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Sample records for anti-hiv non-nucleoside reverse

  1. HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

    DEFF Research Database (Denmark)

    Vanangamudi, Murugesan; Poongavanam, Vasanthanathan; Namasivayam, Vigneshwaran

    2017-01-01

    BACKGROUND: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV-1 RT) is one of the successful chemotherapies for the treatment of HIV infection. Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown to be very promising......: The conformation dependent-alignment based (CoMFA and CoMSIA) methods have been proven very successful ligand based strategy in the drug design. Here, CoMFA and CoMSIA studies reported for structurally distinct NNRTIs including thiazolobenzimidazole, dipyridodiazepinone, 1,1,3-trioxo [1,2,4]-thiadiazine...

  2. Do non-nucleoside reverse transcriptase inhibitors contribute to lipodystrophy?

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    Nolan, David

    2005-01-01

    Lipodystrophy complications, including lipoatrophy (pathological fat loss) and metabolic complications, have emerged as important long-term toxicities associated with antiretroviral therapy in the current era. The wealth of data that has accumulated over the past 6 years has now clarified the contribution of specific antiretroviral drugs to the risk of these clinical endpoints, with evidence that lipoatrophy is strongly associated with the choice of nucleoside reverse transcriptase inhibitor therapy (specifically, stavudine and to a lesser extent zidovudine). The aetiological basis of metabolic complications of antiretroviral therapy has proven to be complex, in that the risk appears to be modulated by a number of lifestyle factors that have made the metabolic syndrome highly prevalent in the general population, with additional contributions from HIV disease status itself, as well as from individual drugs within the HIV protease inhibitor class. The currently licensed non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs, efavirenz and nevirapine, have been proven to have a favourable safety profile in terms of lipodystrophy complications. However, it must be noted that NNRTI drugs also have individual toxicity profiles that must be accounted for when considering and/or monitoring their use in the treatment of HIV infection.

  3. Rilpivirine: a new non-nucleoside reverse transcriptase inhibitor.

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    Sharma, Mamta; Saravolatz, Louis D

    2013-02-01

    Rilpivirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that is approved for HIV-1 treatment-naive adult patients in combination with other antiretroviral agents. The recommended dose is a 25 mg tablet once daily taken orally with a meal. Due to cytochrome P450 3A4 enzyme induction or gastric pH increase, rilpivirine cannot be coadministered with a number of other drugs (anticonvulsants, rifabutin, rifampicin, rifapentine, proton pump inhibitors, systemic dexamethasone and St John's wort). Rilpivirine should be used with caution when coadministered with a drug with a known risk for torsade de pointes. Rilpivirine has a better tolerability than a comparative NNRTI, efavirenz, in clinical trials, with fewer central nervous system adverse effects, rashes, lipid abnormalities and discontinuation rates. Virological failure occurs more commonly with higher baseline viral loads (>100,000 copies/mL) and lower baseline CD4 counts (<50 cells/mm(3)). Seventeen NNRTI mutations have been associated with decreased susceptibility to rilpivirine: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C, M230I/L, Y188L and the combination L100I + K103N. Resistance to rilpivirine largely excludes future use of the NNRTI class.

  4. The structure of FIV reverse transcriptase and its implications for non-nucleoside inhibitor resistance.

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    Meytal Galilee

    2018-01-01

    Full Text Available Reverse transcriptase (RT is the target for the majority of anti-HIV-1 drugs. As with all anti-AIDS treatments, continued success of RT inhibitors is persistently disrupted by the occurrence of resistance mutations. To explore latent resistance mechanisms potentially accessible to therapeutically challenged HIV-1 viruses, we examined RT from the related feline immunodeficiency virus (FIV. FIV closely parallels HIV-1 in its replication and pathogenicity, however, is resistant to all non-nucleoside inhibitors (NNRTI. The intrinsic resistance of FIV RT is particularly interesting since FIV harbors the Y181 and Y188 sensitivity residues absent in both HIV-2 and SIV. Unlike RT from HIV-2 or SIV, previous efforts have failed to make FIV RT susceptible to NNRTIs concluding that the structure or flexibility of the feline enzyme must be profoundly different. We report the first crystal structure of FIV RT and, being the first structure of an RT from a non-primate lentivirus, enrich the structural and species repertoires available for RT. The structure demonstrates that while the NNRTI binding pocket is conserved, minor subtleties at the entryway can render the FIV RT pocket more restricted and unfavorable for effective NNRTI binding. Measuring NNRTI binding affinity to FIV RT shows that the "closed" pocket configuration inhibits NNRTI binding. Mutating the loop residues rimming the entryway of FIV RT pocket allows for NNRTI binding, however, it does not confer sensitivity to these inhibitors. This reveals a further layer of resistance caused by inherent FIV RT variances that could have enhanced the dissociation of bound inhibitors, or, perhaps, modulated protein plasticity to overcome inhibitory effects of bound NNRTIs. The more "closed" conformation of FIV RT pocket can provide a template for the development of innovative drugs that could unlock the constrained pocket, and the resilient mutant version of the enzyme can offer a fresh model for the study

  5. Biophysical Insights into the Inhibitory Mechanism of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

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    Nicolas Sluis-Cremer

    2013-11-01

    Full Text Available HIV-1 reverse transcriptase (RT plays a central role in HIV infection. Current United States Federal Drug Administration (USFDA-approved antiretroviral therapies can include one of five approved non-nucleoside RT inhibitors (NNRTIs, which are potent inhibitors of RT activity. Despite their crucial clinical role in treating and preventing HIV-1 infection, their mechanism of action remains elusive. In this review, we introduce RT and highlight major advances from experimental and computational biophysical experiments toward an understanding of RT function and the inhibitory mechanism(s of NNRTIs.

