempt to reduce drug-related harm. The principle feature of harm reduction is the acceptance of the fact that some drug users cannot be expected to cease their drug use at the present time. Harm reduction is neutral about the long term goals of intervention while according a high priority to short-term realizable goals. Harm reduction should be neutral about legalization. The essence of the concept is to ameliorate adverse consequences of drug use while, at least in the short term, drug use continues.

  10. Synthesis and structural characterisation of a novel phosphine-borane-stabilised dicarbanion and an unusual bis(phosphine-borane).

    PubMed

    Izod, Keith; McFarlane, William; Tyson, Brent V; Clegg, William; Harrington, Ross W

    2004-03-07

    The reaction between the phosphine-borane-substituted alkene [Pr(n)(2)P(BH(3))](Me(3)Si)C[double bond]CH(2) and elemental lithium in THF yields the complex [(pmdeta)Li[Pr(n)(2)P(BH(3))](Me(3)Si)CCH(2)](2)(2b) after recrystallisation; an X-ray crystallographic study of 2b reveals that the lithium is bound to the BH(3) hydrogens of the ligand, with no Li-C(carbanion) contact.

  11. Airborne Pseudolites in a Global Positioning System (GPS) Degraded Environment

    DTIC Science & Technology

    2011-03-01

    continuously two types of encoded pseudo-random noise (PRN) signals via using two center frequencies 4 in the L- band , namely L1 (1575.42 MHz) and L2...Jovanevic, Aleksandar, Nikhil Bhaita, Joseph Noronha, Brijesh Sirpatil, Michael Kirchner, and Deepak Saxena. “ Piercing the Veil ”. GPS World, 30–37, March...difficulties in receiver design. • Pseudolites can operate either at GPS L1, L2 and L5, or any other available frequency band . Similarly, other parameters to

  12. Effects of Multipath and Oversampling on Navigation Using Orthogonal Frequency Division Multiplexed Signals of Opportunity

    DTIC Science & Technology

    2008-03-01

    for military use. The L2 carrier frequency operates at 1227.6 MHz and transmits only the precise code . Each satellite transmits a unique pseudo ...random noise (PRN) code by which it is identified. GPS receivers require a LOS to four satellite signals to accurately estimate a position in three...receiver frequency errors, noise addition, and multipath ef- fects. He also developed four methods for estimating the cross- correlation peak within a sampled

  13. Neutral recycling effects on ITG turbulence

    DOE PAGES

    Stotler, D. P.; Lang, J.; Chang, C. S.; ...

    2017-07-04

    Here, the effects of recycled neutral atoms on tokamak ion temperature gradient (ITG) driven turbulence have been investigated in a steep edge pedestal, magnetic separatrix configuration, with the full-f edge gryokinetic code XGC1. An adiabatic electron model has been used; hence, the impacts of neutral particles and turbulence on the density gradient are not considered, nor are electromagnetic turbulence effects. The neutral atoms enhance the ITG turbulence, first, by increasing the ion temperature gradient in the pedestal via the cooling effects of charge exchange and, second, by a relative reduction in themore » $$E\\times B$$ shearing rate.« less

  14. Neutral recycling effects on ITG turbulence

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stotler, D. P.; Lang, J.; Chang, C. S.

    Here, the effects of recycled neutral atoms on tokamak ion temperature gradient (ITG) driven turbulence have been investigated in a steep edge pedestal, magnetic separatrix configuration, with the full-f edge gryokinetic code XGC1. An adiabatic electron model has been used; hence, the impacts of neutral particles and turbulence on the density gradient are not considered, nor are electromagnetic turbulence effects. The neutral atoms enhance the ITG turbulence, first, by increasing the ion temperature gradient in the pedestal via the cooling effects of charge exchange and, second, by a relative reduction in themore » $$E\\times B$$ shearing rate.« less

  15. Collaboration essential for an energy neutral urban water cycle.

    PubMed

    Frijns, Jos; Mulder, Mirabella; Roorda, Jelle; Schepman, Hans; Voskamp, Tom

    2013-01-01

    Two Dutch water boards prepared a Master Plan with measures to substantially reduce their energy use by 2027. In total, more than 100 measures were identified such as bubble aeration and heat recovery from effluent. Together these measures result in a 90-95% reduction in energy use at the water boards. However, for the whole urban water cycle, thus including the energy required for warm water use in households, the total energy reduction from these measures at the water boards is only 5-6%. To attain the objective to have an energy neutral urban water cycle, collaboration with other sectors such as housing, energy, agriculture and industry will be essential. Active collaboration of the water boards through the incorporation of energy efficient water measures as part of the carbon neutral effort of cities is recognized to be a promising strategy.

  16. Versatile Synthesis of Amino Acid Functional Polymers without Protection Group Chemistry.

    PubMed

    Brisson, Emma R L; Xiao, Zeyun; Franks, George V; Connal, Luke A

    2017-01-09

    The copolymerization of N-isopropylacrylamide (NiPAm) with aldehyde functional monomers facilitates postpolymerization functionalization with amino acids via reductive amination, negating the need for protecting groups. In reductive amination, the imine formed from the condensation reaction between an amine and an aldehyde is reduced to an amine. In this work, we categorize amino acids into four classes based on the functionality of their side chains (acidic, polar neutral, neutral, and basic) and use their amine groups in condensation reactions with aldehyde functional polymers. The dynamic nature of the imine as well as the versatility of reductive amination to functionalize a polymer with a range of amino acids is highlighted. In this manner, amino acid functional polymers are synthesized without the use of protecting groups with high yields, demonstrating the high functional group tolerance of carbonyl condensation chemistry and the subsequent reduction of the imine. Prior to the reduction of the imine bond, transimination reactions are used to demonstrate dynamic polymers that shuffle from a glycine- to a histidine-functional polymer.

  17. The significance for epidemiological studies anti-measles antibody detection examined by enzyme immunoassay (EIA) and plaque reduction neutralization test (PRNT).

    PubMed

    Siennicka, Joanna; Częścik, Agnieszka; Trzcińska, Agnieszka

    2014-01-01

    The paper discusses the role of anti-measles antibodies for protection and significance for epidemiological studies determination of antibodies by different serological methods. The comparison of anti-measles virus antibodies levels measured by enzyme immunoassay (EIA) and Plaque Reduction Neutralization Test (PRNT) was described. It was found that the 200 mIU/ml of anti-measles activity measured by PRNT (level protection against symp- tomatic disease) is equivalent of 636 mIU/ml measured by EIA (Enzygnost®Anti-Measles Virus/IgG, Simens).

  18. Reduction of Left Visual Field Lexical Decision Accuracy as a Result of Concurrent Nonverbal Auditory Stimulation

    ERIC Educational Resources Information Center

    Van Strien, Jan W.

    2004-01-01

    To investigate whether concurrent nonverbal sound sequences would affect visual-hemifield lexical processing, lexical-decision performance of 24 strongly right-handed students (12 men, 12 women) was measured in three conditions: baseline, concurrent neutral sound sequence, and concurrent emotional sound sequence. With the neutral sequence,…

  19. Evidence for task conflict in the Stroop effect.

    PubMed

    Goldfarb, Liat; Henik, Avishai

    2007-10-01

    C. M. MacLeod and P. A. MacDonald (2000) suggested that congruent and incongruent Stroop stimuli cause more task conflict than neutral stimuli because the anterior cingulate cortex is more activated with these stimuli. This study investigated behavioral expression for this pattern. Experiment 1 reduced task conflict control by increasing the proportion of nonword neutrals. Additionally, half the trials had conflict or neutral cues. The control reduction revealed the task conflict. For noncued trials, response time was longer for congruent stimuli than for neutral stimuli (reverse facilitation effect). In addition, response time for congruent stimuli was longer when stimuli were uncued vs. cued. Experiment 2 increased task conflict control by changing the neutral stimuli to noncolor words. Consequently, the task conflict expression disappeared. (c) 2007 APA

  20. Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

    PubMed Central

    van Twillert, Inonge; Bonačić Marinović, Axel A.; Kuipers, Betsy; van Gaans-van den Brink, Jacqueline A. M.; Sanders, Elisabeth A. M.; van Els, Cécile A. C. M.

    2017-01-01

    Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality. PMID:28091579

  1. Angular photogrammetric analysis of the soft tissue profile in 12-year-old southern Chinese.

    PubMed

    Leung, Cindi Sy; Yang, Yanqi; Wong, Ricky Wk; Hägg, Urban; Lo, John; McGrath, Colman

    2014-12-24

    To quantify average angular measurements that define the soft tissue profiles of 12-year-old southern Chinese and to determine gender differences. A random population sample of 514 12-year-old children was recruited (about 10% of a Hong Kong Chinese birth cohort). Photographs were taken in natural head posture and 12 soft tissue landmarks were located on the photos to measure 12 angular measurements using ImageJ (V1.45s) for Windows. Approximately 10% of photographs were reanalyzed and method error was calculated. Angular norm values for the 12 parameters were determined and gender differences were assessed using 2 sample T-test with 95% confidence interval. The response rate was 54.1% (278/514). Norm values for the 12 angular measurements were generated. The greatest variability was found for the nasolabial (Cm-Sn-Ls) and labiomental (Li-Sm-Pg) angles. Gender differences were found in 4 angular parameters: vertical nasal angle (N-Prn/TV) (p < 0.05), cervicomental angle (G-Pg/C-Me) (p < 0.001), facial convexity angle (G-Sn-Pg) (p < 0.01) and total facial convexity angle (G-Prn-Pg)(p < 0.01). Norm values for 12 angular measurements among 12-year-old southern Chinese children were provided and some variability noted. Gender differences were apparent in several angular measurements. This study has implications in developing norm values for southern Chinese and for comparison with other ethnic groups.

  2. The reactivation time in the treatment of AMD: a forgotten key parameter?

    PubMed

    Real, J P; Luna, J D; Palma, S D

    2018-06-01

    Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.

  3. Molecular epidemiology of Bordetella pertussis in the Philippines in 2012-2014.

    PubMed

    Galit, Salvacion Rosario L; Otsuka, Nao; Furuse, Yuki; Almonia, Daryl Joy V; Sombrero, Lydia T; Capeding, Rosario Z; Lupisan, Socorro P; Saito, Mariko; Oshitani, Hitoshi; Hiramatsu, Yukihiro; Shibayama, Keigo; Kamachi, Kazunari

    2015-06-01

    The present study was designed to determine the genotypes of circulating Bordetella pertussis in the Philippines by direct molecular typing of clinical specimens. Nasopharyngeal swabs (NPSs) were collected from 50 children hospitalized with pertussis in three hospitals during 2012-2014. Multilocus variable-number tandem repeat analysis (MLVA) was performed on the DNA extracts from NPSs. B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter, ptxP, were also investigated by DNA sequence-based typing. Twenty-six DNA extracts yielded a complete MLVA profile, which were sorted into 10 MLVA types. MLVA type 34 (MT34), which is rare in Australia, Europe, Japan, and the USA, was the predominant strain (50%). Seven MTs (MT29, MT32, MT33, and MT283-286, total 42%) were single-locus variants of MT34, while two (MT141 and MT287, total 8%) were double-locus variants of MT34. All MTs had the combination of virulence-associated allelic genes, ptxP1-ptxA1-prn1-fim3A. The B. pertussis population in the Philippines comprises genetically related strains. These strains are markedly different from those found in patients from other countries where acellular pertussis vaccines are used. The differences in vaccine types between these other countries and the Philippines, where the whole-cell vaccine is still used, may select for distinct populations of B. pertussis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.

    PubMed

    Chai, Peter R; Carreiro, Stephanie; Innes, Brendan J; Chapman, Brittany; Schreiber, Kristin L; Edwards, Robert R; Carrico, Adam W; Boyer, Edward W

    2017-12-01

    Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3-9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals. The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.

  5. Generation and acceleration of neutral atoms in intense laser plasma experiments

    NASA Astrophysics Data System (ADS)

    Tata, Sheroy; Mondal, Angana; Sarkar, Shobhik; Ved, Yash; Lad, Amit D.; Pasley, John; Colgan, James; Krishnamurthy, M.

    2017-10-01

    The interaction of a high intensity (>=1018 W/cm2), high contrast (>=109), ultra-short (30fs) laser with solid targets generates a highly dense hot plasma. The quasi-static electric fields in such plasmas are well known for ion acceleration via the target normal sheath acceleration process. Under such conditions charge reduction to generate fast neutral atoms is almost inhibited. Improvised Thomson parabola spectrometry with improved signal to noise ratio has enabled us to measure the signals of fast neutral atoms and negative ions having energies in excess of tens of keV. A study on the neutralization of accelerated protons in plasma shows that the neutral atom to all particle ratio rises sharply from a few percent at the highest detectable energy to 50 % at 15 keV. Using usual charge transfer reactions the generation of neutral atoms can not be explained, thus we conjecture that the neutralization of the accelerated ions is not from the hot dense region of the plasma but neutral atom formation takes place by co-propagating ions with low energy electrons enhancing the effective neutral ratio.

  6. Campus-Wide Measures Have Greater Potential | Climate Neutral Research

    Science.gov Websites

    impacts of climate change and fossil-fuel depletion. International scientific bodies addressing climate Potential Pursuing climate neutrality on research campuses fits into the bigger picture of addressing the change are calling for reductions of carbon emissions of 80% by 2050. Because of their size and

  7. Measurement of He neutral temperature in detached plasmas using laser absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Aramaki, M.; Tsujihara, T.; Kajita, S.; Tanaka, H.; Ohno, N.

    2018-01-01

    The reduction of the heat load onto plasma-facing components by plasma detachment is an inevitable scheme in future nuclear fusion reactors. Since the control of the plasma and neutral temperatures is a key issue to the detached plasma generation, we have developed a laser absorption spectroscopy system for the metastable helium temperature measurements and used together with a previously developed laser Thomson scattering system for the electron temperature and density measurements. The thermal relaxation process between the neutral and the electron in the detached plasma generated in the linear plasma device, NAGDIS-II was studied. It is shown that the electron temperature gets close to the neutral temperature by increasing the electron density. On the other hand, the pressure dependence of electron and neutral temperatures shows the cooling effect by the neutrals. The possibility of the plasma fluctuation measurement using the fluctuation in the absorption signal is also shown.

  8. Audit Report. Quick-Reaction Report on the Review of Defense Base Closure and Realignment Budget Data for Carswell, Barksdale, Dyess, Minot, and Tinker Air Force Bases

    DTIC Science & Technology

    1992-11-27

    for 10 construction pr~n’jcts for realigning Carswell AFB was not adeauately documented as required by Air Force Regulation (AFR) 86-1, " Programming ...Engineering Programming , Standard Facility Requirements." paragraph 24-70, allows for a total of 25,200 square feet of space for tne warehouse and...cantonment area, and replaced an existing capability. The fact that a replacement wash rack was previously programmed does not alter this requirement

  9. Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

    PubMed

    Ida, K; Funaba, H; Kado, S; Narihara, K; Tanaka, K; Takeiri, Y; Nakamura, Y; Ohyabu, N; Yamazaki, K; Yokoyama, M; Murakami, S; Ashikawa, N; deVries, P C; Emoto, M; Goto, M; Idei, H; Ikeda, K; Inagaki, S; Inoue, N; Isobe, M; Itoh, K; Kaneko, O; Kawahata, K; Khlopenkov, K; Komori, A; Kubo, S; Kumazawa, R; Liang, Y; Masuzaki, S; Minami, T; Miyazawa, J; Morisaki, T; Morita, S; Mutoh, T; Muto, S; Nagayama, Y; Nakanishi, H; Nishimura, K; Noda, N; Notake, T; Kobuchi, T; Ohdachi, S; Ohkubo, K; Oka, Y; Osakabe, M; Ozaki, T; Pavlichenko, R O; Peterson, B J; Sagara, A; Saito, K; Sakakibara, S; Sakamoto, R; Sanuki, H; Sasao, H; Sasao, M; Sato, K; Sato, M; Seki, T; Shimozuma, T; Shoji, M; Suzuki, H; Sudo, S; Tamura, N; Toi, K; Tokuzawa, T; Torii, Y; Tsumori, K; Yamamoto, T; Yamada, H; Yamada, I; Yamaguchi, S; Yamamoto, S; Yoshimura, Y; Watanabe, K Y; Watari, T; Hamada, Y; Motojima, O; Fujiwara, M

    2001-06-04

    Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

  10. Influence of hot and cold neutrals on scrape-off layer tokamak plasma turbulence

    NASA Astrophysics Data System (ADS)

    Bisai, N.; Kaw, P. K.

    2018-01-01

    The modification of interchange plasma turbulence in the scrape-off layer (SOL) region by the presence of hot and cold neutral gas molecules has been studied. The nonlinear equations have been solved numerically using two different simulations ("uniform-Te" and "varying-Te"), and the results obtained from both of the models have been compared. The hot neutrals, responsible for the increase in the electron density in the SOL, also account for more ionization of the cold molecules. The effect of hot and cold neutrals on the interchange turbulence is almost similar in the "uniform-Te" model, but in the "varying-Te" model, the influence of the hot neutrals is very small, specifically in the far SOL region. The neutral gas in the "varying Te" model decreases the heat load on the material walls by about 7%. A reduction in the radial velocity by about 25% and effective diffusion coefficient of the plasma particles has been found by the influence of the neutral gas.

  11. Catheter Occlusion in Home Infusion: The Influence of Needleless Connector Design on Central Catheter Occlusion.

    PubMed

    Williams, Ann

    Thrombotic catheter occlusion is a common complication associated with central venous catheters (CVCs). A wide variety of needleless connectors that differ greatly in design and function are available for use with CVCs; however, there are a limited number of studies comparing the catheter occlusion rate associated with differently designed needleless connectors. This retrospective observational study compared occlusion rates associated with a split-septum neutral-displacement needleless connector versus those of a solid-surface neutral-reflux needleless connector in patients undergoing home infusion therapy. The neutral-reflux needleless connector was associated with a significant reduction in occlusion rate and thrombolytic use versus the neutral-displacement needleless connector.

  12. Effect of surfactants and temperature on the hyperfiltration performance of poly(ether/urea) membranes

    NASA Technical Reports Server (NTRS)

    Leban, M. I.; Wydeven, T. J.

    1984-01-01

    The individual and combined effects of pasteurization temperature (347 K) and surfactants (anionic, cationic, and neutral) on a poly(ether/urea) thin-film hyperfiltration membrane were studied. Performance of this positively charged membrane was measured in terms of sodium chloride rejection and water flux. The observed effect was mostly on water flux and minimal on salt rejection. Pasteurization temperature caused an irreversible flux decline (flux decline slope of 0.09). The gradual flux reduction caused by neutral and cationic surfactants was reversible, whereas the flux reduction caused by anionic surfactant was irreversible and of similar magnitude to flux reduction caused by pasteurization temperature. The effects of anionic surfactant and pasteurization temperature were additive. Because of flux decline at elevated temperatures the poly(ether/urea) membrane is not very attractive for long-term spaceflight use.

  13. Rapid evolution of troglomorphic characters suggests selection rather than neutral mutation as a driver of eye reduction in cave crabs.

    PubMed

    Klaus, Sebastian; Mendoza, José C E; Liew, Jia Huan; Plath, Martin; Meier, Rudolf; Yeo, Darren C J

    2013-04-23

    This study asked whether reductive traits in cave organisms evolve at a slower pace (suggesting neutral evolution under relaxed selection) than constructive changes, which are likely to evolve under directional selection. We investigated 11 subterranean and seven surface populations of Sundathelphusa freshwater crabs on Bohol Island, Philippines, and examined constructive traits associated with improved food finding in darkness (increased leg and setae length) and reductive traits (reduced cornea size and eyestalk length). All changes occurred rapidly, given that the age of the most recent common ancestor was estimated to be 722-271 ka based on three mitochondrial markers. In order to quantify the speed of character change, we correlated the degree of morphological change with genetic distances between surface and subterranean individuals. The temporal pattern of character change following the transition to subterranean life was indistinguishable for constructive and reductive traits, characterized by an immediate onset and rapid evolutionary change. We propose that the evolution of these reductive traits-just like constructive traits-is most likely driven by strong directional selection.

  14. Effect of electrochemical redox reaction on growth and metabolism of Saccharomyces cerevisiae as an environmental factor.

    PubMed

    Na, Kwan Byung; Hwang, Tae Sik; Lee, Sung Hun; Ahn, Dae Hee; Park, Doo Hyun

    2007-03-01

    The effect of an electrochemically generated oxidation-reduction potential and electric pulse on ethanol production and growth of Saccharomyces cerevisiae ATCC 26603 was experimented and compared with effects of electron mediators (neutral red, benzyl viologen, and thionine), chemical oxidants (hydrogen peroxide and hypochlorite), chemical reductants (sulfite and nitrite), oxygen, and hydrogen. The oxidation (anodic) and reduction (cathodic) potential and electric pulse activated ethanol production and growth, and changed the total soluble protein pattern of the test strain. Neutral red electrochemically reduced activated ethanol production and growth of the test strain, but benzyl viologen and thionine did not. Nitrite inhibited ethanol production but did not influence growth of the test strain. Hydrogen peroxide, hypochlorite, and sulfite did not influence ethanol production and growth of the test strain. Hydrogen and oxygen also did not influence the growth and ethanol production. It shows that the test strain may perceive electrochemically generated oxidation-reduction potential and electric pulse as an environmental factor.

  15. Stroop Dilution Depends on the Nature of the Color Carrier but Not on Its Location

    ERIC Educational Resources Information Center

    Cho, Yang Seok; Lien, Mei-Ching; Proctor, Robert W.

    2006-01-01

    Stroop dilution is the reduction of the Stroop effect in the presence of a neutral word. It has been attributed to competition for attention between the color word and neutral word, to competition between all stimuli in the visual field, and to perceptual interference. Five experiments tested these accounts. The critical manipulation was whether…

  16. Synthesis of amino ester-embedded benzimidazoles: a one-pot sequential protocol under metal-free neutral conditions.

    PubMed

    Roy, Priyabrata; Bodhak, Chandan; Pramanik, Animesh

    2017-02-01

    A one-pot three-component protocol has been developed for the synthesis of amino ester-embedded benzimidazoles under metal-free neutral conditions. Sequentially, the methodology involves coupling of an amino ester with 1-fluoro-2-nitrobenzene, reduction of the coupled nitroarene by sodium dithionite, and cyclization of the corresponding diamine with an aldehyde.

  17. Perchlorate reduction by autotrophic bacteria in the presence of zero-valent iron.

    PubMed

    Yu, Xueyuan; Amrhein, Christopher; Deshusses, Marc A; Matsumoto, Mark R

    2006-02-15

    A series of batch experiments were performed to study the combination of zero-valent iron (ZVI) with perchlorate-reducing microorganisms (PRMs) to remove perchlorate from groundwater. In this method, H2 produced during the process of iron corrosion by water is used by PRMs as an electron donor to reduce perchlorate to chloride. Perchlorate degradation rates followed Monod kinetics, with a normalized maximum utilization rate (rmax) of 9200 microg g(-1) (dry wt) h(-1) and a half-velocity constant (Ks) of 8900 microg L(-1). The overall rate of perchlorate reduction was affected by the biomass density within the system. An increase in the OD600 from 0.025 to 0.08 led to a corresponding 4-fold increase of perchlorate reduction rate. PRM adaptation to the local environment and initiation of perchlorate reduction was rapid under neutral pH conditions. At the initial OD600 of 0.015, perchlorate reduction followed pseudo-first-order reaction rates with constants of 0.059 and 0.033 h(-1) at initial pH 7 and 8, respectively. Once perchlorate reduction was established, the bioreductive process was insensitive to the increases of pH from near neutral to 9.0. In the presence of nitrate, perchlorate reduction rate was reduced, but not inhibited completely.

  18. A Belgian Serosurveillance/Seroprevalence Study of Diphtheria, Tetanus and Pertussis Using a Luminex xMAP Technology-Based Pentaplex.

    PubMed

    Caboré, Raissa Nadège; Piérard, Denis; Huygen, Kris

    2016-05-10

    Serosurveillance and seroprevalence studies are an essential tool to monitor vaccine-preventable diseases. We have developed a magnetic bead-based pentaplex immunoassay (MIA) for the simultaneous detection of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn). The in-house pentaplex MIA showed a good correlation with commercial ELISAs with correlation coefficients between 0.89 for PT and 0.98 for TT. Intra- and inter-assay variability was <10%. A total of 670 anonymized serum samples collected in 2012 in Belgian adults (ages 20-29.9 years) were analyzed. Geometric mean concentrations (GMC) were 0.2 (0.13-0.29) IU/mL for DT, 0.63 (0.45-0.82) IU/mL for TT, 3.9 (2.6-5.8) IU/mL for PT, 16.3 (11.7-22.7) IU/mL for FHA and 15.4 (10.1-23.6) IU/mL for Prn. Antibody concentrations were below the protective level of 0.1 IU/mL in 26.4% of the sera for DT and in 8.6% of the sera for TT. Anti-PT IgG concentrations indicative of recent pertussis infection (>125 IU/mL) were detected in 1.2% of the subjects. High anti-PT antibodies were not correlated with high antibodies against any of the four other vaccine antigens. This pentaplex MIA will be used for a new large-scale Belgian serosurveillance/seroprevalence study of diphtheria, tetanus and pertussis.

  19. Significant advantages of sulfur-doped graphene in neutral media as electrocatalyst for oxygen reduction comparing with Pt/C

    NASA Astrophysics Data System (ADS)

    Shi, Xinxin; Zhang, Jiaona; Huang, Tinglin

    2018-02-01

    Sulfur-doped graphene (SDG) has been found to be an efficient electrocatalyst for oxygen reduction reaction. However, previous studies on the catalytic activity of SDG have been mainly confined to O2-saturated alkaline media which is a typical alkaline fuel cell environment. Air-cathode microbial fuel cells (ACMFCs), as a novel energy conversion and wastewater treatment technology, use the oxygen from air as cathodic reactant in neutral media with low concentration of O2. Thus, it is meaningful to explore the catalytic performance of SDG in such ACMFC environment. The result showed that in ACMFC environment, the peak current density of SDG in CV test was surprisingly 4.5 times higher than that of Pt/C, indicating a much stronger catalytic activity of SDG. Moreover, SDG exhibited a stronger tolerance against the crossover of glucose (a typical anodic fuel in ACMFC) and better stability than Pt/C in neutral media.

  20. A Mixture of Functionally Oligoclonal Humanized Monoclonal Antibodies That Neutralize Clostridium difficile TcdA and TcdB with High Levels of In Vitro Potency Shows In Vivo Protection in a Hamster Infection Model

    PubMed Central

    Davies, Nicola L.; Compson, Joanne E.; MacKenzie, Brendon; O'Dowd, Victoria L.; Oxbrow, Amanda K. F.; Heads, James T.; Turner, Alison; Sarkar, Kaushik; Dugdale, Sarah L.; Jairaj, Mark; Christodoulou, Louis; Knight, David E. O.; Cross, Amanda S.; Hervé, Karine J. M.; Tyson, Kerry L.; Hailu, Hanna; Doyle, Carl B.; Ellis, Mark; Kriek, Marco; Cox, Matthew; Page, Matthew J. T.; Moore, Adrian R.; Lightwood, Daniel J.

    2013-01-01

    Clostridium difficile infections are a major cause of antibiotic-associated diarrhea in hospital and care facility patients. In spite of the availability of effective antibiotic treatments, C. difficile infection (CDI) is still a major cause of patient suffering, death, and substantial health care costs. Clostridium difficile exerts its major pathological effects through the actions of two protein exotoxins, TcdA and TcdB, which bind to and disrupt gut tissue. Antibiotics target the infecting bacteria but not the exotoxins. Administering neutralizing antibodies against TcdA and TcdB to patients receiving antibiotic treatment might modulate the effects of the exotoxins directly. We have developed a mixture of three humanized IgG1 monoclonal antibodies (MAbs) which neutralize TcdA and TcdB to address three clinical needs: reduction of the severity and duration of diarrhea, reduction of death rates, and reduction of the rate of recurrence. The UCB MAb mixture showed higher potency in a variety of in vitro binding and neutralization assays (∼10-fold improvements), higher levels of protection in a hamster model of CDI (82% versus 18% at 28 days), and higher valencies of toxin binding (12 versus 2 for TcdA and 3 versus 2 for TcdB) than other agents in clinical development. Comparisons of the MAb properties also offered some insight into the potential relative importance of TcdA and TcdB in the disease process. PMID:23324518

  1. Estimates of Mumps Seroprevalence May Be Influenced by Antibody Specificity and Serologic Method

    PubMed Central

    McGrew, Marcia; Williams, Nobia J.; Sowers, Sun B.; Bellini, William J.; Hickman, Carole J.

    2014-01-01

    Neutralizing antibodies are assumed to be essential for protection against mumps virus infection, but their measurement is labor- and time-intensive. For this reason, enzyme-linked immunosorbent assays (ELISAs) are typically used to measure mumps-specific IgG levels. However, since there is poor correlation between mumps neutralization titers and ELISAs that measure the presence of mumps-specific IgG levels, ELISAs that better correlate with neutralization are needed. To address this issue, we measured mumps antibody levels by plaque reduction neutralization, by a commercial ELISA (whole-virus antigen), and by ELISAs specific for the mumps nucleoprotein and hemagglutinin. The results indicate that differences in the antibody response to the individual mumps proteins could partially explain the lack of correlation among various serologic tests. Furthermore, the data indicate that some seropositive individuals have low levels of neutralizing antibody. If neutralizing antibody is important for protection, this suggests that previous estimates of immunity based on whole-virus ELISAs may be overstated. PMID:24371258

  2. Assaying Cellular Viability Using the Neutral Red Uptake Assay.

    PubMed

    Ates, Gamze; Vanhaecke, Tamara; Rogiers, Vera; Rodrigues, Robim M

    2017-01-01

    The neutral red uptake assay is a cell viability assay that allows in vitro quantification of xenobiotic-induced cytotoxicity. The assay relies on the ability of living cells to incorporate and bind neutral red, a weak cationic dye, in lysosomes. As such, cytotoxicity is expressed as a concentration-dependent reduction of the uptake of neutral red after exposure to the xenobiotic under investigation. The neutral red uptake assay is mainly used for hazard assessment in in vitro toxicology applications. This method has also been introduced in regulatory recommendations as part of 3T3-NRU-phototoxicity-assay, which was regulatory accepted in all EU member states in 2000 and in the OECD member states in 2004 as a test guideline (TG 432). The present protocol describes the neutral red uptake assay using the human hepatoma cell line HepG2, which is often employed as an alternative in vitro model for human hepatocytes. As an example, the cytotoxicity of acetaminophen and acetyl salicylic acid is assessed.

  3. Disturbed subsurface microbial communities follow equivalent trajectories despite different structural starting points: Microbial community succession and disturbance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Handley, Kim M.; Wrighton, Kelly C.; Miller, Christopher S.

    2014-04-18

    Microbial community structure, and niche and neutral processes can all influence response to disturbance. Here, we provide experimental evidence for niche versus neutral and founding community effects during a bioremediation-related organic carbon disturbance. Subsurface sediment, partitioned into 22 flow-through columns, was stimulated in situ by the addition of acetate as a carbon and electron donor source. This drove the system into a new transient biogeochemical state characterized by iron reduction and enriched Desulfuromonadales, Comamonadaceae and Bacteroidetes lineages. After approximately 1 month conditions favoured sulfate reduction, and were accompanied by a substantial increase in the relative abundance of Desulfobulbus, Desulfosporosinus, Desulfitobacteriummore » and Desulfotomaculum. Two subsets of four to five columns each were switched from acetate to lactate amendment during either iron (earlier) or sulfate (later) reduction. Hence, subsets had significantly different founding communities. All lactate treatments exhibited lower relative abundances of Desulfotomaculum and Bacteroidetes, enrichments of Clostridiales and Psychrosinus species, and a temporal succession from highly abundant Clostridium sensu stricto to Psychrosinus. Regardless of starting point, lactate-switch communities followed comparable structural trajectories, whereby convergence was evident 9 to 16 days after each switch, and significant after 29 to 34 days of lactate addition. Results imply that neither the founding community nor neutral processes influenced succession following perturbation.« less

  4. Divertor heat flux mitigation in the National Spherical Torus Experimenta)

    NASA Astrophysics Data System (ADS)

    Soukhanovskii, V. A.; Maingi, R.; Gates, D. A.; Menard, J. E.; Paul, S. F.; Raman, R.; Roquemore, A. L.; Bell, M. G.; Bell, R. E.; Boedo, J. A.; Bush, C. E.; Kaita, R.; Kugel, H. W.; Leblanc, B. P.; Mueller, D.; NSTX Team

    2009-02-01

    Steady-state handling of divertor heat flux is a critical issue for both ITER and spherical torus-based devices with compact high power density divertors. Significant reduction of heat flux to the divertor plate has been achieved simultaneously with favorable core and pedestal confinement and stability properties in a highly shaped lower single null configuration in the National Spherical Torus Experiment (NSTX) [M. Ono et al., Nucl. Fusion 40, 557 2000] using high magnetic flux expansion at the divertor strike point and the radiative divertor technique. A partial detachment of the outer strike point was achieved with divertor deuterium injection leading to peak flux reduction from 4-6MWm-2to0.5-2MWm-2 in small-ELM 0.8-1.0MA, 4-6MW neutral beam injection-heated H-mode discharges. A self-consistent picture of the outer strike point partial detachment was evident from divertor heat flux profiles and recombination, particle flux and neutral pressure measurements. Analytic scrape-off layer parallel transport models were used for interpretation of NSTX detachment experiments. The modeling showed that the observed peak heat flux reduction and detachment are possible with high radiated power and momentum loss fractions, achievable with divertor gas injection, and nearly impossible to achieve with main electron density, divertor neutral density or recombination increases alone.

  5. Isolation and characterization of an equine rotavirus.

    PubMed Central

    Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

    1983-01-01

    A rotavirus, designated as the H-1 strain, was isolated from a diarrheic foal in primary African green monkey kidney cells and MA104 cells. This cell culture-adapted strain hemagglutinated erythrocytes of human group O, rhesus monkeys, guinea pigs, and sheep. It was found to be similar, if not identical, to porcine rotaviruses (strains OSU, EE, and A-580) by plaque reduction neutralization and hemagglutination inhibition tests, and, in addition, it was found to belong to subgroup 1. This equine rotavirus has an RNA electrophoretic migration pattern which was distinct from those of the three strains of porcine rotavirus. The serological relationship established by plaque reduction neutralization and hemagglutination inhibition tests between the equine (H-1) and porcine (OSU, EE, and A-580) rotaviruses is an example of a rotavirus of the same serotype being isolated from different species. The H-1 strain was distinct from four human rotavirus serotypes (Wa, DS-1, P, and St. Thomas 4) as well as from bovine rotavirus NCDV, simian rotavirus MMU18006, and canine rotavirus CU-1 by plaque reduction neutralization tests. This equine isolate (H-1) was found to be related antigenically to canine CU-1 and bovine NCDV rotaviruses in a one-way fashion by hemagglutination inhibition tests. Images PMID:6313746

  6. Development of a compact superconducting rotating-gantry for heavy-ion therapy

    PubMed Central

    Iwata, Yoshiyuki; Noda, K.; Murakami, T.; Shirai, T.; Furukawa, T.; Fujita, T.; Mori, S.; Sato, S.; Mizushima, K.; Shouda, K.; Fujimoto, T.; Arai, H.; Ogitsu, T.; Obana, T.; Amemiya, N.; Orikasa, T.; Takami, S.; Takayama, S.

    2014-01-01

    An isocentric superconducting rotating-gantry for heavy-ion therapy is being developed [ 1]. This rotating gantry can transport heavy ions having 430 MeV/u to an isocenter with irradiation angles of over ±180°, and is further capable of performing fast raster-scanning irradiation [ 2]. A layout of the beam-transport line for the compact rotating-gantry is presented in Fig. 1. The rotating gantry has 10 superconducting magnets (BM01-10), a pair of the scanning magnets (SCM-X and SCM-Y) and two pairs of beam profile- monitor and steering magnets (ST01-02 and PRN01-02). For BM01-BM06 and BM09-BM10, the combined-function superconducting magnets are employed. Further, these superconducting magnets are designed for fast slewing of the magnetic field to follow the multiple flattop operation of the synchrotron [ 3]. The use of the combined-function superconducting magnets with optimized beam optics allows a compact gantry design with a large scan size at the isocenter; the length and the radius of the gantry will be to be ∼13 and 5.5 m, respectively, which are comparable to those for the existing proton gantries. Furthermore, the maximum scan size at the isocenter is calculated to be as large as ∼200 mm square for heavy-ion beams at the maximum energy of 430 MeV/u. All of the superconducting magnets were designed, and their magnetic fields were calculated using the Opera-3d code [ 4]. With the calculated magnetic fields, beam-tracking simulations were made. The simulation results agreed well with those of the linear beam-optics calculation, proving validity of the final design for the superconducting magnets. The five out of 10 superconducting magnets, as well as the model magnet were currently manufactured. With these magnets, rotation tests, magnetic field measurements and fast slewing tests were conducted. However, we did not observe any significant temperature increase, which may cause a quench problem. Further, results of the magnetic field measurements roughly agreed with those calculated by the Opera-3d code. The design study as well as major tests of the superconducting magnets was completed, and the construction of the superconducting rotating-gantry is in progress. The construction of the superconducting rotating-gantry will be completed at the end of FY2014, and be commissioned within FY2015. Fig. 1.Layout of the superconducting rotating-gantry. The gantry consists of 10 superconducting magnets (BM01–BM10), a pair of the scanning magnets (SCM-X and SCMY), and two pairs of beam profile-monitor and steering magnets (STR01–STR02 and PRN01–PRN02).

  7. Boundary asymptotics for a non-neutral electrochemistry model with small Debye length

    NASA Astrophysics Data System (ADS)

    Lee, Chiun-Chang; Ryham, Rolf J.

    2018-04-01

    This article addresses the boundary asymptotics of the electrostatic potential in non-neutral electrochemistry models with small Debye length in bounded domains. Under standard physical assumptions motivated by non-electroneutral phenomena in oxidation-reduction reactions, we show that the electrostatic potential asymptotically blows up at boundary points with respect to the bulk reference potential as the scaled Debye length tends to zero. The analysis gives a lower bound for the blow-up rate with respect to the model parameters. Moreover, the maximum potential difference over any compact subset of the physical domain vanishes exponentially in the zero-Debye-length limit. The results mathematically confirm the physical description that electrolyte solutions are electrically neutral in the bulk and are strongly electrically non-neutral near charged surfaces.

  8. A weight-neutral versus weight-loss approach for health promotion in women with high BMI: A randomized-controlled trial.

    PubMed

    Mensinger, Janell L; Calogero, Rachel M; Stranges, Saverio; Tylka, Tracy L

    2016-10-01

    Weight loss is the primary recommendation for health improvement in individuals with high body mass index (BMI) despite limited evidence of long-term success. Alternatives to weight-loss approaches (such as Health At Every Size - a weight-neutral approach) have been met with their own concerns and require further empirical testing. This study compared the effectiveness of a weight-neutral versus a weight-loss program for health promotion. Eighty women, aged 30-45 years, with high body mass index (BMI ≥ 30 kg/m(2)) were randomized to 6 months of facilitator-guided weekly group meetings using structured manuals that emphasized either a weight-loss or weight-neutral approach to health. Health measurements occurred at baseline, post-intervention, and 24-months post-randomization. Measurements included blood pressure, lipid panels, blood glucose, BMI, weight, waist circumference, hip circumference, distress, self-esteem, quality of life, dietary risk, fruit and vegetable intake, intuitive eating, and physical activity. Intention-to-treat analyses were performed using linear mixed-effects models to examine group-by-time interaction effects and between and within-group differences. Group-by-time interactions were found for LDL cholesterol, intuitive eating, BMI, weight, and dietary risk. At post-intervention, the weight-neutral program had larger reductions in LDL cholesterol and greater improvements in intuitive eating; the weight-loss program had larger reductions in BMI, weight, and larger (albeit temporary) decreases in dietary risk. Significant positive changes were observed overall between baseline and 24-month follow-up for waist-to-hip ratio, total cholesterol, physical activity, fruit and vegetable intake, self-esteem, and quality of life. These findings highlight that numerous health benefits, even in the absence of weight loss, are achievable and sustainable in the long term using a weight-neutral approach. The trial positions weight-neutral programs as a viable health promotion alternative to weight-loss programs for women of high weight. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Antibacterial properties and reduction of MRSA biofilm with a dressing combining polyabsorbent fibres and a silver matrix.

    PubMed

    Desroche, N; Dropet, C; Janod, P; Guzzo, J

    2016-10-02

    This study was designed to evaluate the antibacterial activity of a wound dressing which combines polyacrylate fibres and a silver lipido-colloid matrix (UrgoClean Ag, silver polyabsorbent dressing), against biofilm of methicillin-resistant Staphylococcus aureus (MRSA). Samples of silver polyabsorbent dressing and the neutral form of this dressing (UrgoClean) were applied to biofilms of MRSA formed on a collagen I-coated surface, cultured for 24 hours. Different exposure times were tested (1, 2, 4 and 7 days) without dressing change. The biofilm reduction was quantified by using culture methods and by confocal laser scanning microscopy experiments. The application of the silver polyabsorbent dressing resulted in a significant decrease of the biofilm population by a log reduction of 4.6, after 24 hours of exposure. Moreover, the antibiofilm activity was maintained for 7 days with reduction values up to 4 log (reduction of biofilm superior to 99.99%). The application of the neutral dressing also induced a significant reduction of the concentration of sessile cells after 1 day (about 0.90 log). The results obtained with this neutral form of the dressing showed that the polyacrylate fibres were able to exert a mechanical disruption of the biofilm architecture. These in vitro experiments demonstrated that silver polyabsorbent dressing was able to strongly reduce the biofilm of MRSA. The antibiofilm mechanism of this dressing can be explained by a dual action of the polyabsorbent fibres (based on ammonium polyacrylate polymer around an acrylic core) which induced a mechanical disruption of the biofilm matrix and/or a sequestration of sessile cells, and the diffusion of silver ions which produced bactericidal activity. This study was supported by Laboratoires Urgo (Dijon). P. Janod is an employee of Laboratoires Urgo. The company had no influence on the experimental design and the interpretation of the results.

  10. Inhibitory Effect of Individual or Combinations of Broadly Neutralizing Antibodies and Antiviral Reagents against Cell-Free and Cell-to-Cell HIV-1 Transmission

    PubMed Central

    Kolodkin-Gal, Dror; Eslamizar, Leila; Owuor, Joshua O.; Mazzola, Emanuele; Gonzalez, Ana M.; Korioth-Schmitz, Birgit; Gelman, Rebecca S.; Montefiori, David C.; Haynes, Barton F.; Schmitz, Joern E.