  6. Structural and Preclinical Studies of Computationally Designed Non-Nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Kudalkar, Shalley N.; Beloor, Jagadish; Chan, Albert H.; Lee, Won-Gil; Jorgensen, William L.; Kumar, Priti; Anderson, Karen S.

    2017-02-06

    The clinical benefits of HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokinetic (PK) properties along with the rapid development of drug-resistant variants. However, the clinical efficacy of these inhibitors can be improved by developing compounds with enhanced pharmacological profiles and heightened antiviral activity. We used computational and structure-guided design to develop two next-generation NNRTI drug candidates, compounds I and II, which are members of a class of catechol diethers. We evaluated the preclinical potential of these compounds in BALB/c mice because of their high solubility (510 µg/ml for compound I and 82.9 µg/ml for compound II), low cytotoxicity, and enhanced antiviral activity against wild-type (WT) HIV-1 RT and resistant variants. Additionally, crystal structures of compounds I and II with WT RT suggested an optimal binding to the NNRTI binding pocket favoring the high anti-viral potency. A single intraperitoneal dose of compounds I and II exhibited a prolonged serum residence time of 48 hours and concentration maximum (Cmax) of 4000- to 15,000-fold higher than their therapeutic/effective concentrations. These Cmax values were 4- to 15-fold lower than their cytotoxic concentrations observed in MT-2 cells. Compound II showed an enhanced area under the curve (0–last) and decreased plasma clearance over compound I and efavirenz, the standard of care NNRTI. Hence, the overall (PK) profile of compound II was excellent compared with that of compound I and efavirenz. Furthermore, both compounds were very well tolerated in BALB/c mice without any detectable acute toxicity. Taken together, these data suggest that compounds I and II possess improved anti-HIV-1 potency, remarkable in vivo safety, and prolonged in vivo circulation time, suggesting strong potential for further development as new NNRTIs for the potential treatment of HIV infection.

  7. Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors.

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    Wilhelm, M; Fishman, J A; Pontikis, R; Aubertin, A M; Wilhelm, F X

    2002-12-01

    Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA. We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors. Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovudine (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested.

  8. Development and Characterization of a Vaginal Film Containing Dapivirine, a Non- nucleoside Reverse Transcriptase Inhibitor (NNRTI), for prevention of HIV-1 sexual transmission.

    Science.gov (United States)

    Akil, Ayman; Parniak, Michael A; Dezzuitti, Charlene S; Moncla, Bernard J; Cost, Marilyn R; Li, Mingguang; Rohan, Lisa Cencia

    2011-06-01

    Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is a potent and promising anti-HIV molecule. It is currently being investigated for use as a vaginal microbicide in two dosage forms, a semi-solid gel and a silicone elastomer ring. Quick-dissolving films are promising and attractive dosage forms that may provide an alternative platform for the vaginal delivery of microbicide drug candidates. Vaginal films may provide advantages such as discreet use, no product leakage during use, lack of requirement for an applicator for insertion, rapid drug release and minimal packaging and reduced wastage. Within this study the in vitro bioactivity of dapivirine as compared to the NNRTI UC781 was further established and a quick dissolve film was developed for vaginal application of dapivirine for prevention of HIV infection. The developed film was characterized with respect to its physical and chemical attributes including water content, mechanical strength, drug release profile, permeability, compatibility with lactobacilli and bioactivity. The anti-HIV activity of the formulated dapivirine film was confirmed in in vitro and ex vivo models. Importantly the physical and chemical properties of the film as well as its bioactivity were maintained for a period of 18 months. In conclusion, a vaginal film containing dapivirine was developed and characterized. The film was shown to prevent HIV-1 infection in vitro and ex vivo and have acceptable characteristics which make this film a promising candidate for testing as vaginal microbicide.

  9. Complete inactivation of HIV-1 using photo-labeled non-nucleoside reverse transcriptase inhibitors.

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    Rios, Adan; Quesada, Jorge; Anderson, Dallas; Goldstein, Allan; Fossum, Theresa; Colby-Germinario, Susan; Wainberg, Mark A

    2011-01-01

    We demonstrate that a photo-labeled derivative of the non-nucleoside reverse transcriptase inhibitor (NNRTI) dapivirine termed DAPY, when used together with exposure to ultraviolet light, was able to completely and irreversibly inactivate both HIV-1 RT activity as well as infectiousness in each of a T cell line and peripheral blood mononuclear cells. Control experiments using various concentrations of DAPY revealed that a combination of exposure to ultraviolet light together with use of the specific, high affinity photo-labeled compound was necessary for complete inactivation to occur. This method of HIV RT inactivation may have applicability toward preservation of an intact viral structure and warrants further investigation in regard to the potential of this approach to elicit a durable, broad protective immune response. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Structure-based methods to predict mutational resistance to diarylpyrimidine non-nucleoside reverse transcriptase inhibitors.

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    Azeem, Syeda Maryam; Muwonge, Alecia N; Thakkar, Nehaben; Lam, Kristina W; Frey, Kathleen M

    2018-01-01

    Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance. In order to aid drug design efforts, it would be efficient and cost effective to pre-evaluate NNRTI compounds in development using a structure-based computational approach. As proof of concept, we applied a residue scan and molecular dynamics strategy using RT crystal structures to predict mutations that confer resistance to DAPYs rilpivirine, etravirine, and investigational microbicide dapivirine. Our predictive values, changes in affinity and stability, are correlative with fold-resistance data for several RT mutants. Consistent with previous studies, mutation K101P is predicted to confer high-level resistance to DAPYs. These findings were further validated using structural analysis, molecular dynamics, and an enzymatic reverse transcription assay. Our results confirm that changes in affinity and stability for mutant complexes are predictive parameters of resistance as validated by experimental and clinical data. In future work, we believe that this computational approach may be useful to predict resistance mutations for inhibitors in development. Published by Elsevier Inc.