    2015-01-01

    ABSTRACT To date, most therapeutic and vaccine candidates for human immunodeficiency virus type 1 (HIV-1) are evaluated preclinically for efficacy against cell-free viral challenges. However, cell-associated HIV-1 is suggested to be a major contributor to sexual transmission by mucosal routes. To determine if neutralizing antibodies or inhibitors block cell-free and cell-associated virus transmission of diverse HIV-1 strains with different efficiencies, we tested 12 different antibodies and five inhibitors against four green fluorescent protein (GFP)-labeled HIV-1 envelope (Env) variants from transmitted/founder (T/F) or chronic infection isolates. We evaluated antibody/inhibitor-mediated virus neutralization using either TZM-bl target cells, in which infectivity was determined by virus-driven luciferase expression, or A3R5 lymphoblastoid target cells, in which infectivity was evaluated by GFP expression. In both the TZM-bl and A3R5 assays, cell-free virus or infected CD4+ lymphocytes were used as targets for neutralization. We further hypothesized that the combined use of specific neutralizing antibodies targeting HIV-1 Env would more effectively prevent cell-associated virus transmission than the use of individual antibodies. The tested antibody combinations included two gp120-directed antibodies, VRC01 and PG9, or VRC01 with the gp41-directed antibody 10E8. Our results demonstrated that cell-associated virus was less sensitive to neutralizing antibodies and inhibitors, particularly using the A3R5 neutralization assay, and the potencies of these neutralizing agents differed among Env variants. A combination of different neutralizing antibodies that target specific sites on gp120 led to a significant reduction in cell-associated virus transmission. These assays will help identify ideal combinations of broadly neutralizing antibodies to use for passive preventive antibody administration and further characterize targets for the most effective neutralizing antibodies/inhibitors. IMPORTANCE Prevention of the transmission of human immunodeficiency virus type 1 (HIV-1) remains a prominent goal of HIV research. The relative contribution of HIV-1 within an infected cell versus cell-free HIV-1 to virus transmission remains debated. It has been suggested that cell-associated virus is more efficient at transmitting HIV-1 and more difficult to neutralize than cell-free virus. Several broadly neutralizing antibodies and retroviral inhibitors are currently being studied as potential therapies against HIV-1 transmission. The present study demonstrates a decrease in neutralizing antibody and inhibitor efficiencies against cell-associated compared to cell-free HIV-1 transmission among different strains of HIV-1. We also observed a significant reduction in virus transmission using a combination of two different neutralizing antibodies that target specific sites on the outermost region of HIV-1, the virus envelope. Therefore, our findings support the use of antibody combinations against both cell-free and cell-associated virus in future candidate therapy regimens. PMID:25995259

  11. Hydraulic retention time and pH affect the performance and microbial communities of passive bioreactors for treatment of acid mine drainage.

    PubMed

    Aoyagi, Tomo; Hamai, Takaya; Hori, Tomoyuki; Sato, Yuki; Kobayashi, Mikio; Sato, Yuya; Inaba, Tomohiro; Ogata, Atsushi; Habe, Hiroshi; Sakata, Takeshi

    2017-12-01

    For acceleration of removing toxic metals from acid mine drainage (AMD), the effects of hydraulic retention time (HRT) and pH on the reactor performance and microbial community structure in the depth direction of a laboratory-scale packed-bed bioreactor containing rice bran as waste organic material were investigated. The HRT was shortened stepwise from 25 to 12 h, 8 h, and 6 to 5 h under the neutral condition using AMD neutralized with limestone (pH 6.3), and from 25 to 20 h, 12 h, and 8 to 7 h under the acid condition using AMD (pH 3.0). Under the neutral condition, the bioreactor stably operated up to 6 h HRT, which was shorter than under the acid condition (up to 20 h HRT). During stable sulfate reduction, both the organic matter-remaining condition and the low oxidation-reduction potential condition in lower parts of the reactor were observed. Principal coordinate analysis of Illumina sequencing data of 16S rRNA genes revealed a dynamic transition of the microbial communities at the boundary between stable and unstable operation in response to reductions in HRT. During stable operation under both the neutral and acid conditions, several fermentative operational taxonomic units (OTUs) from the phyla Firmicutes and Bacteroidetes dominated in lower parts of the bioreactor, suggesting that co-existence of these OTUs might lead to metabolic activation of sulfate-reducing bacteria. In contrast, during unstable operation at shorter HRTs, an OTU from the candidate phylum OP11 were found under both conditions. This study demonstrated that these microorganisms can be used to monitor the treatment of AMD, which suggests stable or deteriorated performance of the system.

  12. Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate

    PubMed Central

    Keck, Zhen-yong; Xia, Jinming; Wang, Yong; Wang, Wenyan; Krey, Thomas; Prentoe, Jannick; Carlsen, Thomas; Li, Angela Ying-Jian; Patel, Arvind H.; Lemon, Stanley M.; Bukh, Jens; Rey, Felix A.; Foung, Steven K. H.

    2012-01-01

    The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1–6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1–6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418–446 and aa611–616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434–446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410–425. The isolation of four HC-84 HMAbs binding to the peptide, aa434–446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus. PMID:22511875

  13. Host Competence: An Organismal Trait to Integrate Immunology and Epidemiology.

    PubMed

    Martin, Lynn B; Burgan, S C; Adelman, James S; Gervasi, Stephanie S

    2016-12-01

    The new fields of ecological immunology and disease ecology have begun to merge, and the classic fields of immunology and epidemiology are beginning to blend with them. This merger is occurring because the integrative study of host-parasite interactions is providing insights into disease in ways that traditional methods have not. With the advent of new tools, mathematical and technological, we could be on the verge of developing a unified theory of infectious disease, one that supersedes the barriers of jargon and tradition. Here we argue that a cornerstone of any such synthesis will be host competence, the propensity of an individual host to generate new infections in other susceptible hosts. In the last few years, the emergence of systems immunology has led to novel insight into how hosts control or eliminate pathogens. Most such efforts have stopped short of considering transmission and the requisite behaviors of infected individuals that mediate it, and few have explicitly incorporated ecological and evolutionary principles. Ultimately though, we expect that the use of a systems immunology perspective will help link suborganismal processes (i.e., health of hosts and selection on genes) to superorganismal outcomes (i.e., community-level disease dynamics and host-parasite coevolution). Recently, physiological regulatory networks (PRNs) were cast as whole-organism regulatory systems that mediate homeostasis and hence link suborganismal processes with the fitness of individuals. Here, we use the PRN construct to develop a roadmap for studying host competence, taking guidance from systems immunology and evolutionary ecology research. We argue that PRN variation underlies heterogeneity in individual host competence and hence host-parasite dynamics. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  14. Relationship Between Visual Acuity and Retinal Thickness During Anti-Vascular Endothelial Growth Factor Therapy for Retinal Diseases.

    PubMed

    Ou, William C; Brown, David M; Payne, John F; Wykoff, Charles C

    2017-08-01

    To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases. Retrospective analysis of clinical trial data. Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression. At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r = -0.24). A medium correlation was identified in pooled DME trial data (r = -0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r = -0.45) and pooled RVO (r = -0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r = -0.27) and RVO (r = -0.72) trials, but not in DME trial data. DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The Evaluation of Undergraduate Nursing Students' Knowledge of Post-op Pain Management after Participation in Simulation.

    PubMed

    Evans, Cecile B; Mixon, Diana K

    2015-12-01

    The purpose of this paper was to assess undergraduate nursing students' pain knowledge after participation in a simulation scenario. The Knowledge and Attitudes of Survey Regarding Pain (KASRP) was used to assess pain knowledge. In addition, reflective questions related to the simulation were examined. Student preferences for education method and reactions to the simulation (SIM) were described. Undergraduate nursing students' knowledge of pain management is reported as inadequate. An emerging pedagogy used to educate undergraduate nurses in a safe, controlled environment is simulation. Literature reports of simulation to educate students' about pain management are limited. As part of the undergraduate nursing student clinical coursework, a post-operative pain management simulation, the SIM was developed. Students were required to assess pain levels and then manage the pain for a late adolescent male whose mother's fear of addiction was a barrier to pain management. The students completed an anonymous written survey that included selected questions from the KASRP and an evaluation of the SIM experience. The students' mean KASRP percent correct was 70.4% ± 8.6%. Students scored the best on items specific to pain assessment and worst on items specific to opiate equivalents and decisions on PRN orders. The students' overall KASRP score post simulation was slightly better than previous studies of nursing students. These results suggest that educators should consider simulations to educate about pain assessment and patient/family education. Future pain simulations should include more opportunities for students to choose appropriate pain medications when provided PRN orders. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  16. Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women

    PubMed Central

    Villarreal Pérez, Jesús Zacarías; Ramírez Aranda, José Manuel; de la O Cavazos, Manuel; Zamudio Osuna, Michelle de J.; Perales Dávila, José; Ballesteros Elizondo, María Romelia; Gómez Meza, Marco Vinicio; García Elizondo, Francisco Javier; Rodríguez González, Azucena M.

    2017-01-01

    ABSTRACT Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine raises controversies on immunogenicity and possible antibody interference. We performed an experimental, double-blind, parallel group controlled clinical trial to evaluate the safety and immunogenicity of the Tdap vaccine in 204 pregnant women and their children and to determine its interference in antibody production. Pregnant women 18 to 38 y of age with 12 to 24 weeks gestation, a low obstetric risk, and without serious disease were randomly selected. The experimental group received 0.5 mL IM of Tdap and the control group normal saline. Six blood samples were drawn before and after solution application, and from the umbilical cord of the infants and at 2, 4, and 6 months of age. Pertactin and Pertussis toxin antibodies and possible interference of maternal antibodies with the vaccine were determined. In the experimental group, antibodies against Bordetella pertussis pertactin (anti-PRN) (112 E/mL 95% CI 89.9–139.9) and antibodies against pertussis toxin (anti-PT) (24.0 E/mL, 95% CI 18.3–31.4) were elevated in the mother before vaccination. These were higher in the umbilical cord and descended in the infant at 2 months (71.4 (95% CI 56.8–89.7 and 10.9; 95% CI 8.7–13.7, respectively). Anti-PT showed a delay in production. Tdap safety was confirmed with only mild local pain at 24 and 48 hours. Anti-PRN and anti-PT antibodies in the infant descend at 2 months of age. There is a delay in anti-PT in children of immunized mothers. Further studies are needed to elucidate its clinical significance. PMID:27686182

  17. Bacterial colonization due to increased nurse workload in an intensive care unit.

    PubMed

    Aycan, Ilker Onguc; Celen, Mustafa Kemal; Yilmaz, Ayhan; Almaz, Mehmet Selim; Dal, Tuba; Celik, Yusuf; Bolat, Esef

    2015-01-01

    The rates of multiresistant bacteria colonization or infection (MRB+) development in intensive care units are very high. The aim of this study was to determine the possible association between the risk of development of nosocomial infections and increased daily nurse workload due to understaffing in intensive care unit. We included 168 patients. Intensity of workload and applied procedures to patients were scored with the Project de Recherché en Nursing and the Omega scores, respectively. The criteria used for infections were those defined by the Centers for Disease Control. Of the 168 patients, 91 (54.2%) were female and 77 (45.8%) were male patients. The mean age of female and male was 64.9 ± 6.2 years and 63.1 ± 11.9 years, respectively. The mean duration of hospitalization in intensive care unit was 18.4 ± 6.1 days. Multiresistant bacteria were isolated from cultures of 39 (23.2%) patients. The development of MRB+ infection was correlated with length of stay, Omega 1, Omega 2, Omega 3, Total Omega, daily PRN, and Total PRN (p < 0.05). There was no correlation between development of MRB+ infection with gender, age and APACHE-II scores (p > 0.05). The risk of nosocomial infection development in an intensive care unit is directly correlated with increased nurse workload, applied intervention, and length of stay. Understaffing in the intensive care unit is an important health problem that especially affects care-needing patients. Nosocomial infection development has laid a heavy burden on the economy of many countries. To control nosocomial infection development in the intensive care unit, nurse workload, staffing level, and working conditions must be arranged. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  18. [Bacterial colonization due to increased nurse workload in an intensive care unit].

    PubMed

    Aycan, Ilker Onguc; Celen, Mustafa Kemal; Yilmaz, Ayhan; Almaz, Mehmet Selim; Dal, Tuba; Celik, Yusuf; Bolat, Esef

    2015-01-01

    the rates of multiresistant bacteria colonization or infection (MRB+) development in intensive care units are very high. The aim of this study was to determine the possible association between the risk of development of nosocomial infections and increased daily nurse workload due to understaffing in intensive care unit. we included 168 patients. Intensity of workload and applied procedures to patients were scored with the Project de Recherché en Nursing and the Omega scores, respectively. The criteria used for infections were those defined by the Centers for Disease Control. of the 168 patients, 91 (54.2%) were female and 77 (45.8%) were male patients. The mean age of female and male was 64.9±6.2 years and 63.1±11.9 years, respectively. The mean duration of hospitalization in intensive care unit was 18.4±6.1 days. Multiresistant bacteria were isolated from cultures of 39 (23.2%) patients. The development of MRB+ infection was correlated with length of stay, Omega 1, Omega 2, Omega 3, Total Omega, daily PRN, and Total PRN (p<0.05). There was no correlation between development of MRB+ infection with gender, age and Apache-II scores (p>0.05). the risk of nosocomial infection development in an intensive care unit is directly correlated with increased nurse workload, applied intervention, and length of stay. Understaffing in the intensive care unit is an important health problem that especially affects care-needing patients. Nosocomial infection development has laid a heavy burden on the economy of many countries. To control nosocomial infection development in the intensive care unit, nurse workload, staffing level, and working conditions must be arranged. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  19. Towards a method for determining age ranges from faces of juveniles on photographs.

    PubMed

    Cummaudo, M; Guerzoni, M; Gibelli, D; Cigada, A; Obertovà, Z; Ratnayake, M; Poppa, P; Gabriel, P; Ritz-Timme, S; Cattaneo, C

    2014-06-01

    The steady increase in the distribution of juvenile pornographic material in recent years strongly required valid methods for estimating the age of the victims. At the present in fact forensic experts still commonly use the assessment of sexual characteristics by Tanner staging, although they have proven to be too subjective and deceiving for age estimation. The objective of this study, inspired by a previous EU project involving Italy, Germany and Lithuania, is to verify the applicability of certain anthropometric indices of faces in order to determine age and to create a database of facial measurements on a population of children in order to improve face ageing techniques. In this study, 1924 standardized facial images in frontal view and 1921 in lateral view of individuals from 7 age groups (3-5 years, 6-8 years, 9-11 years, 12-14 years, 15-17 years, 18-20 years, 21-24 years) underwent metric analysis. Individuals were all of Caucasoid ancestry and Italian nationality. Eighteen anthropometric indices in the frontal view and five in the lateral view were then calculated from the obtained measurements. Indices showing a correlation with age were ch-ch/ex-ex, ch-ch/pu-pu, en-en/ch-ch and se-sto/ex-ex in the frontal view, se-prn/se-sn, se-prn/se-sto and se-sn/se-sto in the lateral view. All the indices increased with age except for en-en/ch-ch, without relevant differences between males and females. These results provide an interesting starting point not only for placing a photographed face in an age range but also for refining the techniques of face ageing and personal identification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Clinical Efficacy and Safety of Ranibizumab Versus Dexamethasone for Central Retinal Vein Occlusion (COMRADE C): A European Label Study.

    PubMed

    Hoerauf, Hans; Feltgen, Nicolas; Weiss, Claudia; Paulus, Eva-Maria; Schmitz-Valckenberg, Steffen; Pielen, Amelie; Puri, Pankaj; Berk, Hüsnü; Eter, Nicole; Wiedemann, Peter; Lang, Gabriele E; Rehak, Matus; Wolf, Armin; Bertelmann, Thomas; Hattenbach, Lars-Olof

    2016-09-01

    To compare the efficacy and safety of the European labels of ranibizumab 0.5 mg vs dexamethasone 0.7 mg in patients with macular edema secondary to central retinal vein occlusion (CRVO). Phase IIIb, multicenter, double-masked, randomized clinical trial. Patients were randomized (1:1) to receive either monthly ranibizumab followed by pro re nata (PRN) treatment (n = 124) or 1 sustained-release dexamethasone implant followed by PRN sham injections (n = 119). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean change in BCVA, and adverse events (AEs). Of 243 patients, 185 (76.1%) completed the study. No difference was observed in BCVA between ranibizumab and dexamethasone at months 1 and 2. From month 3 to month 6, there was significant difference in BCVA gains in favor of ranibizumab. At month 6, mean average BCVA gain was significantly higher with ranibizumab than with dexamethasone (12.86 vs 2.96 letters; difference 9.91 letters, 95% confidence interval [6.51-13.30]; P < .0001). Mean injection number of ranibizumab was 4.52. Ocular AEs were reported in more patients in the dexamethasone than in the ranibizumab group (86.6% vs 55.6%). Using the European labels, similar efficacy was observed for ranibizumab and dexamethasone at months 1 and 2. However, ranibizumab maintained its efficacy throughout the study, whereas dexamethasone declined from month 3 onward. The main limitation of the study was that dexamethasone patients received only a single treatment during the 6-month study. In clinical practice, dexamethasone retreatment may be required earlier than 6 months. Safety findings were similar to those previously reported. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study.

    PubMed

    Ogura, Yuichiro; Roider, Johann; Korobelnik, Jean-François; Holz, Frank G; Simader, Christian; Schmidt-Erfurth, Ursula; Vitti, Robert; Berliner, Alyson J; Hiemeyer, Florian; Stemper, Brigitte; Zeitz, Oliver; Sandbrink, Rupert

    2014-11-01

    To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). Randomized, double-masked, phase 3 study. A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Continuous Infusion Ketorolac for Postoperative Analgesia Following Unilateral Total Knee Arthroplasty.

    PubMed

    Schwinghammer, Amy J; Isaacs, Alex N; Benner, Rodney W; Freeman, Heather; O'Sullivan, Jacob A; Nisly, Sarah A

    2017-06-01

    Previous clinical trials have demonstrated benefit with the addition of continuous infusion (CI) ketorolac to a multimodal pain regimen in surgical patients. Data following major orthopedic surgery are minimal and conflicting. To evaluate CI ketorolac use following unilateral total knee arthroplasty (TKA) through assessment of patient-reported pain scores, opioid consumption, and safety outcomes. This was a retrospective, open-label cohort study that included patients undergoing unilateral TKA at a single-center teaching hospital. Participants were categorized into 2 study groups based on postoperative management: CI ketorolac or opioid protocol (OP). The first group received a ketorolac 30-mg bolus followed by CI 3.6 mg/h plus as-needed (PRN) opioids. The OP group received PRN narcotics in a tiered protocol. The primary end point was comparison of median pain scores. Secondary end points included opioid consumption (morphine equivalent units [MEUs]) in the first 48 hours postoperatively, length of stay, and adverse effects. Of 447 patients screened, 191 were analyzed (CI ketorolac, n = 116; OP, n = 75). Median pain scores were significantly lower in the CI ketorolac group at 48 hours postoperatively (3 [2-4] vs 3.5 [2.5-5], P = 0.033). Cumulative MEUs at 48 hours were significantly lower in the CI ketorolac group (33.9 ± 38.5 mg vs 301.6 ± 36.6 mg, P < 0.001). Patients in the CI ketorolac group experienced less respiratory depression (5.2% vs 25.3%, P < 0.001) and less naloxone administration (0% vs 8%, P = 0.002) compared with the OP group. Other adverse effects were similar among groups. Postoperative CI ketorolac improved pain control while reducing opioid consumption and adverse effects.

  3. Adaptive-passive vibration control systems for industrial applications

    NASA Astrophysics Data System (ADS)

    Mayer, D.; Pfeiffer, T.; Vrbata, J.; Melz, T.

    2015-04-01

    Tuned vibration absorbers have become common for passive vibration reduction in many industrial applications. Lightly damped absorbers (also called neutralizers) can be used to suppress narrowband disturbances by tuning them to the excitation frequency. If the resonance is adapted in-operation, the performance of those devices can be significantly enhanced, or inertial mass can be decreased. However, the integration of actuators, sensors and control electronics into the system raises new design challenges. In this work, the development of adaptive-passive systems for vibration reduction at an industrial scale is presented. As an example, vibration reduction of a ship engine was studied in a full scale test. Simulations were used to study the feasibility and evaluate the system concept at an early stage. Several ways to adjust the resonance of the neutralizer were evaluated, including piezoelectric actuation and common mechatronic drives. Prototypes were implemented and tested. Since vibration absorbers suffer from high dynamic loads, reliability tests were used to assess the long-term behavior under operational conditions and to improve the components. It was proved that the adaptive systems are capable to withstand the mechanical loads in an industrial application. Also a control strategy had to be implemented in order to track the excitation frequency. The most mature concepts were integrated into the full scale test. An imbalance exciter was used to simulate the engine vibrations at a realistic level experimentally. The neutralizers were tested at varying excitation frequencies to evaluate the tracking capabilities of the control system. It was proved that a significant vibration reduction is possible.

  4. Spontaneous modification of carbon surface with neutral red from its diazonium salts for bioelectrochemical systems.

    PubMed

    Guo, Kun; Chen, Xin; Freguia, Stefano; Donose, Bogdan C

    2013-09-15

    This study introduces a novel and simple method to covalently graft neutral red (NR) onto carbon surfaces based on spontaneous reduction of in situ generated NR diazonium salts. Immobilization of neutral red on carbon surface was achieved by immersing carbon electrodes in NR-NaNO2-HCl solution. The functionalized electrodes were characterized by cyclic voltammetry (CV), atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Results demonstrated that NR attached in this way retains high electrochemical activity and proved that NR was covalently bound to the carbon surface via the pathway of reduction of aryl diazonium salts. The NR-modified electrodes showed a good stability when stored in PBS solution in the dark. The current output of an acetate-oxidising microbial bioanode made of NR-modified graphite felts were 3.63±0.36 times higher than the unmodified electrodes, which indicates that covalently bound NR can act as electron transfer mediator to facilitate electron transfer from bacteria to electrodes. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Ebola Virus Neutralizing Antibodies Detectable in Survivors of theYambuku, Zaire Outbreak 40 Years after Infection.

    PubMed

    Rimoin, Anne W; Lu, Kai; Bramble, Matthew S; Steffen, Imke; Doshi, Reena H; Hoff, Nicole A; Mukadi, Patrick; Nicholson, Bradly P; Alfonso, Vivian H; Olinger, Gerrard; Sinai, Cyrus; Yamamoto, Lauren K; Ramirez, Christina M; Okitolonda Wemakoy, Emile; Kebela Illunga, Benoit; Pettitt, James; Logue, James; Bennett, Richard S; Jahrling, Peter; Heymann, David L; Piot, Peter; Muyembe-Tamfum, Jean Jacques; Hensley, Lisa E; Simmons, Graham

    2018-01-04

    The first reported outbreak of Ebola virus disease occurred in 1976 in Yambuku, Democratic Republic of Congo. Antibody responses in survivors 11 years after infection have been documented. However, this report is the first characterization of anti-Ebola virus antibody persistence and neutralization capacity 40 years after infection. Using ELISAs we measured survivor's immunological response to Ebola virus Zaire (EBOV) glycoprotein and nucleoprotein, and assessed VP40 reactivity. Neutralization of EBOV was measured using a pseudovirus approach and plaque reduction neutralization test with live EBOV. Some survivors from the original EBOV outbreak still harbor antibodies against all 3 measures. Interestingly, a subset of these survivors' serum antibodies could still neutralize live virus 40 years postinitial infection. These data provide the longest documentation of both anti-Ebola serological response and neutralization capacity within any survivor cohort, extending the known duration of response from 11 years postinfection to at least 40 years after symptomatic infection. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  6. Highly selective and active CO2 reduction electrocatalysts based on cobalt phthalocyanine/carbon nanotube hybrid structures

    PubMed Central

    Zhang, Xing; Wu, Zishan; Zhang, Xiao; Li, Liewu; Li, Yanyan; Xu, Haomin; Li, Xiaoxiao; Yu, Xiaolu; Zhang, Zisheng; Liang, Yongye; Wang, Hailiang

    2017-01-01

    Electrochemical reduction of carbon dioxide with renewable energy is a sustainable way of producing carbon-neutral fuels. However, developing active, selective and stable electrocatalysts is challenging and entails material structure design and tailoring across a range of length scales. Here we report a cobalt-phthalocyanine-based high-performance carbon dioxide reduction electrocatalyst material developed with a combined nanoscale and molecular approach. On the nanoscale, cobalt phthalocyanine (CoPc) molecules are uniformly anchored on carbon nanotubes to afford substantially increased current density, improved selectivity for carbon monoxide, and enhanced durability. On the molecular level, the catalytic performance is further enhanced by introducing cyano groups to the CoPc molecule. The resulting hybrid catalyst exhibits >95% Faradaic efficiency for carbon monoxide production in a wide potential range and extraordinary catalytic activity with a current density of 15.0 mA cm−2 and a turnover frequency of 4.1 s−1 at the overpotential of 0.52 V in a near-neutral aqueous solution. PMID:28272403

  7. The effects of dissociation on information processing for analogue trauma and neutral stimuli: a laboratory study.

    PubMed

    Olsen, Shira A; Beck, J Gayle

    2012-01-01

    This study investigated the effects of high and low levels of dissociation on information processing for analogue trauma and neutral stimuli. Fifty-four undergraduate females who reported high and low levels of trait dissociation were presented with two films, one depicting traumatic events, the other containing neutral material. Participants completed a divided attention task (yielding a proxy measure of attention), as well as explicit memory (free-recall) and implicit memory (word-stem completion) tasks for both films. Results indicated that the high DES group showed less attention and had poorer recall for the analogue trauma stimuli, relative to the neutral stimuli and the low DES group. These findings suggest that high levels of trait dissociation are associated with reductions in attention and memory for analogue trauma stimuli, relative to neutral stimuli and relative to low trait dissociation. Implications for the role of cognitive factors in the etiology of negative post-trauma responses are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Photoinactivation of Latent Herpes Simplex Virus in Rabbit Kidney Cells

    PubMed Central

    Kelleher, J. J.; Varani, J.

    1976-01-01

    The photoinactivation of actively and nonactively growing herpes simplex virus by neutral red and proflavine was studied in rabbit kidney cells. Active virus growth was inhibited by both dyes under conditions which did not destroy the cells. Neutral red caused a much greater inhibition than proflavine. Neutral red also caused a reduction in the reactivation rate of latent virus when the infected cells were treated during the latent period. In the treated cultures that did reactivate virus, the average length of the latent period was increased over the control value. Proflavine treatment did not reduce the rate of reactivation of latent virus and did not increase the average latent period of the treated cultures. PMID:185948

  9. The effect of subauroral polarization streams on the mid-latitude thermospheric disturbance neutral winds: a universal time effect

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Zhang, Kedeng; Zheng, Zhichao; Ridley, Aaron James

    2018-03-01

    The temporal and spatial variations in thermospheric neutral winds at an altitude of 400 km in response to subauroral polarization streams (SAPS) are investigated using global ionosphere and thermosphere model simulations under the southward interplanetary magnetic field (IMF) condition. During SAPS periods the westward neutral winds in the subauroral latitudes are greatly strengthened at dusk. This is due to the ion drag effect, through which SAPS can accelerate neutral winds in the westward direction. The new findings are that for SAPS commencing at different universal times, the strongest westward neutral winds exhibit large variations in amplitudes. The ion drag and Joule heating effects are dependent on the solar illumination, which exhibit UT variations due to the displacement of the geomagnetic and geographic poles. With more sunlight, stronger westward neutral winds can be generated, and the center of these neutral winds shifts to a later magnetic local time than neutral winds with less solar illumination. In the Northern Hemisphere and Southern Hemisphere, the disturbance neutral wind reaches a maximum at 18:00 and 04:00 UT, and a minimum at 04:00 and 16:00 UT, respectively. There is a good correlation between the neutral wind velocity and cos0.5(SZA) (solar zenith angle). The reduction in the electron density and enhancement in the air mass density at an altitude of 400 km are strongest when the maximum solar illumination collocates with the SAPS. The correlation between the neutral wind velocity and cos0.5(SZA) is also good during the northward IMF period. The effect of a sine-wave oscillation of SAPS on the neutral wind also exhibits UT variations in association with the solar illumination.

  10. ERP evidence for selective drop in attentional costs in uncertain environments: challenging a purely premotor account of covert orienting of attention.

    PubMed

    Lasaponara, Stefano; Chica, Ana B; Lecce, Francesca; Lupianez, Juan; Doricchi, Fabrizio

    2011-07-01

    Several studies have proved that the reliability of endogenous spatial cues linearly modulates the reaction time advantage in the processing of targets at validly cued vs. invalidly cued locations, i.e. the "validity effect". This would imply that with non-predictive cues, no "validity effect" should be observed. However, contrary to this prediction, one could hypothesize that attentional benefits by valid cuing (i.e. the RT advantage for validly vs. neutrally cued targets) can still be maintained with non-predictive cues, if the brain were endowed with mechanisms allowing the selective reduction in costs of reorienting from invalidly cued locations (i.e. the reduction of the RT disadvantage for invalidly vs. neutrally cued targets). This separated modulation of attentional benefits and costs would be adaptive in uncertain contexts where cues predict at chance level the location of targets. Through the joint recording of manual reaction times and event-related cerebral potentials (ERPs), we have found that this is the case and that relying on non-predictive endogenous cues results in abatement of attentional costs and the difference in the amplitude of the P1 brain responses evoked by invalidly vs. neutrally cued targets. In contrast, the use of non-predictive cues leaves unaffected attentional benefits and the difference in the amplitude of the N1 responses evoked by validly vs. neutrally cued targets. At the individual level, the drop in costs with non-predictive cues was matched with equivalent lateral biases in RTs to neutrally and invalidly cued targets presented in the left and right visual field. During the cue period, the drop in costs with non-predictive cues was preceded by reduction of the Early Directing Attention Negativity (EDAN) on posterior occipital sites and by enhancement of the frontal Anterior Directing Attention Negativity (ADAN) correlated to preparatory voluntary orienting. These findings demonstrate, for the first time, that the segregation of mechanisms regulating attentional benefits and costs helps efficiency of orienting in "uncertain" visual spatial contexts characterized by poor probabilistic association between cues and targets. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Kinetics of reduction of plutonium(VI) and neptunium(VI) by sulfide in neutral and alkaline solutions

    USGS Publications Warehouse

    Nash, K.L.; Cleveland, J.M.; Sullivan, J.C.; Woods, M.

    1986-01-01

    The rate of reduction of plutonium(VI) and neptunium(VI) by bisulfide ion in neutral and mildly alkaline solutions has been investigated by the stopped-flow technique. The reduction of both of these ions to the pentavalent oxidation state appears to occur in an intramolecular reaction involving an unusual actinide(VI)-hydroxide-bisulfide complex. For plutonium the rate of reduction is 27.4 (??4.1) s-1 at 25??C with ??H* = +33.2 (??1.0) kJ/mol and ??S* = -106 (??4) J/(mol K). The apparent stability constant for the transient complex is 4.66 (??0.94) ?? 103 M-1 at 25??C with associated thermodynamic parameters of ??Hc = +27.7 (??0.4) kJ/mol and ??Sc = +163 (??2) J/(mol K). The corresponding rate and stability constants are determined for the neptunium system at 25??C (k3 = 139 (??30) s-1, Kc. = 1.31 (??0.32) ?? 103 M-1), but equivalent parameters cannot be determined at reduced temperatures. The reaction rate is decreased by bicarbonate ion. At pH > 10.5, a second reaction mechanism, also involving a sulfide complex, is indicated. ?? 1986 American Chemical Society.

  12. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys.

    PubMed

    Barouch, Dan H; Liu, Jinyan; Li, Hualin; Maxfield, Lori F; Abbink, Peter; Lynch, Diana M; Iampietro, M Justin; SanMiguel, Adam; Seaman, Michael S; Ferrari, Guido; Forthal, Donald N; Ourmanov, Ilnour; Hirsch, Vanessa M; Carville, Angela; Mansfield, Keith G; Stablein, Donald; Pau, Maria G; Schuitemaker, Hanneke; Sadoff, Jerald C; Billings, Erik A; Rao, Mangala; Robb, Merlin L; Kim, Jerome H; Marovich, Mary A; Goudsmit, Jaap; Michael, Nelson L

    2012-01-04

    Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.

  13. Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults.

    PubMed

    Miyaji, Karina Takesaki; Avelino-Silva, Vivian Iida; Simões, Marisol; Freire, Marcos da Silva; Medeiros, Carlos Roberto de; Braga, Patrícia Emilia; Neves, Maria Angélica Acalá; Lopes, Marta Heloisa; Kallas, Esper Georges; Sartori, Ana Marli Christovam

    2017-04-03

    The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged  60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. previously vaccinated healthy persons aged  18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. 46 persons aged  60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

  14. Single-Chain Fv-Based Anti-HIV Proteins: Potential and Limitations

    PubMed Central

    West, Anthony P.; Galimidi, Rachel P.; Gnanapragasam, Priyanthi N. P.

    2012-01-01

    The existence of very potent, broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) offers the potential for prophylaxis against HIV-1 infection by passive immunization or gene therapy. Both routes permit the delivery of modified forms of IgGs. Smaller reagents are favored when considering ease of tissue penetration and the limited capacities of gene therapy vectors. Immunoadhesin (single-chain fragment variable [scFv]-Fc) forms of IgGs are one class of relatively small reagent that has been explored for delivery by adeno-associated virus. Here we investigated the neutralization potencies of immunoadhesins compared to those of their parent IgGs. For the antibodies VRC01, PG9, and PG16, the immunoadhesins showed modestly reduced potencies, likely reflecting reduced affinities compared to those of the parent IgG, and the VRC01 immunoadhesin formed dimers and multimers with reduced neutralization potencies. Although scFv forms of neutralizing antibodies may exhibit affinity reductions, they provide a means of building reagents with multiple activities. Attachment of the VRC01 scFv to PG16 IgG yielded a bispecific reagent whose neutralization activity combined activities from both parent antibodies. Although the neutralization activity due to each component was partially reduced, the combined reagent is attractive since fewer strains escaped neutralization. PMID:22013046

  15. Quantum-chemical studies on the favored and rare tautomers of neutral and redox adenine.

    PubMed

    Raczyńska, Ewa D; Makowski, Mariusz; Zientara-Rytter, Katarzyna; Kolczyńska, Katarzyna; Stępniewski, Tomasz M; Hallmann, Małgorzata

    2013-02-21

    All possible twenty-three prototropic tautomers of neutral and redox adenine (nine amine and fourteen imine forms, including geometric isomerism of the exo ═NH group) were examined in vacuo {DFT(B3LYP)/6-311+G(d,p)}. The NH → NH conversions as well as those usually omitted, NH → CH and CH → CH, were considered. An interesting change of the tautomeric preference occurs when proceeding from neutral to reduced adenine. One-electron reduction favors the nonaromatic amine C8H-N10H tautomer. This tautomeric preference is similar to that (C2H) for reduced imidazole. Water molecules (PCM model) seem to not change this trend. They influence solely the relative energies. The DFT vertical detachment energy in the gas phase is positive for each tautomer, e.g., 0.03 eV for N9H-N10H and 1.84 eV for C8H-N10H. The DFT adiabatic electron affinity for the favored process, neutral N9H-N10H → reduced C8H-N10H (ground states), is equal to 0.18 eV at 0 K (ZPE included). One-electron oxidation does not change the tautomeric preference in the gas phase. The aromatic amine N9H-N10H tautomer is favored for the oxidized molecule similarly as for the neutral one. The DFT adiabatic ionization potential for the favored process, neutral N9H-N10H → oxidized N9H-N10H (ground states), is equal to 8.12 eV at 0 K (ZPE included). Water molecules (PCM model) seem to influence solely the composition of the tautomeric mixture and the relative energies. They change the energies of the oxidation and reduction processes by ca. 2 eV.

  16. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Xinsheng, E-mail: xzhang@iavi.org; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY; Wallace, Olivia L.

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions,more » which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.« less

  17. Comparison of plantar pressures and contact area between normal and cavus foot.

    PubMed

    Fernández-Seguín, Lourdes M; Diaz Mancha, Juan Antonio; Sánchez Rodríguez, Raquel; Escamilla Martínez, Elena; Gómez Martín, Beatriz; Ramos Ortega, Javier

    2014-02-01

    In pes cavus, the medial longitudinal arch elevation reduces the contact surface area and consequently increases the corresponding plantar pressure measurements. This poor distribution of loads may produce associated pathology and pain in this or other areas of the body. Normal reference values need to be established in order to determine which patterns are prone to pathology. To compare the plantar pressures and weight-bearing surface in a population with pes cavus to a population with neutral feet. The sample comprised 68 adults, 34 with pes cavus and 34 with neutral feet. The Footscan USB Gait Clinical System(®) was used as a platform to measure the total contact area and plantar pressure under the forefoot, midfoot, hindfoot, each metatarsal head, and the overall metatarsal area. A statistical analysis of the data was performed using Student's t-test for independent samples. The pes cavus subjects showed a significant reduction in their weight-bearing area [neutral feet: 165.04 ( ± 20.68) cm(2); pes cavus: 118.26 ( ± 30.31) cm(2); p < 0.001] and significantly increased pressures under all zones of the forefoot except the fifth metatarsal [metatarsal pressure: in neutral feet 503,797 ( ± 9.32) kPa; in pes cavus 656.12 ( ± 22.39) kPa; p < 0.001]. Compared to neutral feet, pes cavus feet show a reduction in total contact surface and the load under the first toe. A significant increase is present in the load under the metatarsal areas, but the relative distribution of this load is similar in both groups. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Development and evaluation of a computerized intervention for low distress tolerance and its effect on performance on a neutralization task.

    PubMed

    Macatee, Richard J; Cougle, Jesse R

    2015-09-01

    A growing body of research has linked high distress intolerance (DI) to obsessions, but not other OCD symptom domains. However, existing research is correlational. Experimental studies are needed, but brief methods for reducing DI are lacking. To address these gaps in the literature, a brief, computerized intervention aimed at reducing DI was developed to determine if changing DI affected obsessional phenomena. Individuals reporting high DI were randomized to a treatment or waitlist control group (N = 53). Individuals in the treatment group received the DI treatment (i.e., a 2 h computerized intervention) over two weeks, and then underwent a post-assessment in which DI and obsession-relevant phenomena were measured. Individuals in the control group only received the post-assessment. Analyses revealed a greater reduction in self-reported DI on one measure and smaller decreases in behavioral DI in the intervention condition relative to the waitlist condition, as well as lower in-vivo urges to neutralize an intrusive thought; however, anxious reactivity to the intrusion and neutralization behavior were not affected. Further, bootstrapping analyses revealed that reductions in DI mediated the effect of the intervention on neutralization urges. A clinical sample and placebo control condition were not used. These results provide experimental evidence for the role of DI in obsessional phenomena, specifically in affecting urges to neutralize intrusions, findings consistent with negative reinforcement models of DI. Further, results revealed that DI can be reduced with a brief, computerized intervention, which has important implications for future experimental research and treatment development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

    Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

  20. Fast-ion transport in low density L-mode plasmas at TCV using FIDA spectroscopy and the TRANSP code

    NASA Astrophysics Data System (ADS)

    Geiger, B.; Karpushov, A. N.; Duval, B. P.; Marini, C.; Sauter, O.; Andrebe, Y.; Testa, D.; Marascheck, M.; Salewski, M.; Schneider, P. A.; the TCV Team; the EUROfusion MST1 Team

    2017-11-01

    Experiments with the new neutral beam injection source of TCV have been performed with high fast-ion fractions (>20%) that exhibit a clear reduction of the loop voltage and a clear increase of the plasma pressure in on- and off-axis heating configurations. However, good quantitative agreement between the experimental data and TRANSP predictions is only found when including strong additional fast-ion losses. These losses could in part be caused by turbulence or MHD activity as, e.g. high frequency modes near the frequency of toroidicity induced Alfvén eignmodes are observed. In addition, a newly installed fast-ion D-alpha (FIDA) spectroscopy system measures strong passive radiation and, hence, indicates the presence of high background neutral densities such that charge-exchange losses are substantial. Also the active radiation measured with the FIDA diagnostic, as well as data from a neutral particle analyzer, suggest strong fast-ion losses and large neutral densities. The large neutral densities can be justified since high electron temperatures (3-4 keV), combined with low electron densities (about 2× {10}19 m-3) yield long mean free paths of the neutrals which are penetrating from the walls.

  1. Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

    DOE PAGES

    Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.; ...

    2017-01-27

    Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

  2. 40 CFR 417.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing by Fatty Acid Neutralization Subcategory § 417.32 Effluent limitations...

  3. 40 CFR 417.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing by Fatty Acid Neutralization Subcategory § 417.32 Effluent limitations...

  4. 40 CFR 417.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing by Fatty Acid Neutralization Subcategory § 417.32 Effluent limitations...

  5. 40 CFR 417.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing by Fatty Acid Neutralization Subcategory § 417.32 Effluent limitations...

  6. 40 CFR 417.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing by Fatty Acid Neutralization Subcategory § 417.32 Effluent limitations...

  7. The Impact of Weight Gain on Motivation, Compliance, and Metabolic Control in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Pi-Sunyer, F. Xavier

    2010-01-01

    Patients with type 2 diabetes, approximately 85% of whom are overweight or obese, often have an increased incidence of cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia. Both type 2 diabetes and obesity are independent risk factors for CVD. Unfortunately, many therapies aimed at maintaining and improving glucose control are associated with weight gain. Among the older antidiabetes agents, most, including the insulin secretagogues and sensitizers, can lead to weight gain, except for metformin, which is weight-neutral. Among the newer agents, the dipeptidyl peptidase-4 inhibitors generally are weight-neutral in addition to lowering glucose, while the glucagon-like peptide–1 receptor agonists lead to weight reduction. Patients with type 2 diabetes are at an increased risk for both diabetes-and CV-related outcomes, and weight reduction is an important component of diabetes management. Weight gain in patients with type 2 diabetes can contribute to patient frustration and may negatively impact their compliance to therapeutic regimens. The selection of antidiabetes agents that not only improve glucose control but reduce or have a neutral effect on weight with beneficial effects on lipids are ideal options for managing patients with type 2 diabetes. PMID:19820278

  8. Pressure as a limit to bloater (Coregonus hoyi) vertical migration

    USGS Publications Warehouse

    TeWinkel, Leslie M.; Fleischer, Guy W.

    1998-01-01

    Observations of bloater vertical migration showed a limit to the vertical depth changes that bloater experience. In this paper, we conducted an analysis of maximum differences in pressure encountered by bloater during vertical migration. Throughout the bottom depths studied, bloater experienced maximum reductions in swim bladder volume equal to approximately 50-60% of the volume in midwater. The analysis indicated that the limit in vertical depth change may be related to a maximum level of positive or negative buoyancy for which bloater can compensate using alternative mechanisms such as hydrodynamic lift. Bloater may be limited in the extent of migration by either their depth of neutral buoyancy or the distance above the depth of neutral buoyancy at which they can still maintain their position in the water column. Although a migration limit for the bloater population was evident, individual distances of migration varied at each site. These variations in migration distances may indicate differences in depths of neutral buoyancy within the population. However, in spite of these variations, the strong correlation between shallowest depths of migration and swim bladder volume reduction across depths provides evidence that hydrostatic pressure limits the extent of daily vertical movement in bloater.

  9. Durable rechargeable zinc-air batteries with neutral electrolyte and manganese oxide catalyst

    NASA Astrophysics Data System (ADS)

    Sumboja, Afriyanti; Ge, Xiaoming; Zheng, Guangyuan; Goh, F. W. Thomas; Hor, T. S. Andy; Zong, Yun; Liu, Zhaolin

    2016-11-01

    Neutral chloride-based electrolyte and directly grown manganese oxide on carbon paper are used as the electrolyte and air cathode respectively for rechargeable Zn-air batteries. Oxygen reduction and oxygen evolution reactions on manganese oxide show dependence of activities on the pH of the electrolyte. Zn-air batteries with chloride-based electrolyte and manganese oxide catalyst exhibit satisfactory voltage profile (discharge and charge voltage of 1 and 2 V at 1 mA cm-2) and excellent cycling stability (≈90 days of continuous cycle test), which is attributed to the reduced carbon corrosion on the air cathode and decreased carbonation in neutral electrolyte. This work describes a robust electrolyte system that improves the cycle life of rechargeable Zn-air batteries.

  10. Detection of measles, mumps and rubella viruses by immuno-colorimetric assay and its application in focus reduction neutralization tests.

    PubMed

    Vaidya, Sunil R; Kumbhar, Neelakshi S; Bhide, Vandana S

    2014-12-01

    Measles, mumps and rubella are vaccine-preventable diseases; however limited epidemiological data are available from low-income or developing countries. Thus, it is important to investigate the transmission of these viruses in different geographical regions. In this context, a cell culture-based rapid and reliable immuno-colorimetric assay (ICA) was established and its utility studied. Twenty-three measles, six mumps and six rubella virus isolates and three vaccine strains were studied. Detection by ICA was compared with plaque and RT-PCR assays. In addition, ICA was used to detect viruses in throat swabs (n = 24) collected from patients with suspected measles or mumps. Similarly, ICA was used in a focus reduction neutralization test (FRNT) and the results compared with those obtained by a commercial IgG enzyme immuno assay. Measles and mumps virus were detected 2 days post-infection in Vero or Vero-human signaling lymphocytic activation molecule cells, whereas rubella virus was detected 3 days post-infection in Vero cells. The blue stained viral foci were visible by the naked eye or through a magnifying glass. In conclusion, ICA was successfully used on 35 virus isolates, three vaccine strains and clinical specimens collected from suspected cases of measles and mumps. Furthermore, an application of ICA in a neutralization test (i.e., FRNT) was documented; this may be useful for sero-epidemiological, cross-neutralization and pre/post-vaccine studies. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  11. Optimized plasma etch window of block copolymers and neutral brush layers for enhanced direct self-assembly pattern transfer into a hardmask layer

    NASA Astrophysics Data System (ADS)

    Brakensiek, Nickolas; Xu, Kui; Sweat, Daniel; Hockey, Mary Ann

    2018-03-01

    Directed self-assembly (DSA) of block copolymers (BCPs) is one of the most promising patterning technologies for future lithography nodes. However, one of the biggest challenges to DSA is the pattern transfer by plasma etching from BCP to hardmask (HM) because the etch selectivity between BCP and neutral brush layer underneath is usually not high enough to enable robust pattern transfer. This paper will explore the plasma etch conditions of both BCPs and neutral brush layers that may improve selectivity and allow a more robust pattern transfer of DSA patterns into the hardmask layer. The plasma etching parameters that are under investigation include the selection of oxidative or reductive etch chemistries, as well as plasma gas pressure, power, and gas mixture fractions. Investigation into the relationship between BCP/neutral brush layer materials with varying chemical compositions and the plasma etching conditions will be highlighted. The culmination of this work will demonstrate important etch parameters that allow BCPs and neutral brush layers to be etched into the underlying hardmask layer with a large process window.

  12. Global Model of Time-Modulated Electronegative Discharges for Neutral Radical and Electron Temperature Control

    NASA Astrophysics Data System (ADS)

    Kim, Sungjin; Lieberman, M. A.; Lichtenberg, A. J.

    2003-10-01

    Control and reduction of neutral radical flux/ion flux ratio and electron temperature Te is required for next generation etching in the microelectronics industry. We investigate time-modulated power for these purposes using a volume-averaged (global) oxygen discharge model, We consider pressures of 10-50 mTorr and plasma densities of 10^10-10^11 cm-3. In this regime, the discharge is found to be weakly electronegative. The modulation period and the duty ratio (on-time/period) are varied to determine the optimum conditions for reduction of FR= O-atom flux/ion flux and T_e. Two chambers with different height/diameter ratios (<< 1, and unity) are examined to determine the influence of the surface-area/volume ratio. At a fixed duty ratio, both FR and Te are found to have minimum values as the pulse period is varied, with the minimum value decreasing as the duty ratio decreases. Significant reductions in FR and Te are found. Support provided by Lam Research, NSF Grant ECS-0139956, California industries, and UC-SMART Contract SM99-10051.

  13. HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

    PubMed Central

    Amador-Cañizares, Yalena; Martínez-Donato, Gillian; Álvarez-Lajonchere, Liz; Vasallo, Claudia; Dausá, Mariacarla; Aguilar-Noriega, Daylen; Valenzuela, Carmen; Raíces, Ivette; Dubuisson, Jean; Wychowski, Czeslaw; Cinza-Estévez, Zurina; Castellanos, Marlén; Núñez, Magdalys; Armas, Anny; González, Yaimé; Revé, Ismariley; Guerra, Ivis; Pérez Aguiar, Ángel; Dueñas-Carrera, Santiago

    2014-01-01

    AIM: To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230. METHODS: CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided. RESULTS: From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response. CONCLUSION: CIGB-230, combined with IFN-α-based therapy, modifies the immune response in chronic patients. The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV. PMID:24415868

  14. Phage display antibodies against ectromelia virus that neutralize variola virus: Selection and implementation for p35 neutralizing epitope mapping.

    PubMed

    Khlusevich, Yana; Matveev, Andrey; Baykov, Ivan; Bulychev, Leonid; Bormotov, Nikolai; Ilyichev, Ivan; Shevelev, Georgiy; Morozova, Vera; Pyshnyi, Dmitrii; Tikunova, Nina

    2018-04-01

    In this study, five phage display antibodies (pdAbs) against ectromelia virus (ECTV) were selected from vaccinia virus (VACV)-immune phage-display library of human single chain variable fragments (scFv). ELISA demonstrated that selected pdAbs could recognize ECTV, VACV, and cowpox virus (CPXV). Atomic force microscopy visualized binding of the pdAbs to VACV. Three of the selected pdAbs neutralized variola virus (VARV) in the plaque reduction neutralization test. Western blot analysis of ECTV, VARV, VACV, and CPXV proteins indicated that neutralizing pdAbs bound orthopoxvirus 35 kDa proteins, which are encoded by the open reading frames orthologous to the ORF H3L in VACV. The fully human antibody fh1A was constructed on the base of the VH and VL domains of pdAb, which demonstrated a dose-dependent inhibition of plaque formation after infection with VARV, VACV, and CPXV. To determine the p35 region responsible for binding to neutralizing pdAbs, a panel of truncated p35 proteins was designed and expressed in Escherichia coli cells, and a minimal p35 fragment recognized by selected neutralizing pdAbs was identified. In addition, peptide phage-display combinatorial libraries were applied to localize the epitope. The obtained data indicated that the epitope responsible for recognition by the neutralizing pdAbs is discontinuous and amino acid residues located within two p35 regions, 15-19 aa and 232-237 aa, are involved in binding with neutralizing anti-p35 antibodies. Copyright © 2018. Published by Elsevier B.V.

  15. The neutralizing role of IgM during early Chikungunya virus infection

    PubMed Central

    Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

    2017-01-01

    The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

  16. Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test.

    PubMed

    Lukman, Nurhayati; Salim, Gustiani; Kosasih, Herman; Susanto, Nugroho Harry; Parwati, Ida; Fitri, Silvita; Alisjahbana, Bachti; Widjaja, Susana; Williams, Maya

    2016-01-01

    Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73).

  17. Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability

    PubMed Central

    Chen, Zhe; Cave, Kyle R.

    2013-01-01

    Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention. PMID:23761777

  18. Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability.

    PubMed

    Chen, Zhe; Cave, Kyle R

    2013-01-01

    Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention.

  19. Characterization of iminothiosulfine-type ions [HNCS 2] rad +/ rad - and their neutral counterparts by mass spectrometry and computational chemistry

    NASA Astrophysics Data System (ADS)

    Vivekananda, S.; Raghunath, P.; Bhanuprakash, K.; Srinivas, R.; Trikoupis, Moschoula A.; Terlouw, Johan K.

    2000-12-01

    Electron ionization of rhodanine yields iminothiosulfine ions H- N C- S- Srad + , 1brad + , which readily communicate with the higher energy cyclic isomer H- N CS2rad + , 1arad + . CBS-QB3 and G AUSSIAN-2 model chemistries predict that one electron reduction reverses the stability order but that the (singlet) neutrals remain connected via a negligible energy barrier. Neutralization-reionization (NR) experiments demonstrate that singlet 1a and its heterocumulene isomer 1b are stable species in the gas-phase. However, the co-generated triplet species readily dissociate into 3S2rad + + HNC. Confirmatory experimental evidence comes from charge reversal (CR) and NR experiments on the cyclic anion H- N CS2rad - , 1arad - .

  20. Optimization and Validation of the TZM-bl Assay for Standardized Assessments of Neutralizing Antibodies Against HIV-1

    PubMed Central

    Sarzotti-Kelsoe, Marcella; Bailer, Robert T; Turk, Ellen; Lin, Chen-li; Bilska, Miroslawa; Greene, Kelli M.; Gao, Hongmei; Todd, Christopher A.; Ozaki, Daniel A.; Seaman, Michael S.; Mascola, John R.; Montefiori, David C.

    2014-01-01

    The TZM-bl assay measures antibody-mediated neutralization of HIV-1 as a function of reductions in HIV-1 Tat-regulated firefly luciferase (Luc) reporter gene expression after a single round of infection with Env-pseudotyped viruses. This assay has become the main endpoint neutralization assay used for the assessment of preclinical and clinical trial samples by a growing number of laboratories worldwide. Here we present the results of the formal optimization and validation of the TZM-bl assay, performed in compliance with Good Clinical Laboratory Practice (GCLP) guidelines. The assay was evaluated for specificity, accuracy, precision, limits of detection and quantitation, linearity, range and robustness. The validated manual TZM-bl assay was also adapted, optimized and qualified to an automated 384-well format. PMID:24291345

  1. Hospice Use and Pain Management in Elderly Nursing Home Residents With Cancer.

    PubMed

    Hunnicutt, Jacob N; Tjia, Jennifer; Lapane, Kate L

    2017-03-01

    Pain management is suboptimal in nursing homes. To estimate the extent to which receipt of hospice in nursing homes (NHs) increases the receipt of pain management for residents with cancer at the end of life. Study participants included Medicare beneficiaries with cancer who were NH residents in the last 90 days of life in 2011-2012 (n = 78,160). Residents in pain on hospice were matched to like residents without hospice by facility, type of pain assessment (self-report/staff assessment), and weeks until death (9064 matched strata, 16,968 unique residents). Minimum Data Set 3.0 provided information on residents' pain prevalence and receipt of pain management (scheduled analgesics, as needed [pro re nata {PRN}] medication, nonpharmacologic interventions). We developed conditional logistic models to estimate the association between hospice use and pain management, stratified by self-reported and staff-assessed pain. We found that pain prevalence was higher in residents using hospice versus those without hospice (e.g., residents who self-reported pain: hospice: 59.9%, 95% CIs = 59.3%-60.5%; nonhospice: 50.0%, 95% CI = 49.4%-50.6%). In matched analyses, untreated pain was uncommon (self-reported pain: 2.9% and 5.6% in hospice users and nonusers, respectively). Hospice use was associated with receipt of scheduled analgesics (self-reported: adjusted odds ratio = 1.85, 95% CI = 1.73-1.971) and PRN medication (self-reported: adjusted odds ratio = 1.31, 95% CI = 1.20-1.43). Pain prevalence and the association between hospice and pain management were similar in residents with staff-assessed pain. Untreated pain at the end of life among residents with cancer in NHs is unusual. Hospice is associated with increased pain management among those with documented pain. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  2. Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain

    PubMed Central

    Webster, Lynn R; Brenner, Darren M; Barrett, Andrew C; Paterson, Craig; Bortey, Enoch; Forbes, William P

    2015-01-01

    Background Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia. Methods Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks. In the OLT, patients (n=1,034) on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks. Results Minimal fluctuations of median morphine equivalent dose from baseline (BL) were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d), RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0) and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d). No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1) of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, −0.2 to 0.1). Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all). Conclusion Methylnaltrexone did not affect opioid-mediated analgesia in patients with chronic noncancer pain and OIC. PMID:26586963

  3. A Greek family with a follicular variant of familial papillary thyroid carcinoma: TCO, MNG1, fPTC/PRN, and NMTC1 excluded as susceptibility loci.

    PubMed

    Tsilchorozidou, Tasoula; Vafiadou, Eleni; Yovos, John G; Romeo, Giovani; McKay, James; Lesueur, Fabienne; Bonora, Elena

    2005-12-01

    The familial form of nonmedullary thyroid carcinoma (FNMTC) has been recognized as a distinct clinical entity and is characterized by multifocality and a more severe phenotype than its sporadic counterpart. The majority of FNMTC pedigrees are small in size, show variable modes of inheritance, and may present with a variety of additional benign thyroid disorders. The existence of marked phenotypic differences between FNMTC families suggests that there is genetic heterogeneity. Recent studies have mapped a susceptibility locus for FNMTC at 2q21. This locus appears particular relevant to families with at least one case of the follicular variant of papillary thyroid cancer (fvPTC). We describe the clinical and pathologic characteristics of a large three-generation fPTC kindred, with two of the four PTC patients presented with the follicular variant of PTC. It is of interest the occurrence of PTC in three siblings within a period of 3 years. In addition, multinodular goiter (MNG) was diagnosed in seven individuals, lymphocytic thyroiditis in four, while one diagnosed with a benign adenoma. From the PTC patients, one had MNG and fvPTC, one MNG, lymphocytic thyroiditis and papillary pattern of PTC, one lymphocytic thyroiditis and fvPTC, and one MNG and papillary pattern of PTC. The inheritance pattern was autosomal dominant with incomplete penetrance and women were affected more frequently than men. Considering all PTC-affected individuals, the limit of detection (LOD) score we got for this family on 2q21 was 0.5. The low LOD score is caused by a PTC patient who does not share the affected haplotype, suggesting that maybe a new locus for PTC predisposition is present in this kindred. Linkage analysis also excluded TCO, MNG, and fPTC/PRN as susceptibility loci to FNMTC in this family.

  4. [Clinical parameters of patients with neovascular age-related macular degeneration : Longterm treatment results of an outpatient clinic].

    PubMed

    Wassel, S; Tsompanidi, E; Tahmaz, E; Hörster, B; Hoerster, R

    2018-05-22

    The clinical outcome of neovascular age-related macular degeneration (nAMD) depends on constant follow-up and consistent treatment. Data about the long-term course of intensive anti-vascular endothelial growth factor (VEGF) therapy from outpatient clinics are rare. The aim of the study was to characterize a population of nAMD patients with long-term follow-up and intensive anti-VEGF therapy. In a supra-regional outpatient clinic, we retrospectively identified patients who had received at least 30 intravitreal anti-VEGF injections and were followed for at least 4 years. All patients received an optical coherence tomography(OCT)-controlled Pro-Re-Nata (PRN) therapy regimen according to German guidelines. We identified 43 patients. Visual acuity at baseline was 0.44 ± 0.24 (1.0-0.1) logMAR. At the end of the follow-up period, visual acuity was 0.63 ± 3.6 (1.3-0.1) logMAR. Patients received a mean of 36.3 ± 8.0 (30-62) injections and were followed for a mean of 6.1 ± 1.8 (4-12) years. They received 6.12 ± 1.5 (3.1-9.9) injections per year. The number of injections in treatment-year one was with 3.67 ± 1.9 (1-8) significantly lower than the mean (p < 0.0001). Despite intensive PRN therapy, visual acuity slowly decreased over time. The mean number of injections was comparable to that of prospective studies. The low number of injections in treatment-year 1 may have been due to a lack of experience with the new treatment agents. The slow decrease in visual acuity in clinical routine as opposed to clinical studies may be attributed to a delay between occurrence of disease activity and treatment.

  5. Nitrogen-neutrality: a step towards sustainability

    NASA Astrophysics Data System (ADS)

    Leip, Adrian; Leach, Allison; Musinguzi, Patrick; Tumwesigye, Trust; Olupot, Giregon; Tenywa, John Stephen; Mudiope, Joseph; Hutton, Olivia; Cordovil, Claudia M. d. S.; Bekunda, Mateete; Galloway, James

    2014-11-01

    We propose a novel indicator measuring one dimension of the sustainability of an entity in modern societies: Nitrogen-neutrality. N-neutrality strives to offset Nr releases an entity exerts on the environment from the release of reactive nitrogen (Nr) to the environment by reducing it and by offsetting the Nr releases elsewhere. N-neutrality also aims to increase awareness about the consequences of unintentional releases of nitrogen to the environment. N-neutrality is composed of two quantified elements: Nr released by an entity (e.g. on the basis of the N footprint) and Nr reduction from management and offset projects (N offset). It includes management strategies to reduce nitrogen losses before they occur (e.g., through energy conservation). Each of those elements faces specific challenges with regard to data availability and conceptual development. Impacts of Nr releases to the environment are manifold, and the impact profile of one unit of Nr release depends strongly on the compound released and the local susceptibility to Nr. As such, N-neutrality is more difficult to conceptualize and calculate than C-neutrality. We developed a workable conceptual framework for N-neutrality which was adapted for the 6th International Nitrogen Conference (N2013, Kampala, November 2013). Total N footprint of the surveyed meals at N2013 was 66 kg N. A total of US 3050 was collected from the participants and used to offset the conference’s N footprint by supporting the UN Millennium Village cluster Ruhiira in South-Western Uganda. The concept needs further development in particular to better incorporate the spatio-temporal variability of impacts and to standardize the methods to quantify the required N offset to neutralize the Nr releases impact. Criteria for compensation projects need to be sharply defined to allow the development of a market for N offset certificates.

  6. Selection of Clostridium spp. in biological sand filters neutralizing synthetic acid mine drainage.

    PubMed

    Ramond, Jean-Baptiste; Welz, Pamela J; Le Roes-Hill, Marilize; Tuffin, Marla I; Burton, Stephanie G; Cowan, Don A

    2014-03-01

    In this study, three biological sand filter (BSF) were contaminated with a synthetic iron- [1500 mg L⁻¹ Fe(II), 500 mg L⁻¹ Fe(III)] and sulphate-rich (6000 mg L⁻¹ SO₄²⁻) acid mine drainage (AMD) (pH = 2), for 24 days, to assess the remediation capacity and the evolution of autochthonous bacterial communities (monitored by T-RFLP and 16S rRNA gene clone libraries). To stimulate BSF bioremediation involving sulphate-reducing bacteria, a readily degradable carbon source (glucose, 8000 mg L⁻¹) was incorporated into the influent AMD. Complete neutralization and average removal efficiencies of 81.5 (±5.6)%, 95.8 (±1.2)% and 32.8 (±14.0)% for Fe(II), Fe(III) and sulphate were observed, respectively. Our results suggest that microbial iron reduction and sulphate reduction associated with iron precipitation were the main processes contributing to AMD neutralization. The effect of AMD on BSF sediment bacterial communities was highly reproducible. There was a decrease in diversity, and notably a single dominant operational taxonomic unit (OTU), closely related to Clostridium beijerinckii, which represented up to 65% of the total community at the end of the study period. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  7. Cr(VI) reduction from contaminated soils by Aspergillus sp. N2 and Penicillium sp. N3 isolated from chromium deposits.

    PubMed

    Fukuda, Tsubasa; Ishino, Yasuhiro; Ogawa, Akane; Tsutsumi, Kadzuyo; Morita, Hiroshi

    2008-10-01

    Aspergillus sp. N2 and Penicillium sp. N3 are chromate-resistant filamentous fungi that were isolated from Cr(VI) contaminated soil based on their ability to decrease hexavalent chromium levels in the growth medium. After 120 h of growth in a medium containing 50 ppm Cr(VI) at near neutral pH, Aspergillus sp. N2 reduced the Cr(VI) concentration by about 75%. Penicillium sp. N3 was able to reduce the Cr(VI) concentration by only 35%. However, Penicillium sp. N3 reduced the Cr(VI) concentration in the medium by 93% under acidic conditions. Interestingly, the presence of Cu(II) enhanced the Cr(VI) reducing ability of Aspergillus sp. N2 and Penicillium sp. N3 at near neutral pH. Aspergillus sp. N2 and Penicillium sp. N3 reduced the Cr(VI) concentration in the growth medium to a virtually undetectable level within 120 h. For both Aspergillus sp. N2 and Penicillium sp. N3, mycelial seed cultures were more efficient at Cr(VI) reduction than conidium seed cultures. The mechanisms of Cr(VI) reduction in Aspergillus sp. N2 and Penicillium sp. N3 were enzymatic reduction and sorption to mycelia. Enzymatic activity contributed significantly to Cr(VI) reduction. Aspergillus sp. N2 and Penicillium sp. N3 reduced the levels of Cr(VI) in polluted soil samples, suggesting that these strains might be useful for cleaning up chromium-contaminated sites.

  8. Culture impacts the magnitude of the emotion-induced memory trade-off effect.

    PubMed

    Gutchess, Angela; Garner, Lauryn; Ligouri, Laura; Konuk, Ayse Isilay; Boduroglu, Aysecan

    2017-10-04

    The present study assessed the extent to which culture impacts the emotion-induced memory trade-off effect. This trade-off effect occurs because emotional items are better remembered than neutral ones, but this advantage comes at the expense of memory for backgrounds such that neutral backgrounds are remembered worse when they occurred with an emotional item than with a neutral one. Cultures differ in their prioritisation of focal object versus contextual background information, with Westerners focusing more on objects and Easterners focusing more on backgrounds. Americans, a Western culture, and Turks, an Eastern-influenced culture, incidentally encoded positive, negative, and neutral items placed against neutral backgrounds, and then completed a surprise memory test with the items and backgrounds tested separately. Results revealed a reduced trade-off for Turks compared to Americans. Although both groups exhibited an emotional enhancement in item memory, Turks did not show a decrement in memory for backgrounds that had been paired with emotional items. These findings complement prior ones showing reductions in trade-off effects as a result of task instructions. Here, we suggest that a contextual-focus at the level of culture can mitigate trade-off effects in emotional memory.

  9. Brain enlargement and dental reduction were not linked in hominin evolution

    PubMed Central

    Smaers, Jeroen B.; Holloway, Ralph L.

    2017-01-01

    The large brain and small postcanine teeth of modern humans are among our most distinctive features, and trends in their evolution are well studied within the hominin clade. Classic accounts hypothesize that larger brains and smaller teeth coevolved because behavioral changes associated with increased brain size allowed a subsequent dental reduction. However, recent studies have found mismatches between trends in brain enlargement and posterior tooth size reduction in some hominin species. We use a multiple-variance Brownian motion approach in association with evolutionary simulations to measure the tempo and mode of the evolution of endocranial and dental size and shape within the hominin clade. We show that hominin postcanine teeth have evolved at a relatively consistent neutral rate, whereas brain size evolved at comparatively more heterogeneous rates that cannot be explained by a neutral model, with rapid pulses in the branches leading to later Homo species. Brain reorganization shows evidence of elevated rates only much later in hominin evolution, suggesting that fast-evolving traits such as the acquisition of a globular shape may be the result of direct or indirect selection for functional or structural traits typical of modern humans. PMID:28049819

  10. Self-generated zonal flows in the plasma turbulence driven by trapped-ion and trapped-electron instabilities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Drouot, T.; Gravier, E.; Reveille, T.

    This paper presents a study of zonal flows generated by trapped-electron mode and trapped-ion mode micro turbulence as a function of two plasma parameters—banana width and electron temperature. For this purpose, a gyrokinetic code considering only trapped particles is used. First, an analytical equation giving the predicted level of zonal flows is derived from the quasi-neutrality equation of our model, as a function of the density fluctuation levels and the banana widths. Then, the influence of the banana width on the number of zonal flows occurring in the system is studied using the gyrokinetic code. Finally, the impact of themore » temperature ratio T{sub e}/T{sub i} on the reduction of zonal flows is shown and a close link is highlighted between reduction and different gyro-and-bounce-average ion and electron density fluctuation levels. This reduction is found to be due to the amplitudes of gyro-and-bounce-average density perturbations n{sub e} and n{sub i} gradually becoming closer, which is in agreement with the analytical results given by the quasi-neutrality equation.« less

  11. Attentional distractor interference may be diminished by concurrent working memory load in normal participants and traumatic brain injury patients.

    PubMed

    Gil-Gómez de Liaño, Beatriz; Umiltà, Carlo; Stablum, Franca; Tebaldi, Francesca; Cantagallo, Anna

    2010-12-01

    A reduction in congruency effects under working memory (WM) load has been previously described using different attentional paradigms (e.g., Kim, Kim, & Chun, 2005; Smilek, Enns, Eastwood, & Merikle, 2006). One hypothesis is that different types of WM load have different effects on attentional selection, depending on whether a specific memory load demands resources in common with target or distractor processing. In particular, if information in WM is related to the distractors in the selective attention task, there is a reduction in distraction (Kim et al., 2005). However, although previous results seem to point to a decrease in interference under high WM load conditions (Kim et al., 2005), the lack of a neutral baseline for the congruency effects makes it difficult to differentiate between a decrease in interference or in facilitation. In the present work we included neutral trials in the task introduced by Kim et al. (2005) and tested normal participants and traumatic brain injury patients. Results support a reduction in the processing of distractors under WM load, at least for incongruent trials in both groups. Theoretical as well as applied implications are discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Growth-suppressing and algicidal properties of an extract from Arundo donax, an invasive riparian plant, against Prymnesium parvum, an invasive harmful alga.

    PubMed

    Patiño, Reynaldo; Rashel, Rakib H; Rubio, Amede; Longing, Scott

    2018-01-01

    This study examined the ability of acidic and neutral/alkaline fractions of a methanolic extract from giant reed (Arundo donax) and of two of its constituents, gramine and skatole, to inhibit growth of the ichthyotoxic golden alga (Prymnesium parvum) in batch culture. For this study, growth suppression was defined as inhibition of maximum cell density, algicidal activity as early occurrence of negative growth, and algistatic activity as lack of net growth. The acidic fraction did not affect algal growth. The neutral/alkaline fraction showed growth-suppressing and algicidal activities but no signs of algistatic activity - namely, cells in cultures surviving a partial-algicidal exposure concentration (causing transient negative growth) were later able to initiate positive growth but at higher concentrations, algicidal activity was full and irreversible. Gramine suppressed growth more effectively than skatole and at the highest concentration tested, gramine also showed partial-algicidal and algistatic activity. While the partial-algicidal activities of the neutral/alkaline fraction and of gramine were short-lived (≤6days) and thus may share similar mechanisms, algistatic activity was unique to gramine and persisted for >3 weeks. Given gramine's reported concentration in the neutral/alkaline fraction, its corresponding level of algicidal activity is much lower than the fraction's suggesting the latter contains additional potent algicides. Inhibition of maximum cell density by all test compounds was associated with reductions in exponential growth rate, and in the case of the neutral/alkaline fraction and gramine also reductions in early (pre-exponential) growth. These results indicate that giant reed is a potential source of natural products to control golden alga blooms. Giant reed is an invasive species in North America, thus also providing incentive for research into strategies to couple management efforts for both species. Published by Elsevier B.V.

  13. Growth-suppressing and algicidal properties of an extract from Arundo donax, an invasive riparian plant, against Prymnesium parvum, an invasive harmful alga

    USGS Publications Warehouse

    Patino, Reynaldo; Rashel, Rakib H.; Rubio, Amede; Longing, Scott

    2018-01-01

    This study examined the ability of acidic and neutral/alkaline fractions of a methanolic extract from giant reed (Arundo donax) and of two of its constituents, gramine and skatole, to inhibit growth of the ichthyotoxic golden alga (Prymnesium parvum) in batch culture. For this study, growth suppression was defined as inhibition of maximum cell density, algicidal activity as early occurrence of negative growth, and algistatic activity as lack of net growth. The acidic fraction did not affect algal growth. The neutral/alkaline fraction showed growth-suppressing and algicidal activities but no signs of algistatic activity – namely, cells in cultures surviving a partial-algicidal exposure concentration (causing transient negative growth) were later able to initiate positive growth but at higher concentrations, algicidal activity was full and irreversible. Gramine suppressed growth more effectively than skatole and at the highest concentration tested, gramine also showed partial-algicidal and algistatic activity. While the partial-algicidal activities of the neutral/alkaline fraction and of gramine were short-lived (≤6 days) and thus may share similar mechanisms, algistatic activity was unique to gramine and persisted for >3 weeks. Given gramine’s reported concentration in the neutral/alkaline fraction, its corresponding level of algicidal activity is much lower than the fraction’s suggesting the latter contains additional potent algicides. Inhibition of maximum cell density by all test compounds was associated with reductions in exponential growth rate, and in the case of the neutral/alkaline fraction and gramine also reductions in early (pre-exponential) growth. These results indicate that giant reed is a potential source of natural products to control golden alga blooms. Giant reed is an invasive species in North America, thus also providing incentive for research into strategies to couple management efforts for both species.

  14. Differential profiles and inhibitory effect on rotavirus vaccines of nonantibody components in breast milk from mothers in developing and developed countries.

    PubMed

    Moon, Sung-Sil; Tate, Jacqueline E; Ray, Pratima; Dennehy, Penelope H; Archary, Derseree; Coutsoudis, Anna; Bland, Ruth; Newell, Marie-Louise; Glass, Roger I; Parashar, Umesh; Jiang, Baoming

    2013-08-01

    Live oral rotavirus vaccines have been less immunogenic and efficacious for children of developing countries than for those in middle income and industrialized countries, and the basis for these differences is not fully understood. Recently, we demonstrated that breastmilk from mothers in India had significantly higher IgA and neutralizing activity against rotavirus that could reduce the effective titer of rotavirus vaccines reaching the gut when compared with that from mothers in the United States. We extended our study to understand the specific contribution of those nonantibody components in breastmilk to the neutralizing activity against rotavirus vaccine we observed. Breastmilk samples were collected from mothers of breast-feeding infants aged between 4 and 29 weeks (ie, vaccine eligible age) in India (N = 40), South Africa (N = 50) and the United States (N = 51). We examined breastmilk for lactoferrin, lactadherin, rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains (Rotarix, RotaTeq G1 and 116E) using enzyme immunoassays, a plaque reduction assay or a microneutralization assay. We observed higher levels of lactoferrin, lactadherin, IgA and neutralizing activity in breastmilk specimens from Indian and South African women than those from American women. We demonstrated positive associations between levels of lactoferrin or IgA and neutralizing activity in Indian and South African specimens, but not in American specimens. We demonstrated that the inhibitory effect of lactoferrin was dose- or species-dependent, as evidenced by greater reduction in titer of Rotarix and 116E by human lactoferrin. Lactadherin also exhibited inhibitory activity to rotavirus vaccines but appeared to be less effective. The lower immunogenicity and efficacy of rotavirus vaccines in developing countries could be explained, in part, by synergistic inhibitory effect of high levels of antibody and nonantibody components in breastmilk consumed by infants at the time of immunization. Therefore, there is a need for alternative rotavirus vaccine strategies in breast-feeding populations.

  15. The steps of activating a prospective CO 2 hydrogenation catalyst with combined CO 2 capture and reduction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lao, D. B.; Galan, B. R.; Linehan, J. C.

    2016-08-10

    Combining carbon capture and reduction is an efficient strategy to alleviate the high energy requirements for seperation, compression, and storage of CO2 prior to reduction. Recent studies have shown that catalytic hydrogenations of CO2 can be performed without added pressure of CO2 using switchable ionic liquids. It’s ambiguous whether the alkylcarbonate (captured CO2) is reduced as it is in dynamic equilibrium with neutral CO2 in solution. New studies are presented to elucidate the reactivity of CO2 and CO2 captured in solution.

  16. Annealing of radiation damage in low resistivity silicon solar cells

    NASA Technical Reports Server (NTRS)

    Weinberg, I.; Swartz, C. K.

    1980-01-01

    The reduction of the temperatures required to restore cell performance after irradiation was investigated with emphasis on the annealing characteristics of two groups of cells containing different amounts of oxygen and carbon. Examination of defect behavior in irradiated boron doped silicon leads to the tentative conclusion that further reduction in annealing temperature could be achieved by decreasing the carbon concentration and either neutralizing the divacancy and/or minimizing its formation as a result of irradiation. A significant reduction in the temperature required to remove radiation induced degradation in 0.1 ohm centimeter silicon solar cells was achieved.

  17. Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

    PubMed

    Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S; Nogueira, Lilian; Schoofs, Till; Krassnig, Lisa; Butler, Allison; Millard, Katrina; Fitzsimons, Tomas; Daniell, Xiaoju; Dizon, Juan P; Shimeliovich, Irina; Montefiori, David C; Caskey, Marina; Nussenzweig, Michel C

    2018-03-01

    Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potency of these antibodies have primarily been evaluated by using panels of HIV-1 Env-pseudotyped viruses produced in 293T cells expressing molecularly cloned Env proteins. Here we report on the ability of five bNAbs currently in clinical development to neutralize circulating primary HIV-1 isolates derived from peripheral blood mononuclear cells (PBMCs) and compare the results to those obtained with the pseudovirus panels used to characterize the bNAbs. The five bNAbs demonstrated significantly less breadth and potency against clinical isolates produced in PBMCs than against Env-pseudotyped viruses. The magnitude of this difference in neutralizing activity varied, depending on the antibody epitope. Glycan-targeting antibodies showed differences of only 3- to 4-fold, while antibody 10E8, which targets the membrane-proximal external region, showed a nearly 100-fold decrease in activity between published Env-pseudotyped virus panels and PBMC-derived primary isolates. Utilizing clonal PBMC-derived primary isolates and molecular clones, we determined that the observed discrepancy in bNAb performance is due to the increased sensitivity to neutralization exhibited by 293T-produced Env-pseudotyped viruses. We also found that while full-length molecularly cloned viruses produced in 293T cells exhibit greater sensitivity to neutralization than PBMC-derived viruses do, Env-pseudotyped viruses produced in 293T cells generally exhibit even greater sensitivity to neutralization. As the clinical development of bNAbs progresses, it will be critical to determine the relevance of each of these in vitro neutralization assays to in vivo antibody performance. IMPORTANCE Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Antibodies with exceptional neutralizing activity against HIV-1 may provide several advantages to traditional HIV drugs, including an improved side-effect profile, a reduced dosing frequency, and immune enhancement. The activity of these antibodies has been established in vitro by utilizing HIV-1 Env-pseudotyped viruses derived from circulating viruses but produced in 293T cells by pairing Env proteins with a backbone vector. We tested PBMC-produced circulating viruses against five anti-HIV-1 antibodies currently in clinical development. We found that the activity of these antibodies against PBMC isolates is significantly less than that against 293T Env-pseudotyped viruses. This decline varied among the antibodies tested, with some demonstrating moderate reductions in activity and others showing an almost 100-fold reduction. As the development of these antibodies progresses, it will be critical to determine how the results of different in vitro tests correspond to performance in the clinic. Copyright © 2018 Cohen et al.

  18. Sadness and susceptibility to judgmental bias: the case of anchoring.

    PubMed

    Bodenhausen, G V; Gabriel, S; Lineberger, M

    2000-07-01

    In a wide range of empirical paradigms, sadness has been associated with more extensive and detail-oriented thinking than happiness, resulting in reductions in judgmental bias that arise from reliance on stereotypes and other simple decision heuristics. It was hypothesized that anchoring would constitute a significant exception to this general pattern. Recent research on anchoring indicates that an active thought process underlies the emergence of this bias. If sad people are likely to think more actively about the judgmental anchor than their neutral-mood counterparts, their subsequent judgments should be more likely to be assimilated toward this reference point. This prediction was confirmed in two experiments demonstrating that sad people are indeed more susceptible to anchoring bias than are people in a neutral mood. Moreover, this effect generalized over judgments in positive, neutral, and negative content domains.

  19. Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction

    PubMed Central

    Panikkar, Archana; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A.; Wykes, Michelle; Moss, Denis J.; Rickinson, Alan; Balfour, Henry H.

    2015-01-01

    Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. PMID:26109734

  20. Reversible conversion of valence-tautomeric copper metal-organic frameworks dependent single-crystal-to-single-crystal oxidation/reduction: a redox-switchable catalyst for C-H bonds activation reaction.

    PubMed

    Huang, Chao; Wu, Jie; Song, Chuanjun; Ding, Ran; Qiao, Yan; Hou, Hongwei; Chang, Junbiao; Fan, Yaoting

    2015-06-28

    Upon single-crystal-to-single-crystal (SCSC) oxidation/reduction, reversible structural transformations take place between the anionic porous zeolite-like Cu(I) framework and a topologically equivalent neutral Cu(I)Cu(II) mixed-valent framework. The unique conversion behavior of the Cu(I) framework endowed it as a redox-switchable catalyst for the direct arylation of heterocycle C-H bonds.

  1. Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus.

    PubMed

    Kang, Mi-Sun; Lim, Hae-Soon; Oh, Jong-Suk; Lim, You-Jin; Wuertz-Kozak, Karin; Harro, Janette M; Shirtliff, Mark E; Achermann, Yvonne

    2017-03-01

    The increasing prevalence of methicillin-resistant Staphylococcus aureus has become a major public health threat. While lactobacilli were recently found useful in combating various pathogens, limited data exist on their therapeutic potential for S. aureus infections. The aim of this study was to determine whether Lactobacillus salivarius was able to produce bactericidal activities against S. aureus and to determine whether the inhibition was due to a generalized reduction in pH or due to secreted Lactobacillus product(s). We found an 8.6-log10 reduction of planktonic and a 6.3-log10 reduction of biofilm S. aureus. In contrast, the previously described anti-staphylococcal effects of L. fermentum only caused a 4.0-log10 reduction in planktonic S. aureus cells, with no effect on biofilm S. aureus cells. Killing of S. aureus was partially pH dependent, but independent of nutrient depletion. Cell-free supernatant that was pH neutralized and heat inactivated or proteinase K treated had significantly reduced killing of L. salivarius than with pH-neutralized supernatant alone. Proteomic analysis of the L. salivarius secretome identified a total of five secreted proteins including a LysM-containing peptidoglycan binding protein and a protein peptidase M23B. These proteins may represent potential novel anti-staphylococcal agents that could be effective against S. aureus biofilms. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. The reductive half-reaction of xanthine dehydrogenase from Rhodobacter capsulatus: the role of Glu232 in catalysis.

    PubMed

    Hall, James; Reschke, Stefan; Cao, Hongnan; Leimkühler, Silke; Hille, Russ

    2014-11-14

    The kinetic properties of an E232Q variant of the xanthine dehydrogenase from Rhodobacter capsulatus have been examined to ascertain whether Glu(232) in wild-type enzyme is protonated or unprotonated in the course of catalysis at neutral pH. We find that kred, the limiting rate constant for reduction at high [xanthine], is significantly compromised in the variant, a result that is inconsistent with Glu(232) being neutral in the active site of the wild-type enzyme. A comparison of the pH dependence of both kred and kred/Kd from reductive half-reaction experiments between wild-type and enzyme and the E232Q variant suggests that the ionized Glu(232) of wild-type enzyme plays an important role in catalysis by discriminating against the monoanionic form of substrate, effectively increasing the pKa of substrate by two pH units and ensuring that at physiological pH the neutral form of substrate predominates in the Michaelis complex. A kinetic isotope study of the wild-type R. capsulatus enzyme indicates that, as previously determined for the bovine and chicken enzymes, product release is principally rate-limiting in catalysis. The disparity in rate constants for the chemical step of the reaction and product release, however, is not as great in the bacterial enzyme as compared with the vertebrate forms. The results indicate that the bacterial and bovine enzymes catalyze the chemical step of the reaction to the same degree and that the faster turnover observed with the bacterial enzyme is due to a faster rate constant for product release than is seen with the vertebrate enzyme. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Utilization of Electrically Reduced Neutral Red by Actinobacillus succinogenes: Physiological Function of Neutral Red in Membrane-Driven Fumarate Reduction and Energy Conservation

    PubMed Central

    Park, D. H.; Zeikus, J. G.

    1999-01-01

    Neutral red (NR) functioned as an electronophore or electron channel enabling either cells or membranes purified from Actinobacillus succinogenes to drive electron transfer and proton translocation by coupling fumarate reduction to succinate production. Electrically reduced NR, unlike methyl or benzyl viologen, bound to cell membranes, was not toxic, and chemically reduced NAD. The cell membrane of A. succinogenes contained high levels of benzyl viologen-linked hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U) activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not. Proton translocation by whole cells was dependent on either electrically reduced NR or H2 as the electron donor and on the fumarate concentration. During the growth of Actinobacillus on glucose plus electrically reduced NR in an electrochemical bioreactor system versus on glucose alone, electrically reduced NR enhanced glucose consumption, growth, and succinate production by about 20% while it decreased acetate production by about 50%. The rate of fumarate reduction to succinate by purified membranes was twofold higher with electrically reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)-4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited succinate production from H2 plus fumarate but not from electrically reduced NR plus fumarate. Thus, NR appears to replace the function of menaquinone in the fumarate reductase complex, and it enables A. succinogenes to utilize electricity as a significant source of metabolic reducing power. PMID:10198002

  4. Zonal wind observations during a geomagnetic storm

    NASA Technical Reports Server (NTRS)

    Miller, N. J.; Spencer, N. W.