  11. 3D QSAR Studies of DAMNI Analogs as Possible Non-nucleoside Reverse Transcriptase Inhibitors

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    S. Ganguly

    2008-01-01

    Full Text Available The non-nucleoside inhibitors of HIV-1-reverse transcriptase (NNRTIs are an important class of drugs employed in antiviral therapy. Recently, a novel family of NNRTIs commonly referred to as 1-[2-diarylmethoxy] ethyl 2-methyl-5-nitroimidazoles (DAMNI derivatives have been discovered. The 3D-QSAR studies on DAMNI derivatives as NNRTIs was performed by comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA methods to determine the factors required for the activity of these compounds. The global minimum energy conformer of the template molecule 15, the most active molecule of the series, was obtained by simulated annealing method and used to build the structures of the molecules in the dataset. The combination of steric and electrostatic fields in CoMSIA gave the best results with cross-validated and conventional correlation coefficients of 0.654 and 0.928 respectively. The predictive ability of CoMFA and CoMSIA were determined using a test set of ten DAMNI derivatives giving predictive correlation coefficients of 0.92 and 0.98 respectively indicating good predictive power. Further, the robustness of the models was verified by bootstrapping analysis. The information obtained from CoMFA and CoMSIA 3D contour maps may be of utility in the design of more potent DAMNI analogs as NNRTIs in future.

  12. 3D-QSAR CoMFA of a series of DABO derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors.

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    de Brito, Monique Araújo; Rodrigues, Carlos Rangel; Cirino, José Jair Vianna; de Alencastro, Ricardo Bicca; Castro, Helena Carla; Albuquerque, Magaly Girão

    2008-08-01

    A series of 74 dihydroalkoxybenzyloxopyrimidines (DABOs), a class of highly potent non-nucleoside reverse transcriptase inhibitors (NNRTIs), was retrieved from the literature and studied by comparative molecular field analysis (CoMFA) in order to derive three-dimensional quantitative structure-activity relationship (3D-QSAR) models. The CoMFA study has been performed with a training set of 59 compounds, testing three alignments and four charge schemes (DFT, HF, AM1, and PM3) and using defaults probe atom (Csp (3), +1 charge), cutoffs (30 kcal.mol (-1) for both steric and electrostatic fields), and grid distance (2.0 A). The best model ( N = 59), derived from Alignment 1 and PM3 charges, shows q (2) = 0.691, SE cv = 0.475, optimum number of components = 6, r (2) = 0.930, SEE = 0.226, and F-value = 115.544. The steric and electrostatic contributions for the best model were 43.2% and 56.8%, respectively. The external predictive ability (r (2) pred = 0.918) of the resultant best model was evaluated using a test set of 15 compounds. In order to design more potent DABO analogues as anti-HIV/AIDS agents, attention should be taken in order to select a substituent for the 4-oxopyrimidine ring, since, as revealed by the best CoMFA model, there are a steric restriction at the C2-position, a electron-rich group restriction at the C6-position ( para-substituent of the 6-benzyl group), and a steric allowed region at the C5-position.

  13. Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl) methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1

    Czech Academy of Sciences Publication Activity Database

    Šimon, Petr; Baszczyňski, Ondřej; Šaman, David; Stepan, G.; Hu, E.; Lansdon, E. B.; Jansa, P.; Janeba, Zlatko

    2016-01-01

    Roč. 122, Oct 21 (2016), s. 185-195 ISSN 0223-5234 Institutional support: RVO:61388963 Keywords : diarylpyrimidine (DAPY) * etravirine * human immunodeficiency virus ( HIV ) * non-nucleoside reverse transcriptase inhibitors * NNRTIs * rilpivirine Subject RIV: CC - Organic Chemistry Impact factor: 4.519, year: 2016

  14. The development of HEPT-type HIV non-nucleoside reverse transcriptase inhibitors and its implications for DABO family.

    Science.gov (United States)

    Chen, Wenmin; Zhan, Peng; Wu, Jingde; Li, Zhenyu; Liu, Xinyong

    2012-01-01

    1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) was discovered as the first HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 1989. The research on HEPT derivatives (HEPTs) has been lasted for more than 20 years and HEPT family is probably the most investigated NNRTI. Extensive molecular modifications on HEPT have led to many highly potent compounds with broad-resistance spectrum and optimal pharmacokinetic profiles. Moreover, X-crystallographic studies of HEPTs/RT complexes revealed the binding mode of HEPTs and the action mechanism of NNRTI, which has greatly facilitated the design of novel NNRTIs. Recently, the development of HEPTs was accelerated by the application of the "follow-on"-based chemical evolution strategies, such as designed multiple ligands (DMLs) and molecular hybridization (MH). Herein, this article will provide an insight into the development of HEPTs, including structural modifications, crystal structure of RT complexed with HEPTs and its structure-activity relationship (SAR). Additionally, this review also covers the emerging HEPT related dual inhibitors and HEPT-pyridinone hybrids, as well as the contributions of HEPTs to the development of dihydro-alkoxy-benzyl-oxopyrimidine (DABO) family, thus highlighting the importance of HEPTs on the development of NNRTIs.

  15. Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India.

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    Saravanan, Shanmugam; Kausalya, Bagavathi; Gomathi, Selvamurthi; Sivamalar, Sathasivam; Pachamuthu, Balakrishnan; Selvamuthu, Poongulali; Pradeep, Amrose; Sunil, Solomon; Mothi, Sarvode N; Smith, Davey M; Kantor, Rami

    2017-06-01

    We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings. To complement these investigations, we also analyzed the sequences in Stanford database, Monogram weighted score, and DUET weighted score algorithms for ETR susceptibility and found almost perfect agreement between the three algorithms in predicting ETR susceptibility from genotypic data.

  16. Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Markus Hecht

    Full Text Available Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50 were calculated and compared to the blood levels in our patients and published data.The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml, Nevirapine 239 μmol/l (= 63,786 ng/ml, Etravirine 89.0 μmol/l (= 38,740 ng/ml, Lersivirine 543 μmol/l (= 168,523 ng/ml, Delavirdine 171 μmol/l (= 78,072 ng/ml, Rilpivirine 24.4 μmol/l (= 8941 ng/ml. As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml, of Rilpivirine 144 ng/ml (range 0-572 ng/ml and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml. Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic

  17. Design and synthesis of N₁-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors.

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    Monforte, Anna-Maria; Ferro, Stefania; De Luca, Laura; Lo Surdo, Giuseppa; Morreale, Francesca; Pannecouque, Christophe; Balzarini, Jan; Chimirri, Alba

    2014-02-15

    A series of novel N1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives.

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    Ragno, Rino; Artico, Marino; De Martino, Gabriella; La Regina, Giuseppe; Coluccia, Antonio; Di Pasquali, Alessandra; Silvestri, Romano

    2005-01-13

    Three-dimensional quantitative structure-activity relationship (3-D QSAR) studies and docking simulations were developed on indolyl aryl sulfones (IASs), a class of novel HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (Silvestri, et al. J. Med. Chem. 2003, 46, 2482-2493) highly active against wild type and some clinically relevant resistant strains (Y181C, the double mutant K103N-Y181C, and the K103R-V179D-P225H strain, highly resistant to efavirenz). Predictive 3-D QSAR models using the combination of GRID and GOLPE programs were obtained using a receptor-based alignment by means of docking IASs into the non-nucleoside binding site (NNBS) of RT. The derived 3-D QSAR models showed conventional correlation (r(2)) and cross-validated (q(2)) coefficients values ranging from 0.79 to 0.93 and from 0.59 to 0.84, respectively. All described models were validated by an external test set compiled from previously reported pyrryl aryl sulfones (Artico, et al. J. Med. Chem. 1996, 39, 522-530). The most predictive 3-D QSAR model was then used to predict the activity of novel untested IASs. The synthesis of six designed derivatives (prediction set) allowed disclosure of new IASs endowed with high anti-HIV-1 activities.

  19. Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen

    DEFF Research Database (Denmark)

    Fox, Zoe; Phillips, Andrew; Cohen, Cal

    2008-01-01

    the NRTIs, or by replacing the NNRTI with another drug before interruption. Simultaneous interruption of all antiretrovirals was discouraged. Resuppression rates 4-8 months after reinitiating NNRTI-therapy were assessed, as was the detection of drug-resistance mutations within 2 months of the treatment...... regimen. NNRTI drug-resistance mutations were observed in a relatively high proportion of patients. These data provide additional support for a staggered or switched interruption strategy for NNRTI drugs.......BACKGROUND: Interruption of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimen is often necessary, but must be performed with caution because NNRTIs have a low genetic barrier to resistance. Limited data exist to guide clinical practice on the best interruption strategy to use...

  20. Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration.

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    Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm Christopher; Smith, Davey M

    2007-01-01

    Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Cross-sectional analysis. Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI.

  1. Active Methamphetamine Use is Associated with Transmitted Drug Resis-tance to Non-Nucleoside Reverse Transcriptase Inhibitors in Individuals with HIV Infection of Unknown Duration

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    Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm. Christopher; Smith, Davey M

    2007-01-01

    Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Design: Cross-sectional analysis. Methods: Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq™, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Results: Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Conclusion: Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI. PMID:18923691

  2. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

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    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  3. Diaryltriazine non-nucleoside reverse transcriptase inhibitors are potent candidates for pre-exposure prophylaxis in the prevention of sexual HIV transmission.

    Science.gov (United States)

    Ariën, Kevin K; Venkatraj, Muthusamy; Michiels, Johan; Joossens, Jurgen; Vereecken, Katleen; Van der Veken, Pieter; Abdellati, Saïd; Cuylaerts, Vicky; Crucitti, Tania; Heyndrickx, Leo; Heeres, Jan; Augustyns, Koen; Lewi, Paul J; Vanham, Guido

    2013-09-01

    Pre-exposure prophylaxis and topical microbicides are important strategies in the prevention of sexual HIV transmission, especially since partial protection has been shown in proof-of-concept studies. In search of new candidate drugs with an improved toxicity profile and with activity against common non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV, we have synthesized and investigated a library of 60 new diaryltriazine analogues. From this library, 15 compounds were evaluated in depth using a broad armamentarium of in vitro assays that are part of a preclinical testing algorithm for microbicide development. Antiviral activity was assessed in a cell line, and in primary human cells, against both subtype B and subtype C HIV-1 and against viruses resistant to therapeutic NNRTIs and the candidate NNRTI microbicide dapivirine. Toxicity towards primary blood-derived cells, cell lines originating from the female reproductive tract and female genital microflora was also studied. We identified several compounds with highly potent antiviral activity and toxicity profiles that are superior to that of dapivirine. In particular, compound UAMC01398 is an interesting new candidate that warrants further investigation because of its superior toxicity profile and potent activity against dapivirine-resistant viruses.

  4. Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens.