    1986-01-01

    In situ measurements taken by the Wind and Temperature Spectrometer (WATS) onboard the Dynamics Explorer 2 spacecraft during a geomagnetic storm display zonal wind velocities that are reduced in the corotational direction as the storm intensifies. The data were taken within the altitudes 275 to 475 km in the dusk local time sector equatorward of the auroral region. Characteristic variations in the value of the Dst index of horizontal geomagnetic field strength are used to monitor the storm evolution. The detected global rise in atmospheric gas temperature indicates the development of thermospheric heating. Concurrent with that heating, reductions in corotational wind velocities were measured equatorward of the auroral region. Just after the sudden commencement, while thermospheric heating is intense in both hemispheres, eastward wind velocities in the northern hemisphere show reductions ranging from 500 m/s over high latitudes to 30 m/s over the geomagnetic equator. After 10 hours storm time, while northern thermospheric heating is diminishing, wind velocity reductions, distinct from those initially observed, begin to develop over southern latitudes. In the latter case, velocity reductions range from 300 m/s over the highest southern latitudes to 150 m/s over the geomagnetic equator and extend into the Northern Hemisphere. The observations highlight the interhemispheric asymmetry in the development of storm effects detected as enhanced gas temperatures and reduced eastward wind velocities. Zonal wind reductions over high latitudes can be attributed to the storm induced equatorward spread of westward polar cap plasma convection and the resulting plasma-neutral collisions. However, those collisions are less significant over low latitudes; so zonal wind reductions over low latitudes must be attributed to an equatorward extension of a thermospheric circulation pattern disrupted by high latitude collisions between neutrals transported via eastward winds and ions convecting westward.

  5. Improving management of constipation in an inpatient setting using a care bundle.

    PubMed

    Linton, Andrew

    2014-01-01

    Constipation is a common occurrence on geriatric in-patient wards. It can result in delirium and other complications including bowel obstruction. Over treatment with laxatives can result in iatrogenic diahorrea, which can lead to dehydration, delirium, and the false positive labeling and unnecessary treatment of clostridium difficile carriers. This can result in increased morbidity and mortality, and a longer stay in hospital. This means that improving the assessment and treatment of constipation should improve patient outcomes and result in significant hospital cost savings. Multidisciplinary discussion and planning resulted in the delivery of our constipation project. This aimed to encourage the early assessment and treatment of constipation of inpatients on a geriatric rehabilitation ward. The goal was to prevent significant constipation by intervening early, improving the prescription of laxatives, and titrating them when the constipation has resolved. This involved educational sessions, non-pharmacological alternatives to laxatives (optimisation of hydration, exercise, and high fibre foods), laxative prescription guidance, and twice weekly laxative ward rounds. The profile of laxative prescription changed in keeping with our guidance. There was a reduction in overall laxative prescription by a third and the prescription of "PRN" laxatives was eliminated. This hopefully resulted in reduced morbidity for the patients and reduced length of stay. There was a cost savings on the laxative bill on average per day of the project, which when extrapolated to a 365 day year was £1226.40. This doesn't include potential savings gained from reduced complications of constipation and reduced length of stay, which are hard to accurately measure.

  6. Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa.

    PubMed

    McKinley, Scott A; Chen, Alex; Shi, Feng; Wang, Simi; Mucha, Peter J; Forest, M Gregory; Lai, Samuel K

    2014-01-01

    Eliciting broadly neutralizing antibodies (bnAb) in cervicovaginal mucus (CVM) represents a promising "first line of defense" strategy to reduce vaginal HIV transmission. However, it remains unclear what levels of bnAb must be present in CVM to effectively reduce infection. We approached this complex question by modeling the dynamic tally of bnAb coverage on HIV. This analysis introduces a critical, timescale-dependent competition: to protect, bnAb must accumulate at sufficient stoichiometry to neutralize HIV faster than virions penetrate CVM and reach target cells. We developed a model that incorporates concentrations and diffusivities of HIV and bnAb in semen and CVM, kinetic rates for binding (kon) and unbinding (koff) of select bnAb, and physiologically relevant thicknesses of CVM and semen layers. Comprehensive model simulations lead to robust conclusions about neutralization kinetics in CVM. First, due to the limited time virions in semen need to penetrate CVM, substantially greater bnAb concentrations than in vitro estimates must be present in CVM to neutralize HIV. Second, the model predicts that bnAb with more rapid kon, almost independent of koff, should offer greater neutralization potency in vivo. These findings suggest the fastest arriving virions at target cells present the greatest likelihood of infection. It also implies the marked improvements in in vitro neutralization potency of many recently discovered bnAb may not translate to comparable reduction in the bnAb dose needed to confer protection against initial vaginal infections. Our modeling framework offers a valuable tool to gaining quantitative insights into the dynamics of mucosal immunity against HIV and other infectious diseases.

  7. Progress toward School Finance Equity Goals in Indiana, Iowa, and Illinois.

    ERIC Educational Resources Information Center

    Hickrod, G. Alan; And Others

    1980-01-01

    Concludes that a state may make very uneven progress toward some general equity goal if that equity goal is operationalized in different ways. A preference for tax disparity, expenditure disparity reduction, or wealth neutrality gains may have to be expressed. (Author/IRT)

  8. Energy Challenges: Isolating Results Due to Behavior Change

    ERIC Educational Resources Information Center

    Boulton, Kelly; Pallant, Eric; Bradshaw-Wilson, Casey; Choate, Beth; Carbone, Ian

    2017-01-01

    Purpose: Approximately 700 colleges and universities have committed to climate neutrality, which will require significant reductions in energy consumption. This paper aims to explore the effectiveness of an Annual Energy Challenge in curtailing electricity use by changing consumption behaviors at one liberal arts college.…

  9. A Membrane-Free Neutral pH Formate Fuel Cell Enabled by a Selective Nickel Sulfide Oxygen Reduction Catalyst.

    PubMed

    Yan, Bing; Concannon, Nolan M; Milshtein, Jarrod D; Brushett, Fikile R; Surendranath, Yogesh

    2017-06-19

    Polymer electrolyte membranes employed in contemporary fuel cells severely limit device design and restrict catalyst choice, but are essential for preventing short-circuiting reactions at unselective anode and cathode catalysts. Herein, we report that nickel sulfide Ni 3 S 2 is a highly selective catalyst for the oxygen reduction reaction in the presence of 1.0 m formate. We combine this selective cathode with a carbon-supported palladium (Pd/C) anode to establish a membrane-free, room-temperature formate fuel cell that operates under benign neutral pH conditions. Proof-of-concept cells display open circuit voltages of approximately 0.7 V and peak power values greater than 1 mW cm -2 , significantly outperforming the identical device employing an unselective platinum (Pt) cathode. The work establishes the power of selective catalysis to enable versatile membrane-free fuel cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. A retrospective analysis of sera collected by the Hemorrhagic Fever Commission during the Korean Conflict.

    PubMed

    LeDuc, J W; Ksiazek, T G; Rossi, C A; Dalrymple, J M

    1990-11-01

    More than 600 sera from 245 patients with a clinical diagnosis of hemorrhagic fever were preserved by the Hemorrhagic Fever Commission during the Korean Conflict, 1951-1954. These sera were tested for IgM- and IgG-specific antibodies to Hantaan virus by enzyme immunoassay and for hantaviral antigen by immunoassay; one serum from each patient was tested by plaque reduction neutralization using both Hantaan and Seoul viruses. Only 15 patients failed to develop antihantaviral antibodies; most sera contained high titered IgM antibody on admission, and all were IgM-seropositive by day 7 after onset. Attempts to detect hantaviral antigen were unsuccessful. All seropositive patients had highest plaque reduction neutralization titers to Hantaan virus, suggesting that this virus was responsible for the disease seen. These results confirm that hemorrhagic fever of the Korean Conflict was due to Hantaan virus and demonstrate that measurement of specific IgM antibody is the method of choice for diagnosis of acute disease.

  11. Riboflavin Is an Active Redox Cofactor in the Na+-pumping NADH:Quinone Oxidoreductase (Na+-NQR) from Vibrio cholerae*

    PubMed Central

    Juárez, Oscar; Nilges, Mark J.; Gillespie, Portia; Cotton, Jennifer; Barquera, Blanca

    2008-01-01

    Here we present new evidence that riboflavin is present as one of four flavins in Na+-NQR. In particular, we present conclusive evidence that the source of the neutral radical is not one of the FMNs and that riboflavin is the center that gives rise to the neutral flavosemiquinone. The riboflavin is a bona fide redox cofactor and is likely to be the last redox carrier of the enzyme, from which electrons are donated to quinone. We have constructed a double mutant that lacks both covalently bound FMN cofactors (NqrB-T236Y/NqrC-T225Y) and have studied this mutant together with the two single mutants (NqrB-T236Y and NqrC-T225Y) and a mutant that lacks the noncovalently bound FAD in NqrF (NqrF-S246A). The double mutant contains riboflavin and FAD in a 0.6:1 ratio, as the only flavins in the enzyme; noncovalently bound flavins were detected. In the oxidized form, the double mutant exhibits an EPR signal consistent with a neutral flavosemiquinone radical, which is abolished on reduction of the enzyme. The same radical can be observed in the FAD deletion mutant. Furthermore, when the oxidized enzyme reacts with ubiquinol (the reduced form of the usual electron acceptor) in a process that reverses the physiological direction of the electron flow, a single kinetic phase is observed. The kinetic difference spectrum of this process is consistent with one-electron reduction of a neutral flavosemiquinone. The presence of riboflavin in the role of a redox cofactor is thus far unique to Na+-NQR. PMID:18832377

  12. Assessment of immunogenic potential of Vero adapted formalin inactivated vaccine derived from novel ECSA genotype of Chikungunya virus.

    PubMed

    Tiwari, Mugdha; Parida, Manmohan; Santhosh, S R; Khan, Mohsin; Dash, Paban Kumar; Rao, P V Lakshmana

    2009-04-21

    The recent resurgence of Chikungunya virus (CHIKV) in India and Indian Ocean Islands with unusual clinical severity is a matter of great public health concern. Despite the fact that CHIKV resurgence is associated with epidemic of unprecedented magnitude, no approved licensed vaccine is currently available. In the present study, a Vero cell adapted purified formalin inactivated prototype vaccine candidate was prepared using a current Indian strain implicated with the explosive epidemic during 2006. The bulk preparation of the vaccine candidate was undertaken in microcarrier based spinner culture using cytodex-1 in virus production serum free medium. The inactivation of the virus was accomplished through standard formalin inactivation protocol. The mice were immunized subcutaneously with alhydrogel gel formulation of inactivated virus preparation. The assessment of both humoral and cell-mediated immune response was accomplished through ELISA, plaque reduction neutralization test (PRNT), microcytotoxicity assay and cytokine production assay. The results revealed that formalin inactivated vaccine candidate induced both high titered ELISA (1:51,200) and plaque reduction neutralizing antibodies (1:6400) with peak antibody titer being observed during 6 -- 8 weeks of post-vaccination. In the absence of suitable murine challenge model, the protective efficacy was established by both in vitro and in vivo neutralization tests. Further assessment of cellular immunity through in vitro stimulation of spleenocytes from immunized mice revealed augmentation of high levels of both pro- and anti-inflammatory cytokines, indicating a mixed balance of Th1 and Th2 response. These findings suggest that the formalin inactivated Chikungunya vaccine candidate reported in this study has very good immunogenic potential to neutralize the virus infectivity by augmenting both humoral and cell-mediated immune response.

  13. Screening test for neutralizing antibodies against yellow fever virus, based on a flavivirus pseudotype.

    PubMed

    Mercier-Delarue, Séverine; Durier, Christine; Colin de Verdière, Nathalie; Poveda, Jean-Dominique; Meiffrédy, Vincent; Fernandez Garcia, Maria Dolores; Lastère, Stéphane; Césaire, Raymond; Manuggera, Jean-Claude; Molina, Jean-Michel; Amara, Ali; Simon, François

    2017-01-01

    Given the possibility of yellow fever virus reintroduction in epidemiologically receptive geographic areas, the risk of vaccine supply disruption is a serious issue. New strategies to reduce the doses of injected vaccines should be evaluated very carefully in terms of immunogenicity. The plaque reduction test for the determination of neutralizing antibodies (PRNT) is particularly time-consuming and requires the use of a confinement laboratory. We have developed a new test based on the use of a non-infectious pseudovirus (WN/YF17D). The presence of a reporter gene allows sensitive determination of neutralizing antibodies by flow cytometry. This WN/YF17D test was as sensitive as PRNT for the follow-up of yellow fever vaccinees. Both tests lacked specificity with sera from patients hospitalized for acute Dengue virus infection. Conversely, both assays were strictly negative in adults never exposed to flavivirus infection or vaccination, and in patients sampled some time after acute Dengue infection. This WN/YF17D test will be particularly useful for large epidemiological studies and for screening for neutralizing antibodies against yellow fever virus.

  14. The effect of residual water on antacid properties of sucralfate gel dried by microwaves.

    PubMed

    Gainotti, Alessandro; Losi, Elena; Colombo, Paolo; Santi, Patrizia; Sonvico, Fabio; Baroni, Daniela; Massimo, Gina; Colombo, Gaia; Del Gaudio, Pasquale

    2006-01-20

    The aim of this work was to study the acid neutralization characteristics of microwave-dried sucralfate gel in relation to the water content and physical structure of the substance. Several dried sucralfate gels were compared with humid sucralfate gel and sucralfate nongel powder in terms of neutralization rate and buffering capacity. Humid sucralfate gel and microwave-dried gel exhibited antacid effectiveness. In particular, the neutralization rate of dried gel powders was inversely related to the water content: as the water content of dried powders decreased, the acid reaction rate linearly increased. The relationship was due to the different morphology of dried sucralfate gels. In fact, the porosity of the dried samples increased with the water reduction. However, the acid neutralization equivalent revealed that the dried sucralfate gel became more resistant to acid attack in the case of water content below 42%. Then, the microwave drying procedure had the opposite effect on the reactivity of the aluminum hydroxide component of dried sucralfate gel powders, since the rate of the reaction increased whereas the buffering capacity decreased as the amount of water was reduced.

  15. The effect of residual water on antacid properties of sucralfate gel dried by microwaves.

    PubMed

    Gainotti, Alessandro; Losi, Elena; Colombo, Paolo; Santi, Patrizia; Sonvico, Fabio; Baroni, Daniela; Massimo, Gina; Colombo, Gaia; Del Gaudio, Pasquale

    2006-03-01

    The aim of this work was to study the acid neutralization characteristics of microwave-dried sucralfate gel in relation to the water content and physical structure of the substance. Several dried sucralfate gels were compared with humid sucralfate gel and sucralfate nongel powder in terms of neutralization rate and buffering capacity. Humid sucralfate gel and microwave-dried gel exhibited antacid effectiveness. In particular, the neutralization rate of dried gel powders was inversely related to the water content: as the water content of dried powders decreased, the acid reaction rate linearly increased. The relationship was due to the different morphology of dried sucralfate gels. In fact, the porosity of the dried samples increased with the water reduction. However, the acid neutralization equivalent revealed that the dried sucralfate gel became more resistant to acid attack in the case of water content below 42%. Then, the microwave drying procedure had the opposite effect on the reactivity of the aluminum hydroxide component of dried sucralfate gel powders, since the rate of the reaction increased whereas the buffering capacity decreased as the amount of water was reduced.

  16. A current disruption mechanism in the neutral sheet - A possible trigger for substorm expansions

    NASA Technical Reports Server (NTRS)

    Lui, A. T. Y.; Mankofsky, A.; Chang, C.-L.; Papadopoulos, K.; Wu, C. S.

    1990-01-01

    A linear analysis is performed to investigate the kinetic cross-field streaming instability in the earth's magnetotail neutral sheet region. Numerical solution of the dispersion equation shows that the instability can occur under conditions expected for the neutral sheet just prior to the onset of substorm expansion. The excited waves are obliquely propagating whistlers with a mixed polarization in the lower hybrid frequency range. The ensuing turbulence of this instability can lead to a local reduction of the cross-tail current causing it to continue through the ionosphere to form a substorm current wedge. A substorm expansion onset scenario is proposed based on this instability in which the relative drift between ions and electrons is primarily due to unmagnetized ions undergoing current sheet acceleration in the presence of a cross-tail electric field. The required electric field strength is within the range of electric field values detected in the neutral sheet region during substorm intervals. The skew in local time of substorm onset location and the three conditions under which substorm onset is observed can be understood on the basis of the proposed scenario.

  17. Efficacy of Neutral Electrolyzed Water, Quaternary Ammonium and Lactic Acid-Based Solutions in Controlling Microbial Contamination of Food Cutting Boards Using a Manual Spraying Technique.

    PubMed

    Al-Qadiri, Hamzah M; Ovissipour, Mahmoudreza; Al-Alami, Nivin; Govindan, Byju N; Shiroodi, Setareh Ghorban; Rasco, Barbara

    2016-05-01

    Bactericidal activity of neutral electrolyzed water (NEW), quaternary ammonium (QUAT), and lactic acid-based solutions was investigated using a manual spraying technique against Salmonella Typhimurium, Escherichia coli O157:H7, Campylobacter jejuni, Listeria monocytogenes and Staphylococcus aureus that were inoculated onto the surface of scarred polypropylene and wooden food cutting boards. Antimicrobial activity was also examined when using cutting boards in preparation of raw chopped beef, chicken tenders or salmon fillets. Viable counts of survivors were determined as log10 CFU/100 cm(2) within 0 (untreated control), 1, 3, and 5 min of treatment at ambient temperature. Within the first minute of treatment, NEW and QUAT solutions caused more than 3 log10 bacterial reductions on polypropylene surfaces whereas less than 3 log10 reductions were achieved on wooden surfaces. After 5 min of treatment, more than 5 log10 reductions were achieved for all bacterial strains inoculated onto polypropylene surfaces. Using NEW and QUAT solutions within 5 min reduced Gram-negative bacteria by 4.58 to 4.85 log10 compared to more than 5 log10 reductions in Gram-positive bacteria inoculated onto wooden surfaces. Lactic acid treatment was significantly less effective (P < 0.05) compared to NEW and QUAT treatments. A decline in antimicrobial effectiveness was observed (0.5 to <2 log10 reductions were achieved within the first minute) when both cutting board types were used to prepare raw chopped beef, chicken tenders or salmon fillets. © 2016 Institute of Food Technologists®

  18. Laboratory investigation of flux reduction from dense non-aqueous phase liquid (DNAPL) partial source zone remediation by enhanced dissolution

    NASA Astrophysics Data System (ADS)

    Kaye, Andrew J.; Cho, Jaehyun; Basu, Nandita B.; Chen, Xiaosong; Annable, Michael D.; Jawitz, James W.

    2008-11-01

    This study investigated the benefits of partial removal of dense nonaqueous phase liquid (DNAPL) source zones using enhanced dissolution in eight laboratory scale experiments. The benefits were assessed by characterizing the relationship between reductions in DNAPL mass and the corresponding reduction in contaminant mass flux. Four flushing agents were evaluated in eight controlled laboratory experiments to examine the effects of displacement fluid property contrasts and associated override and underride on contaminant flux reduction ( Rj) vs. mass reduction ( Rm) relationships ( Rj( Rm)): 1) 50% ethanol/50% water (less dense than water), 2) 40% ethyl-lactate/60% water (more dense than water), 3) 18% ethanol/26% ethyl-lactate/56% water (neutrally buoyant), and 4) 2% Tween-80 surfactant (also neutrally buoyant). For each DNAPL architecture evaluated, replicate experiments were conducted where source zone dissolution was conducted with a single flushing event to remove most of the DNAPL from the system, and with multiple shorter-duration floods to determine the path of the Rj( Rm) relationship. All of the single-flushing experiments exhibited similar Rj( Rm) relationships indicating that override and underride effects associated with cosolvents did not significantly affect the remediation performance of the agents. The Rj( Rm) relationship of the multiple injection experiments for the cosolvents with a density contrast with water tended to be less desirable in the sense that there was less Rj for a given Rm. UTCHEM simulations supported the observations from the laboratory experiments and demonstrated the capability of this model to predict Rj( Rm) relationships for non-uniformly distributed NAPL sources.

  19. Expeditious neutralization assay for human metapneumovirus based on a recombinant virus expressing Renilla luciferase.

    PubMed

    Zhou, Min; Kitagawa, Yoshinori; Yamaguchi, Mayu; Uchiyama, Chika; Itoh, Masae; Gotoh, Bin

    2013-01-01

    Human metapneumovirus (HMPV) is a common cause of respiratory diseases in persons of all ages. Because of its slow replication and weak cytopathic effect in cultured cells, conventional neutralization assays for HMPV require around one week for completion. The purpose of this study is to establish a rapid neutralization assay based on a recombinant virus expressing Renilla luciferase (Rluc). A recombinant HMPV expressing both Rluc and green fluorescent protein (GFP) was created by reverse genetics method. Two-fold serial dilutions of human 23 sera were made in a 96-well plate and incubated with 50 pfu/well of the recombinant virus at 4°C for 1 h. The mixtures were then transferred to LLC-MK2 cells in a 96-well plate, incubated for 2 h, and replaced with trypsin-free fresh media. After incubation at 32°C for 24 h, the cells were lysed and measured for Rluc activity. The neutralization titer was defined as the reciprocal of the highest serum dilution that resulted in 50% reduction of Rluc activity. The novel assay could be completed within 24 h and eliminated the requirement of trypsin supporting multistep replication in cultured cells, as well as laborious processes including the plaque assay with immunostaining. Neutralization titers correlated well with those determined by a GFP-based assay previously developed. The neutralization assay based on Rluc activity is the fastest and the most straightforward of all previous assays, and may be available for high throughput screening of neutralizing antibodies. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Redox Specificity of 2-Hydroxyacid-Coupled NAD+/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics

    PubMed Central

    Durani, Susheel

    2013-01-01

    With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD+-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in “reactivity” of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on “reactive” arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of “reactive” arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD+ (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme. PMID:24391777

  1. Eliciting affect via immersive virtual reality: a tool for adolescent risk reduction.

    PubMed

    Hadley, Wendy; Houck, Christopher D; Barker, David H; Garcia, Abbe Marrs; Spitalnick, Josh S; Curtis, Virginia; Roye, Scott; Brown, Larry K

    2014-04-01

    A virtual reality environment (VRE) was designed to expose participants to substance use and sexual risk-taking cues to examine the utility of VR in eliciting adolescent physiological arousal. 42 adolescents (55% male) with a mean age of 14.54 years (SD = 1.13) participated. Physiological arousal was examined through heart rate (HR), respiratory sinus arrhythmia (RSA), and self-reported somatic arousal. A within-subject design (neutral VRE, VR party, and neutral VRE) was utilized to examine changes in arousal. The VR party demonstrated an increase in physiological arousal relative to a neutral VRE. Examination of individual segments of the party (e.g., orientation, substance use, and sexual risk) demonstrated that HR was significantly elevated across all segments, whereas only the orientation and sexual risk segments demonstrated significant impact on RSA. This study provides preliminary evidence that VREs can be used to generate physiological arousal in response to substance use and sexual risk cues.

  2. Immobilization in Neutral Rotation for a Glenohumeral Dislocation Using a Sling and Splint

    PubMed Central

    2008-01-01

    The purpose of this manuscript is to provide an expedient means of immobilizing a glenohumeral dislocation in neutral rotation. This technique for post-reduction immobilization of a glenohumeral dislocation is inexpensive and easy to fabricate. Anterior glenohumeral dislocations often involve an avulsion of the labrum from the glenoid rim. In contrast to immobilization in internal rotation, positioning the shoulder in 0-45° of external rotation approximates the labrum and glenoid rim. It is hypothesized that placing the shoulder in a more externally rotated position could allow for better healing and increased joint stability. This technique places the shoulder in neutral rotation, because 45° of external rotation is awkward and may interfere with certain activities of daily living. Structural aluminum malleable (SAM) splints are used as an alternative to a bolster sling. The SAM splints are lightweight, simply shaped, and easily stored. PMID:21509136

  3. Selective REM-sleep deprivation does not diminish emotional memory consolidation in young healthy subjects.

    PubMed

    Morgenthaler, Jarste; Wiesner, Christian D; Hinze, Karoline; Abels, Lena C; Prehn-Kristensen, Alexander; Göder, Robert

    2014-01-01

    Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional) between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever.

  4. Effect of ferrous sulfate and nitrohumic acid neutralization on the leaching of metals from a combined bauxite residue.

    PubMed

    Ren, Jie; Liu, Jidong; Chen, Juan; Liu, Xiaolian; Li, Fasheng; Du, Ping

    2017-04-01

    Bauxite residue neutralization is intended to open opportunities for revegetation and reuse of the residue. Ferrous sulfate (FS) and nitrohumic acid (NA) were two kinds of materials studied for pH reduction of the residue from 10.6 to 8.3 and 8.1, respectively. The effects of FS and NA on the leaching of metals from a combined bauxite residue were investigated by using sequential and multiple extraction procedures. Neutralization with FS and NA restricted the leaching of Al, V, and Pb from the residue but promoted the leaching of Fe, Cu, Mn, and Ni, consistent with the changes in the potentially mobile fractions. With the exceptions of Pb and Ni, leaching of metals increased during a 10-day extraction period. However, the maximum leaching of Al, V, Pb, Fe, Cu, Mn, and Ni from neutralized bauxite residue were 0.46 mg/L, 59.3, 12.9, 167, 95.3, 15.5, and 14.5 μg/L, respectively, which were under the corresponding limits in the National Standard (GB/T 14848-93). Although it is necessary to consider the continued leaching of metals during neutralization, both maximum and accumulation leaching concentrations of metals from a combined bauxite residue were too low to pose a potential environmental risk.

  5. D-region ion-neutral coupled chemistry (Sodankylä Ion Chemistry, SIC) within the Whole Atmosphere Community Climate Model (WACCM 4) - WACCM-SIC and WACCM-rSIC

    NASA Astrophysics Data System (ADS)

    Kovács, Tamás; Plane, John M. C.; Feng, Wuhu; Nagy, Tibor; Chipperfield, Martyn P.; Verronen, Pekka T.; Andersson, Monika E.; Newnham, David A.; Clilverd, Mark A.; Marsh, Daniel R.

    2016-09-01

    This study presents a new ion-neutral chemical model coupled into the Whole Atmosphere Community Climate Model (WACCM). The ionospheric D-region (altitudes ˜ 50-90 km) chemistry is based on the Sodankylä Ion Chemistry (SIC) model, a one-dimensional model containing 307 ion-neutral and ion recombination, 16 photodissociation and 7 photoionization reactions of neutral species, positive and negative ions, and electrons. The SIC mechanism was reduced using the simulation error minimization connectivity method (SEM-CM) to produce a reaction scheme of 181 ion-molecule reactions of 181 ion-molecule reactions of 27 positive and 18 negative ions. This scheme describes the concentration profiles at altitudes between 20 km and 120 km of a set of major neutral species (HNO3, O3, H2O2, NO, NO2, HO2, OH, N2O5) and ions (O2+, O4+, NO+, NO+(H2O), O2+(H2O), H+(H2O), H+(H2O)2, H+(H2O)3, H+(H2O)4, O3-, NO2-, O-, O2, OH-, O2-(H2O), O2-(H2O)2, O4-, CO3-, CO3-(H2O), CO4-, HCO3-, NO2-, NO3-, NO3-(H2O), NO3-(H2O)2, NO3-(HNO3), NO3-(HNO3)2, Cl-, ClO-), which agree with the full SIC mechanism within a 5 % tolerance. Four 3-D model simulations were then performed, using the impact of the January 2005 solar proton event (SPE) on D-region HOx and NOx chemistry as a test case of four different model versions: the standard WACCM (no negative ions and a very limited set of positive ions); WACCM-SIC (standard WACCM with the full SIC chemistry of positive and negative ions); WACCM-D (standard WACCM with a heuristic reduction of the SIC chemistry, recently used to examine HNO3 formation following an SPE); and WACCM-rSIC (standard WACCM with a reduction of SIC chemistry using the SEM-CM method). The standard WACCM misses the HNO3 enhancement during the SPE, while the full and reduced model versions predict significant NOx, HOx and HNO3 enhancements in the mesosphere during solar proton events. The SEM-CM reduction also identifies the important ion-molecule reactions that affect the partitioning of odd nitrogen (NOx), odd hydrogen (HOx) and O3 in the stratosphere and mesosphere.

  6. Reduction of substituted p-Benzoquinones by Fe II near neutral pH

    USDA-ARS?s Scientific Manuscript database

    The oxidation of dihydroxyaromatics to benzoquinones by FeIII (hydr)oxides is important in respiratory electron shuttling by microorganisms and has been extensively studied. Prior publications have noted that the Gibbs Free Energy (DG) for the forward reaction is sensitive to dihydroxyaromatic struc...

  7. Joint Polar Satellite System (JPSS) Common Ground System (CGS) Overview and Architectural Tenets

    NASA Astrophysics Data System (ADS)

    Miller, S. W.; Grant, K. D.; Jamilkowski, M. L.

    2013-12-01

    The National Oceanic and Atmospheric Administration (NOAA) and National Aeronautics and Space Administration (NASA) are jointly acquiring the next-generation civilian weather and environmental satellite system: the Joint Polar Satellite System (JPSS). The Joint Polar Satellite System will replace the afternoon orbit component and ground processing system of the current Polar-orbiting Operational Environmental Satellites (POES) managed by NOAA. The JPSS satellites will carry a suite of sensors designed to collect meteorological, oceanographic, climatological and geophysical observations of the Earth. The ground processing system for JPSS is known as the JPSS Common Ground System (JPSS CGS). Developed and maintained by Raytheon Intelligence and Information Systems (IIS), the CGS is a multi-mission enterprise system serving NOAA, NASA and their national and international partners. The CGS provides a wide range of support to a number of missions: 1) Command and control and mission management for the Suomi National Polar Partnership (S-NPP) mission today, expanding this support to the JPSS-1 satellite and the Polar Free Flyer mission in 2017 2) Data acquisition via a Polar Receptor Network (PRN) for S-NPP, the Japan Aerospace Exploration Agency's (JAXA) Global Change Observation Mission - Water (GCOM-W1), POES, and the Defense Meteorological Satellite Program (DMSP) and Coriolis/WindSat for the Department of Defense (DoD) 3) Data routing over a global fiber Wide Area Network (WAN) for S-NPP, JPSS-1, Polar Free Flyer, GCOM-W1, POES, DMSP, Coriolis/WindSat, the NASA Space Communications and Navigation (SCaN, which includes several Earth Observing System [EOS] missions), MetOp for the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT), and the National Science Foundation (NSF) 4) Environmental data processing and distribution for S-NPP, GCOM-W1 and JPSS-1 The CGS architecture will receive a technology refresh in 2015 to satisfy several key objectives: 1) 'Operationalizing' Suomi NPP, which had originally been intended as a risk reduction mission 2) Leveraging lessons learned to date in multi-mission support 3) Taking advantage of newer, more reliable and efficient technologies 4) Satisfying new requirements and constraints due to the continually evolving budgetary environment To meet these needs, we are upgrading the CGS in the following ways: 1) Performing a system-wide technology refresh for enhanced performance and security 2) Establishing a new front end architecture and augmenting the PRN for mission data transport 3) Standardizing data protocols to accommodate an even wider variety of missions 4) Enhancing flexibility and modularity in IDPS for new and evolving algorithms 5) Achieving comprehensive situational awareness 6) Deploying a full backup capability for Continuity of Operations (COOP) 7) Providing an enclave in compliance with the latest security standards from the National Institute of Standards and Technology (NIST) 800-53 This paper will provide an overview of the CGS as it is deployed and operating today, along with a summary of the architectural tenets that will facilitate even easier incorporation of new missions and applications in 2015.

  8. Prokaryotic selectivity and LPS-neutralizing activity of short antimicrobial peptides designed from the human antimicrobial peptide LL-37.

    PubMed

    Nan, Yong Hai; Bang, Jeong-Kyu; Jacob, Binu; Park, Il-Seon; Shin, Song Yub

    2012-06-01

    To develop novel antimicrobial peptides (AMPs) with shorter lengths, improved prokaryotic selectivity and retained lipolysaccharide (LPS)-neutralizing activity compared to human cathelicidin AMP, LL-37, a series of amino acid-substituted analogs based on IG-19 (residues 13-31 of LL-37) were synthesized. Among the IG-19 analogs, the analog a4 showed the highest prokaryotic selectivity, but much lower LPS-neutralizing activity compared to parental LL-37. The analogs, a5, a6, a7 and a8 with higher hydrophobicity displayed LPS-neutralizing activity comparable to that of LL-37, but much lesser prokaryotic selectivity. These results indicate that the proper hydrophobicity of the peptides is crucial to exert the amalgamated property of LPS-neutralizing activity and prokaryotic selectivity. Furthermore, to increase LPS-neutralizing activity of the analog a4 without a remarkable decrease in prokaryotic selectivity, we synthesized Trp-substituted analogs (a4-W1 and a4-W2), in which Phe(5) or Phe(15) of a4 is replaced by Trp. Despite their same prokaryotic selectivity, a4-W2 displayed much higher LPS-neutralizing activity compared to a4-W1. When compared with parental LL-37, a4-W2 showed retained LPS-neutralizing activity and 2.8-fold enhanced prokaryotic selectivity. These results suggest that the effective site for Trp-substitution when designing novel AMPs with higher LPS-neutralizing activity, without a remarkable reduction in prokaryotic selectivity, is the amphipathic interface between the end of the hydrophilic side and the start of the hydrophobic side rather than the central position of the hydrophobic side in their α-helical wheel projection. Taken together, the analog a4-W2 can serve as a promising template for the development of therapeutic agents for the treatment of endotoxic shock and bacterial infection. Copyright © 2012. Published by Elsevier Inc.

  9. Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction.

    PubMed

    Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

    2015-09-01

    Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System.

    PubMed

    Louis, Cynthia; Cook, Andrew D; Lacey, Derek; Fleetwood, Andrew J; Vlahos, Ross; Anderson, Gary P; Hamilton, John A

    2015-07-01

    M-CSF (or CSF-1) and GM-CSF can regulate the development and function of the mononuclear phagocyte system (MPS). To address some of the outstanding and sometimes conflicting issues surrounding this biology, we undertook a comparative analysis of the effects of neutralizing mAbs to these CSFs on murine MPS populations in the steady-state and during acute inflammatory reactions. CSF-1 neutralization, but not of GM-CSF, in normal mice rapidly reduced the numbers of more mature Ly6C(-) monocytes in blood and bone marrow, without any effect on proliferating precursors, and also the numbers of the resident peritoneal macrophages, observations consistent with CSF-1 signaling being essential only at a relatively late state in steady-state MPS development; in contrast, GM-CSF neutralization had no effect on the numbers of these particular populations. In Ag-induced peritonitis (AIP), thioglycolate-induced peritonitis, and LPS-induced lung inflammation, CSF-1 neutralization lowered inflammatory macrophage number; in the AIP model, this reduced number was not due to suppressed proliferation. More detailed studies with the convenient AIP model indicated that CSF-1 neutralization led to a relatively uniform reduction in all inflammatory cell populations; GM-CSF neutralization, in contrast, was more selective, resulting in the preferential loss among the MPS populations of a cycling, monocyte-derived inflammatory dendritic cell population. Some mechanistic options for the specific CSF-dependent biologies enumerated are discussed. Copyright © 2015 by The American Association of Immunologists, Inc.

  11. Flavivirus-induced antibody cross-reactivity

    PubMed Central

    Mansfield, Karen L.; Horton, Daniel L.; Johnson, Nicholas; Li, Li; Barrett, Alan D. T.; Smith, Derek J.; Galbraith, Sareen E.; Solomon, Tom

    2011-01-01

    Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae. PMID:21900425

  12. Flavivirus-induced antibody cross-reactivity.

    PubMed

    Mansfield, Karen L; Horton, Daniel L; Johnson, Nicholas; Li, Li; Barrett, Alan D T; Smith, Derek J; Galbraith, Sareen E; Solomon, Tom; Fooks, Anthony R

    2011-12-01

    Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

  13. Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes.

    PubMed

    Vaidya, Sunil R; Dvivedi, Garima M; Jadhav, Santoshkumar M

    2016-01-01

    The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.

  14. Ambient aerosols remain highly acidic despite dramatic sulfate reductions

    NASA Astrophysics Data System (ADS)

    Nenes, Athanasios; Weber, Rodney; Guo, Hongyu; Russell, Armistead

    2016-04-01

    The pH of fine particles has many vital environmental impacts. By affecting aerosol concentrations, chemical composition and toxicity, particle pH is linked to regional air quality and climate, and adverse effects on human health. Sulfate is often the main acid component that drives pH of fine particles (i.e., PM2.5) and is neutralized to varying degrees by gas phase ammonia. Sulfate levels have decreased by approximately 70% over the Southeastern United States in the last fifteen years, but measured ammonia levels have been fairly steady implying the aerosol may becoming more neutral. Using a chemically comprehensive data set, combined with a thermodynamic analysis, we show that PM2.5 in the Southeastern U.S. is highly acidic (pH between 0 and 2), and that pH has remained relatively unchanged throughout the past decade and a half of decreasing sulfate. Even with further sulfate reductions, pH buffering by gas-particle partitioning of ammonia is expected to continue until sulfate drops to near background levels, indicating that fine particle pH will remain near current levels into the future. These results are non-intuitive and reshape expectations of how sulfur emission reductions impact air quality in the Southeastern U.S. and possibly other regions across the globe.

  15. Effect of Stress Ratio and Loading Frequency on the Corrosion Fatigue Behavior of Smooth Steel Wire in Different Solutions

    PubMed Central

    Wang, Songquan; Zhang, Dekun; Hu, Ningning; Zhang, Jialu

    2016-01-01

    In this work, the effects of loading condition and corrosion solution on the corrosion fatigue behavior of smooth steel wire were discussed. The results of polarization curves and weight loss curves showed that the corrosion of steel wire in acid solution was more severe than that in neutral and alkaline solutions. With the extension of immersion time in acid solution, the cathodic reaction of steel wire gradually changed from the reduction of hydrogen ion to the reduction of oxygen, but was always the reduction of hydrogen ion in neutral and alkaline solutions. The corrosion kinetic parameters and equivalent circuits of steel wires were also obtained by simulating the Nyquist diagrams. In corrosion fatigue test, the effect of stress ratio and loading frequency on the crack initiation mechanism was emphasized. The strong corrosivity of acid solution could accelerate the nucleation of crack tip. The initiation mechanism of crack under different conditions was summarized according to the side and fracture surface morphologies. For the crack initiation mechanism of anodic dissolution, the stronger the corrosivity of solution was, the more easily the fatigue crack source formed, while, for the crack initiation mechanism of deformation activation, the lower stress ratio and higher frequency would accelerate the generation of corrosion fatigue crack source. PMID:28773869

  16. Optimizing Escherichia coli's metabolism for fuel cell applications

    NASA Astrophysics Data System (ADS)

    Nieves, Ismael U.

    In the last few years there have been many publications about applications that center on the generation of electrons from bacterial cells. These applications take advantage of the catabolic diversity of microbes to generate electrical power. The practicality of these applications depends on the microorganism's ability to effectively donate electrons, either directly to the electrode or indirectly through the use of a mediator. After establishing the limitations of electrical output in microbial fuel cells (MFCs) imposed by the bacterial cells, a spectrophotometric assay measuring the indirect reduction of the electronophore neutral red via iron reduction was used to measure electron production from Escherichia coli resting cells. Using this assay I identified NADH dehydrogenase I as a likely site of neutral red reduction. The only previously reported site of interaction between E. coli cells and NR is at the hydrogenases. Although we cannot rule out the possibility that NR is reduced by soluble hydrogenases in the cytoplasm, this previous report indicated that hydrogenase activity does not account for all of the NR reduction activity. Supporting this, data in this thesis suggest that the hydrogenases play a small role in NR reduction. It seems that NR reduction is largely taking place within the cytoplasmic membrane of the bacterial cells, serving as a substrate of enzymes that typically reduce quinones. Furthermore, it seems that under the experimental conditions used here, E. coli's catabolism of glucose is rather inefficient. Instead of using the complete TCA cycle, the bacterial cells are carrying out fermentation, leading to incomplete oxidation of the fuel and low yields of electrons. The results obtained from the TC31 strain suggest that eliminating fermentation pathways to improve NR reduction was the correct approach. Following up on this a new strain was created, KN02, which, in addition to the mutations on strain TC31, lacks acetate kinase activity.

  17. Carbon Offsets | Climate Neutral Research Campuses | NREL

    Science.gov Websites

    offsets may fit into climate action plans for your research campus. Options Considerations Sample Project United States. Instead, several organizations offer certification, so the buyer must carefully research a seller's claims for carbon reduction. Today, carbon offsets are widely available. For example, the Chicago

  18. World Reference Center for Arboviruses.

    DTIC Science & Technology

    1984-03-01

    revised the taxonomy of Bunyaviridae, Orbivirus, Rhabdoviridae , Arenaviridae, and Togaviridae. Outbreaks were diagnosed such as Rift Valley fever in...Flavivirus), Rhabdoviridae , Reoviridae (genus Orbivirus), and Bunyaviridae (genera Bunyavirus, Nairovirus, Phlebovirus, and Uukuvirus). Reference sera and...family Rhabdoviridae was done by complement fixation, immunofluorescence, and plaque reduction neutralization involving 51 viruses. A similar revision

  19. A Laboratory Procedure for the Reduction of Chromium(VI) to Chromium(III).

    ERIC Educational Resources Information Center

    Lunn, George; Sansone, Eric B.

    1989-01-01

    Chromium(VI) compounds are classified as oxidizers and must be specially packaged and transported for disposal while Cr(III) compounds are considered nonoxidizers. A process which reduces Cr(VI) to Cr(III) by adding sodium metabisulfite followed by neutralization with magnesium hydroxide is explored. (MVL)

  20. Carbon Offsets and Renewable Energy Certificates | Climate Neutral Research

    Science.gov Websites

    Campuses | NREL Carbon Offsets and Renewable Energy Certificates Carbon Offsets and Renewable Energy Certificates Carbon offsets are typically less expensive than installing hardware or undertaking climate reduction targets. While research campuses should not rely on carbon offsets long term, they can

  1. Ontogenetic Tooth Reduction in Stenopterygius quadriscissus (Reptilia: Ichthyosauria): Negative Allometry, Changes in Growth Rate, and Early Senescence of the Dental Lamina

    PubMed Central

    Dick, Daniel G.; Maxwell, Erin E.