    Science.gov (United States)

    Bunupuradah, Torsak; Ananworanich, Jintanat; Chetchotisakd, Ploenchan; Kantipong, Pacharee; Jirajariyavej, Supunnee; Sirivichayakul, Sunee; Munsakul, Warangkana; Prasithsirikul, Wisit; Sungkanuparph, Somnuek; Bowonwattanuwong, Chureeratana; Klinbuayaem, Virat; Petoumenos, Kathy; Hirschel, Bernard; Bhakeecheep, Sorakij; Ruxrungtham, Kiat

    2011-01-01

    We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA>1,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS; ≥ 4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS; 2.5-3.5 and ≥ 4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Median (IQR) age was 38 (34-42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8-4.5) years. Median (IQR) CD4(+) T-cell count and HIV RNA were 194 (121-280) cells/mm³ and 4.1 (3.6-4.6) log₁₀ copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥ 4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5-3.5 and ≥4, respectively. Only HIV RNA ≥ 4 log₁₀ copies/ml at failure was associated with both Monogram WS ≥ 4 (OR 2.3, 95% CI 1.3-3.9; P=0.003) and DUET WS ≥ 2.5 (OR 1.9, 95% CI 1.1-3.3; P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.

  5. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

    Science.gov (United States)

    Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

    2015-01-01

    Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once

  6. Introducing Catastrophe-QSAR. Application on Modeling Molecular Mechanisms of Pyridinone Derivative-Type HIV Non-Nucleoside Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Marius Lazea

    2011-12-01

    Full Text Available The classical method of quantitative structure-activity relationships (QSAR is enriched using non-linear models, as Thom’s polynomials allow either uni- or bi-variate structural parameters. In this context, catastrophe QSAR algorithms are applied to the anti-HIV-1 activity of pyridinone derivatives. This requires calculation of the so-called relative statistical power and of its minimum principle in various QSAR models. A new index, known as a statistical relative power, is constructed as an Euclidian measure for the combined ratio of the Pearson correlation to algebraic correlation, with normalized t-Student and the Fisher tests. First and second order inter-model paths are considered for mono-variate catastrophes, whereas for bi-variate catastrophes the direct minimum path is provided, allowing the QSAR models to be tested for predictive purposes. At this stage, the max-to-min hierarchies of the tested models allow the interaction mechanism to be identified using structural parameter succession and the typical catastrophes involved. Minimized differences between these catastrophe models in the common structurally influential domains that span both the trial and tested compounds identify the “optimal molecular structural domains” and the molecules with the best output with respect to the modeled activity, which in this case is human immunodeficiency virus type 1 HIV-1 inhibition. The best molecules are characterized by hydrophobic interactions with the HIV-1 p66 subunit protein, and they concur with those identified in other 3D-QSAR analyses. Moreover, the importance of aromatic ring stacking interactions for increasing the binding affinity of the inhibitor-reverse transcriptase ligand-substrate complex is highlighted.

  7. Diarylpyrimidine-dihydrobenzyloxopyrimidine hybrids: new, wide-spectrum anti-HIV-1 agents active at (sub)-nanomolar level.

    Science.gov (United States)

    Rotili, Dante; Tarantino, Domenico; Artico, Marino; Nawrozkij, Maxim B; Gonzalez-Ortega, Emmanuel; Clotet, Bonaventura; Samuele, Alberta; Esté, José A; Maga, Giovanni; Mai, Antonello

    2011-04-28

    Here, we describe a novel small series of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that combine peculiar structural features of diarylpyrimidines (DAPYs) and dihydro-alkoxy-benzyl-oxopyrimidines (DABOs). These DAPY-DABO hybrids (1-4) showed a characteristic SAR profile and a nanomolar anti-HIV-1 activity at both enzymatic and cellular level. In particular, the two compounds 4d and 2d, with a (sub)nanomolar activity against wild-type and clinically relevant HIV-1 mutant strains, were selected as lead compounds for next optimization studies.

  8. Development and validation of a rapid reversed-phase HPLC method for the determination of the non-nucleoside reverse transcriptase inhibitor dapivirine from polymeric nanoparticles.

    Science.gov (United States)

    das Neves, José; Sarmento, Bruno; Amiji, Mansoor M; Bahia, Maria Fernanda

    2010-06-05

    The objective of this work was to develop and validate a rapid reversed-phase (RP) high-performance liquid chromatography (HPLC) method for the in vitro pharmaceutical characterization of dapivirine-loaded polymeric nanoparticles. Chromatographic runs were performed on a RP C18 column with a mobile phase comprising acetonitrile-0.5% (w/v) triethanolamine solution in isocratic mode (80:20, v/v) at a flow rate of 1 ml/min. Dapivirine was detected at a wavelength of 290 nm. The method was shown to be specific, linear in the range of 1-50 microg/ml (R(2)=0.9998), precise at the intra-day and inter-day levels as reflected by the relative standard deviation values (less than 0.85%), accurate (recovery rate of 100.17+/-0.35%), and robust to changes in the mobile phase and column brand. The detection and quantitation limits were 0.08 and 0.24 microg/ml, respectively. The method was successfully used to determine the loading capacity and association efficiency of dapivirine in poly(lactic-co-glycolic acid)-based nanoparticles and its in vitro release. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  9. Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains.

    Science.gov (United States)

    Monforte, Anna Maria; De Luca, Laura; Buemi, Maria Rosa; Agharbaoui, Fatima E; Pannecouque, Christophe; Ferro, Stefania

    2018-02-01

    Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of human immunodeficiency virus (HIV) infection. These regimens are extremely effective in suppressing virus replication. Recently, our research group identified some N 1 -aryl-2-arylthioacetamido-benzimidazoles as a novel class of NNRTIs. In this research work we report the design, the synthesis and the structure-activity relationship studies of new compounds (20-34) in which some structural modifications have been introduced in order to investigate their effects on reverse transcriptase (RT) inhibition and to better define the features needed to increase the antiviral activity. Most of the new compounds proved to be highly effective in inhibiting both RT enzyme at nanomolar concentrations and HIV-1 replication in MT4 cells with minimal cytotoxicity. Among them, the most promising N 1 -aryl-2-arylthioacetamido-benzimidazoles and N 1 -aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A. Computational approaches were applied in order to rationalize the potency of the new synthesized inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Molecular docking and 3D-QSAR studies on triazolinone and pyridazinone, non-nucleoside inhibitor of HIV-1 reverse transcriptase.

    Science.gov (United States)

    Sivan, Sree Kanth; Manga, Vijjulatha

    2010-06-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors of the HIV-1 reverse transcriptase. Recently a series of Triazolinone and Pyridazinone were reported as potent inhibitors of HIV-1 wild type reverse transcriptase. In the present study, docking and 3D quantitative structure activity relationship (3D QSAR) studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 31 molecules. Ligands were built and minimized using Tripos force field and applying Gasteiger-Hückel charges. These ligands were docked into protein active site using GLIDE 4.0. The docked poses were analyzed; the best docked poses were selected and aligned. CoMFA and CoMSIA fields were calculated using SYBYL6.9. The molecules were divided into training set and test set, a PLS analysis was performed and QSAR models were generated. The model showed good statistical reliability which is evident from the r2 nv, q2 loo and r2 pred values. The CoMFA model provides the most significant correlation of steric and electrostatic fields with biological activities. The CoMSIA model provides a correlation of steric, electrostatic, acceptor and hydrophobic fields with biological activities. The information rendered by 3D QSAR model initiated us to optimize the lead and design new potential inhibitors.

  11. Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands.

    Science.gov (United States)

    Sancineto, Luca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Manfroni, Giuseppe; Corazza, Gianmarco; Cecchetti, Violetta; Marcello, Alessandro; Daelemans, Dirk; Pannecouque, Christophe; Tabarrini, Oriana

    2014-09-01

    It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. A trypsin inhibitor from rambutan seeds with antitumor, anti-HIV-1 reverse transcriptase, and nitric oxide-inducing properties.

    Science.gov (United States)

    Fang, Evandro Fei; Ng, Tzi Bun

    2015-04-01

    Nephelium lappaceum L., commonly known as "rambutan," is a typical tropical tree and is well known for its juicy and sweet fruit which has an exotic flavor. Chemical studies on rambutan have led to the identification of various components such as monoterpene lactones and volatile compounds. Here, a 22.5-kDa trypsin inhibitor (N . lappaceum trypsin inhibitor (NLTI)) was isolated from fresh rambutan seeds using liquid chromatographical techniques. NLTI reduced the proteolytic activities of both trypsin and α-chymotrypsin. Dithiothreitol reduced the trypsin inhibitory activity of NLTI at a concentration of 1 mM, indicating that an intact disulfide bond is essential to the activity. NLTI inhibited HIV-1 reverse transcriptase with an IC50 of 0.73 μM. In addition, NLTI manifested a time- and dose-dependent inhibitory effect on growth in many tumor cells. NLTI is one of the few trypsin inhibitors with nitric oxide-inducing activity and may find application in tumor therapy.

  13. Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

    Science.gov (United States)

    Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

    2011-01-01

    Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

  14. Testing of viscous anti-HIV microbicides using Lactobacillus

    OpenAIRE

    Moncla, B.J.; Pryke, K.; Rohan, L. C.; Yang, H.

    2011-01-01

    The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30 min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To...

  15. Design, Conformation, and Crystallography of 2-Naphthyl Phenyl Ethers as Potent Anti-HIV Agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won-Gil; Chan, Albert H.; Spasov, Krasimir A.; Anderson, Karen S.; Jorgensen, William L.

    2016-12-08

    Catechol diethers that incorporate a 7-cyano-2-naphthyl substituent are reported as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Many of the compounds have 1–10 nM potencies toward wild-type HIV-1. An interesting conformational effect allows two unique conformers for the naphthyl group in complexes with HIV-RT. X-ray crystal structures for 4a and 4f illustrate the alternatives.

  16. Lectins with Anti-HIV Activity: A Review

    Directory of Open Access Journals (Sweden)

    Ouafae Akkouh

    2015-01-01

    Full Text Available Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin lectin, concanavalin A, Galanthus nivalis (snowdrop agglutinin-related lectins, Musa acuminata (banana lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus. The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

  17. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation.

    Directory of Open Access Journals (Sweden)

    Bridgette Janine Connell

    Full Text Available Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS as well as to an antibody (mAb 17b directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1.

  18. Quarter Century of Anti-HIV CAR T Cells.

    Science.gov (United States)

    Wagner, Thor A

    2018-04-01

    A therapy that might cure HIV is a very important goal for the 30-40 million people living with HIV. Chimeric antigen receptor T cells have recently had remarkable success against certain leukemias, and there are reasons to believe they could be successful for HIV. This manuscript summarizes the published research on HIV CAR T cells and reviews the current anti-HIV chimeric antigen receptor strategies. Research on anti-HIV chimeric antigen receptor T cells has been going on for at least the last 25 years. First- and second-generation anti-HIV chimeric antigen receptors have been developed. First-generation anti-HIV chimeric antigen receptors were studied in clinical trials more than 15 years ago, but did not have meaningful clinical efficacy. There are some reasons to be optimistic about second-generation anti-HIV chimeric antigen receptor T cells, but they have not yet been tested in vivo.

  19. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  20. Testing of viscous anti-HIV microbicides using Lactobacillus.