    2015-01-01

    We explore the functional, developmental, and evolutionary processes which are argued to produce tooth reduction in the extinct marine reptile Stenopterygius quadriscissus (Reptilia: Ichthyosauria). We analyze the relationship between mandible growth and tooth size, shape, and count, to establish an ontogenetic trend. The pattern in S. quadriscissus is consistent with hypotheses of tooth size reduction by neutral selection, and this unusual morphology (a functionally edentulous rostrum) was produced by a series of different evolutionary developmental changes that are known for other taxa showing tooth reduction and loss. Specifically, this species evolved functional edentulism by evolutionary changes in the growth allometry of the dentition and by altering growth rates through ontogeny. This observation supports previous hypotheses that S. quadriscissus underwent ontogenetic tooth reduction. Tooth reduction in S. quadriscissus may be caused by unique selective pressures resulting from prey choice and feeding behavior, expanding our current understanding of the mechanisms producing tooth reduction. PMID:26579712

  2. Ontogenetic Tooth Reduction in Stenopterygius quadriscissus (Reptilia: Ichthyosauria): Negative Allometry, Changes in Growth Rate, and Early Senescence of the Dental Lamina.

    PubMed

    Dick, Daniel G; Maxwell, Erin E

    2015-01-01

    We explore the functional, developmental, and evolutionary processes which are argued to produce tooth reduction in the extinct marine reptile Stenopterygius quadriscissus (Reptilia: Ichthyosauria). We analyze the relationship between mandible growth and tooth size, shape, and count, to establish an ontogenetic trend. The pattern in S. quadriscissus is consistent with hypotheses of tooth size reduction by neutral selection, and this unusual morphology (a functionally edentulous rostrum) was produced by a series of different evolutionary developmental changes that are known for other taxa showing tooth reduction and loss. Specifically, this species evolved functional edentulism by evolutionary changes in the growth allometry of the dentition and by altering growth rates through ontogeny. This observation supports previous hypotheses that S. quadriscissus underwent ontogenetic tooth reduction. Tooth reduction in S. quadriscissus may be caused by unique selective pressures resulting from prey choice and feeding behavior, expanding our current understanding of the mechanisms producing tooth reduction.

  3. Modes of Large-Scale Brain Network Organization during Threat Processing and Posttraumatic Stress Disorder Symptom Reduction during TF-CBT among Adolescent Girls.

    PubMed

    Cisler, Josh M; Sigel, Benjamin A; Kramer, Teresa L; Smitherman, Sonet; Vanderzee, Karin; Pemberton, Joy; Kilts, Clinton D

    2016-01-01

    Posttraumatic stress disorder (PTSD) is often chronic and disabling across the lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and mediating neural mechanisms are not well understood. Here, we test whether PTSD symptom reduction during TF-CBT is associated with individual differences in large-scale brain network organization during emotion processing. Twenty adolescent girls, aged 11-16, with PTSD related to assaultive violence completed a 12-session protocol of TF-CBT. Participants completed an emotion processing task, in which neutral and fearful facial expressions were presented either overtly or covertly during 3T fMRI, before and after treatment. Analyses focused on characterizing network properties of modularity, assortativity, and global efficiency within an 824 region-of-interest brain parcellation separately during each of the task blocks using weighted functional connectivity matrices. We similarly analyzed an existing dataset of healthy adolescent girls undergoing an identical emotion processing task to characterize normative network organization. Pre-treatment individual differences in modularity, assortativity, and global efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction. Patients who responded better to treatment had greater network modularity and assortativity but lesser efficiency, a pattern that closely resembled the control participants. At a group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, but this was more pronounced among participants with less symptom improvement. The results support the hypothesis that modularized and resilient brain organization during emotion processing operate as mechanisms enabling symptom reduction during TF-CBT.

  4. Laboratory investigation of flux reduction from dense non-aqueous phase liquid (DNAPL) partial source zone remediation by enhanced dissolution.

    PubMed

    Kaye, Andrew J; Cho, Jaehyun; Basu, Nandita B; Chen, Xiaosong; Annable, Michael D; Jawitz, James W

    2008-11-14

    This study investigated the benefits of partial removal of dense nonaqueous phase liquid (DNAPL) source zones using enhanced dissolution in eight laboratory scale experiments. The benefits were assessed by characterizing the relationship between reductions in DNAPL mass and the corresponding reduction in contaminant mass flux. Four flushing agents were evaluated in eight controlled laboratory experiments to examine the effects of displacement fluid property contrasts and associated override and underride on contaminant flux reduction (R(j)) vs. mass reduction (R(m)) relationships (R(j)(R(m))): 1) 50% ethanol/50% water (less dense than water), 2) 40% ethyl-lactate/60% water (more dense than water), 3) 18% ethanol/26% ethyl-lactate/56% water (neutrally buoyant), and 4) 2% Tween-80 surfactant (also neutrally buoyant). For each DNAPL architecture evaluated, replicate experiments were conducted where source zone dissolution was conducted with a single flushing event to remove most of the DNAPL from the system, and with multiple shorter-duration floods to determine the path of the R(j)(R(m)) relationship. All of the single-flushing experiments exhibited similar R(j)(R(m)) relationships indicating that override and underride effects associated with cosolvents did not significantly affect the remediation performance of the agents. The R(j)(R(m)) relationship of the multiple injection experiments for the cosolvents with a density contrast with water tended to be less desirable in the sense that there was less R(j) for a given R(m). UTCHEM simulations supported the observations from the laboratory experiments and demonstrated the capability of this model to predict R(j)(R(m)) relationships for non-uniformly distributed NAPL sources.

  5. Benzoisothiazolone Organo/Copper-Cocatalyzed Redox Dehydrative Construction of Amides and Peptides from Carboxylic Acids using (EtO)3P as the Reductant and O2 in Air as the Terminal Oxidant.

    PubMed

    Liebeskind, Lanny S; Gangireddy, Pavankumar; Lindale, Matthew G

    2016-06-01

    Carboxylic acids and amine/amino acid reactants can be converted to amides and peptides at neutral pH within 5-36 h at 50 °C using catalytic quantities of a redox-active benzoisothiazolone and a copper complex. These catalytic "oxidation-reduction condensation" reactions are carried out open to dry air using O2 as the terminal oxidant and a slight excess of triethyl phosphite as the reductant. Triethyl phosphate is the easily removed byproduct. These simple-to-run catalytic reactions provide practical and economical procedures for the acylative construction of C-N bonds.

  6. Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats.

    PubMed

    Kading, Rebekah C; Kityo, Robert M; Mossel, Eric C; Borland, Erin M; Nakayiki, Teddie; Nalikka, Betty; Nyakarahuka, Luke; Ledermann, Jeremy P; Panella, Nicholas A; Gilbert, Amy T; Crabtree, Mary B; Peterhans, Julian Kerbis; Towner, Jonathan S; Amman, Brian R; Sealy, Tara K; Nichol, Stuart T; Powers, Ann M; Lutwama, Julius J; Miller, Barry R

    2018-01-01

    Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion:  Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats ( Epomophorus labiatus ) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.

  7. Transition from positive to neutral in mutation fixation along with continuing rising fitness in thermal adaptive evolution.

    PubMed

    Kishimoto, Toshihiko; Iijima, Leo; Tatsumi, Makoto; Ono, Naoaki; Oyake, Ayana; Hashimoto, Tomomi; Matsuo, Moe; Okubo, Masato; Suzuki, Shingo; Mori, Kotaro; Kashiwagi, Akiko; Furusawa, Chikara; Ying, Bei-Wen; Yomo, Tetsuya

    2010-10-21

    It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution.

  8. Characterization of the glycoprotein of infectious hematopoietic necrosis virus using neutralizing monoclonal antibodies

    USGS Publications Warehouse

    Huang, Chienjin; Chien, Maw-Sheng; Landolt, Marsha; Winton, James

    1994-01-01

    To study the antigenic nature of the glycoprotein (G protein) of infectious hematopoietic necrosis virus (IHNV), 31 neutralizing monoclonal antibodies (MAbs) were produced against a reference isolate of the virus. The MAbs were compared using a neutralization assay, an enzyme-linked immunosorbent assay (ELISA), and by immunoblotting of the G protein in the native, reduced, and deglycosylated forms. Hybridoma culture fluids of the various MAbs could be diluted from 1:2 to 1:512 and still completely neutralize 1 X 104 plaque-forming units of IHNV. Similarly, the end point dilutions that produced optical density readings of 0.1 or greater in the ELISA were 1:40 to 1:10240. Western blotting showed that all of the MAbs reacted with the G protein in the unreduced (i.e. native) conformation; however, only 9 nine of the MAbs were able to react with the G protein following reduction by 2-mercaptoethanol. Deglycosylation of the protein did not influence the binding ability of any of the MAbs. These data indicate that all the MAbs recognized amino acid sequences on the protein itself and that the IHNV glycoprotein contains linear as well as conformation-dependent neutralizing epitopes. When rainbow trout Oncorhynchus mykiss fingerlings were passively immunized with MAbs against either a linear or a conformation-dependent epitope, the fish were protected against challenge with wild-type IHNV.

  9. Unraveling Selection in the Mitochondrial Genome of Drosophila

    PubMed Central

    Ballard, JWO.; Kreitman, M.

    1994-01-01

    We examine mitochondrial DNA variation at the cytochrome b locus within and between three species of Drosophila to determine whether patterns of variation conform to the predictions of neutral molecular evolution. The entire 1137-bp cytochrome b locus was sequenced in 16 lines of Drosophila melanogaster, 18 lines of Drosophila simulans and 13 lines of Drosophila yakuba. Patterns of variation depart from neutrality by several test criteria. Analysis of the evolutionary clock hypothesis shows unequal rates of change along D. simulans lineages. A comparison within and between species of the ratio of amino acid replacement change to synonymous change reveals a relative excess of amino acid replacement polymorphism compared to the neutral prediction, suggestive of slightly deleterious or diversifying selection. There is evidence for excess homozygosity in our world wide sample of D. melanogaster and D. simulans alleles, as well as a reduction in the number of segregating sites in D. simulans, indicative of selective sweeps. Furthermore, a test of neutrality for codon usage shows the direction of mutations at third positions differs among different topological regions of the gene tree. The analyses indicate that molecular variation and evolution of mtDNA are governed by many of the same selective forces that have been shown to govern nuclear genome evolution and suggest caution be taken in the use of mtDNA as a ``neutral'' molecular marker. PMID:7851772

  10. Genetic depletion at adaptive but not neutral loci in an endangered bird species.

    PubMed

    Hartmann, Stefanie A; Schaefer, H Martin; Segelbacher, Gernot

    2014-12-01

    Many endangered species suffer from the loss of genetic diversity, but some populations may be able to thrive even if genetically depleted. To investigate the underlying genetic processes of population bottlenecks, we apply an innovative approach for assessing genetic diversity in the last known population of the endangered Pale-headed Brushfinch (Atlapetes pallidiceps) in Ecuador. First, we measure genetic diversity at eleven neutral microsatellite loci and adaptive SNP variation in five Toll-like receptor (TLR) immune system genes. Bottleneck tests confirm genetic drift as the main force shaping genetic diversity in this species and indicate a 99 % reduction in population size dating back several hundred years. Second, we compare contemporary microsatellite diversity with historic museum samples of A. pallidiceps, finding no change in genetic diversity. Third, we compare genetic diversity in the Pale-headed Brushfinch with two co-occurring-related brushfinch species (Atlapetes latinuchus, Buarremon torquatus), finding a reduction of up to 91% diversity in the immune system genes but not in microsatellites. High TLR diversity is linked to decreased survival probabilities in A. pallidiceps. Low TLR diversity is thus probably an adaptation to the specific selection regime within its currently very restricted distribution (approximately 200 ha), but could severely restrict the adaptive potential of the species in the long run. Our study illustrates the importance of investigating both neutral and adaptive markers to assess the effect of population bottlenecks and for recommending specific management plans in endangered species. © 2014 John Wiley & Sons Ltd.

  11. Impact of vitreomacular adhesion on ranibizumab mono- and combination therapy for neovascular age-related macular degeneration.

    PubMed

    Waldstein, Sebastian M; Ritter, Markus; Simader, Christian; Mayr-Sponer, Ulrike; Kundi, Michael; Schmidt-Erfurth, Ursula

    2014-08-01

    To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranibizumab monotherapy and verteporfin photodynamic therapy (PDT) combination therapy for neovascular age-related macular degeneration. Post hoc analysis of prospective randomized 12-month multicenter clinical trial data. Total of 255 treatment-naïve patients with subfoveal choroidal neovascularization. Assessment of the vitreomacular interface on monthly optical coherence tomography with division of patients into the following categories according to continuous 1-year grading: posterior vitreous detachment (n=154), dynamic release of vitreomacular adhesion (n=32), stable vitreomacular adhesion (n=51). Mean best-corrected visual acuity (BCVA) letter and central retinal thickness changes at month 12 in the vitreomacular interface groups. Mean BCVA changes at month 12 were +3.5 (posterior vitreous detachment), +4.3 (release of vitreomacular adhesion), and +6.3 (vitreomacular adhesion) in patients receiving monotherapy (P=.767), and +0.1 (posterior vitreous detachment), +6.6 (release of vitreomacular adhesion), and +9.2 (vitreomacular adhesion) in patients receiving combination therapy (P=.009). Mean central retinal thickness changes were -113 μm (posterior vitreous detachment), -89 μm (release of vitreomacular adhesion), and -122 μm (vitreomacular adhesion) in monotherapy (P=.725) and -121 μm (posterior vitreous detachment), -113 μm (release of vitreomacular adhesion), and -113 μm (vitreomacular adhesion) in combination therapy (P=.924). Mean ranibizumab retreatments during 12 months were 4.9 (posterior vitreous detachment), 6.6 (release of vitreomacular adhesion), and 5.3 (vitreomacular adhesion) in monotherapy (P=.018) and 4.7 (posterior vitreous detachment), 5.2 (release of vitreomacular adhesion), and 5.8 (vitreomacular adhesion) in combination therapy (P=.942). This study adds evidence that the vitreomacular interface status impacts functional outcomes and retreatment requirements. Patients with posterior vitreous detachment achieve acceptable results with fewer injections in PRN monotherapy, but lose potential vision gain with PDT. Patients with other vitreomacular interface configurations may potentially achieve optimized vision outcomes by combination of antiangiogenic treatment and vaso-occlusive PDT. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. More action needed: Psychotropic prescribing in Australian residential aged care.

    PubMed

    Westbury, Juanita; Gee, Peter; Ling, Tristan; Kitsos, Alex; Peterson, Gregory

    2018-02-01

    For at least two decades, concerns have been raised about inappropriate psychotropic prescribing in Australian residential aged care facilities, due to their modest therapeutic benefit and increased risk of falls and mortality. To date, the majority of prevalence data has been collected in Sydney exclusively and it is not known if recent initiatives to promote appropriate psychotropic prescribing have impacted utilisation. Thus, we aimed to comprehensively analyse psychotropic use in a large national sample of residential aged care facility residents. A cross-sectional, retrospective cohort study of residents from 150 residential aged care facilities distributed nationally during April 2014-October 2015. Antipsychotic, anxiolytic/hypnotic and antidepressant utilisation was assessed, along with anticonvulsant and anti-dementia drug use. Negative binomial regression analysis was used to examine variation in psychotropic use. Full psychotropic prescribing data was available from 11,368 residents. Nearly two-thirds (61%) were taking psychotropic agents regularly, with over 41% prescribed antidepressants, 22% antipsychotics and 22% of residents taking benzodiazepines. Over 30% and 11% were charted for 'prn' (as required) benzodiazepines and antipsychotics, respectively. More than 16% of the residents were taking sedating antidepressants, predominantly mirtazapine. South Australian residents were more likely to be taking benzodiazepines ( p < 0.05) and residents from New South Wales/Australian Capital Territory less likely to be taking them ( p < 0.01), after adjustment for rurality and size of residential aged care facility. Residents located in New South Wales/Australian Capital Territory were also significantly less likely to take antidepressants ( p < 0.01), as were residents from outer regional residential aged care facilities ( p < 0.01). Antipsychotic use was not associated with State, rurality or residential aged care facility size. Regular antipsychotic use appears to have decreased in residential aged care facilities but benzodiazepine prevalence is higher, particularly in South Australian residential aged care facilities. Sedating antidepressant and 'prn' psychotropic prescribing is widespread. Effective interventions to reduce the continued reliance on psychotropic management, in conjunction with active promotion of non-pharmacological strategies, are urgently required.

  13. Increase in pertussis cases along with high prevalence of two emerging genotypes of Bordetella pertussis in Perú, 2012.

    PubMed

    Bailon, H; León-Janampa, N; Padilla, C; Hozbor, D

    2016-08-17

    As has occurred in many regions worldwide, in 2012 the incidence of pertussis increased in Perú. This epidemiologic situation has been associated with a waning vaccine-induced immunity and the adaptation of Bordetella pertussis to vaccine-induced immunity along with improved diagnostic methods. The study comprised a total of 840 pertussis-suspected cases reported in Perú during 2012. We summarize here the distribution of pertussis cases according to age and immunization status along with the immunization-coverage rate. Laboratory diagnosis was performed by culture test and real-time polymerase-chain reaction (PCR). B. pertussis bacteria recovered from infected patients were characterized by pulsed-field gel electrophoresis (PFGE), and the DNA sequencing of the pertussis-toxin (promoter and subunit A), pertactin, and fimbriae (fim2 and fim3) genes. From the total pertussis-suspected cases, 191 (22.7 %) infections were confirmed by real-time PCR and 18 through cultivation of B. pertussis (2.1 %), while one infection of B. parapertussis (0.11 %) was also detected by culture. Pertussis was significantly higher in patients that had had 0-3 vaccine doses (pentavalent vaccine alone) than in those who had had 4-5 vaccine doses (pentavalent plus DwPT boosters) at 94.3 vs. 5.7 %, respectively (p < 0.00001). The relative risk (RR) for patients with 4-5 doses compared to those with fewer than 4 doses or no dose was 0.23 (95 % Confidence Interval: 0.11-0.44), while the vaccine effectiveness was 77 % and coverage 50.5 %. Genetic analysis of B. pertussis isolates from different Peruvian regions detected two clonal groups as identified by PFGE. Those two groups corresponded to the B. pertussis genotypes emerging worldwide ptxP3-ptxA1-prn2 or 9-fim3-1 and ptxP3-ptxA1-prn2 or 9-fim3-2. Two emerging B. pertussis genotypes similar to isolates involved in worldwide epidemics were detected in Perú. Low vaccine coverage (<50 %) and genetic divergence between the vaccine-producing strain and the local isolates could contribute to this pertussal epidemic.

  14. Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial.

    PubMed

    Brown, David M; Ou, William C; Wong, Tien P; Kim, Rosa Y; Croft, Daniel E; Wykoff, Charles C

    2018-05-01

    To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). Phase I/II prospective, randomized, controlled clinical trial. Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 μm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT improved 302 and 152 μm (P = 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P = 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P = 0.30). In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  15. Enhanced vanadium (V) reduction and bioelectricity generation in microbial fuel cells with biocathode

    NASA Astrophysics Data System (ADS)

    Qiu, Rui; Zhang, Baogang; Li, Jiaxin; Lv, Qing; Wang, Song; Gu, Qian

    2017-08-01

    Microbial fuel cells (MFCs) represent a promising approach for remediation of toxic vanadium (V) contaminated environment. Herein, enhanced V(V) reduction and bioelectricity generation are realized in MFCs with biocathode. Synergistically electrochemical and microbial reductions result in the nearly complete removals of V(V) within 7 d operation with initial concentration of 200 mg L-1. Maximum power density of 529 ± 12 mW m-2 is obtained. Electrochemical tests reveal that biocathode promotes electron transfers and reduces charge transfer resistance. XPS analysis confirms that V(IV) is the main reduction product, which precipitates naturally under neutral conditions. High-throughput 16S rRNA gene sequencing analysis indicates that the newly appeared Dysgonomonas is responsible for V(V) reduction and Klebsiella contributes mainly to bioelectricity generation in MFCs with biocathode. This study further improves the performance of remediating V(V) contaminated environment based on MFC technology.

  16. Serologic and mucosal immune response to rotavirus infection in the rabbit model.

    PubMed Central

    Conner, M E; Gilger, M A; Estes, M K; Graham, D Y

    1991-01-01

    We examined the humoral immune response to rotavirus infection in specific pathogen-free rabbits inoculated and challenged orally with rabbit Ala rotavirus (7.5 x 10(5) to 1 x 10(7) PFU). The humoral immune response in both serologic and mucosal samples was monitored by using total antibody enzyme-linked immunosorbent assays (ELISAs), isotype-specific ELISAs, and plaque reduction neutralization assays. Following a primary infection, all rabbits shed virus and serologic and mucosal antibody responses were initially detected by 1 week postinoculation. Intestinal immunoglobulin M was detected by 3 days postinoculation, and secretory immunoglobulin A was detected by 6 days postinoculation. Following challenge, rabbits were protected (no detectable virus shedding) from infection. An anamnestic immune response was observed only with mucosal neutralizing antibodies, and all serologic and mucosal immune responses persisted at high levels until at least 175 days postchallenge (204 days postinoculation). Detection of neutralization responses was influenced by the virus strain used in the neutralization assay; all inoculated rabbits developed detectable serum and intestinal neutralizing antibodies against the infecting (Ala) virus strain. Neutralization activity in both serum and mucosal samples was generally, but not exclusively, homotypic (VP7 serotype 3) after both primary and challenge inoculations with Ala virus. Heterotypic serum neutralization activity was observed with serotype 8 (9 of 12 rabbits) and 9 (12 of 12 rabbits) viruses and may be based on reactivity with the outer capsid protein VP4 or on a shared epitope in the C region of VP7. Comparisons of heterologous (serotype 3) and heterotypic neutralizing responses in mucosal and serologic samples revealed that 43% (21 of 49) of the responses were discordant. In 19 of 49 (39%) of these cases, a heterotypic serologic response was seen in the absence of a heterotypic mucosal response, but in 2 of 49 (4%) instances, a heterotypic mucosal response was seen in the absence of a concomitant serologic response. These results provide insight into factors which may affect detection of heterotypic responses. PMID:1850029

  17. Capillary Electrophoresis of Mono- and Oligosaccharides.

    PubMed

    Toppazzini, Mila; Coslovi, Anna; Rossi, Marco; Flamigni, Anna; Baiutti, Edi; Campa, Cristiana

    2016-01-01

    This chapter reports an overview of the recent advances in the analysis of mono- and oligosaccharides by capillary electrophoresis (CE); furthermore, relevant reviews and research articles recently published in the field are tabulated. Additionally, pretreatments and procedures applied to uncharged and acidic carbohydrates (i.e., monosaccharides and lower oligosaccharides carrying carboxylate, sulfate, or phosphate groups) are described.Representative examples of such procedures are reported in detail, upon describing robust methodologies for the study of (1) neutral oligosaccharides derivatized by reductive amination and by formation of glycosylamines; (2) sialic acid derivatized with 2-aminoacridone, released from human serum immunoglobulin G; (3) anomeric couples of neutral glycosides separated using borate-based buffers; (4) unsaturated, underivatized oligosaccharides from lyase-treated alginate.

  18. Biomass Compositional Analysis Laboratory Procedures | Bioenergy | NREL

    Science.gov Websites

    Compositional Analysis This procedure describes methods for sample drying and size reduction, obtaining samples methods used to determine the amount of solids or moisture present in a solid or slurry biomass sample as values? We have found that neutral detergent fiber (NDF) and acid detergent fiber (ADF) methods report

  19. Schools under Pressure: The External Environment and Recent Organizational Reforms.

    ERIC Educational Resources Information Center

    Salganik, Laura H.

    Reductions in resources and increases in external demands place schools under pressure that can be relieved to some extent by organizational changes. When resources are sufficient, these changes may take the form of technical rationality--that is, decisions concerning policy and practices are made on the basis of neutral, measurable data rather…

  20. 40 CFR 430.33 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... times. Subpart C [BCT effluent limitations for unbleached kraft-neutral sulfite semi-chemical (cross recovery) process and/or a combined unbleached kraft and semi-chemical process, wherein the spent semi-chemical cooking liquor is burned within the unbleached kraft chemical recovery system] Pollutant or...

  1. 40 CFR 430.33 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... times. Subpart C [BCT effluent limitations for unbleached kraft-neutral sulfite semi-chemical (cross recovery) process and/or a combined unbleached kraft and semi-chemical process, wherein the spent semi-chemical cooking liquor is burned within the unbleached kraft chemical recovery system] Pollutant or...

  2. Metal-Folded Single-Chain Nanoparticle: Nanoclusters and Self-Assembled Reduction-Responsive Sub-5-nm Discrete Subdomains.

    PubMed

    Cao, Hui; Cui, Zhigang; Gao, Pan; Ding, Yi; Zhu, Xuechao; Lu, Xinhua; Cai, Yuanli

    2017-09-01

    Easy access to discrete nanoclusters in metal-folded single-chain nanoparticles (metal-SCNPs) and independent ultrafine sudomains in the assemblies via coordination-driven self-assembly of hydrophilic copolymer containing 9% imidazole groups is reported herein. 1 H NMR, dynamic light scattering, and NMR diffusion-ordered spectroscopy results demonstrate self-assembly into metal-SCNPs (>70% imidazole-units folded) by neutralization in the presence of Cu(II) in water to pH 4.6. Further neutralization induces self-assembly of metal-SCNPs (pH 4.6-5.0) and shrinkage (pH 5.0-5.6), with concurrent restraining residual imidazole motifs and hydrophilic segment, which organized into constant nanoparticles over pH 5.6-7.5. Atomic force microscopy results evidence discrete 1.2 nm nanoclusters and sub-5-nm subdomains in metal-SCNP and assembled nanoparticle. Reduction of metal center using sodium ascorbate induces structural rearrangement to one order lower than the precursor. Enzyme mimic catalysis required media-tunable discrete ultrafine interiors in metal-SCNPs and assemblies have hence been achieved. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes

    PubMed Central

    Vaidya, Sunil R.; Dvivedi, Garima M.; Jadhav, Santoshkumar M.

    2016-01-01

    Background & objectives: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. Methods: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. Results: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Interpretation & conclusions: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. PMID:26997012

  4. Enhanced Neutralization Potency of Botulinum Neurotoxin Antibodies Using a Red Blood Cell-Targeting Fusion Protein

    PubMed Central

    Adekar, Sharad P.; Segan, Andrew T.; Chen, Cindy; Bermudez, Rodney; Elias, M. D.; Selling, Bernard H.; Kapadnis, B. P.; Simpson, Lance L.; Simon, Paul M.; Dessain, Scott K.

    2011-01-01

    Botulinum neurotoxin (BoNT) potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC) in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP) to link biotinylated molecules to glycophorin A (GPA) on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo. PMID:21399689

  5. Suppression of diamagnetism by neutrals pressure in partially ionized, high-beta plasma

    NASA Astrophysics Data System (ADS)

    Shinohara, Shunjiro; Kuwahara, Daisuke; Yano, Kazuki; Fruchtman, Amnon

    2016-12-01

    Suppression of diamagnetism in a partially ionized plasma with high beta was experimentally investigated by the use of Langmuir and Hall sensor probes, focusing on a neutrals pressure effect. The plasma beta, which is the ratio of plasma to vacuum magnetic pressures, varied from ˜1% to >100% while the magnetic field varied from ˜120 G to ˜1 G. Here, a uniform magnetized argon plasma was operated mostly in an inductive mode, using a helicon plasma source of the Large Helicon Plasma Device [S. Shinohara et al., Phys. Plasmas 16, 057104 (2009)] with a diameter of 738 mm and an axial length of 4860 mm. Electron density varied from 5 × 1015 m-3 to <3 × 1018 m-3, while an argon fill pressure was varied from ˜0.02 Pa to 0.75 Pa as well as the magnetic field mentioned above, with the fixed radio frequency (rf) and power of 7 MHz and ˜3.5 kW, respectively. The observed magnetic field reduction rate, a decrease of the magnetic field divided by the vacuum one, was up to 18%. However, in a certain parameter regime, where the product of ion and electron Hall terms is a key parameter, the measured diamagnetic effect was smaller than that expected by the plasma beta. This suppressed diamagnetism is explained by the neutrals pressure replacing magnetic pressure in balancing plasma pressure. Diamagnetism is weakened if neutrals pressure is comparable to the plasma pressure and if the coupling of plasma and neutrals pressures by ion-neutral collisions is strong enough.

  6. Engineering a synthetic anaerobic respiration for reduction of xylose to xylitol using NADH output of glucose catabolism by Escherichia coli AI21.

    PubMed

    Iverson, Andrew; Garza, Erin; Manow, Ryan; Wang, Jinhua; Gao, Yuanyuan; Grayburn, Scott; Zhou, Shengde

    2016-04-16

    Anaerobic rather than aerobic fermentation is preferred for conversion of biomass derived sugars to high value redox-neutral and reduced commodities. This will likely result in a higher yield of substrate to product conversion and decrease production cost since substrate often accounts for a significant portion of the overall cost. To this goal, metabolic pathway engineering has been used to optimize substrate carbon flow to target products. This approach works well for the production of redox neutral products such as lactic acid from redox neutral sugars using the reducing power NADH (nicotinamide adenine dinucleotide, reduced) generated from glycolysis (2 NADH per glucose equivalent). Nevertheless, greater than two NADH per glucose catabolized is needed for the production of reduced products (such as xylitol) from redox neutral sugars by anaerobic fermentation. The Escherichia coli strain AI05 (ΔfrdBC ΔldhA ΔackA Δ(focA-pflB) ΔadhE ΔptsG ΔpdhR::pflBp 6-(aceEF-lpd)), previously engineered for reduction of xylose to xylitol using reducing power (NADH equivalent) of glucose catabolism, was further engineered by 1) deleting xylAB operon (encoding for xylose isomerase and xylulokinase) to prevent xylose from entering the pentose phosphate pathway; 2) anaerobically expressing the sdhCDAB-sucABCD operon (encoding for succinate dehydrogenase, α-ketoglutarate dehydrogenase and succinyl-CoA synthetase) to enable an anaerobically functional tricarboxcylic acid cycle with a theoretical 10 NAD(P)H equivalent per glucose catabolized. These reducing equivalents can be oxidized by synthetic respiration via xylose reduction, producing xylitol. The resulting strain, AI21 (pAI02), achieved a 96 % xylose to xylitol conversion, with a yield of 6 xylitol per glucose catabolized (molar yield of xylitol per glucose consumed (YRPG) = 6). This represents a 33 % improvement in xylose to xylitol conversion, and a 63 % increase in xylitol yield per glucose catabolized over that achieved by AI05 (pAI02). Increasing reducing power (NADH equivalent) output per glucose catabolized was achieved by anaerobic expression of both the pdh operon (pyruvate dehydrogenase) and the sdhCDAB-sucABCD operon, resulting in a strain capable of generating 10 NADH equivalent per glucose under anaerobic condition. The new E. coli strain AI21 (pAI02) achieved an actual 96 % conversion of xylose to xylitol (via synthetic respiration), and 6 xylitol (from xylose) per glucose catabolized (YRPG = 6, the highest known value). This strategy can be used to engineer microbial strains for the production of other reduced products from redox neutral sugars using glucose as a source of reducing power.

  7. Current profile redistribution driven by neutral beam injection in a reversed-field pinch

    NASA Astrophysics Data System (ADS)

    Parke, E.; Anderson, J. K.; Brower, D. L.; Den Hartog, D. J.; Ding, W. X.; Johnson, C. A.; Lin, L.

    2016-05-01

    Neutral beam injection in reversed-field pinch (RFP) plasmas on the Madison Symmetric Torus [Dexter et al., Fusion Sci. Technol. 19, 131 (1991)] drives current redistribution with increased on-axis current density but negligible net current drive. Internal fluctuations correlated with tearing modes are observed on multiple diagnostics; the behavior of tearing mode correlated structures is consistent with flattening of the safety factor profile. The first application of a parametrized model for island flattening to temperature fluctuations in an RFP allows inferrence of rational surface locations for multiple tearing modes. The m = 1, n = 6 mode is observed to shift inward by 1.1 ± 0.6 cm with neutral beam injection. Tearing mode rational surface measurements provide a strong constraint for equilibrium reconstruction, with an estimated reduction of q0 by 5% and an increase in on-axis current density of 8% ± 5%. The inferred on-axis current drive is consistent with estimates of fast ion density using TRANSP [Goldston et al., J. Comput. Phys. 43, 61 (1981)].

  8. Eliciting Affect via Immersive Virtual Reality: A Tool for Adolescent Risk Reduction

    PubMed Central

    Houck, Christopher D.; Barker, David H.; Garcia, Abbe Marrs; Spitalnick, Josh S.; Curtis, Virginia; Roye, Scott; Brown, Larry K.

    2014-01-01

    Objective A virtual reality environment (VRE) was designed to expose participants to substance use and sexual risk-taking cues to examine the utility of VR in eliciting adolescent physiological arousal. Methods 42 adolescents (55% male) with a mean age of 14.54 years (SD = 1.13) participated. Physiological arousal was examined through heart rate (HR), respiratory sinus arrhythmia (RSA), and self-reported somatic arousal. A within-subject design (neutral VRE, VR party, and neutral VRE) was utilized to examine changes in arousal. Results The VR party demonstrated an increase in physiological arousal relative to a neutral VRE. Examination of individual segments of the party (e.g., orientation, substance use, and sexual risk) demonstrated that HR was significantly elevated across all segments, whereas only the orientation and sexual risk segments demonstrated significant impact on RSA. Conclusions This study provides preliminary evidence that VREs can be used to generate physiological arousal in response to substance use and sexual risk cues. PMID:24365699

  9. Description of a Prospective 17DD Yellow Fever Vaccine Cohort in Recife, Brazil

    PubMed Central

    de Melo, Andréa Barbosa; da Silva, Maria da Paz C.; Magalhães, Maria Cecília F.; Gonzales Gil, Laura Helena Vega; Freese de Carvalho, Eduardo M.; Braga-Neto, Ulisses M.; Bertani, Giovani Rota; Marques, Ernesto T. A.; Cordeiro, Marli Tenório

    2011-01-01

    From September 2005 to March 2007, 238 individuals being vaccinated for the first time with the yellow fever (YF) -17DD vaccine were enrolled in a cohort established in Recife, Brazil. A prospective study indicated that, after immunization, anti-YF immunoglobulin M (IgM) and anti-YF IgG were present in 70.6% (IgM) and 98.3% (IgG) of the vaccinated subjects. All vaccinees developed protective immunity, which was detected by the plaque reduction neutralization test (PRNT) with a geometric mean titer of 892. Of the 238 individuals, 86.6% had IgG antibodies to dengue virus; however, the presence of anti-dengue IgG did not interfere significantly with the development of anti-YF neutralizing antibodies. In a separate retrospective study of individuals immunized with the 17DD vaccine, the PRNT values at 5 and 10 years post-vaccination remained positive but showed a significant decrease in neutralization titer (25% with PRNT titers < 100 after 5 years and 35% after 10 years). PMID:21976581

  10. Search for active-sterile neutrino mixing using neutral-current interactions in NOvA

    NASA Astrophysics Data System (ADS)

    Adamson, P.; Aliaga, L.; Ambrose, D.; Anfimov, N.; Antoshkin, A.; Arrieta-Diaz, E.; Augsten, K.; Aurisano, A.; Backhouse, C.; Baird, M.; Bambah, B. A.; Bays, K.; Behera, B.; Bending, S.; Bernstein, R.; Bhatnagar, V.; Bhuyan, B.; Bian, J.; Blackburn, T.; Bolshakova, A.; Bromberg, C.; Brown, J.; Brunetti, G.; Buchanan, N.; Butkevich, A.; Bychkov, V.; Campbell, M.; Catano-Mur, E.; Childress, S.; Choudhary, B. C.; Chowdhury, B.; Coan, T. E.; Coelho, J. A. B.; Colo, M.; Cooper, J.; Corwin, L.; Cremonesi, L.; Cronin-Hennessy, D.; Davies, G. S.; Davies, J. P.; Derwent, P. F.; Dharmapalan, R.; Ding, P.; Djurcic, Z.; Dukes, E. C.; Duyang, H.; Edayath, S.; Ehrlich, R.; Feldman, G. J.; Frank, M. J.; Gabrielyan, M.; Gallagher, H. R.; Germani, S.; Ghosh, T.; Giri, A.; Gomes, R. A.; Goodman, M. C.; Grichine, V.; Groh, M.; Group, R.; Grover, D.; Guo, B.; Habig, A.; Hartnell, J.; Hatcher, R.; Hatzikoutelis, A.; Heller, K.; Himmel, A.; Holin, A.; Howard, B.; Hylen, J.; Jediny, F.; Judah, M.; Kafka, G. K.; Kalra, D.; Kasahara, S. M. S.; Kasetti, S.; Keloth, R.; Kolupaeva, L.; Kotelnikov, S.; Kourbanis, I.; Kreymer, A.; Kumar, A.; Kurbanov, S.; Lackey, T.; Lang, K.; Lee, W. M.; Lin, S.; Lokajicek, M.; Lozier, J.; Luchuk, S.; Maan, K.; Magill, S.; Mann, W. A.; Marshak, M. L.; Matera, K.; Matveev, V.; Méndez, D. P.; Messier, M. D.; Meyer, H.; Miao, T.; Miller, W. H.; Mishra, S. R.; Mohanta, R.; Moren, A.; Mualem, L.; Muether, M.; Mufson, S.; Murphy, R.; Musser, J.; Nelson, J. K.; Nichol, R.; Niner, E.; Norman, A.; Nosek, T.; Oksuzian, Y.; Olshevskiy, A.; Olson, T.; Paley, J.; Patterson, R. B.; Pawloski, G.; Pershey, D.; Petrova, O.; Petti, R.; Phan-Budd, S.; Plunkett, R. K.; Poling, R.; Potukuchi, B.; Principato, C.; Psihas, F.; Radovic, A.; Rameika, R. A.; Rebel, B.; Reed, B.; Rocco, D.; Rojas, P.; Ryabov, V.; Sachdev, K.; Sail, P.; Samoylov, O.; Sanchez, M. C.; Schroeter, R.; Sepulveda-Quiroz, J.; Shanahan, P.; Sheshukov, A.; Singh, J.; Singh, J.; Singh, P.; Singh, V.; Smolik, J.; Solomey, N.; Song, E.; Sousa, A.; Soustruznik, K.; Strait, M.; Suter, L.; Talaga, R. L.; Tas, P.; Thayyullathil, R. B.; Thomas, J.; Tian, X.; Tognini, S. C.; Tripathi, J.; Tsaris, A.; Urheim, J.; Vahle, P.; Vasel, J.; Vinton, L.; Vold, A.; Vrba, T.; Wang, B.; Wetstein, M.; Whittington, D.; Wojcicki, S. G.; Wolcott, J.; Yadav, N.; Yang, S.; Zalesak, J.; Zamorano, B.; Zwaska, R.; NOvA Collaboration

    2017-10-01

    We report results from the first search for sterile neutrinos mixing with active neutrinos through a reduction in the rate of neutral-current interactions over a baseline of 810 km between the NOvA detectors. Analyzing a 14-kton detector equivalent exposure of 6.05 ×1020 protons-on-target in the NuMI beam at Fermilab, we observe 95 neutral-current candidates at the Far Detector compared with 83.5 ±9.7 (stat ) ±9.4 (syst ) events predicted assuming mixing only occurs between active neutrino species. No evidence for νμ→νs transitions is found. Interpreting these results within a 3 +1 model, we place constraints on the mixing angles θ24<20.8 ° and θ34<31.2 ° at the 90% C.L. for 0.05 eV2≤Δ m412≤0.5 eV2 , the range of mass splittings that produce no significant oscillations over the Near Detector baseline.

  11. Hydrobiogeochemical interactions in 'anoxic' limestone drains for neutralization of acidic mine drainage

    USGS Publications Warehouse

    Robbins, E.I.; Cravotta, C.A.; Savela, C.E.; Nord, G.L.

    1999-01-01

    Processes affecting neutralization of acidic coal mine drainage were evaluated within 'anoxic' limestone drains (ALDs). Influents had pH???3.5 and dissolved oxygen <2 mg/l. Even though effluents were near neutral (pH 6 and alkalinity acidity), two of the four ALDs were failing due to clogging. Mineral-saturation indices indicated the potential for dissolution of calcite and gypsum, and precipitation of Al3+ and Fe3+ compounds. Cleavage mounts of calcite and gypsum that were suspended within the ALDs and later examined microscopically showed dissolution features despite coatings by numerous bacteria, biofilms, and Fe-Al-Si precipitates. In the drain exhibiting the greatest flow reduction, Al-hydroxysulfates had accumulated on limestone surfaces and calcite etch points, thus causing the decline in transmissivity and dissolution. Therefore, where Al loadings are high and flow rates are low, a pre-treatment step is indicated to promote Al removal before diverting acidic mine water into alkalinity-producing materials. ?? 1998 Elsevier Science Ltd.

  12. Variations in thermo-optical properties of neutral red dye with laser ablated gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Prakash, Anitha; Pathrose, Bini P.; Mathew, S.; Nampoori, V. P. N.; Radhakrishnan, P.; Mujeeb, A.

    2018-05-01

    We have investigated the thermal and optical properties of neutral red dye incorporated with different weight percentage of gold nanoparticles prepared by laser ablation method. Optical absorption studies confirmed the production of spherical nanoparticles and also the interactions of the dye molecules with gold nanoparticles. The quenching of fluorescence and the reduction in the lifetime of gold incorporated samples were observed and was due to the non-radiative energy transfer between the dye molecules and gold nanoparticles. Dual beam thermal lens technique has been employed to measure the heat diffusion in neutral red with various weight percentage of gold nano sol dispersed in ethanol. The significant outcome of the experiment is that, the overall heat diffusion is slower in the presence of gold nano sol compared to that of dye alone sample. Brownian motion is suggested to be the main mechanism of heat transfer under the present conditions. The thermal diffusivity variations of samples with respect to different excitation power of laser were also studied.

  13. Study of the combined effect of electro-activated solutions and heat treatment on the destruction of spores of Clostridium sporogenes and Geobacillus stearothermophilus in model solution and vegetable puree.