    Science.gov (United States)

    Moncla, B J; Pryke, K; Rohan, L C; Yang, H

    2012-02-01

    The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To demonstrate the toxicity of formulated products a new assay was developed for use with viscous and non-viscous samples that we have termed the Lactobacillus toxicity test. We found that the vortex mixing of vaginal Lactobacillus species can lead to reductions in bacterial viability. Lactobacillus can survive briefly, about 2s, but viability declines with increased vortex mixing. The addition of heat inactivated serum or bovine serum albumin, but not glycerol, prevented the decrease in bacterial viability. Bacillus atrophaeus spores also demonstrated loss of viability upon extended mixing. We observed that many of the excipients used in film formulation and the films themselves also afford protection from the killing during vortex mixing. This method is of relevance for toxicity for cidal activities of viscous products. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Dual door entry to exciplex emission in a chimeric DNA duplex containing non-nucleoside-nucleoside pair.

    Science.gov (United States)

    Bag, Subhendu Sekhar; Talukdar, Sangita; Kundu, Rajen; Saito, Isao; Jana, Subhashis

    2014-01-25

    Dual door entry to exciplex formation was established in a chimeric DNA duplex wherein a fluorescent non-nucleosidic base surrogate () is paired against a fluorescent nucleosidic base surrogate (). Packing of the nucleobases via intercalative stacking interactions led to an exciplex emission either via FRET from the donor or direct excitation of the FRET acceptor .

  2. Contribution of the anti HIV/AIDS community conversation programs ...

    African Journals Online (AJOL)

    Background: HIV/AIDS has now been around for about three and half decades since first diagnosed in 1981. If we wish to curb the spread of HIV/AIDS effectively and sustainably, we need to design strategies that help mobilizing communities at large. Anti-HIV/AIDS Community Conversation (CC) Programs are part of ...

  3. Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years

    Directory of Open Access Journals (Sweden)

    Hanadi Sinokrot

    2017-10-01

    Full Text Available Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally, VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and non-nucleoside analogues prodrugs, the most promising are nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues have witnessed productive era in the recent past few years. The era of non-interferon based treatment of hepatitis (through direct inhibitors of NS5A has dawned.

  4. Will dapivirine redeem the promises of anti-HIV microbicides? Overview of product design and clinical testing.

    Science.gov (United States)

    das Neves, José; Martins, João Pedro; Sarmento, Bruno

    2016-08-01

    Microbicides are being developed in order to prevent sexual transmission of HIV. Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is one of the leading drug candidates in the field, currently being tested in various dosage forms, namely vaginal rings, gels, and films. In particular, a ring allowing sustained drug release for 1month is in an advanced stage of clinical testing. Two parallel phase III clinical trials are underway in sub-Saharan Africa and results are expected to be released in early 2016. This article overviews the development of dapivirine and its multiple products as potential microbicides, with particular emphasis being placed on clinical evaluation. Also, critical aspects regarding regulatory approval, manufacturing, distribution, and access are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Flazinamide, a novel β-carboline compound with anti-HIV actions

    International Nuclear Information System (INIS)

    Wang Yunhua; Tang Jianguo; Wang Ruirui; Yang Liumeng; Dong Zejun; Du Li; Shen Xu; Liu Jikai; Zheng Yongtang

    2007-01-01

    A β-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)-β-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38 μM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89 μM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77 μM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle

  6. Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2006-10-01

    Full Text Available Abstract Background Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP, a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. Methods The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP, the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. Results The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate, cellulose sulfate, carrageenan, CAP (in soluble form and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold diminished in the presence of SP (33.3%. Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. Conclusion The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.

  7. Nanomedicine in the development of anti-HIV microbicides.

    Science.gov (United States)

    das Neves, José; Nunes, Rute; Rodrigues, Francisca; Sarmento, Bruno

    2016-08-01

    Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Nelfinavir and Non-Nucleoside Reverse Transcriptase Inhibitor-Based Salvage Regimes in Heavily Hiv Pretreated Patients

    Directory of Open Access Journals (Sweden)

    Jean-Guy Baril

    2003-01-01

    Full Text Available OBJECTIVE: To assess the efficacy of nelfinavir mesylate (NFV in combination with delavirdine mesylate(DLV or efavirenz (EFV and other antiretroviral agents following virological failure on other protease inhibitor (PI-based regimens.

  9. Compounds acting against HIV: Imidazo[1,2-a]pyridines as non-nucleoside reverse transcriptase inhibitors (NNRTIs)

    CSIR Research Space (South Africa)

    Bode, M

    2010-09-01

    Full Text Available .6 µM N N NH Cl Res Act = 3% IC50 = 2 µM MAGI IC50 = 0.2 µM N N NH Cl Res Act = 5% IC50 = 3.5 µM MAGI IC50 = 0.18 µM N N NH Cl Res Act = 13% IC50 = 8 µM MAGI IC50 = 0.6 µM N N NH Cl Cl Res Act = 4% IC50 = 1.5 µM MAGI IC50... 2010 www.csir.co.za N N NH N N NH Cl N N NH Cl CN IC50= 4.4 uM (RT) IC50= 0.16 uM (PBMC) IC50= 0.41 uM (MAGI) cf . Nevirapine IC50=0.67 uM (RT) IC50=0.033 uM (PBMC) IC50= 29 uM (RT) IC50= 41 uM (PBMC) cf...

  10. Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors

    CSIR Research Space (South Africa)

    Bode, ML

    2011-06-01

    Full Text Available ? Discovery Studio 2.5.5). The crystal structures of both the wild-type and K103N mutant forms of HIV-1 RT containing the diarylpyrimidine inhibitor rilpivirine (TMC-278) were used (pdb codes MEE and 3MEG, respectively).27 Etravirine (TMC-125... These drugs act by binding to a lipophilic, non-substrate binding pocket located about 10? from the substrate binding site. Binding induces conformational changes in the catalytic site, slowing catalytic activity markedly.3 About fifty structurally diverse...