    PubMed

    Liato, Viacheslav; Labrie, Steve; Viel, Catherine; Benali, Marzouk; Aïder, Mohammed

    2015-10-01

    The combined effect of heat treatment and electro-activated solution (EAS) on the heat resistance of spores of Clostridium sporogenes and Geobacillus stearothermophilus was assessed under various heating and exposure time combinations. The acid and neutral EAS showed the highest inhibitory activity, indicating that these solutions may be considered as strong sporicidal disinfectants. These EAS were able to cause a reduction of ≥6 log of spores of C. sporogenes at 60 °C in only 1 min of exposition. For G. stearothermophilus spores, a reduction of 4.5 log was observed at 60 °C in 1 min, while in 5 min, ≥7 log CFU/ml reduction was observed. Inoculated puree of pea and corn were used as a food matrix for the determination of the heat resistance of these spores during the treatments in glass capillaries. The inactivation kinetics of the spores was studied in an oil bath. Combined treatment by EAS and temperature demonstrated a significant decrease in the heat resistance of C. sporogenes. The D100°C in pea puree with NaCl solution was 66.86 min while with acid and neutral EAS it was reduced down to 3.97 and 2.19 min, respectively. The spore of G. stearothermophilus displayed higher heat resistance as confirmed by other similar studies. Its D130°C in pea puree showed a decrease from 1.45 min in NaCl solution down to 1.30 and 0.93 min for acid and neutral EAS, respectively. The differences between the spores of these species are attributable to their different sensitivities with respect to pH, Redox potential and oxygen. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Efficacy of Neutral pH Electrolyzed Water in Reducing Escherichia coli O157:H7 and Salmonella Typhimurium DT 104 on Fresh Produce Items using an Automated Washer at Simulated Food Service Conditions.

    PubMed

    Afari, George K; Hung, Yen-Con; King, Christopher H

    2015-08-01

    The objective of this study was to determine the efficacy of neutral pH electrolyzed (NEO) water (155 mg/L free chlorine, pH 7.5) in reducing Escherichia coli O157:H7 and Salmonella Typhimurium DT 104 on romaine lettuce, iceberg lettuce, and tomatoes washed in an automated produce washer for different times and washing speeds. Tomatoes and lettuce leaves were spot inoculated with 100 μL of a 5 strain cocktail mixture of either pathogen and washed with 10 or 8 L of NEO water, respectively. Washing lettuce for 30 min at 65 rpm led to the greatest reductions, with 4.2 and 5.9 log CFU/g reductions achieved for E. coli O157:H7 and S. Typhimurium respectively on romaine, whereas iceberg lettuce reductions were 3.2 and 4.6 log CFU/g for E. coli O157:H7 and S. Typhimurium respectively. Washing tomatoes for 10 min at 65 rpm achieved reductions greater than 8 and 6 log CFU/tomato on S. Typhimurium and E. coli O157:H7 respectively. All pathogens were completely inactivated in NEO water wash solutions. No detrimental effects on the visual quality of the produce studied were observed under all treatment conditions. Results show the adoption of this washing procedure in food service operations could be useful in ensuring produce safety. © 2015 Institute of Food Technologists®

  15. NEXT Long-Duration Test Neutralizer Performance and Erosion Characteristics

    NASA Technical Reports Server (NTRS)

    Herman, Daniel A.; Soulas, George C.; Patterson, Michael J.

    2009-01-01

    The NASA's Evolutionary Xenon Thruster (NEXT) program is developing the next-generation ion propulsion system with significant enhancements beyond the state-of-the-art to provide future NASA science missions with enhanced capabilities at a low total development cost. A Long-Duration Test (LDT) was initiated in June 2005, to verify the NEXT propellant throughput capability to a qualification-level of 450 kg, 1.5 times the anticipated throughput requirement of 300 kg per thruster based on mission analyses. As of September 2, 2009, the thruster has accumulated 24,400 hr of operation with extensive durations at the following input powers: 6.9, 4.7, 1.1, and 0.5 kW. The thruster has processed 434 kg of xenon, surpassing the NASA Solar Technology Application Readiness (NSTAR) program thruster propellant throughput demonstrated during the extended life testing of the Deep Space 1 flight spare ion thruster and approaching the NEXT development qualification throughput goal of 450 kg. The NEXT LDT has demonstrated a total impulse of 16.1 10(exp 6zzz0 N s; the highest total impulse ever demonstrated by an ion thruster. A reduction in neutralizer flow margin has been the only appreciable source of thruster performance degradation. The behavior of the neutralizer is not easily predicted due to both erosion and deposition observed in previous wear tests. Spot-to-plume mode transition flow data and in-situ erosion results for the LDT neutralizer are discussed. This loss of flow margin has been addressed through a combination of a design change in the prototype-model neutralizer to increase flow margin at low emission current and to update the NEXT throttle table to ensure adequate flow margin as a function of propellant throughput processed. The new throttle table will be used for future LDT operations. The performance of the NEXT LDT neutralizer is consistent with that observed for long-life hollow cathodes. The neutralizer life-limiting failure modes are progressing as expected and the neutralizer data indicate none of the neutralizer failures are imminent.

  16. Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.

    PubMed

    Wong, Terianne M; Petrovsky, Nikolai; Bissel, Stephanie J; Wiley, Clayton A; Ross, Ted M

    2016-08-02

    Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which Advax TM adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either Advax TM adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with Advax TM was similar to Imject Alum. Overall, RSV vaccine formulated with Advax TM had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared to unvaccinated mice.

  17. Analysis by RNA-RNA hybridization assay of intertypic rotaviruses suggests that gene reassortment occurs in vivo.

    PubMed Central

    Midthun, K; Valdesuso, J; Hoshino, Y; Flores, J; Kapikian, A Z; Chanock, R M

    1987-01-01

    Antigenic characterization of human and animal rotaviruses by the plaque reduction neutralization assay has shown the existence of naturally occurring intertypes. Antiserum to M37, a rotavirus strain isolated from an asymptomatic neonate, neutralizes both Wa and ST3 strains, which are classified as serotype 1 and serotype 4 human rotaviruses, respectively. Likewise, antiserum to SB-1A, a porcine rotavirus, neutralizes rotavirus strains belonging to serotype 4 or 5. Plaque reduction neutralization assay of reassortant rotaviruses produced in vitro from these intertypes indicates that these viruses share one antigenically related outer capsid protein, VP3, with one serotype and another antigenically related outer capsid protein, VP7, with the other serotype. Thus, M37 is related to ST3 on the basis of its fourth-gene product, VP3, and to Wa on the basis of its ninth-gene product, VP7, whereas SB-1A is related to Gottfried (serotype 4 porcine rotavirus) via VP7 and to OSU (serotype 5 porcine rotavirus) via VP3. RNA-RNA hybridization studies revealed a high degree of homology between the VP3 or VP7 gene segments responsible for shared serotype specificity. Thus, the fourth gene segments of M37 and ST3 were highly homologous, while M37 and Wa had homology between their ninth gene segments. SB-1A and Gottfried were homologous not only with respect to the ninth gene but had complete homology in all other genes except the fourth gene. The fourth gene of SB-1A was highly homologous with the fourth gene of OSU. These observations suggested that SB-1A was a naturally occurring reassortant between Gottfried-like and OSU-like porcine rotavirus strains. Our observations also suggested that intertypes may result from genetic reassortment in nature. Images PMID:3029162

  18. A Technique for the Growth of Epidermal Sheets Obtained from Patients Undergoing Reduction Mammoplasty.

    DTIC Science & Technology

    1991-03-06

    flask with Dispase, a neutral protease and attached to petrolatum gauze. At this point the sheets could be used as skin grafts . Progress: 1...a composite in vitro skin graft . We believe that development of an artificial dermis as part of a composite in vitro graft is where our future

  19. ISE structural dynamic experiments

    NASA Technical Reports Server (NTRS)

    Lock, Malcolm H.; Clark, S. Y.

    1988-01-01

    The topics are presented in viewgraph form and include the following: directed energy systems - vibration issue; Neutral Particle Beam Integrated Space Experiment (NPB-ISE) opportunity/study objective; vibration sources/study plan; NPB-ISE spacecraft configuration; baseline slew analysis and results; modal contributions; fundamental pitch mode; vibration reduction approaches; peak residual vibration; NPB-ISE spacecraft slew experiment; goodbye ISE - hello Zenith Star Program.

  20. Synthesis and characterization of Pd(II)-methyl complexes with N-heterocyclic carbene-amine ligands.

    PubMed

    Warsink, Stefan; de Boer, Sandra Y; Jongens, Lianne M; Fu, Ching-Feng; Liu, Shiuh-Tzung; Chen, Jwu-Ting; Lutz, Martin; Spek, Anthony L; Elsevier, Cornelis J

    2009-09-21

    A number of palladium(ii) complexes with a heteroditopic NHC-amine ligand and their precursor silver(i) carbene complexes have been efficiently prepared and their structural features have been investigated. The heteroditopic coordination of this ligand class was unequivocally shown by NMR-spectroscopy and X-ray crystallographic analysis. The neutral and cationic cis-methyl-palladium(NHC) complexes are not prone to reductive elimination, which is normally a major degenerative pathway for this type of complex. In contrast, under carbon monoxide atmosphere rapid reductive elimination of the acyl-imidazolium salt was observed.

  1. Generation of Monoclonal Antibodies against Dengue Virus Type 4 and Identification of Enhancing Epitopes on Envelope Protein.

    PubMed

    Tang, Chung-Tao; Liao, Mei-Ying; Chiu, Chien-Yu; Shen, Wen-Fan; Chiu, Chiung-Yi; Cheng, Ping-Chang; Chang, Gwong-Jen J; Wu, Han-Chung

    2015-01-01

    The four serotypes of dengue virus (DENV1-4) pose a serious threat to global health. Cross-reactive and non-neutralizing antibodies enhance viral infection, thereby exacerbating the disease via antibody-dependent enhancement (ADE). Studying the epitopes targeted by these enhancing antibodies would improve the immune responses against DENV infection. In order to investigate the roles of antibodies in the pathogenesis of dengue, we generated a panel of 16 new monoclonal antibodies (mAbs) against DENV4. Using plaque reduction neutralization test (PRNT), we examined the neutralizing activity of these mAbs. Furthermore, we used the in vitro and in vivo ADE assay to evaluate the enhancement of DENV infection by mAbs. The results indicate that the cross-reactive and poorly neutralizing mAbs, DD11-4 and DD18-5, strongly enhance DENV1-4 infection of K562 cells and increase mortality in AG129 mice. The epitope residues of these enhancing mAbs were identified using virus-like particle (VLP) mutants. W212 and E26 are the epitope residues of DD11-4 and DD18-5, respectively. In conclusion, we generated and characterized 16 new mAbs against DENV4. DD11-4 and D18-5 possessed non-neutralizing activities and enhanced viral infection. Moreover, we identified the epitope residues of enhancing mAbs on envelope protein. These results may provide useful information for development of safe dengue vaccine.

  2. Immune correlates of protection against yellow fever determined by passive immunization and challenge in the hamster model.

    PubMed

    Julander, Justin G; Trent, Dennis W; Monath, Thomas P

    2011-08-11

    Live, attenuated yellow fever (YF) 17D vaccine is highly efficacious but causes rare, serious adverse events resulting from active replication in the host and direct viral injury to vital organs. We recently reported development of a potentially safer β-propiolactone-inactivated whole virion YF vaccine (XRX-001), which was highly immunogenic in mice, hamsters, monkeys, and humans [10,11]. To characterize the protective efficacy of neutralizing antibodies stimulated by the inactivated vaccine, graded doses of serum from hamsters immunized with inactivated XRX-001 or live 17D vaccine were transferred to hamsters by the intraperitoneal (IP) route 24h prior to virulent, viscerotropic YF virus challenge. Neutralizing antibody (PRNT(50)) titers were determined in the sera of treated animals 4h before challenge and 4 and 21 days after challenge. Neutralizing antibodies were shown to mediate protection. Animals having 50% plaque reduction neutralization test (PRNT(50)) titers of ≥40 4h before challenge were completely protected from disease as evidenced by viremia, liver enzyme elevation, and protection against illness (weight change) and death. Passive titers of 10-20 were partially protective. Immunization with the XRX-001 vaccine stimulated YF neutralizing antibodies that were equally effective (based on dose response) as antibodies stimulated by live 17D vaccine. The results will be useful in defining the level of seroprotection in clinical studies of new yellow fever vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Charged aerodynamics of a Low Earth Orbit cylinder

    NASA Astrophysics Data System (ADS)

    Capon, C. J.; Brown, M.; Boyce, R. R.

    2016-11-01

    This work investigates the charged aerodynamic interaction of a Low Earth Orbiting (LEO) cylinder with the ionosphere. The ratio of charge to neutral drag force on a 2D LEO cylinder with diffusely reflecting cool walls is derived analytically and compared against self-consistent electrostatic Particle-in-Cell (PIC) simulations. Analytical calculations predict that neglecting charged drag in an O+ dominated LEO plasma with a neutral to ion number density ratio of 102 will cause a 10% over-prediction of O density based on body accelerations when body potential (ɸB) is ≤ -390 V. Above 900 km altitude in LEO, where H+ becomes the dominant ion species, analytical predictions suggest charge drag becomes equivalent to neutral drag for ɸB ≤ -0.75 V. Comparing analytical predictions against PIC simulations in the range of 0 < - ɸB < 50 V found that analytical charged drag was under-estimated for all body potentials; the degree of under-estimation increasing with ɸB. Based on the -50 V PIC simulations, our in-house 6 degree of freedom orbital propagator saw a reduction in the semi-major axis of a 10 kg satellite at 700 km of 6.9 m/day and 0.98 m/day at 900 km compared that caused purely by neutral drag - 0.67 m/day and 0.056 m/day respectively. Hence, this work provides initial evidence that charged aerodynamics may become significant compared to neutral aerodynamics for high voltage LEO bodies.

  4. A molecular molybdenum-oxo catalyst for generating hydrogen from water.

    PubMed

    Karunadasa, Hemamala I; Chang, Christopher J; Long, Jeffrey R

    2010-04-29

    A growing awareness of issues related to anthropogenic climate change and an increase in global energy demand have made the search for viable carbon-neutral sources of renewable energy one of the most important challenges in science today. The chemical community is therefore seeking efficient and inexpensive catalysts that can produce large quantities of hydrogen gas from water. Here we identify a molybdenum-oxo complex that can catalytically generate gaseous hydrogen either from water at neutral pH or from sea water. This work shows that high-valency metal-oxo species can be used to create reduction catalysts that are robust and functional in water, a concept that has broad implications for the design of 'green' and sustainable chemistry cycles.

  5. [Cardiovascular Effects of Antidiabetic Therapies].

    PubMed

    Laubner, Katharina; Seufert, Jochen

    2017-05-01

    Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin. Concerning GLP-1-RAs, Lixisenatide has a neutral cardiovascular effect, whereas Liraglutide and Semaglutide reduce cardiovascular outcomes. The SGLT2-inhibitor Empagliflozin reduces cardiovascular mortality, total mortality and hospitalization by heart failure. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Reduction of the misinformation effect by arousal induced after learning.

    PubMed

    English, Shaun M; Nielson, Kristy A

    2010-11-01

    Misinformation introduced after events have already occurred causes errors in later retrieval. Based on literature showing that arousal induced after learning enhances delayed retrieval, we investigated whether post-learning arousal can reduce the misinformation effect. 251 participants viewed four short film clips, each followed by a retention test, which for some participants included misinformation. Afterward, participants viewed another film clip that was either arousing or neutral. One week later, the arousal group recognized significantly more veridical details and endorsed significantly fewer misinformation items than the neutral group. The findings suggest that arousal induced after learning reduced source confusion, allowing participants to better retrieve accurate details and to better reject misinformation. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Can Gender-Fair Language Reduce Gender Stereotyping and Discrimination?

    PubMed

    Sczesny, Sabine; Formanowicz, Magda; Moser, Franziska

    2016-01-01

    Gender-fair language (GFL) aims at reducing gender stereotyping and discrimination. Two principle strategies have been employed to make languages gender-fair and to treat women and men symmetrically: neutralization and feminization. Neutralization is achieved, for example, by replacing male-masculine forms (policeman) with gender-unmarked forms (police officer), whereas feminization relies on the use of feminine forms to make female referents visible (i.e., the applicant… he or she instead of the applicant… he). By integrating research on (1) language structures, (2) language policies, and (3) individual language behavior, we provide a critical review of how GFL contributes to the reduction of gender stereotyping and discrimination. Our review provides a basis for future research and for scientifically based policy-making.

  8. Can Gender-Fair Language Reduce Gender Stereotyping and Discrimination?

    PubMed Central

    Sczesny, Sabine; Formanowicz, Magda; Moser, Franziska

    2016-01-01

    Gender-fair language (GFL) aims at reducing gender stereotyping and discrimination. Two principle strategies have been employed to make languages gender-fair and to treat women and men symmetrically: neutralization and feminization. Neutralization is achieved, for example, by replacing male-masculine forms (policeman) with gender-unmarked forms (police officer), whereas feminization relies on the use of feminine forms to make female referents visible (i.e., the applicant… he or she instead of the applicant… he). By integrating research on (1) language structures, (2) language policies, and (3) individual language behavior, we provide a critical review of how GFL contributes to the reduction of gender stereotyping and discrimination. Our review provides a basis for future research and for scientifically based policy-making. PMID:26869947

  9. "We all look the same to me": positive emotions eliminate the own-race in face recognition.

    PubMed

    Johnson, Kareem J; Fredrickson, Barbara L

    2005-11-01

    Extrapolating from the broaden-and-build theory, we hypothesized that positive emotion may reduce the own-race bias in facial recognition. In Experiments 1 and 2, Caucasian participants (N = 89) viewed Black and White faces for a recognition task. They viewed videos eliciting joy, fear, or neutrality before the learning (Experiment 1) or testing (Experiment 2) stages of the task. Results reliably supported the hypothesis. Relative to fear or a neutral state, joy experienced before either stage improved recognition of Black faces and significantly reduced the own-race bias. Discussion centers on possible mechanisms for this reduction of the own-race bias, including improvements in holistic processing and promotion of a common in-group identity due to positive emotions.

  10. Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.

    PubMed

    Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-Thasan, Niranjan; Feroldi, Emmanuel; Reid, Mark

    2010-11-01

    A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

  11. Neutralizing antibodies respond to a bivalent dengue DNA vaccine or/and a recombinant bivalent antigen.

    PubMed

    Zhang, Zhi-Shan; Weng, Yu-Wei; Huang, Hai-Long; Zhang, Jian-Ming; Yan, Yan-Sheng

    2015-02-01

    There is currently no effective vaccine to prevent dengue infection, despite the existence of multiple studies on potential methods of immunization. The aim of the present study was to explore the effect of DNA and/or recombinant protein on levels of neutralizing antibodies. For this purpose, envelope domain IIIs of dengue serotypes 1 and 2 (DEN-1/2)were spliced by a linker (Gly‑Gly‑Ser‑Gly‑Ser)3 and cloned into the prokaryotic expression plasmid pET30a (+) and eukaryotic vector pcDNA3.1 (+). The chimeric bivalent protein was expressed in Escherichia coli, and one‑step purification by high‑performance liquid chromatography was conducted. Protein expression levels of the DNA plasmid were tested in BHK‑21 cells by indirect immunofluorescent assay. In order to explore a more effective immunization strategy and to develop neutralizing antibodies against the two serotypes, mice were inoculated with recombinant bivalent protein, the DNA vaccine, or the two given simultaneously. Presence of the specific antibodies was tested by ELISA and the presence of the neutralizing antibodies was determined by plaque reduction neutralization test. Results of the analysis indicated that the use of a combination of DNA and protein induced significantly higher titers of neutralizing antibodies against either DEN‑1 or DEN‑2 (1:64.0 and 1:76.1, respectively) compared with the DNA (1:24.7 and 1:26.9, DEN‑1 and DEN‑2, respectively) or the recombinant protein (1:34.9 and 1:45.3 in DEN‑1 and DEN‑2, respectively). The present study demonstrated that the combination of recombinant protein and DNA as an immunization strategy may be an effective method for the development of a vaccine to prevent dengue virus infection.

  12. Concomitant or sequential administration of live attenuated japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine

    PubMed Central

    Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-thasan, Niranjan; Feroldi, Emmanuel

    2010-01-01

    A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered sequentially. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test (PRNT50). Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82–100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart. PMID:20864814

  13. Effect of different soil layers on porewater to remediate acidic surface environment at a close mine site.

    PubMed

    Salinas Villafane, Omar R; Igarashi, Toshifumi; Harada, Shusaku; Kurosawa, Mitsuru; Takase, Toshio

    2012-12-01

    This paper describes the chemistry of porewater when constructing different soil layers on acidic weathered rock of a closed mine to remediate the surface environment. Three cases were set on a flat surface of the site, all under different layer systems. Case 1 was only composed of weathered rocks. A top neutralization layer was constructed on the weathered rocks in case 2, whereas both an upper low-permeable and middle neutralization layers were constructed on the weathered rocks in case 3. The low-permeable layer of 30 cm thick consists of clay, and the neutralization layer of 30 cm thick consists of the mixture of the weathered rock and calcium carbonate as a neutralizer. Porewater sampling systems and soil sensors to measure temperature, water content, and electrical conductivity were set at different depths. In case 1, steadily high concentrations of heavy metals were observed regardless of the depth, and the pH ranged from 2 to 4. In cases 2 and 3, a dramatic decrease in concentrations of heavy metals was observed, even below the neutralization layer. For both cases, pH values were circumneutral. There were no significant seasonable changes in heavy metals concentrations and pH of porewater by considering the temperature and precipitation. In addition, the water content of the layers in case 3 fluctuated more mildly than that in cases 1 and 2, indicating that the low-permeable layer reduced the rate of infiltration. Therefore, a significant reduction in the load of heavy metals released from the site can be achieved by both implementing neutralization and low-permeable layers.

  14. Development and evaluation of a novel high-throughput image-based fluorescent neutralization test for detection of Zika virus infection.

    PubMed

    Koishi, Andrea Cristine; Suzukawa, Andréia Akemi; Zanluca, Camila; Camacho, Daria Elena; Comach, Guillermo; Duarte Dos Santos, Claudia Nunes

    2018-03-01

    Zika virus (ZIKV) is an emerging arbovirus belonging to the genus flavivirus that comprises other important public health viruses, such as dengue (DENV) and yellow fever (YFV). In general, ZIKV infection is a self-limiting disease, however cases of Guillain-Barré syndrome and congenital brain abnormalities in newborn infants have been reported. Diagnosing ZIKV infection remains a challenge, as viral RNA detection is only applicable until a few days after the onset of symptoms. After that, serological tests must be applied, and, as expected, high cross-reactivity between ZIKV and other flavivirus serology is observed. Plaque reduction neutralization test (PRNT) is indicated to confirm positive samples for being more specific, however it is laborious intensive and time consuming, representing a major bottleneck for patient diagnosis. To overcome this limitation, we developed a high-throughput image-based fluorescent neutralization test for ZIKV infection by serological detection. Using 226 human specimens, we showed that the new test presented higher throughput than traditional PRNT, maintaining the correlation between results. Furthermore, when tested with dengue virus samples, it showed 50.53% less cross reactivity than MAC-ELISA. This fluorescent neutralization test could be used for clinical diagnosis confirmation of ZIKV infection, as well as for vaccine clinical trials and seroprevalence studies.

  15. Dual Modifications Strategy to Quantify Neutral and Sialylated N-Glycans Simultaneously by MALDI-MS

    PubMed Central

    2015-01-01

    Differences in ionization efficiency among neutral and sialylated glycans prevent direct quantitative comparison by their respective mass spectrometric signals. To overcome this challenge, we developed an integrated chemical strategy, Dual Reactions for Analytical Glycomics (DRAG), to quantitatively compare neutral and sialylated glycans simultaneously by MALDI-MS. Initially, two glycan samples to be compared undergo reductive amination with 2-aminobenzoic acid and 2-13[C6]-aminobenzoic acid, respectively. The different isotope-incorporated glycans are then combined and subjected to the methylamidation of the sialic acid residues in one mixture, homogenizing the ionization responses for all neutral and sialylated glycans. By this approach, the expression change of relevant glycans between two samples is proportional to the ratios of doublet signals with a static 6 Da mass difference in MALDI-MS and the change in relative abundance of any glycan within samples can also be determined. The strategy was chemically validated using well-characterized N-glycans from bovine fetuin and IgG from human serum. By comparing the N-glycomes from a first morning (AM) versus an afternoon (PM) urine sample obtained from a single donor, we further demonstrated the ability of DRAG strategy to measure subtle quantitative differences in numerous urinary N-glycans. PMID:24766348

  16. Dual modifications strategy to quantify neutral and sialylated N-glycans simultaneously by MALDI-MS.

    PubMed

    Zhou, Hui; Warren, Peter G; Froehlich, John W; Lee, Richard S

    2014-07-01

    Differences in ionization efficiency among neutral and sialylated glycans prevent direct quantitative comparison by their respective mass spectrometric signals. To overcome this challenge, we developed an integrated chemical strategy, Dual Reactions for Analytical Glycomics (DRAG), to quantitatively compare neutral and sialylated glycans simultaneously by MALDI-MS. Initially, two glycan samples to be compared undergo reductive amination with 2-aminobenzoic acid and 2-(13)[C6]-aminobenzoic acid, respectively. The different isotope-incorporated glycans are then combined and subjected to the methylamidation of the sialic acid residues in one mixture, homogenizing the ionization responses for all neutral and sialylated glycans. By this approach, the expression change of relevant glycans between two samples is proportional to the ratios of doublet signals with a static 6 Da mass difference in MALDI-MS and the change in relative abundance of any glycan within samples can also be determined. The strategy was chemically validated using well-characterized N-glycans from bovine fetuin and IgG from human serum. By comparing the N-glycomes from a first morning (AM) versus an afternoon (PM) urine sample obtained from a single donor, we further demonstrated the ability of DRAG strategy to measure subtle quantitative differences in numerous urinary N-glycans.

  17. Seeing fearful body language rapidly freezes the observer's motor cortex.

    PubMed

    Borgomaneri, Sara; Vitale, Francesca; Gazzola, Valeria; Avenanti, Alessio

    2015-04-01

    Fearful body language is a salient signal alerting the observer to the presence of a potential threat in the surrounding environment. Although detecting potential threats may trigger an immediate reduction of motor output in animals (i.e., freezing behavior), it is unclear at what point in time similar reductions occur in the human motor cortex and whether they originate from excitatory or inhibitory processes. Using single-pulse and paired-pulse transcranial magnetic stimulation (TMS), here we tested the hypothesis that the observer's motor cortex implements extremely fast suppression of motor readiness when seeing emotional bodies - and fearful body expressions in particular. Participants observed pictures of body postures and categorized them as happy, fearful or neutral while receiving TMS over the right or left motor cortex at 100-125 msec after picture onset. In three different sessions, we assessed corticospinal excitability, short intracortical inhibition (SICI) and intracortical facilitation (ICF). Independently of the stimulated hemisphere and the time of the stimulation, watching fearful bodies suppressed ICF relative to happy and neutral body expressions. Moreover, happy expressions reduced ICF relative to neutral actions. No changes in corticospinal excitability or SICI were found during the task. These findings show extremely rapid bilateral modulation of the motor cortices when seeing emotional bodies, with stronger suppression of motor readiness when seeing fearful bodies. Our results provide neurophysiological support for the evolutionary notions that emotion perception is inherently linked to action systems and that fear-related cues induce an urgent mobilization of motor reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Inhibitory effect of breast milk on infectivity of live oral rotavirus vaccines.

    PubMed

    Moon, Sung-Sil; Wang, Yuhuan; Shane, Andi L; Nguyen, Trang; Ray, Pratima; Dennehy, Penelope; Baek, Luck Ju; Parashar, Umesh; Glass, Roger I; Jiang, Baoming

    2010-10-01

    Live oral rotavirus vaccines have been less immunogenic and efficacious among children in poor developing countries compared with middle income and industrialized countries for reasons that are not yet completely understood. We assessed whether the neutralizing activity of breast milk could lower the titer of vaccine virus and explain this difference in vitro. Breast milk samples were collected from mothers who were breast-feeding infants 4 to 29 weeks of age (ie, vaccine eligible age) in India (N = 40), Vietnam (N = 77), South Korea (N = 34), and the United States (N = 51). We examined breast milk for rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains-RV1, RV5 G1, and 116E using enzyme immunoassays. The inhibitory effect of breast milk on RV1 was further examined by a plaque reduction assay. Breast milk from Indian women had the highest IgA and neutralizing titers against all 3 vaccine strains, while lower but comparable median IgA and neutralizing titers were detected in breast milk from Korean and Vietnamese women, and the lowest titers were seen in American women. Neutralizing activity was greatest against the 2 vaccine strains of human origin, RV1 and 116E. This neutralizing activity in one half of the breast milk specimens from Indian women could reduce the effective titer of RV1 by ∼2 logs, of 116E by 1.5 logs, and RV5 G1 strain by ∼1 log more than that of breast milk from American women. The lower immunogenicity and efficacy of rotavirus vaccines in poor developing countries could be explained, in part, by higher titers of IgA and neutralizing activity in breast milk consumed by their infants at the time of immunization that could effectively reduce the potency of the vaccine. Strategies to overcome this negative effect, such as delaying breast-feeding at the time of immunization, should be evaluated.

  19. Immunogenicity of an interferon-beta1a product.

    PubMed

    Kauffman, M A; Sterin-Prync, A; Papouchado, M; González, E; Vidal, A J; Grossberg, S E; Chuppa, S; Odoriz, B; Vrech, C; Diez, R A; Ferro, H H

    2011-01-01

    In order to determine whether Blastoferon®, a biosimilar interferon (IFN)- beta 1a formulation, shares epitopes with other known IFN-beta products, a series of neutralization bioassays were performed with a set of well-characterized anti-IFN- beta monoclonal antibodies and human sera (World Health Organization Reference Reagents). The bioassay was the interferon-induced inhibition of virus cytopathic effect on human cells in culture (EMC virus and A-549 cells). Computer-calculated results were reported as Tenfold Reduction Units (TRU)/ml. To further assess Blastoferon® immunogenicity, in vivo production of anti-IFN beta antibodies was determined in sera of patients included in the pharmacovigilance plan of Blastoferon® by the level of IFN- beta 1a binding antibodies (by enzyme immunoassay -EIA) and neutralizing antibodies (in the Wish-VSV system). The highly characterized neutralizing monoclonal antibodies A1 and A5 that bind to specific regions of the IFN- beta molecule reacted positively with the three beta 1a IFNs: Blastoferon®, Rebif®, and the IFN- beta WHO Second International Standard 00/572. As expected, the non-neutralizing monoclonal antibodies B4 and B7 did not neutralize any of the IFN- beta preparations. The commercially available monoclonal antibody B-02 reacted essentially equally with Rebif® and Blastoferon®. The WHO Reference Reagent human serum anti-IFN- beta polyclonal antibody neutralized all the IFN- beta products, whereas the WHO Reference Reagent human serum anti-IFN-alpha polyclonal antibody G037-501-572 appropriately failed to react with any of the IFN- beta products. On the basis of in vitro reactivity with known, well-characterized monoclonal and polyclonal antibody preparations, Blastoferon® shares immunological determinants with other human interferon- beta products, especially IFN- beta 1a. In vivo antibodies were detected by EIA in 72.9% of 37 chronically treated multiple sclerosis patients, whereas neutralizing antibodies were found in 8.1% of them. Blastoferon® appears to have immunological characteristics comparable to other IFN- beta 1a products.

  20. Incorporation of IgG Depletion in a Neutralization Assay Facilitates Differential Diagnosis of Zika and Dengue in Secondary Flavivirus Infection Cases.

    PubMed

    Calvert, Amanda E; Boroughs, Karen L; Laven, Janeen; Stovall, Janae L; Luy, Betty E; Kosoy, Olga I; Huang, Claire Y-H

    2018-06-01

    Zika virus (ZIKV) has emerged as a major global public health concern due to its link as a causative agent of human birth defects. Laboratory diagnosis of suspected ZIKV infections by serological testing of specimens collected a week or more after symptom onset primarily relies on detection of anti-ZIKV-specific IgM antibodies by enzyme-linked immunosorbent assay coupled with detection of ZIKV-specific neutralizing antibody by neutralization tests. A definitive diagnosis based on serological assays is possible during primary ZIKV infections; however, due to the cross-reactivity of antibodies elicited during flaviviral infections, a definitive diagnosis is not always possible, especially among individuals who have previously been exposed to closely related flaviviruses, such as dengue virus (DENV). Here, we investigated the neutralizing IgM antibody profiles of 33 diagnostic specimens collected from individuals with suspected primary and secondary flaviviral infections acquired when visiting areas experiencing active ZIKV transmission in 2015 and 2016. Specimens collected between 1 day and 3 months postexposure were tested for ZIKV and dengue virus type 1 (DENV1) and type 2 (DENV2) by the plaque reduction neutralization test (PRNT) before and after IgG depletion. We found that IgG depletion prior to neutralization testing had little effect in differentiating samples from individuals with secondary infections taken less than 3 weeks postexposure; however, IgG depletion significantly reduced the cross-reactive neutralizing antibody titers and increased the percentage of cases discernible by PRNT from 15.4% (95% confidence interval [CI], 4.3 to 42.2%) to 76.9% (95% CI, 49.7 to 91.8%) for samples collected between roughly 3 and 12 weeks postexposure. These results highlight the potential of IgG depletion to improve the specificity of PRNT for better confirmation and differential diagnosis of flavivirus infections. Copyright © 2018 American Society for Microbiology.

  1. Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

    PubMed

    Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

    2015-01-01

    Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESN<3 yr, and HIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

  2. Ontario's Poverty Reduction Strategy: A Critical Discourse Analysis.

    PubMed

    Benbow, Sarah; Gorlick, Carolyne; Forchuk, Cheryl; Ward-Griffin, Catherine; Berman, Helene

    2016-01-01

    This article overviews the second phase of a two-phase study which examined experiences of health and social exclusion among mothers experiencing homelessness in Ontario, Canada. A critical discourse analysis was employed to analyze the policy document, Realizing Our Potential: Ontario's Poverty Reduction Strategy, 2014-2019. In nursing, analysis of policy is an emerging form of scholarship, one that draws attention to the macro levels influencing health and health promotion, such as the social determinants of health, and the policies that impact them. The clear neo-liberal underpinnings, within the strategy, with a focus on productivity and labor market participation leave little room for an understanding of poverty reduction from a human rights perspective. Further, gender-neutrality rendered the poverty experienced by women, and mothers, invisible. Notably, there were a lack of deadlines, target dates, and thorough action and evaluation plans. Such absence troubles whether poverty reduction is truly a priority for the government, and society as a whole.

  3. Influence of nitrate, sulfate and operational parameters on the bioreduction of perchlorate using an up-flow packed bed reactor at high salinity.

    PubMed

    Chung, J; Shin, S; Oh, J

    2010-05-01

    In this study we have investigated whether electron acceptors, such as nitrate or sulphate ions, competitively inhibit the reduction of perchlorate in brine in continuous up-flow packed bed bioreactors. The effect of pH and hydraulic retention time (HRT) on the reduction of perchlorate at high salinity has also been examined. Reduction of perchlorate was found to be only moderately influenced by nitrate (under 163 mg N L-'), implying that there was no significant microbial competition for electron acceptors. As a result of microbial diversity, there were few differences between microbial communities fed with a variety of media, suggesting that most nitrate-reducing bacteria are able to reduce perchlorate at high salinity. Reduction of perchlorate was almost complete at relatively high sulfate levels (1000 mg L(-1)), neutral pH (6-8) and relatively long HRTs (> 10 h).

  4. Solvent-driven reductive activation of carbon dioxide by gold anions.

    PubMed

    Knurr, Benjamin J; Weber, J Mathias

    2012-11-14

    Catalytic activation and electrochemical reduction of CO(2) for the formation of chemically usable feedstock and fuel are central goals for establishing a carbon neutral fuel cycle. The role of solvent molecules in catalytic processes is little understood, although solvent-solute interactions can strongly influence activated intermediate species. We use vibrational spectroscopy of mass-selected Au(CO(2))(n)(-) cluster ions to probe the solvation of AuCO(2)(-) as a model for a reactive intermediate in the reductive activation of a CO(2) ligand by a single-atom catalyst. For the first few solvent molecules, solvation of the complex preferentially occurs at the CO(2) moiety, enhancing reductive activation through polarization of the excess charge onto the partially reduced ligand. At higher levels of solvation, direct interaction of additional solvent molecules with the Au atom diminishes reduction. The results show how the solvation environment can enhance or diminish the effects of a catalyst, offering design criteria for single-atom catalyst engineering.

  5. Antimicrobial effect of electrolyzed oxidizing water against Escherichia coli O157:H7 and Listeria monocytogenes on fresh strawberries (Fragaria x ananassa).

    PubMed

    Udompijitkul, P; Daeschel, M A; Zhao, Y

    2007-11-01

    Antibacterial activity of electrolyzed oxidizing (EO) water prepared from 0.05% or 0.10% (w/v) sodium chloride (NaCl) solutions against indigenous bacteria associated with fresh strawberries (Fragaria x ananassa) was evaluated. The efficacy of EO water and sodium hypochlorite (NaOCl) solution in eliminating and controlling the growth of Listeria monocytogenes and Escherichia coli O157:H7 inoculated onto strawberries stored at 4 +/- 1 degrees C up to 15 d was investigated at exposure time of 1, 5, or 10 min. Posttreatment neutralization of fruit surfaces was also determined. More than 2 log(10) CFU/g reductions of aerobic mesophiles were obtained in fruits washed for 10 or 15 min in EO water prepared from 0.10% (w/v) NaCl solution. Bactericidal activity of the disinfectants against L. monocytogenes and E. coli O157:H7 was not affected by posttreatment neutralization, and increasing exposure time did not significantly increase the antibacterial efficacy against both pathogens. While washing fruit surfaces with distilled water resulted in 1.90 and 1.27 log(10) CFU/mL of rinse fluid reduction of L. monocytogenes and E. coli O157:H7, respectively, >/= 2.60 log(10) CFU/mL of rinse fluid reduction of L. monocytogenes and up to 2.35 and 3.12 log(10) CFU/mL of rinse fluid reduction of E. coli O157:H7 were observed on fruit surfaces washed with EO water and NaOCl solution, respectively. Listeria monocytogenes and E. coli O157:H7 populations decreased over storage regardless of prior treatment. However, EO water and aqueous NaOCl did not show higher antimicrobial potential than water treatment during refrigeration storage.

  6. Reduced Potency and Incomplete Neutralization of Broadly Neutralizing Antibodies against Cell-to-Cell Transmission of HIV-1 with Transmitted Founder Envs.

    PubMed

    Li, Hongru; Zony, Chati; Chen, Ping; Chen, Benjamin K

    2017-05-01

    Broadly neutralizing antibodies (bNAbs) have been isolated from HIV-1 patients and can potently block infection of a wide spectrum of HIV-1 subtypes. These antibodies define common epitopes shared by many viral isolates. While bNAbs potently antagonize infection with cell-free virus, inhibition of HIV-1 transmission from infected to uninfected CD4 + T cells through virological synapses (VS) has been found to require greater amounts of antibody. In this study, we examined two well-studied molecular clones and two transmitted/founder (T/F) clones for their sensitivities to a panel of bNAbs in cell-free and cell-to-cell infection assays. We observed resistance of cell-to-cell transmission to antibody neutralization that was reflected not only by reductions of antibody potency but also by decreases in maximum neutralization capacity relative to the levels seen with cell-free infections. BNAbs targeting different epitopes exhibited incomplete neutralization against cell-associated virus with T/F Envs, which was not observed with the cell-free form of the same virus. We further identified the membrane-proximal internal tyrosine-based sorting motif as a determinant that can affect the incomplete neutralization of these T/F clones in cell-to-cell infection. These findings indicate that the signal that affects surface expression and/or internalization of Env from the plasma membrane can modulate the presentation of neutralizing epitopes on infected cells. These results highlight that a fraction of virus can escape from high concentrations of antibody through cell-to-cell infection while remaining sensitive to neutralization in cell-free infection. The ability to fully inhibit cell-to-cell transmission may represent an important consideration in the development of antibodies for treatment or prophylaxis. IMPORTANCE In recent years, isolation of new-generation HIV-1 bNAbs has invigorated HIV vaccine research. These bNAbs display remarkable potency and breadth of coverage against cell-free virus; however, they exhibit a diminished ability to block HIV-1 cell-to-cell transmission. The mechanism(s) by which HIV-1 resists neutralization when transmitting through VS remains uncertain. We examined a panel of bNAbs for their ability to neutralize HIV-1 T/F viruses in cell-to-cell infection assays. We found that some antibodies exhibit not only reduced potency but also decreased maximum neutralization capacity or in vitro efficacy against cell-to-cell infection of HIV-1 with T/F Envs compared to cell-free infection of the same virus. We further identified the membrane-proximal internal tyrosine-based sorting motif YXXL as a determinant that can affect the incomplete neutralization phenotype of these T/F clones. When the maximum neutralization capacity falls short of 100%, this can have a major impact on the ability of antibodies to halt viral replication. Copyright © 2017 American Society for Microbiology.

  7. Reduced Financial Resources and the Strategic Position of Community Colleges: How an "Embedded Community College" Can Neutralize External Pressures

    ERIC Educational Resources Information Center

    Namuo, Clyne G. H.

    2013-01-01

    This multi-site case study is really the story of three same-state community colleges (Bridge and Buffer Community College, Grants and Reserves Community College, and Crystal Ball Community College) two years after they suffered a potentially catastrophic 50% reduction in state allocations. This study examined their responses to those reductions…

  8. Probing the inner space of resorcinarene molecular capsules with nitroxide guests.

    PubMed

    Mileo, Elisabetta; Yi, Song; Bhattacharya, Papri; Kaifer, Angel E

    2009-01-01

    In quarantine: Nitroxide spin probes are encapsulated by hexameric resorcinarene molecular capsules in dichloromethane solutions (see picture). A substantial reduction in the tumbling rates occurs upon encapsulation of two cationic probes and one neutral probe. As the molecular volume of the probe increases, the tumbling rate of the probe reflects the overall tumbling rate of the entire supramolecular assembly.

  9. World Reference Center for Arboviruses

    DTIC Science & Technology

    1991-05-08

    Japanese encephalitis virus and acted as sentinels. By molecular hniques it was shown that the dengue-2 viruses in Venezuela and Brazil are very...12 A. Molecular epidemiology of dengue viruses ................... 12 B. Vaccinia virus recombinants expressing Japanese...of Kagoshima virus (strain KC-05Y84) to the Palyam group. Plaque reduction neutralization tests were done with eight viruses of the Palyam serogroup

  10. Optimization of a novel enzyme treatment process for early-stage processing of sheepskins.

    PubMed

    Lim, Y F; Bronlund, J E; Allsop, T F; Shilton, A N; Edmonds, R L

    2010-01-01

    An enzyme treatment process for early-stage processing of sheepskins has been previously reported by the Leather and Shoe Research Association of New Zealand (LASRA) as an alternative to current industry operations. The newly developed process had marked benefits over conventional processing in terms of a lowered energy usage (73%), processing time (47%) as well as water use (49%), but had been developed as a "proof of principle''. The objective of this work was to develop the process further to a stage ready for adoption by industry. Mass balancing was used to investigate potential modifications for the process based on the understanding developed from a detailed analysis of preliminary design trials. Results showed that a configuration utilising a 2 stage counter-current system for the washing stages and segregation and recycling of enzyme float prior to dilution in the neutralization stage was a significant improvement. Benefits over conventional processing include a reduction of residual TDS by 50% at the washing stages and 70% savings on water use overall. Benefits over the un-optimized LASRA process are reduction of solids in product after enzyme treatment and neutralization stages by 30%, additional water savings of 21%, as well as 10% savings of enzyme usage.

  11. Reductive capacity measurement of waste forms for secondary radioactive wastes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Um, Wooyong; Yang, Jung-Seok; Serne, R. Jeffrey

    2015-12-01

    The reductive capacities of dry ingredients and final solid waste forms were measured using both the Cr(VI) and Ce(IV) methods and the results were compared. Blast furnace slag (BFS), sodium sulfide, SnF2, and SnCl2 used as dry ingredients to make various waste forms showed significantly higher reductive capacities compared to other ingredients regardless of which method was used. Although the BFS exhibits appreciable reductive capacity, it requires greater amounts of time to fully react. In almost all cases, the Ce(IV) method yielded larger reductive capacity values than those from the Cr(VI) method and can be used as an upper boundmore » for the reductive capacity of the dry ingredients and waste forms, because the Ce(IV) method subjects the solids to a strong acid (low pH) condition that dissolves much more of the solids. Because the Cr(VI) method relies on a neutral pH condition, the Cr(VI) method can be used to estimate primarily the waste form surface-related and readily dissolvable reductive capacity. However, the Cr(VI) method does not measure the total reductive capacity of the waste form, the long-term reductive capacity afforded by very slowly dissolving solids, or the reductive capacity present in the interior pores and internal locations of the solids.« less

  12. Reduction of gate leakage current on AlGaN/GaN high electron mobility transistors by electron-beam irradiation.

    PubMed

    Oh, S K; Song, C G; Jang, T; Kim, Kwang-Choong; Jo, Y J; Kwak, J S

    2013-03-01

    This study examined the effect of electron-beam (E-beam) irradiation on the AIGaN/GaN HEMTs for the reduction of gate leakage. After E-beam irradiation, the gate leakage current significantly decreased from 2.68 x 10(-8) A to 4.69 x 10(-9) A at a drain voltage of 10 V. The maximum drain current density of the AIGaN/GaN HEMTs with E-beam irradiation increased 14%, and the threshold voltage exhibited a negative shift, when compared to that of the AIGaN/GaN HEMTs before E-beam irradiation. These results strongly suggest that the reduction of gate leakage current resulted from neutralization nitrogen vacancies and removing of oxygen impurities.

  13. The pH and pCO2 dependence of sulfate reduction in shallow-sea hydrothermal CO2 – venting sediments (Milos Island, Greece)

    PubMed Central

    Bayraktarov, Elisa; Price, Roy E.; Ferdelman, Timothy G.; Finster, Kai

    2013-01-01

    Microbial sulfate reduction (SR) is a dominant process of organic matter mineralization in sulfate-rich anoxic environments at neutral pH. Recent studies have demonstrated SR in low pH environments, but investigations on the microbial activity at variable pH and CO2 partial pressure are still lacking. In this study, the effect of pH and pCO2 on microbial activity was investigated by incubation experiments with radioactive 35S targeting SR in sediments from the shallow-sea hydrothermal vent system of Milos, Greece, where pH is naturally decreased by CO2 release. Sediments differed in their physicochemical characteristics with distance from the main site of fluid discharge. Adjacent to the vent site (T ~40–75°C, pH ~5), maximal sulfate reduction rates (SRR) were observed between pH 5 and 6. SR in hydrothermally influenced sediments decreased at neutral pH. Sediments unaffected by hydrothermal venting (T ~26°C, pH ~8) expressed the highest SRR between pH 6 and 7. Further experiments investigating the effect of pCO2 on SR revealed a steep decrease in activity when the partial pressure increased from 2 to 3 bar. Findings suggest that sulfate reducing microbial communities associated with hydrothermal vent system are adapted to low pH and high CO2, while communities at control sites required a higher pH for optimal activity. PMID:23658555

  14. The pH and pCO2 dependence of sulfate reduction in shallow-sea hydrothermal CO2 - venting sediments (Milos Island, Greece).

    PubMed

    Bayraktarov, Elisa; Price, Roy E; Ferdelman, Timothy G; Finster, Kai

    2013-01-01

    Microbial sulfate reduction (SR) is a dominant process of organic matter mineralization in sulfate-rich anoxic environments at neutral pH. Recent studies have demonstrated SR in low pH environments, but investigations on the microbial activity at variable pH and CO2 partial pressure are still lacking. In this study, the effect of pH and pCO2 on microbial activity was investigated by incubation experiments with radioactive (35)S targeting SR in sediments from the shallow-sea hydrothermal vent system of Milos, Greece, where pH is naturally decreased by CO2 release. Sediments differed in their physicochemical characteristics with distance from the main site of fluid discharge. Adjacent to the vent site (T ~40-75°C, pH ~5), maximal sulfate reduction rates (SRR) were observed between pH 5 and 6. SR in hydrothermally influenced sediments decreased at neutral pH. Sediments unaffected by hydrothermal venting (T ~26°C, pH ~8) expressed the highest SRR between pH 6 and 7. Further experiments investigating the effect of pCO2 on SR revealed a steep decrease in activity when the partial pressure increased from 2 to 3 bar. Findings suggest that sulfate reducing microbial communities associated with hydrothermal vent system are adapted to low pH and high CO2, while communities at control sites required a higher pH for optimal activity.

  15. Organic carbon and reducing conditions lead to cadmium immobilization by secondary Fe mineral formation in a pH-neutral soil.

    PubMed

    Muehe, E Marie; Adaktylou, Irini J; Obst, Martin; Zeitvogel, Fabian; Behrens, Sebastian; Planer-Friedrich, Britta; Kraemer, Ute; Kappler, Andreas

    2013-01-01

    Cadmium (Cd) is of environmental relevance as it enters soils via Cd-containing phosphate fertilizers and endangers human health when taken up by crops. Cd is known to associate with Fe(III) (oxyhydr)oxides in pH-neutral to slightly acidic soils, though it is not well understood how the interrelation of Fe and Cd changes under Fe(III)-reducing conditions. Therefore, we investigated how the mobility of Cd changes when a Cd-bearing soil is faced with organic carbon input and reducing conditions. Using fatty acid profiles and quantitative PCR, we found that both fermenting and Fe(III)-reducing bacteria were stimulated by organic carbon-rich conditions, leading to significant Fe(III) reduction. The reduction of Fe(III) minerals was accompanied by increasing soil pH, increasing dissolved inorganic carbon, and decreasing Cd mobility. SEM-EDX mapping of soil particles showed that a minor fraction of Cd was transferred to Ca- and S-bearing minerals, probably carbonates and sulfides. Most of the Cd, however, correlated with a secondary iron mineral phase that was formed during microbial Fe(III) mineral reduction and contained mostly Fe, suggesting an iron oxide mineral such as magnetite (Fe3O4). Our data thus provide evidence that secondary Fe(II) and Fe(II)/Fe(III) mixed minerals could be a sink for Cd in soils under reducing conditions, thus decreasing the mobility of Cd in the soil.

  16. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    NASA Astrophysics Data System (ADS)

    May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan

    2004-09-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  17. High-Accuracy Global Time and Frequency Transfer with a Space-Borne Hydrogen Maser Clock

    DTIC Science & Technology

    1982-12-01

    of t h e s p a c e c l o c k is modu la t ed on t h e c l o c k downl ink car r ie r using PRN p h a s e modula- t i o n (5). The s p a...is t o a c c o u n t f o r r e la t i s t i c e f f e c t s w i t h i n a f r a c t i o n a l f r e q u e n c y error of 0 . T h i s r...Mockler , and J . M . R ichardson , Metrologia , 1, p. 114, 1965. ( 1 3 ) Glaze, D . J . , Helmut Hellwig, Steve J a r v i s , J r . , A

  18. Does a wander garden influence inappropriate behaviors in dementia residents?

    PubMed

    Detweiler, Mark B; Murphy, Pamela F; Myers, Laura C; Kim, Kye Y

    2008-01-01

    The effect on resident behaviors of adding a wander garden to an existing dementia facility was investigated. 34 male residents were observed for 12 months before and after opening the garden. Behaviors were assessed using the Cohen-Mansfield Agitation Inventory Short Form (CMAI), incident reports, as needed medications (pro re nata [PRN]), and surveys of staff and residents' family members as indices of affect. Final CMAI scores and total PRNs employed were lower than baseline values with a trend for residents who used the garden more often to have less agitated behavior. Verbal inappropriate behaviors did not change significantly whereas physical incidents increased. Staff and family members felt that the wander garden decreased inappropriate behaviors and improved mood and quality of life of the dementia residents. Study design characteristics and garden management may have affected behaviors both positively and negatively. Additional studies are needed to explore the benefits of wander gardens for dementia residents.

  19. Properties of an unusual DNA primase from an archaeal plasmid

    PubMed Central

    Beck, Kirsten; Lipps, Georg

    2007-01-01

    Primases are specialized DNA-dependent RNA polymerases that synthesize a short oligoribonucleotide complementary to single-stranded template DNA. In the context of cellular DNA replication, primases are indispensable since DNA polymerases are not able to start DNA polymerization de novo. The primase activity of the replication protein from the archaeal plasmid pRN1 synthesizes a rather unusual mixed primer consisting of a single ribonucleotide at the 5′ end followed by seven deoxynucleotides. Ribonucleotides and deoxynucleotides are strictly required at the respective positions within the primer. Furthermore, in contrast to other archaeo-eukaryotic primases, the primase activity is highly sequence-specific and requires the trinucleotide motif GTG in the template. Primer synthesis starts outside of the recognition motif, immediately 5′ to the recognition motif. The fidelity of the primase synthesis is high, as non-complementary bases are not incorporated into the primer. PMID:17709343

  20. Summary of Synoptic Meteorological Observations. Indonesian Coastal Marine Areas. Volume 2. Area 8 - West Borneo, Area 9 - Karimata Strait, Area 10 - Southwest Java Sea, Area 11 - South Central Java, Area 12 - Southeast Java, Area 13 - Southeast Java Sea, Area 14 - Northeast Java Sea

    DTIC Science & Technology

    1975-04-01

    5 ’ :00 0 1’.20 2. 219 39 : .:0 :00 .0 A.. AP99 120 , ~ ~ ~ ~ ~ -y- ,M -.7yT ,, T , . , .,77M III II P~ kID : (¢E(’Ll) 9•3-977AREA 0009 KARIMATA STRAIT...TYPE OTHER WEATHER PHENOMENA kNO 01D RAIN PAIN VAIL RAIG SNOW OTHER HAI. PORN AT PCPN PAST ?HOR FOG FOG WO SMOKE SPRAY NO SHoR PON FRZN 06 TIME HOUR LTNG...NAONO DIR RAIN RAIN ORIL RCZG SNOW OTHER HAIL PCORN A? FCN PAST THOR OTOH HAZE SPRy NOUST SI ? R G PUG W SMOK SPRAY No PHft PCN PRN OPTM OR LTNG Wa PORN

  1. Microbial reduction of manganese oxides - Interactions with iron and sulfur

    NASA Technical Reports Server (NTRS)

    Myers, Charles R.; Nealson, Kenneth H.

    1988-01-01

    Alteromonas putrefaciens (strain MR-1) is capable of rapid Mn(IV) reduction under conditions of neutral pH and temperatures characteristic of the Oneida Lake, New York, sediments from which it was isolated. MR-1 also reduces Fe(3+) to Fe(2+), and disproportionates thiosulfate to sulfide and sulfite; independently, the Fe(2+) and sulfide act as rapid reductants of Mn. The addition of Fe(3+) or thiosulfate to cultures of MR-1 in the presence of oxidized Mn increases the rate and the extent of Mn reduction relative to that observed in the absence of Fe(3+) or thiosulfate. Furthermore, when Fe(3+) and Mn oxides are present conjointly, Fe(2+) does not appear until the reduction of the oxidized Mn is complete. These results demonstrate that the observed rates of Fe(2+) and sulfide production may underestimate the total rates of Fe and sulfate reduction in those environments containing oxidized Mn. These results also demonstrate the potential impact that a single microbe can exert on sediment geochemistry, and provide the basis for preliminary models of the complexity of microbial and geochemical interactions that occur.

  2. West Nile seroprevalence study in Bolivian horses, 2011.

    PubMed

    Mazzei, Maurizio; Savini, Giovanni; Di Gennaro, Annapia; Macchioni, Fabio; Prati, Maria Cristina; Guzmàn, Limberg Rojas; Tolari, Francesco

    2013-12-01

    West Nile virus (WNV) is a mosquito-borne virus belonging to the family Flaviviridae included in the Japanese encephalitis antigenic complex (JEAC). A seroepidemiological study was carried out in 2011 using 160 horse sera collected from different areas of Bolivia to investigate the presence of WNV antibody. A high proportion (59.4%) of the tested sera were positive to a commercially available WNV competitive enzyme-linked immunosorbent assay (C-ELISA). Sixty-six randomly selected C-ELISA-positive sera were further tested by WNV plaque reduction neutralization test (PRNT), virus neutralization (VN), and immunoglobulin M (IgM)-WNV ELISA to exclude false-positive results due to possible cross-reactions to other members of the JEAC and to investigate if the horses were recently infected. No WNV IgM was detected in these samples, whereas neutralizing antibodies were found in 21 and 18 samples by PRNT and VN, respectively. In conclusion, a high proportion of the Bolivian horses included in this study reacted serologically against viruses of the JEAC. WNV was partially responsible (31.8%) for these reactions, supporting the conclusion that WNV circulated in Bolivia.

  3. Current profile redistribution driven by neutral beam injection in a reversed-field pinch

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Parke, E.; Department of Physics, University of Wisconsin-Madison 1150 University Ave., Madison, Wisconsin 53706; Anderson, J. K.

    2016-05-15

    Neutral beam injection in reversed-field pinch (RFP) plasmas on the Madison Symmetric Torus [Dexter et al., Fusion Sci. Technol. 19, 131 (1991)] drives current redistribution with increased on-axis current density but negligible net current drive. Internal fluctuations correlated with tearing modes are observed on multiple diagnostics; the behavior of tearing mode correlated structures is consistent with flattening of the safety factor profile. The first application of a parametrized model for island flattening to temperature fluctuations in an RFP allows inferrence of rational surface locations for multiple tearing modes. The m = 1, n = 6 mode is observed to shift inward by 1.1 ± 0.6 cm withmore » neutral beam injection. Tearing mode rational surface measurements provide a strong constraint for equilibrium reconstruction, with an estimated reduction of q{sub 0} by 5% and an increase in on-axis current density of 8% ± 5%. The inferred on-axis current drive is consistent with estimates of fast ion density using TRANSP [Goldston et al., J. Comput. Phys. 43, 61 (1981)].« less

  4. Search for active-sterile neutrino mixing using neutral-current interactions in NOvA

    DOE PAGES

    Adamson, P.; Aliaga, L.; Ambrose, D.; ...

    2017-10-30

    Here, we report results from the first search for sterile neutrinos mixing with active neutrinos through a reduction in the rate of neutral-current interactions over a baseline of 810 km between the NOvA detectors. Analyzing a 14-kton detector equivalent exposure of 6.05 × 10 20 protons-on-target in the NuMI beam at Fermilab, we observe 95 neutral-current candidates at the Far Detector compared with 83.5 ± 9.7(stat) ± 9.4(syst) events predicted assuming mixing only occurs between active neutrino species. No evidence for νμ→νs transitions is found. Interpreting these results within a 3+1 model, we place constraints on the mixing angles θ 24more » < 20.8° and θ 34 < 31.2° at the 90% C.L. for 0.05 eV 2 ≤ Δm 41 2 ≤ 0.5 eV 2, the range of mass splittings that produce no significant oscillations over the Near Detector baseline.« less

  5. Isolation, propagation, and characterization of a second equine rotavirus serotype.

    PubMed Central

    Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

    1983-01-01

    A rotavirus designated strain H-2 was isolated in primary African green monkey kidney cells from a foal with diarrhea. This cell culture-adapted strain was found to be similar, if not identical, to simian rotavirus (strains MMU18006 and SA-11) and canine rotavirus (strain CU-1) and, in addition, demonstrated a one-way antigenic relationship with five human rotavirus strains (P, B, no. 14, no. 15, and YO) of the third human rotavirus serotype by the plaque reduction neutralization test. This is the fifth example of an animal rotavirus which shares serotypic specificity with a human rotavirus. The H-2 strain is distinct from the H-1 strain (Y. Hoshino et al., J. Clin. Microbiol., in press) of equine rotavirus not only in serotypic specificity by neutralization but also in subgroup specificity, hemagglutinating activity, and RNA electrophoretic migration pattern, thus establishing the existence of a second equine rotavirus serotype. This H-2 isolate is also distinct by neutralization from three other human rotavirus serotypes, 1 (Wa), 2 (DS-1), and 4 (St. Thomas no. 4), as well as bovine (NCDV), and porcine (OSU) rotaviruses. Images PMID:6309657

  6. Expression of enhancing-activity-free neutralizing antibody against dengue type 1 virus in plasmid-inoculated mice.

    PubMed

    Yamanaka, Atsushi; Pitaksajjakul, Pannamthip; Ramasoota, Pongrama; Konishi, Eiji

    2015-11-09

    Most candidate dengue vaccines currently under development induce neutralizing antibodies, which are considered important for immunoprotection. However, the concomitant induction of infection-enhancing antibodies is an unavoidable concern. In contrast, a neutralizing antibody developed for passive immunotherapy has been engineered to eliminate its enhancing activity. Therefore, a strategy for the long-term expression of enhancing-activity-free neutralizing antibodies may resolve this concern. A mouse monoclonal antibody, 7F4, of the IgG3 subclass and with no detectable enhancing activity, was selected as the model neutralizing antibody to evaluate the potential of this strategy. Equal amounts of commercial vector (pFUSE)-based plasmids containing 7F4 heavy (H)- or light (L)-chain variable region genes were mixed and used for the cotransfection of 293T cells and co-delivery into ICR and BALB/c mice. The recombinant plasmids were designed to express IgG2b or IgG3 subclass antibodies (p7F4G2b or p7F4G3, respectively). 293T cells transfected with 2 μg of p7F4G2b or p7F4G3 produced approximately 15,000 or 800 ng/ml IgG in the culture fluids, respectively. The dose is expressed as the total amount of H- and L-chain plasmids. Neutralizing antibody was detected dose-dependently in ICR mice inoculated with 50-200 μg of p7F4G2b. A 1:2 dilution of sera from ICR and BALB/c mice inoculated with 100 μg of p7F4G3 showed average plaque reduction levels of >70% on day 3 and >90% on days 5-9. BALB/c mice maintained detectable neutralizing antibody for at least 3 months. The neutralizing antibody expressed by p7F4G3 in mice showed no enhancing activity. Although the expression of neutralizing antibodies from immunoglobulin genes is a type of passive immunization, its durability can be utilized as a dengue vaccine strategy. This "proof-of-concept" study using a mouse model demonstrates that the enhancing-activity-free characteristic of this strategy augurs well for dengue vaccine development, although further improvement is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Parvovirus B19 empty capsids as antigen carriers for presentation of antigenic determinants of dengue 2 virus.

    PubMed

    Amexis, Georgios; Young, Neal S

    2006-09-15

    For the production of dengue-vaccine candidates, empty capsids, or virus-like particles (VLPs), of parvovirus B19 that carry dengue 2-specific epitopes were employed as antigen carriers. Two epitopes (comprising amino acids 352-368 and 386-397) of domain BIII of the envelope glycoprotein were chosen to produce recombinant B19 VLPs for immunization of BALB/c mice. Serum samples from immunized mice revealed that recombinant B19 VLPs elicited strong humoral immune responses. In summary, this B19 VLP-vaccine platform produced high (> or =2.0 x 10(5)) anti-dengue 2 titers and robust (< or =1 120) 50%-plaque-reduction neutralization test (PRNT(50)) titers, which effectively neutralized live dengue 2 virus in PRNT(50) assays.

  8. Exploring the Photoreduction of Au(III) Complexes in the Gas-Phase

    NASA Astrophysics Data System (ADS)

    Marcum, Jesse C.; Kaufman, Sydney H.; Weber, J. Mathias

    2010-06-01

    We have used photodissociation spectroscopy to probe the electronic structure and photoreduction of Au(III) in gas-phase complexes containing Cl- and OH-. The gas-phase electronic spectrum of [AuCl_4]- closely resembles the aqueous solution spectrum, showing a lack of strong solvatochromic shifts. Substitution of Cl- ligands with OH- results in a strong blue shift, in agreement with ligand-field theory. Upon excitation, [AuCl_4]- can dissociate by loss of either one or two neutral Cl atoms, resulting in the reduction of gold from Au(III) to Au(II) and Au(I) respectively. The hydroxide substituted complex, [AuCl_2(OH)_2]-, demonstrates similar behavior but the only observable fragment channel is the loss of two neutral OH ligands, leading only to Au(I).

  9. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases.

    PubMed

    Dinarello, Charles A; Simon, Anna; van der Meer, Jos W M

    2012-08-01

    Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.

  10. Neutral Red versus MTT assay of cell viability in the presence of copper compounds.

    PubMed

    Gomez Perez, Mariela; Fourcade, Lyvia; Mateescu, Mircea Alexandru; Paquin, Joanne

    2017-10-15

    Copper is essential for numerous physiological functions, and copper compounds may display therapeutic as well as cytotoxic effects. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay is a standard test largely used in cytotoxicity studies. This report shows that low micromolar levels of copper compounds such as Cu(II)Urea 2 , Cu(II)Ser 2 and CuCl 2 can interfere with the MTT assay making improper the detection of formazan product of MTT reduction. Comparatively, the Neutral Red assay appears to be sensitive and showing no interference with these compounds. The lactate dehydrogenase alternative assay cannot be used because of inhibitory effect of these copper compounds on the enzyme activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. High-Energy Emissions Induced by Air Density Fluctuations of Discharges

    NASA Astrophysics Data System (ADS)

    Köhn, C.; Chanrion, O.; Neubert, T.

    2018-05-01

    Bursts of X-rays and γ-rays are observed from lightning and laboratory sparks. They are bremsstrahlung from energetic electrons interacting with neutral air molecules, but it is still unclear how the electrons achieve the required energies. It has been proposed that the enhanced electric field of streamers, found in the corona of leader tips, may account for the acceleration; however, their efficiency is questioned because of the relatively low production rate found in simulations. Here we emphasize that streamers usually are simulated with the assumption of homogeneous gas, which may not be the case on the small temporal and spatial scales of discharges. Since the streamer properties strongly depend on the reduced electric field E/n, where n is the neutral number density, fluctuations may potentially have a significant effect. To explore what might be expected if the assumption of homogeneity is relaxed, we conducted simple numerical experiments based on simulations of streamers in a neutral gas with a radial gradient in the neutral density, assumed to be created, for instance, by a previous spark. We also studied the effects of background electron density from previous discharges. We find that X-radiation and γ-radiation are enhanced when the on-axis air density is reduced by more than ˜25%. Pre-ionization tends to reduce the streamer field and thereby the production rate of high-energy electrons; however, the reduction is modest. The simulations suggest that fluctuations in the neutral densities, on the temporal and spacial scales of streamers, may be important for electron acceleration and bremsstrahlung radiation.

  12. Physico-chemical analysis of tannery solid waste and structural characterization of its isolated humic acids after composting.

    PubMed

    Amir, Soumia; Benlboukht, Fatima; Cancian, Nadia; Winterton, Peter; Hafidi, Mohamed

    2008-12-30

    In Marrakech, solid by-products from tanneries are highly polluting, generating large amounts of nitrogenous and organic matter. In the present study composting is tested as a cost-effective method for waste management to overcome many of the environmental hazards and produce a stable, rich material for soil fertilization. Two composting trials were conducted after neutralization by ammonia or lime. The aim of the neutralization was to avoid the antimicrobial effects of the acidity in the tannery waste, thus ensuring correct composting. Different techniques such as elemental analysis and 13C NMR spectroscopy were applied to analyse humic acids isolated from raw and composted materials, and to monitor the process of tannery waste composting, and the stability and maturity of the final product according to the means of neutralization. Comparison of data showed similar behaviour in both trials, but the composting process appeared to be more complete following neutralization with lime. The C, H and N content decreased, while the O increased. The FTIR and 13C NMR spectra show the decrease of aliphatic compounds demonstrated by the reduction of absorbance around 2922cm(-1) and of the resonance in the C-alkyl area around 0-55ppm. The humic acids newly formed during composting were richer in the O-N alkyl and oxidized aromatic structures that increased almost twofold on composting after neutralization with lime. The first principal component axis PC1 (54%) separated C-aliphatic, C-carboxylic and other less stable and less polycondensed compounds such as polyphenols from the more polycondensed O-N alkyl and oxidized C-aromatic compounds.

  13. Does Maximal External Tibial Component Rotation Influence Tibiofemoral Load Distribution in the Primary Knee Arthroplasty Setting: A Comparison of Neutral vs Maximal Anatomical External Rotatory States.

    PubMed

    Manning, William A; Ghosh, Kanishka M; Blain, Alasdair P; Longstaff, Lee M; Rushton, Steven P; Deehan, David J

    2017-06-01

    Tibial component rotation at time of knee arthroplasty can influence conformity, load transmission across the polyethylene surface, and perhaps ultimately determined survivorship. Optimal tibial component rotation on the cut surface is reliant on standard per operative manual stressing. This subjective assessment aims to balance constraint and stability of the articulation through a full arc of movement. Using a cadaveric model, computer navigation and under defined, previously validated loaded conditions mimicking the in vivo setting, the influence of maximal tibial component external rotation compared with the neutral state was examined for changes in laxity and tibiofemoral continuous load using 3D displacement measurement and an orthosensor continuous load sensor implanted within the polyethylene spacer in a simulated single radius total knee arthroplasty. No significant difference was found throughout arc of motion (0-115 degrees of flexion) for maximal varus and/or valgus or rotatory laxity between the 2 states. The neutral state achieved equivalence for mediolateral load distribution at each point of flexion. We have found that external rotation of the tibial component increased medial compartment load in comparison with the neutral position. Compared with the neutral state, external rotation consistently effected a marginal, but not significant reduction in lateral load under similar loading conditions. The effects were most pronounced in midflexion. On the basis of these findings, we would advocate for the midtibial tubercle point to determine tibial component rotation and caution against component external rotation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity.

    PubMed

    De Martinis, Massimo; Franceschi, Claudio; Monti, Daniela; Ginaldi, Lia

    2005-04-11

    Immunosenescence is the consequence of the continuous attrition caused by chronic antigenic stress. The most important characteristics of immunosenescence (accumulation of memory and effector T cells, reduction of naive T cells, shrinkage of T cell repertoire, reduction of the immunological space) are compatible with this assumption. Immunosenescence can be taken as proof that the beneficial effects of the immune system, devoted to the neutralization of harmful agents early in life, become detrimental late in life, in a period not foreseen by evolution. This perspective could explain the mechanisms of the ageing process as well as the pathogenesis of age-related diseases.

  15. The sexual double standard in African American adolescent women's sexual risk reduction socialization.

    PubMed

    Fasula, Amy M; Miller, Kim S; Wiener, Jeffrey

    2007-01-01

    This study explored the sexual double standard (SDS) (in which males are afforded more freedom and power than females in heterosexual interactions) in African American mothers' sexual messages to sons and daughters. We used a convenience sample of 129 African American adolescents, aged 14 to 17 years, and their mothers who reported SDS attitudes. Qualitative analyses revealed gender differences based on an SDS in mothers' sexual risk reduction socialization. Mothers typically took a proactive approach with sons and a neutral or prohibitive approach with daughters. Findings provide directions for socially relevant programs for African American parents, schools, and communities.

  16. Induction of Heterologous Tier 2 HIV-1-Neutralizing and Cross-Reactive V1/V2-Specific Antibodies in Rabbits by Prime-Boost Immunization

    PubMed Central

    Townsley, Samantha; Mohamed, Zeinab; Guo, Wenjin; McKenna, Jennifer; Cleveland, Brad; LaBranche, Celia; Beaumont, David; Shen, Xiaoying; Yates, Nicole L.; Pinter, Abraham; Tomaras, Georgia D.; Ferrari, Guido; Montefiori, David C.

    2016-01-01

    ABSTRACT Poxvirus prime-protein boost used in the RV144 trial remains the only immunization strategy shown to elicit a modest level of protection against HIV-1 acquisition in humans. Although neutralizing antibodies (NAb) were generated, they were against sensitive viruses, not the more resistant “tier 2” isolates that dominate circulating strains. Instead, risk reduction correlated with antibodies recognizing epitopes in the V1/V2 region of HIV-1 envelope glycoprotein (Env). Here, we examined whether tier 2 virus NAb and V1/V2-specific non-NAb could be elicited by a poxvirus prime-gp120 boost strategy in a rabbit model. We studied two clade B Envs that differ in multiple parameters, including tissue origin, neutralization sensitivity, and presence of the N197 (N7) glycan that was previously shown to modulate the exposure of conserved epitopes on Env. We demonstrate that immunized rabbits generated cross-reactive neutralizing activities against >50% of the tier 2 global HIV-1 isolates tested. Some of these activities were directed against the CD4 binding site (CD4bs). These rabbits also generated antibodies that recognized protein scaffolds bearing V1/V2 sequences from diverse HIV-1 isolates and mediated antibody-dependent cellular cytotoxicity. However, there are subtle differences in the specificities and the response rates of V1/V2-specific antibodies between animals immunized with different Envs, with or without the N7 glycan. These findings demonstrate that antibody responses that have been correlated with protection against HIV-1 acquisition in humans can be elicited in a preclinical model by a poxvirus prime-gp120 boost strategy and that improvements may be achievable by optimizing the nature of the priming and boosting immunogens. IMPORTANCE The only vaccine approach shown to elicit any protective efficacy against HIV-1 acquisition is based on a poxvirus prime-protein boost regimen (RV144 Thai trial). Reduction of risk was associated with nonneutralizing antibodies targeting the V1/V2 loops of the envelope protein gp120. However, the modest efficacy (31.2%) achieved in this trial highlights the need to examine approaches and factors that may improve vaccine-induced responses, including cross-reactive neutralizing activities. We show here that rabbits immunized with a novel recombinant vaccinia virus prime-gp120 protein boost regimen generated antibodies that recognize protein scaffolds bearing V1/V2 sequences from diverse HIV-1 isolates and mediated antibody-dependent cellular cytotoxicity. Importantly, immunized rabbits also showed neutralizing activities against heterologous tier 2 HIV-1 isolates. These findings may inform the design of prime-boost immunization approaches and help improve the protective efficacy of candidate HIV-1 vaccines. PMID:27440894

  17. Induction of Heterologous Tier 2 HIV-1-Neutralizing and Cross-Reactive V1/V2-Specific Antibodies in Rabbits by Prime-Boost Immunization.

    PubMed

    Townsley, Samantha; Mohamed, Zeinab; Guo, Wenjin; McKenna, Jennifer; Cleveland, Brad; LaBranche, Celia; Beaumont, David; Shen, Xiaoying; Yates, Nicole L; Pinter, Abraham; Tomaras, Georgia D; Ferrari, Guido; Montefiori, David C; Hu, Shiu-Lok

    2016-10-01

    Poxvirus prime-protein boost used in the RV144 trial remains the only immunization strategy shown to elicit a modest level of protection against HIV-1 acquisition in humans. Although neutralizing antibodies (NAb) were generated, they were against sensitive viruses, not the more resistant "tier 2" isolates that dominate circulating strains. Instead, risk reduction correlated with antibodies recognizing epitopes in the V1/V2 region of HIV-1 envelope glycoprotein (Env). Here, we examined whether tier 2 virus NAb and V1/V2-specific non-NAb could be elicited by a poxvirus prime-gp120 boost strategy in a rabbit model. We studied two clade B Envs that differ in multiple parameters, including tissue origin, neutralization sensitivity, and presence of the N197 (N7) glycan that was previously shown to modulate the exposure of conserved epitopes on Env. We demonstrate that immunized rabbits generated cross-reactive neutralizing activities against >50% of the tier 2 global HIV-1 isolates tested. Some of these activities were directed against the CD4 binding site (CD4bs). These rabbits also generated antibodies that recognized protein scaffolds bearing V1/V2 sequences from diverse HIV-1 isolates and mediated antibody-dependent cellular cytotoxicity. However, there are subtle differences in the specificities and the response rates of V1/V2-specific antibodies between animals immunized with different Envs, with or without the N7 glycan. These findings demonstrate that antibody responses that have been correlated with protection against HIV-1 acquisition in humans can be elicited in a preclinical model by a poxvirus prime-gp120 boost strategy and that improvements may be achievable by optimizing the nature of the priming and boosting immunogens. The only vaccine approach shown to elicit any protective efficacy against HIV-1 acquisition is based on a poxvirus prime-protein boost regimen (RV144 Thai trial). Reduction of risk was associated with nonneutralizing antibodies targeting the V1/V2 loops of the envelope protein gp120. However, the modest efficacy (31.2%) achieved in this trial highlights the need to examine approaches and factors that may improve vaccine-induced responses, including cross-reactive neutralizing activities. We show here that rabbits immunized with a novel recombinant vaccinia virus prime-gp120 protein boost regimen generated antibodies that recognize protein scaffolds bearing V1/V2 sequences from diverse HIV-1 isolates and mediated antibody-dependent cellular cytotoxicity. Importantly, immunized rabbits also showed neutralizing activities against heterologous tier 2 HIV-1 isolates. These findings may inform the design of prime-boost immunization approaches and help improve the protective efficacy of candidate HIV-1 vaccines. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Foot strike pattern in children during shod-unshod running.

    PubMed

    Latorre Román, Pedro Ángel; Balboa, Fernando Redondo; Pinillos, Felipe García

    2017-10-01

    The purpose of this study was to determine the foot strike patterns (FSPs) and neutral support (no INV/EVE and no foot rotation) in children, as well as to determine the influence of shod/unshod conditions and sex. A total of 713 children, aged 6 to 16 years, participated in this study (Age=10.28±2.71years, body mass index [BMI]=19.70±3.91kg/m 2 , 302 girls and 411 boys). A sagittal and frontal-plane video (240Hz) was recorded using a high-speed camcorder, to record the following variables: rearfoot strike (RFS), midfoot strike (MFS), forefoot strike (FFS), inversion/eversion (INV/EVE) and foot rotation on initial contact. RFS prevalence was similar between boys and girls in both shod and unshod conditions. In the unshod condition there was a significant reduction (p<0.001) of RFS prevalence both in boys (shod condition=83.95% vs. 62.65% unshod condition) and in girls (shod condition=87.85% vs. 62.70% unshod condition). No significant differences were found in INV/EVE and foot rotation between sex groups. In the unshod condition there was a significant increase (p<0.001) of neutral support (no INV/EVE) both in boys (shod condition=12.55% vs. 22.22% unshod condition) and in girls (shod condition=17.9% vs. 28.15% unshod condition). In addition, in the unshod condition there is a significant reduction (p<0.001) of neutral support (no foot rotation) both in boys (shod condition=21.55% vs. 11.10% unshod condition) and in girls (shod condition=21.05% vs. 11.95% unshod condition). In children, RFS prevalence is lower than adult's population. Additionally, barefoot running reduced the prevalence of RFS and INV/EVE, however increased foot rotation. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Alternative mechanistic explanation for ligand-dependent selectivities in copper-catalyzed N- and O-arylation reactions.

    PubMed

    Yu, Hai-Zhu; Jiang, Yuan-Ye; Fu, Yao; Liu, Lei

    2010-12-29

    The ligand-dependent selectivities in Ullmann-type reactions of amino alcohols with iodobenzene by β-diketone- and 1,10-phenanthroline-ligated Cu(I) complexes were recently explained by the single-electron transfer and iodine atom transfer mechanisms (Jones, G. O., Liu, P., Houk, K. N., and Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 6205.). The present study shows that an alternative, oxidative addition/reductive elimination mechanism may also explain the selectivities. Calculations indicate that a Cu(I) complex with a negatively charged β-diketone ligand is electronically neutral, so that oxidative addition of ArI to a β-diketone-ligated Cu(I) prefers to occur (and occur readily) in the absence of the amino alcohol. Thus, coordination of the amino alcohol in its neutral form can only occur at the Cu(III) stage where N-coordination is favored over O-coordination. The coordination step is the rate-limiting step and the outcome is that N-arylation is favored with the β-diketone ligand. On the other hand, a Cu(I) complex with a neutral 1,10-phenanthroline ligand is positively charged, so that oxidative addition of ArI to a 1,10-phenanthroline-ligated Cu(I) has to get assistance from a deprotonated amino alcohol substrate. This causes oxidative addition to become the rate-limiting step in the 1,10-phenanthroline-mediated reaction. The immediate product of the oxidative addition step is found to undergo facile reductive elimination to provide the arylation product. Because O-coordination of a deprotonated amino alcohol is favored over N-coordination in the oxidative addition transition state, O-arylation is favored with the 1,10-phenanthroline ligand.

  20. Preparing a Climate Action Plan and Setting Priorities | Climate Neutral

    Science.gov Websites

    . Cost/benefit (dollar per ton of carbon): Other carbon reduction measures, however, have a low rate of highest cost-benefit ratios. Unfortunately, these measures may not address the energy sectors with the good return (i.e. a high cost-benefit ratio) with measures yielding a lower return. A portfolio allows

  1. The Evolution of Counterrevolutionary Doctrine in the U.S. Military. The Second Seminole; Philippine and Vietnam Wars. Did We Learn our Lessons

    DTIC Science & Technology

    1993-04-01

    Management and Budget. Paperwork Reduction Project (0704-011). Washington. DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. .REPOR.DAT13. RPORT TYPE AND DATES...his support bas and will to fWgh Lasly, as pointed out, the Army stumbled onto the tactic of neutralizing the memy leadeship . Howevr, litnk qportance

  2. Effects of grip force on median nerve deformation at different wrist angles

    PubMed Central

    Nakashima, Hiroki; Muraki, Satoshi

    2016-01-01

    The present study investigated the effects of grip on changes in the median nerve cross-sectional area (MNCSA) and median nerve diameter in the radial-ulnar direction (D1) and dorsal-palmar direction (D2) at three wrist angles. Twenty-nine healthy participants (19 men [mean age, 24.2 ± 1.6 years]; 10 women [mean age, 24.0 ± 1.6 years]) were recruited. The median nerve was examined at the proximal carpal tunnel region in three grip conditions, namely finger relaxation, unclenched fist, and clenched fist. Ultrasound examinations were performed in the neutral wrist position (0°), at 30°wrist flexion, and at 30°wrist extension for both wrists. The grip condition and wrist angle showed significant main effects (p < 0.01) on the changes in the MNCSA, D1, and D2. Furthermore, significant interactions (p < 0.01) were found between the grip condition and wrist angle for the MNCSA, D1, and D2. In the neutral wrist position (0°), significant reductions in the MNCSA, D1, and D2 were observed when finger relaxation changed to unclenched fist and clenched fist conditions. Clenched fist condition caused the highest deformations in the median nerve measurements (MNCSA, approximately −25%; D1, −13%; D2, −12%). The MNCSA was significantly lower at 30°wrist flexion and 30°wrist extension than in the neutral wrist position (0°) at unclenched fist and clenched fist conditions. Notably, clenched fist condition at 30°wrist flexion showed the highest reduction of the MNCSA (−29%). In addition, 30°wrist flexion resulted in a lower D1 at clenched fist condition. In contrast, 30°wrist extension resulted in a lower D2 at both unclenched fist and clenched fist conditions. Our results suggest that unclenched fist and clenched fist conditions cause reductions in the MNCSA, D1, and D2. More importantly, unclenched fist and clenched fist conditions at 30°wrist flexion and 30°wrist extension can lead to further deformation of the median nerve. PMID:27688983

  3. Neutral mood induction during reconsolidation reduces accuracy, but not vividness and anxiety of emotional episodic memories.

    PubMed

    Liu, Guanyu; McNally, Richard J

    2017-03-01

    Consolidated memories become labile upon reactivation and as a result have to go through reconsolidation to become re-stabilized. This property of memory may potentially be used to reduce the impact of highly negative episodic memories. Because detailed and vivid negative memories are mediated by high arousal, if arousal is lessened during reconsolidation, memory accuracy and vividness should diminish. In this study, we examined this hypothesis. Participants (N = 72) viewed a stressful, suspenseful video on Day 1 to develop negative episodic memories. Then, 24-29 h later, they saw a brief reminder of the stressful video (or not), and then viewed a neutral, calming (or positive) video. Another 24-29 h later, participants were tested on the accuracy, vividness, and anxiety associated with their memory of the stressful video on Day 1. Participants who watched the reminder and then the neutral video showed reduced memory accuracy compared to participants in the other groups. Despite the reduction in memory accuracy, their memory vividness and anxiety associated with the stressful video did not decrease. The use of undergraduates prevents generalizations to clinical populations. Also, the study did not test long-term memories that were more than 2 days old. Neutral mood induction during reconsolidation reduces the accuracy of highly negative episodic memories. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Bottleneck Effect on Evolutionary Rate in the Nearly Neutral Mutation Model

    PubMed Central

    Araki, H.; Tachida, H.

    1997-01-01

    Variances of evolutionary rates among lineages in some proteins are larger than those expected from simple Poisson processes. This phenomenon is called overdispersion of the molecular clock. If population size N is constant, the overdispersion is observed only in a limited range of 2Nσ under the nearly neutral mutation model, where σ represents the standard deviation of selection coefficients of new mutants. In this paper, we investigated effects of changing population size on the evolutionary rate by computer simulations assuming the nearly neutral mutation model. The size was changed cyclically between two numbers, N(1) and N(2) (N(1) > N(2)), in the simulations. The overdispersion is observed if 2N(2)σ is less than two and the state of reduced size (bottleneck state) continues for more than ~0.1/u generations, where u is the mutation rate. The overdispersion results mainly because the average fitnesses of only a portion of populations go down when the population size is reduced and only in these populations subsequent advantageous substitutions occur after the population size becomes large. Since the fitness reduction after the bottleneck is stochastic, acceleration of the evolutionary rate does not necessarily occur uniformly among loci. From these results, we argue that the nearly neutral mutation model is a candidate mechanism to explain the overdispersed molecular clock. PMID:9335622

  5. Electron density and gas density measurements in a millimeter-wave discharge

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schaub, S. C., E-mail: sschaub@mit.edu; Hummelt, J. S.; Guss, W. C.

    2016-08-15

    Electron density and neutral gas density have been measured in a non-equilibrium air breakdown plasma using optical emission spectroscopy and two-dimensional laser interferometry, respectively. A plasma was created with a focused high frequency microwave beam in air. Experiments were run with 110 GHz and 124.5 GHz microwaves at powers up to 1.2 MW. Microwave pulses were 3 μs long at 110 GHz and 2.2 μs long at 124.5 GHz. Electron density was measured over a pressure range of 25 to 700 Torr as the input microwave power was varied. Electron density was found to be close to the critical density, where the collisional plasma frequency is equal tomore » the microwave frequency, over the pressure range studied and to vary weakly with input power. Neutral gas density was measured over a pressure range from 150 to 750 Torr at power levels high above the threshold for initiating breakdown. The two-dimensional structure of the neutral gas density was resolved. Intense, localized heating was found to occur hundreds of nanoseconds after visible plasma formed. This heating led to neutral gas density reductions of greater than 80% where peak plasma densities occurred. Spatial structure and temporal dynamics of gas heating at atmospheric pressure were found to agree well with published numerical simulations.« less

  6. Infection with non-lethal West Nile virus Eg101 strain induces immunity that protects mice against the lethal West Nile virus NY99 strain.

    PubMed

    Kumar, Mukesh; O'Connell, Maile; Namekar, Madhuri; Nerurkar, Vivek R

    2014-06-06

    Herein we demonstrate that infection of mice with West Nile virus (WNV) Eg101 provides protective immunity against lethal challenge with WNV NY99. Our data demonstrated that WNV Eg101 is largely non-virulent in adult mice when compared to WNV NY99. By day 6 after infection, WNV-specific IgM and IgG antibodies, and neutralizing antibodies were detected in the serum of all WNV Eg101 infected mice. Plaque reduction neutralization test data demonstrated that serum from WNV Eg101 infected mice neutralized WNV Eg101 and WNV NY99 strains with similar efficiency. Three weeks after infection, WNV Eg101 immunized mice were challenged subcutaneously or intracranially with lethal dose of WNV NY99 and observed for additional three weeks. All the challenged mice were protected against disease and no morbidity and mortality was observed in any mice. In conclusion, our data for the first time demonstrate that infection of mice with WNV Eg101 induced high titers of WNV specific IgM and IgG antibodies, and cross-reactive neutralizing antibodies, and the resulting immunity protected all immunized animals from both subcutaneous and intracranial challenge with WNV NY99. These observations suggest that WNV Eg101 may be a suitable strain for the development of a vaccine in humans against virulent strains of WNV.

  7. Fe(II) oxidation during acid mine drainage neutralization in a pilot-scale Sequencing Batch Reactor.

    PubMed

    Zvimba, J N; Mathye, M; Vadapalli, V R K; Swanepoel, H; Bologo, L

    2013-01-01

    This study investigated Fe(II) oxidation during acid mine drainage (AMD) neutralization using CaCO3 in a pilot-scale Sequencing Batch Reactor (SBR) of hydraulic retention time (HRT) of 90 min and sludge retention time (SRT) of 360 min in the presence of air. The removal kinetics of Fe(II), of initial concentration 1,033 ± 0 mg/L, from AMD through oxidation to Fe(III) was observed to depend on both pH and suspended solids, resulting in Fe(II) levels of 679 ± 32, 242 ± 64, 46 ± 16 and 28 ± 0 mg/L recorded after cycles 1, 2, 3 and 4 respectively, with complete Fe(II) oxidation only achieved after complete neutralization of AMD. Generally, it takes 30 min to completely oxidize Fe(II) during cycle 4, suggesting that further optimization of SBR operation based on both pH and suspended solids manipulation can result in significant reduction of the number of cycles required to achieve acceptable Fe(II) oxidation for removal as ferric hydroxide. Overall, complete removal of Fe(II) during AMD neutralization is attractive as it promotes recovery of better quality waste gypsum, key to downstream gypsum beneficiation for recovery of valuables, thereby enabling some treatment-cost recovery and prevention of environmental pollution from dumping of sludge into landfills.

  8. Pertussis outbreak, southeastern Minnesota, 2012.

    PubMed

    Theofiles, Alexander G; Cunningham, Scott A; Chia, Nicholas; Jeraldo, Patricio R; Quest, Daniel J; Mandrekar, Jayawant N; Patel, Robin

    2014-10-01

    To describe clinical and laboratory findings from the 2012 southeastern Minnesota pertussis outbreak. Patients were selected for 2 parts of the study. In the first part, nasopharyngeal swabs from a convenience sample of 265 unique patients were used for both the clinician-requested polymerase chain reaction (PCR) test and culture. B pertussis isolates were tested for macrolide susceptibility and typed using whole genome sequencing and pulsed-field gel electrophoresis. Pertactin gene sequences were analyzed to identify pertactin-deficient B pertussis. In the second part, all patients seen at Mayo Clinic in Rochester, Minnesota, who had PCR results positive for Bordetella pertussis or Bordetella parapertussis between January 1, 2012, and December 31, 2012, were analyzed for patient demographic features and vaccination records. One hundred sixty patients had results positive for B pertussis, and 21 patients had results positive for B parapertussis. Among the 265 swabs cultured, B pertussis was detected by both culture and PCR in 11. One swab was positive for B pertussis by culture alone, and 13 were positive by PCR alone. Polymerase chain reaction detected B pertussis more frequently than did culture (P=.001). No macrolide resistance was detected. All 12 isolates tested had an altered pertactin gene, including 9 with a signal sequence deletion, 2 with insertion sequence disruptions, and 1 with a premature stop codon. Nine and 3 isolates were pertactin types prn1 and prn2, respectively. Whole genome sequencing and pulsed-field gel electrophoresis detected the presence of multiple B pertussis strains. The mean age of patients with pertussis was younger than that of those without pertussis (15.6 and 25.5 years, respectively; P=.002). Compared with those whose test results were negative for B pertussis, fewer patients with positive results had received whole-cell pertussis vaccine (P=.02). In the subgroup who had received acellular vaccine exclusively, the time since the most recent pertussis vaccination in those with results positive for B pertussis was longer than that in those with negative results (1363 vs 1010 days; P=.004). The 2012 pertussis outbreak in southeastern Minnesota included multiple strains of B pertussis, all putatively lacking pertactin. Our findings may indicate decreased efficacy of (and waning immunity from) acellular vaccines as contributors to the outbreak. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. The Impact of Massage and Reading on Children's Pain and Anxiety After Cardiovascular Surgery: A Pilot Study.

    PubMed

    Staveski, Sandra L; Boulanger, Karen; Erman, Lee; Lin, Li; Almgren, Christina; Journel, Chloe; Roth, Stephen J; Golianu, Brenda

    2018-06-14

    The purpose of this pilot study was three-fold: 1) to evaluate the safety and feasibility of instituting massage therapy in the immediate postoperative period after congenital heart surgery, 2) to examine the preliminary results on effects of massage therapy versus standard of care plus three reading visits on postoperative pain and anxiety, and 3) to evaluate preliminary effects of opioid and benzodiazepine exposure in patients receiving massage therapy compared with reading controls. Prospective, randomized controlled trial. An academic children's hospital. Sixty pediatric heart surgery patients between ages 6 and 18 years. Massage therapy and reading. There were no adverse events related to massage or reading interventions in either group. Our investigation found no statistically significant difference in Pain or State-Trait Anxiety scores in the initial 24 hours after heart surgery (T1) and within 48 hours of transfer to the acute care unit (T2) after controlling for age, gender, and Risk Adjustment for Congenital Heart Surgery 1 score. However, children receiving massage therapy had significantly lower State-Trait Anxiety scores after receiving massage therapy at time of discharge (T3; p = 0.0075) than children receiving standard of care plus three reading visits. We found no difference in total opioid exposure during the first 3 postoperative days between groups (median [interquartile range], 0.80 mg/kg morphine equivalents [0.29-10.60] vs 1.13 mg/kg morphine equivalents [0.72-6.14]). In contrast, children receiving massage therapy had significantly lower total benzodiazepine exposure in the immediate 3 days following heart surgery (median [interquartile range], 0.002 mg/kg lorazepam equivalents [0-0.03] vs 0.03 mg/kg lorazepam equivalents [0.02-0.09], p = 0.0253, Wilcoxon rank-sum) and number of benzodiazepine PRN doses (0.5 [0-2.5] PRN vs 2 PRNs (1-4); p = 0.00346, Wilcoxon rank-sum). Our pilot study demonstrated the safety and feasibility of implementing massage therapy in the immediate postoperative period in pediatric heart surgery patients. We found decreased State-Trait Anxiety scores at discharge and lower total exposure to benzodiazepines. Preventing postoperative complications such as delirium through nonpharmacologic interventions warrants further evaluation.

  10. Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III, randomized study.

    PubMed

    Rivera, Luis; Schwarz, Tino F; Kim, Kyung-Hyo; Kim, Yun-Kyung; Behre, Ulrich; Cha, Sung-Ho; Jo, Dae Sun; Lee, Jacob; Lee, Jin-Soo; Cheuvart, Brigitte; Jastorff, Archana; Van der Wielen, Marie

    2018-06-27

    This study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults. In this phase III, randomized, partially-blind study (NCT01767376), healthy 11-25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti-tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre-defined clinical criteria. Safety was also evaluated. Non-inferiority of immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for 4 meningococcal serogroups and of the percentage of participants with antibody concentrations >1 IU/ml for D and T. Among the pertussis antigens, non-inferiority criteria for geometric mean concentrations (GMCs) were reached for PT, but not met for FHA and PRN. Across all groups, ≥93.2% of participants had vaccine responses to each meningococcal serogroup, ≥99.1% were seroprotected against T and D, and ≥85.5% had booster responses to each pertussis antigen. Robust increases in antibody GMTs/GMCs were observed for all antigens between pre-and post-vaccination. Both vaccines had clinically acceptable safety profiles. Immune responses to MenACWY-TT and to the T and D antigens from Tdap were not impacted by their co-administration. The lower antibody concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents. Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  11. Control of electron transfer in the cytochrome system of mitochondria by pH, transmembrane pH gradient and electrical potential. The cytochromes b-c segment.

    PubMed

    Papa, S; Lorusso, M; Izzo, G; Capuano, F

    1981-02-15

    1. A study is presented of the effects of pH, transmembrane pH gradient and electrical potential on oxidoreductions of b and c cytochromes in ox heart mitochondria and 'inside-out' submitochondrial particles. 2. Kinetic analysis shows that, in mitochondria at neutral pH, there is a restraint on the aerobic oxidation of cytochrome b566 with respect to cytochrome b562. Valinomycin plus K+ accelerates cytochrome b566 oxidation and retards net oxidation of cytochrome b562. At alkaline pH the rate of cytochrome b566 oxidation approaches that of cytochrome b562 and the effects of valinomycin on b cytochromes are impaired. 3. At slightly acidic pH, oxygenation of antimycin-supplemented mitochondria causes rapid reduction of cytochrome b566 and small delayed reduction of cytochrome b562. Valinomycin or a pH increase in the medium promote reduction of cytochrome b562 and decrease net reduction of cytochrome b566. 4. Addition of valinomycin to mitochondria and submitochondrial particles in the respiring steady state causes, at pH values around neutrality, preferential oxidation of cytochrome b566 with respect to cytochrome b562. The differential effect of valinomycin on oxidation of cytochromes b566 and b562 is enhanced by substitution of 1H2O of the medium with 2H2O and tends to disappear as the pH of the medium is raised to alkaline values. 5. Nigericin addition in the aerobic steady state causes, both in mitochondria and submitochondrial particles, preferential oxidation of cytochrome b562 with respect to cytochrome b566. This is accompanied by c cytochrome oxidation in mitochondria but c cytochrome reduction in submitochondrial particles. 6. In mitochondria as well as in submitochondrial particles, the aerobic transmembrane potential (delta psi) does not change by raising the pH of the external medium from neutrality to alkalinity. The transmembrane pH gradient (delta pH) on the other hand, decrease slightly. 7. The results presented provide evidence that the delta psi component of the aerobic delta microH+ (the sum of the proton chemical and electrical activities) exerts a pH-dependent constraint on forward electron flow from cytochrome b566 to cytochrome b562. This effect is explained as a consequence of anisotropic location of cytochromes b566 and b562 in the membrane and the pH-dependence of the redox function of these cytochromes. Transmembrane delta pH, on the other hand, exerts control on electron flow from cytochrome b562 to c cytochromes.

  12. Modeling thermospheric neutral density

    NASA Astrophysics Data System (ADS)

    Qian, Liying

    Satellite drag prediction requires determination of thermospheric neutral density. The NCAR Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIEGCM) and the global-mean Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model (TIMEGCM) were used to quantify thermospheric neutral density and its variations, focusing on annual/semiannual variation, the effect of using measured solar irradiance on model calculations of solar-cycle variation, and global change in the thermosphere. Satellite drag data and the MSIS00 empirical model were utilized to compare to the TIEGCM simulations. The TIEGCM simulations indicated that eddy diffusion and its annual/semiannual variation is a mechanism for annual/semiannual density variation in the thermosphere. It was found that eddy diffusion near the turbopause can effectively influence thermospheric neutral density. Eddy diffusion, together with annual insolation variation and large-scale circulation, generated global annual/semiannual density variation observed by satellite drag. Using measured solar irradiance as solar input for the TIEGCM improved the solar-cycle dependency of the density calculation shown in F10.7 -based thermospheric empirical models. It has been found that the empirical models overestimate density at low solar activity. The TIEGCM simulations did not show such solar-cycle dependency. Using historic measurements of CO2 and F 10.7, simulations of the global-mean TIMEGCM showed that thermospheric neutral density at 400 km had an average long-term decrease of 1.7% per decade from 1970 to 2000. A forecast of density decrease for solar cycle 24 suggested that thermospheric density will decrease at 400 km from present to the end of solar cycle 24 at a rate of 2.7% per decade. Reduction in thermospheric density causes less atmospheric drag on earth-orbiting space objects. The implication of this long-term decrease of thermospheric neutral density is that it will increase the lifetime of satellites, but also it will increase the amount of space junk.

  13. Lexical Predictability During Natural Reading: Effects of Surprisal and Entropy Reduction.

    PubMed

    Lowder, Matthew W; Choi, Wonil; Ferreira, Fernanda; Henderson, John M

    2018-06-01

    What are the effects of word-by-word predictability on sentence processing times during the natural reading of a text? Although information complexity metrics such as surprisal and entropy reduction have been useful in addressing this question, these metrics tend to be estimated using computational language models, which require some degree of commitment to a particular theory of language processing. Taking a different approach, this study implemented a large-scale cumulative cloze task to collect word-by-word predictability data for 40 passages and compute surprisal and entropy reduction values in a theory-neutral manner. A separate group of participants read the same texts while their eye movements were recorded. Results showed that increases in surprisal and entropy reduction were both associated with increases in reading times. Furthermore, these effects did not depend on the global difficulty of the text. The findings suggest that surprisal and entropy reduction independently contribute to variation in reading times, as these metrics seem to capture different aspects of lexical predictability. Copyright © 2018 Cognitive Science Society, Inc.

  14. CHARGE-2 rocket observations of vehicle charging and charge neutralization

    NASA Astrophysics Data System (ADS)

    Banks, P. M.; Gilchrist, B. E.; Neubert, T.; Myers, N.; Raitt, W. J.; Williamson, P. R.; Fraser-Smith, A. C.; Sasaki, S.

    Observations of electrical charging and other phenomena have been made in the ionosphere with the CHARGE-2 tethered rocket system. In this experiment, two electrically connected payloads with a variety of plasma instruments measured effects associated with operation of a 1 keV, 40 mA electron gun and a 450-volt dc power supply. During electron beam operations, it was found that both mother and daughter payloads reached high positive potentials as a consequence of the restricted electron current collecting area of the payloads. During neutral gas thruster firings, the payload potentials were dramatically reduced, indicating that electrical discharges could effectively ground each payload to plasma potential. Other thruster-related effects were also seen, including substantial reductions of return current-associated electrical noise at HF and VLF and large increases in 3914 A light in the plasma sheath.

  15. Digestion of Crystalline Silicotitanate (CST)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DARREL, WALKER

    2004-11-04

    Researchers tested methods for chemically dissolving crystalline silicotitanate (CST) as a substitute for mechanical grinding to reduce particle size before vitrification. Testing used the commercially available form of CST, UOP IONSIV(R) IE-911. Reduction of the particle size to a range similar to that of the glass frit used by the Defense Waste Processing Facility (DWPF) could reduce problems with coupling cesium ion exchange to the vitrification process. This study found that IONSIV(R) IE-911 dissolves completely using a combination of acid, hydrogen peroxide, and fluoride ion. Neutralization of the resulting acidic solution precipitates components of the IONSIV(R) IE-911. Digestion requires extremelymore » corrosive conditions. Also, large particles may reform during neutralization, and the initiation and rate of gas generation are unpredictable. Therefore, the method is not recommended as a substitute for mechanical grinding.« less

  16. Effects of additional vapors on sterilization of microorganism spores with plasma-excited neutral gas

    NASA Astrophysics Data System (ADS)

    Matsui, Kei; Ikenaga, Noriaki; Sakudo, Noriyuki

    2015-01-01

    Some fundamental experiments are carried out in order to develop a plasma process that will uniformly sterilize both the space and inner wall of the reactor chamber at atmospheric pressure. Air, oxygen, argon, and nitrogen are each used as the plasma source gas to which mixed vapors of water and ethanol at different ratios are added. The reactor chamber is remotely located from the plasma area and a metal mesh for eliminating charged particles is installed between them. Thus, only reactive neutral particles such as plasma-excited gas molecules and radicals are utilized. As a result, adding vapors to the source gas markedly enhances the sterilization effect. In particular, air with water and/or ethanol vapor and oxygen with ethanol vapor show more than 6-log reduction for Geobacillus stearothermophilus spores.

  17. Structure determination of the neutral exopolysaccharide produced by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1.

    PubMed

    Van Calsteren, Marie-Rose; Gagnon, Fleur; Nishimura, Junko; Makino, Seiya

    2015-09-02

    The neutral exopolysaccharide (NPS) of Lactobacillus delbrueckii subsp. bulgaricus strain OLL1073R-1 was purified and characterized. The molecular mass was 5.0×10(6) g/mol. Sugar and absolute configuration analyses gave the following composition: d-Glc, 1; d-Gal, 1.5. The NPS was also submitted to periodate oxidation followed by borohydride reduction and Smith degradation. Sugar and methylation analyses, (1)H and (13)C nuclear magnetic resonance, and mass spectrometry of the NPS or of its specifically modified products allowed determining the repeating unit sequence: {2)Glc(α1-3)Glc(β1-3)[Gal(β1-4)]Gal(β1-4)Gal(α1-}n. The structure is compared to that of exopolysaccharides produced by other Lactobacillus bulgaricus strains. Copyright © 2015. Published by Elsevier Ltd.

  18. Reduction of N2 by supported tungsten clusters gives a model of the process by nitrogenase

    PubMed Central

    Murakami, Junichi; Yamaguchi, Wataru

    2012-01-01

    Metalloenzymes catalyze difficult chemical reactions under mild conditions. Mimicking their functions is a challenging task and it has been investigated using homogeneous systems containing metal complexes. The nitrogenase that converts N2 to NH3 under mild conditions is one of such enzymes. Efforts to realize the biological function have continued for more than four decades, which has resulted in several reports of reduction of N2, ligated to metal complexes in solutions, to NH3 by protonation under mild conditions. Here, we show that seemingly distinct supported small tungsten clusters in a dry environment reduce N2 under mild conditions like the nitrogenase. N2 is reduced to NH3 via N2H4 by addition of neutral H atoms, which agrees with the mechanism recently proposed for the N2 reduction on the active site of nitrogenase. The process on the supported clusters gives a model of the biological N2 reduction. PMID:22586517

  19. [The use of expressive writing in the course of care for cancer patients to reduce emotional distress: analysis of the literature].

    PubMed

    Gallo, Isabella; Garrino, Lorenza; Di Monte, Valerio

    2015-01-01

    The emotional distress represents one of the symptoms most frequently reported in the cancer patient in therapy, increasing the risk of developing a disease depressive. Through the analysis of the literature we want to assess whether the use of expressive writing on cancer patients in their care pathway compared to the use of writing neutral reduces emotional distress. The bibliographic search was conducted using the databases CINAHL, PubMed, Cochrane Library and PsycInfo. The results of research conducted on 7 randomized controlled trials, including 3 pilot studies have shown after expressive writing sessions (experimental group) versus neutral writing (control group) a significant reduction in distress in the experimental group early stages of cancer (p = 0,0183); in patients with a diagnosis of metastatic assigned to the group expressive writing there was a statistically significant relevance in the reduction of mood disorders (p = 0,03).Were determined statistically significant group differences also with respect to some measure on the quality of sleep (p = 0,04). The expressive writing did not produce significant reductions in psychological distress and improvements in physical health (p > 0,20) in patients diagnosed with metastatic disease of long duration and, in the palliative care there have been results of feasibility for poor adherence at follow-up. From the results it is evident that the strategies of expressive writing improves the management of the disease, reduce the physical and psychological symptoms related to the tumor while reducing the emotional distress in patients at an early stage of the disease.

  20. Persistence of Antibodies to West Nile Virus in Naturally Infected Rock Pigeons (Columba livia)

    PubMed Central

    Gibbs, Samantha E. J.; Hoffman, Douglas M.; Stark, Lillian M.; Marlenee, Nicole L.; Blitvich, Bradley J.; Beaty, Barry J.; Stallknecht, David E.

    2005-01-01

    Wild caught rock pigeons (Columba livia) with antibodies to West Nile virus were monitored for 15 months to determine antibody persistence and compare results of three serologic techniques. Antibodies persisted for the entire study as detected by epitope-blocking enzyme-linked immunosorbent assay and plaque reduction neutralization test. Maternal antibodies in squabs derived from seropositive birds persisted for an average of 27 days. PMID:15879030

  1. ELECTROLYTIC REDUCTION OF NITRIC ACID SOLUTIONS

    DOEpatents

    Alter, H.W.; Barney, D.L.

    1958-09-30

    A process is presented for the treatment of radioactivc waste nitric acid solutions. The nitric acid solution is neutralized with an alkali metal hydroxide in an amount sufficient to precipitate insoluble hydroxides, and after separation of the precipitate the solution is electrolyzed to convert the alkali nitrate formed, to alkali hydroxide, gaseous ammonla and oxygen. The solution is then reusable after reducing the volume by evaporating the water and dissolved ammonia.

  2. Evaluation of Potential Energy Loss Reduction and Savings for U. S. Army Electrical Distribution Systems

    DTIC Science & Technology

    1993-09-01

    Different Size Transformers (Per Transformer ) 41 15 Additional Energy Losses for Mis-Sized Transformers (Per Transformer ) 42 16 Power System ...directly affects the amount of neutral line power loss in the system . Since most Army three-phase loads are distribution transformers spread out over a...61 Balancing Three-Phase Loads Balancing Feeder Circuit Loads Power Factor Correction Optimal Transformer Sizing Conductor Sizing Combined

  3. Characterization of Attenuated Strains of Rift Valley Fever Virus

    DTIC Science & Technology

    1988-01-01

    confirmed as RVF virus by a plaque-reduction neutralization test (PRNT) (Earley et al., 1967) using antibody produced against ZH501. Viral replication in...original exposure. Sera were obtained from surviving hamsters and assayed for RVF virus antibody . The Reed-Muench formula (Reed & Muench, 1938) was used to... antibody production. we obtained sera from surviving hamsters that had been inoculated with the various RVF strains. Virus assays. We evaluated

  4. A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep.

    PubMed

    Faburay, Bonto; Lebedev, Maxim; McVey, D Scott; Wilson, William; Morozov, Igor; Young, Alan; Richt, Juergen A

    2014-10-01

    Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species.

  5. Serologic survey of domestic animals for zoonotic arbovirus infections in the Lacandón Forest region of Chiapas, Mexico.

    PubMed

    Ulloa, Armando; Langevin, Stanley A; Mendez-Sanchez, J D; Arredondo-Jimenez, Juan I; Raetz, Janae L; Powers, Ann M; Villarreal-Treviño, C; Gubler, Duane J; Komar, Nicholas

    2003-01-01

    A serologic survey in domestic animals (birds and mammals) was conducted in four communities located in the Lacandón Forest region of northeastern Chiapas, Mexico, during June 29 to July 1, 2001, with the objective to identify zoonotic arboviruses circulating in this area. We collected 202 serum samples from healthy domestic chickens, geese, ducks, turkeys, horses and cattle. The samples were tested by plaque-reduction neutralization test for antibodies to selected mosquito-borne flaviviruses (family Flaviviridae), including St. Louis encephalitis (SLE), Rocio (ROC), Ilheus (ILH), Bussuquara (BSQ), and West Nile (WN) viruses, and selected alphaviruses (family Togaviridae), including Western equine encephalitis (WEE), Eastern equine encephalomyelitis (EEE), and Venezuelan equine encephalitis (VEE) viruses. Neutralizing antibodies to SLE virus were detected in two (8%) of 26 turkeys, 15 (23%) of 66 cattle, and three (60%) of five horses. Antibodies to VEE virus were detected in 29 (45%) of 65 cattle. Because some of these animals were as young as 2 months old, we demonstrated recent activity of these two viruses. Sub-typing of the VEE antibody responses indicated that the etiologic agents of these infections belonged to the IE variety of VEE, which has been reported from other regions of Chiapas. WN virus-neutralizing antibodies were detected in a single cattle specimen (PRNT(90) = 1:80) that also circulated SLE virus-neutralizing antibodies (PRNT(90) = 1:20), suggesting that WN virus may have been introduced into the region. We also detected weak neutralizing activity to BSQ virus in four cattle and a chicken specimen, suggesting the presence of this or a closely related virus in Mexico. There was no evidence for transmission of the other viruses (ROC, ILH, EEE, WEE) in the study area.

  6. Interleukin-13 neutralization by two distinct receptor blocking mechanisms reduces immunoglobulin E responses and lung inflammation in cynomolgus monkeys.

    PubMed

    Kasaian, Marion T; Tan, Xiang-Yang; Jin, Macy; Fitz, Lori; Marquette, Kimberly; Wood, Nancy; Cook, Timothy A; Lee, Julie; Widom, Angela; Agostinelli, Rita; Bree, Andrea; Schlerman, Franklin J; Olland, Stephane; Wadanoli, Michael; Sypek, Joseph; Gill, Davinder; Goldman, Samuel J; Tchistiakova, Lioudmila

    2008-06-01

    Interleukin (IL)-13 is a key cytokine driving allergic and asthmatic responses and contributes to airway inflammation in cynomolgus monkeys after segmental challenge with Ascaris suum antigen. IL-13 bioactivity is mediated by a heterodimeric receptor (IL-13Ralpha1/IL-4Ralpha) and can be inhibited in vitro by targeting IL-13 interaction with either chain. However, in cytokine systems, in vitro neutralization activity may not always predict inhibitory function in vivo. To address the efficacy of two different IL-13 neutralization mechanisms in a primate model of atopic disease, two humanized monoclonal antibodies to IL-13 were generated, with highly homologous properties, differing in epitope recognition. Ab01 blocks IL-13 interaction with IL-4Ralpha, and Ab02 blocks IL-13 interaction with IL-13Ralpha1. In a cynomolgus monkey model of IgE responses to A. suum antigen, both Ab01 and Ab02 effectively reduced serum titers of Ascaris-specific IgE and diminished ex vivo Ascaris-triggered basophil histamine release, assayed 8 weeks after a single administration of antibody. The two antibodies also produced comparable reductions in pulmonary inflammation after lung segmental challenge with Ascaris antigen. Increased serum levels of IL-13, lacking demonstrable biological activity, were seen postchallenge in animals given either anti-IL-13 antibody but not in control animals given human IgG of irrelevant specificity. These findings demonstrate a potent effect of IL-13 neutralization on IgE-mediated atopic responses in a primate system and show that IL-13 can be efficiently neutralized by targeting either the IL-4Ralpha-binding epitope or the IL-13Ralpha1-binding epitope.

  7. Antigenic profile of African horse sickness virus serotype 4 VP5 and identification of a neutralizing epitope shared with bluetongue virus and epizootic hemorrhagic disease virus.

    PubMed

    Martínez-Torrecuadrada, J L; Langeveld, J P; Venteo, A; Sanz, A; Dalsgaard, K; Hamilton, W D; Meloen, R H; Casal, J I

    1999-05-10

    African horse sickness virus (AHSV) causes a fatal disease in horses. The virus capsid is composed of a double protein layer, the outermost of which is formed by two proteins: VP2 and VP5. VP2 is known to determine the serotype of the virus and to contain the neutralizing epitopes. The biological function of VP5, the other component of the capsid, is unknown. In this report, AHSV VP5, expressed in insect cells alone or together with VP2, was able to induce AHSV-specific neutralizing antibodies. Moreover, two VP5-specific monoclonal antibodies (MAbs) that were able to neutralize the virus in a plaque reduction assay were generated. To dissect the antigenic structure of AHSV VP5, the protein was cloned in Escherichia coli using the pET3 system. The immunoreactivity of both MAbs, and horse and rabbit polyclonal antisera, with 17 overlapping fragments from VP5 was analyzed. The most immunodominant region was found in the N-terminal 330 residues of VP5, defining two antigenic regions, I (residues 151-200) and II (residues 83-120). The epitopes were further defined by PEPSCAN analysis with 12mer peptides, which determined eight antigenic sites in the N-terminal half of the molecule. Neutralizing epitopes were defined at positions 85-92 (PDPLSPGE) for MAb 10AE12 and at 179-185 (EEDLRTR) for MAb 10AC6. Epitope 10AE12 is highly conserved between the different orbiviruses. MAb 10AE12 was able to recognize bluetongue virus VP5 and epizootic hemorrhagic disease virus VP5 by several techniques. These data will be especially useful for vaccine development and diagnostic purposes. Copyright 1999 Academic Press.

  8. Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination.

    PubMed

    Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric

    2017-09-02

    Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT 50 ) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2-3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries.

  9. Solvent dielectric effect and side chain mutation on the structural stability of Burkholderia cepacia lipase active site: a quantum mechanical/molecular mechanics study.

    PubMed

    Tahan, A; Monajjemi, M

    2011-12-01

    Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing.

  10. Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination

    PubMed Central

    Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric

    2017-01-01

    ABSTRACT Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT50) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2–3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries. PMID:28598256

  11. Context-dependent activation of reduced autobiographical memory specificity as an avoidant coping style.

    PubMed

    Debeer, Elise; Raes, Filip; Williams, J Mark G; Hermans, Dirk

    2011-12-01

    According to the affect-regulation hypothesis (Williams et al., 2007), reduced autobiographical memory specificity (rAMS) or overgeneral memory (OGM) might be considered a cognitive avoidance strategy; that is, people learn to avoid the emotionally painful consequences associated with the retrieval of specific negative memories. Based on this hypothesis, one would predict significant negative associations between AMS and avoidant coping. However, studies investigating this prediction have led to equivocal results. In the present study we tested a possible explanation for these contradictory findings. It was hypothesized that rAMS (in part) reflects an avoidant coping strategy, which might only become apparent under certain conditions, that is, conditions that signal the possibility of 'danger.' To test this hypothesis, we assessed AMS and behavioral avoidance but experimentally manipulated the instructions. In the neutral condition, two parallel versions of the Autobiographical Memory Test (AMT) were presented under neutral instructions. In the threat condition, the first AMT was presented under neutral instructions, while the second AMT was presented under 'threat instructions.' Results showed no significant correlations between avoidance and OGM under neutral conditions but significant and markedly stronger correlations under threat conditions, with more avoidance being associated with fewer specific and more categoric memories. In addition, high avoiders showed a stronger reduction in AMS in the threat condition as compared with the neutral condition, while low avoiders showed no such difference between conditions. The data confirm that OGM can be considered as part of a broader avoidant coping style. However, more importantly, they show that, at least in nonclinical individuals, the activation of this coping style may depend on the context. (c) 2011 APA, all rights reserved.

  12. A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

    PubMed Central

    Lebedev, Maxim; McVey, D. Scott; Wilson, William; Morozov, Igor; Young, Alan

    2014-01-01

    Abstract Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species. PMID:25325319

  13. Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies.

    PubMed

    Campi-Azevedo, Ana Carolina; Peruhype-Magalhães, Vanessa; Coelho-Dos-Reis, Jordana Grazziela; Costa-Pereira, Christiane; Yamamura, Anna Yoshida; Lima, Sheila Maria Barbosa de; Simões, Marisol; Campos, Fernanda Magalhães Freire; de Castro Zacche Tonini, Aline; Lemos, Elenice Moreira; Brum, Ricardo Cristiano; de Noronha, Tatiana Guimarães; Freire, Marcos Silva; Maia, Maria de Lourdes Sousa; Camacho, Luiz Antônio Bastos; Rios, Maria; Chancey, Caren; Romano, Alessandro; Domingues, Carla Magda; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

    2017-09-01

    Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Analysis by plaque reduction neutralization assay of intertypic rotaviruses suggests that gene reassortment occurs in vivo.

    PubMed Central

    Hoshino, Y; Sereno, M M; Midthun, K; Flores, J; Chanock, R M; Kapikian, A Z

    1987-01-01

    The SB-1A rotavirus recovered from a diarrheic piglet in the United States is a naturally occurring intertypic rotavirus. When studied by reciprocal neutralization tests, the SB-1A virus was similar, if not identical, to the porcine Gottfried virus (serotype 4) and the porcine OSU virus (serotype 5). Analysis of reassortant viruses prepared from the SB-1A virus and the serotype 2 human DS-1 virus revealed that the antigenic specificity of the outer capsid protein VP3 of SB-1A was shared with the OSU virus, while the antigenic specificity of another outer capsid protein, VP7, of SB-1A appeared to be shared with the Gottfried virus. This suggests that SB-1A is a naturally occurring reassortant rotavirus between OSU-like and Gottfried-like porcine rotaviruses. In addition, using a genetic approach, we found evidence that the fourth gene was responsible for the predominantly one-way cross-neutralizing reactivity between canine rotavirus strain CU-1 (serotype 3) and porcine rotavirus strains SB-1A (serotypes 4 and 5) and OSU (serotype 5). Assignment of hemagglutination function to the fourth genome segment of porcine rotaviruses SB-1A and OSU and canine rotavirus CU-1 confirmed a similar previous gene assignment established for certain rotaviruses. Analysis of single gene 4 substitution reassortants confirmed our previous finding that VP3 was as potent in stimulating neutralizing antibodies as VP7. The observations confirm the need for a binary system of rotavirus classification and nomenclature similar to that used for the influenza A viruses; in such a system the neutralization specificity of both VP3 and VP7 would be indicated. Images PMID:2434522

  15. Deconstructing the Emotion Regulatory Properties of Mindfulness: An Electrophysiological Investigation

    PubMed Central

    Lin, Yanli; Fisher, Megan E.; Roberts, Sean M. M.; Moser, Jason S.

    2016-01-01

    The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects—differentiated as a meditative practice, state of mind and dispositional trait—on the late positive potential (LPP), an event-related potentials (ERPs) indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully) failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice. PMID:27656139

  16. Effect of culture age on 1,3-dinitrobenzene metabolism and indicators of cellular toxicity in rat testicular cells.

    PubMed

    Brown, C D; Miller, M G

    1991-01-01

    The metabolism and toxicity of 1,3-dinitrobenzene(1,3-DNB) were examined in rat testicular cells that had been cultured for various amounts of time. The three cell systems utilized were: freshly isolated suspensions of Sertoli/germ cells; the same Sertoli/germ cells co-cultured for 24 hr; and Sertoli cell-enriched monolayers derived from the co-cultures and cultured for 96 hr. Indicators of toxicity were MTT reduction, neutral red incorporation, cellular ATP levels and lactate secretion into the media. 1,3-DNB (5-50 mum) caused a significant concentration-dependent decline in cellular ATP levels in the fresh cell suspension, but not in the cells that had been cultured for longer. No changes were observed either in MTT reduction or neutral red incorporation. Increased secretion of lactate into the media also did not prove to be a sensitive indicator of toxicity. Interestingly, 1,3-DNB metabolism to nitroaniline, nitroacetanilide and a covalently bound species was two to three times greater in the fresh cells, compared with either the 24- or 96-hr cell cultures. The data indicate that time in culture may have significant effects on both the capacity of testicular cells to metabolize 1,3-DNB and susceptibility to toxicity.

  17. Efficacy of Nd:YAG and GaAlAs lasers in comparison to 2% fluoride gel for the treatment of dentinal hypersensitivity.

    PubMed

    Soares, Marília De Lima; Porciúncula, Geane Bandeira; Lucena, Mara Ilka Holanda Medeiros De; Gueiros, Luiz Alcino Monteiro; Leão, Jair Carneiro; Carvalho, Alessandra De Albuquerque Tavares

    2016-01-01

    Lasers demonstrate excellent therapeutic action and are often employed in dentistry for the treatment of diverse clinical conditions. The aim of this study was to compare the efficacy of neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser, gallium-aluminum-arsenide (GaAlAs) laser, and 2% neutral fluoride gel in the treatment of dentinal hypersensitivity. Twenty-three patients were evaluated, involving a total of 48 quadrants with at least 1 tooth with dentinal hypersensitivity (89 teeth total). Pain intensity was recorded on a visual analog scale at the time of clinical examination (baseline), immediately after treatment, and 1 week posttreatment. Teeth were treated with 60 seconds of 2% neutral fluoride gel application or 60 seconds of laser treatment-Nd:YAG laser at a distance of 0.5 cm (unfocused; 1 W and 10 Hz for 60 seconds, perpendicular to the cervical surfaces) or GaAlAs laser in contact (40 mW; 4 J/cm²; spot: 0.028 cm²; 15 seconds per point on 4 points [mesial, medial, distal, and apical])-as well as sham treatments so that patients remained blind to their treatment group. All treatments provided adequate pain reduction immediately posttreatment, but laser treatments resulted in significantly greater reductions in pain intensity.

  18. Attention Training in Individuals with Generalized Social Phobia: A Randomized Controlled Trial

    PubMed Central

    Amir, Nader; Beard, Courtney; Taylor, Charles T.; Klumpp, Heide; Elias, Jason; Burns, Michelle; Chen, Xi

    2009-01-01

    We conducted a randomized, double-blind placebo-controlled trial to examine the efficacy of an attention training procedure in reducing symptoms of social anxiety in forty-four individuals diagnosed with Generalized Social Phobia (GSP). Attention training comprised a probe detection task where pictures of faces with either a threatening or neutral emotional expression cued different locations on the computer screen. In the Attention Modification Program (AMP), participants responded to a probe that always followed neutral faces when paired with a threatening face, thereby directing attention away from threat. In the Attention Control Condition (ACC), the probe appeared with equal frequency in the position of the threat and neutral faces. Results revealed that the AMP facilitated attention disengagement from threat from pre- to post-assessment, and reduced clinician- and self-reported symptoms of social anxiety relative to the ACC. Participants no longer meeting DSM-IV criteria for GSP at post-assessment were 50% in the AMP and 14% in the ACC. Symptom reduction in the AMP group was maintained during four-month follow-up assessment. These results suggest that computerized attention training procedures may be beneficial for treating social phobia. PMID:19803575

  19. Posture variation among office workers when using different information and communication technologies at work and away from work.

    PubMed

    Ciccarelli, Marina; Straker, Leon; Mathiassen, Svend Erik; Pollock, Clare

    2014-01-01

    Office workers perform tasks using different information and communication technologies (ICT) involving various postures. Adequate variation in postures and muscle activity is generally believed to protect against musculoskeletal complaints, but insufficient information exists regarding the effect on postural variation of using different ICT. Thus, this study among office workers aimed to determine and compare postures and postural variation associated with using distinct types of ICT. Upper arm, head and trunk postures of 24 office workers were measured with the Physiometer over a whole day in their natural work and away-from-work environments. Postural variation was quantified using two indices: APDF(90-10) and EVA(sd). Various ICT had different postural means and variation. Paper-based tasks had more non-neutral, yet also more variable postures. Electronics-based tasks had more neutral postures, with less postural variability. Tasks simultaneously using paper- and electronics-based ICT had least neutral and least variable postures. Tasks without ICT usually had the most posture variability. Interspersing tasks involving different ICT could increase overall exposure variation among office workers and may thus contribute to musculoskeletal risk reduction.

  20. The role of fear and expectancies in capture of covert attention by spiders.

    PubMed

    Devue, Christel; Belopolsky, Artem V; Theeuwes, Jan

    2011-08-01

    Fear-related stimuli are often prioritized during visual selection but it remains unclear whether capture by salient objects is more likely to occur when individuals fear those objects. In this study, participants with high and low fear of spiders searched for a circle while on some trials a completely irrelevant fear-related (spider) or neutral distractor (butterfly/leaf) was presented simultaneously in the display. Our results show that when you fear spiders and you are not sure whether a spider is going to be present, then any salient distractor (i.e., a butterfly) grabs your attention, suggesting that mere expectation of a spider triggered compulsory monitoring of all irrelevant stimuli. However, neutral stimuli did not grab attention when high spider fearful people knew that a spider could not be present during a block of trials, treating the neutral stimuli just as the low spider fearful people do. Our results show that people that fear spiders inspect potential spider-containing locations in a compulsory fashion even though directing attention to this location is completely irrelevant for the task. Reduction of capture can only be accomplished when people that fear spiders do not expect a spider to be present. 2011 APA, all rights reserved

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