  11. Decrease of vitamin D concentration in patients with HIV infection on a non nucleoside reverse transcriptase inhibitor-containing regimen

    Directory of Open Access Journals (Sweden)

    Colebunders Robert

    2010-11-01

    Full Text Available Abstract Background Vitamin D is an important determinant of bone health and also plays a major role in the regulation of the immune system. Interestingly, vitamin D status before the start of highly active antiretroviral therapy (HAART has been recently associated with HIV disease progression and overall mortality in HIV-positive pregnant women. We prospectively studied vitamin D status in HIV individuals on HAART in Belgium. We selected samples from HIV-positive adults starting HAART with a pre-HAART CD4 T-cell count >100 cells/mm3 followed up for at least 12 months without a treatment change. We compared 25-hydroxyvitamin D plasma [25-(OHD] concentration in paired samples before and after 12 months of HAART. 25-(OHD levels are presented using two different cut-offs: Results Vitamin D deficiency was common before HAART, the frequency of plasma 25-(OHD concentrations below 20 ng/ml and 30 below ng/ml was 43.7% and 70.1% respectively. After 12 months on HAART, the frequency increased to 47.1% and 81.6%. HAART for 12 months was associated with a significant decrease of plasma 25-(OHD concentration (p = 0.001. Decreasing plasma 25-(OHD concentration on HAART was associated in the multivariate model with NNRTI-based regimen (p = 0.001 and lower body weight (p = 0.008. Plasma 25-(OHD concentrations decreased significantly in both nevirapine and efavirenz-containing regimens but not in PI-treated patients. Conclusions Vitamin D deficiency is frequent in HIV-positive individuals and NNRTI therapy further decreases 25-(OHD concentrations. Consequently, vitamin D status need to be checked regularly in all HIV-infected patients and vitamin D supplementation should be given when needed.

  12. Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide.

    Science.gov (United States)

    La Regina, Giuseppe; Coluccia, Antonio; Brancale, Andrea; Piscitelli, Francesco; Gatti, Valerio; Maga, Giovanni; Samuele, Alberta; Pannecouque, Christophe; Schols, Dominique; Balzarini, Jan; Novellino, Ettore; Silvestri, Romano

    2011-03-24

    New indolylarylsulfone derivatives bearing cyclic substituents at indole-2-carboxamide linked through a methylene/ethylene spacer were potent inhibitors of the WT HIV-1 replication in CEM and PBMC cells with inhibitory concentrations in the low nanomolar range. Against the mutant L100I and K103N RT HIV-1 strains in MT-4 cells, compounds 20, 24-26, 36, and 40 showed antiviral potency superior to that of NVP and EFV. Against these mutant strains, derivatives 20, 24-26, and 40 were equipotent to ETV. Molecular docking experiments on this novel series of IAS analogues have also suggested that the H-bond interaction between the nitrogen atom in the carboxamide chain of IAS and Glu138:B is important in the binding of these compounds. These results are in accordance with the experimental data obtained on the WT and on the mutant HIV-1 strains tested.

  13. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  14. Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design.

    Science.gov (United States)

    Benmansour, Fatiha; Trist, Iuni; Coutard, Bruno; Decroly, Etienne; Querat, Gilles; Brancale, Andrea; Barral, Karine

    2017-01-05

    With the aim to help drug discovery against dengue virus (DENV), a fragment-based drug design approach was applied to identify ligands targeting a main component of DENV replication complex: the NS5 AdoMet-dependent mRNA methyltransferase (MTase) domain, playing an essential role in the RNA capping process. Herein, we describe the identification of new inhibitors developed using fragment-based, structure-guided linking and optimization techniques. Thermal-shift assay followed by a fragment-based X-ray crystallographic screening lead to the identification of three fragment hits binding DENV MTase. We considered linking two of them, which bind to proximal sites of the AdoMet binding pocket, in order to improve their potency. X-ray crystallographic structures and computational docking were used to guide the fragment linking, ultimately leading to novel series of non-nucleoside inhibitors of flavivirus MTase, respectively N-phenyl-[(phenylcarbamoyl)amino]benzene-1-sulfonamide and phenyl [(phenylcarbamoyl)amino]benzene-1-sulfonate derivatives, that show a 10-100-fold stronger inhibition of 2'-O-MTase activity compared to the initial fragments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Quercetin derivatives as non-nucleoside inhibitors for dengue polymerase: molecular docking, molecular dynamics simulation, and binding free energy calculation.

    Science.gov (United States)

    Anusuya, Shanmugam; Gromiha, M Michael

    2017-10-01

    Dengue is an important public health problem in tropical and subtropical regions of the world. Neither vaccine nor an antiviral medication is available to treat dengue. This insists the need of drug discovery for dengue. In order to find a potent lead molecule, RNA-dependent RNA polymerase which is essential for dengue viral replication is chosen as a drug target. As Quercetin showed antiviral activity against several viruses, quercetin derivatives developed by combinatorial library synthesis and mined from PubChem databases were screened for a potent anti-dengue viral agent. Our study predicted Quercetin 3-(6″-(E)-p-coumaroylsophoroside)-7-rhamnoside as a dengue polymerase inhibitor. The results were validated by molecular dynamics simulation studies which reveal water bridges and hydrogen bonds as major contributors for the stability of the polymerase-lead complex. Interactions formed by this compound with residues Trp795, Arg792 and Glu351 are found to be essential for the stability of the polymerase-lead complex. Our study demonstrates Quercetin 3-(6″-(E)-p-coumaroylsophoroside)-7-rhamnoside as a potent non-nucleoside inhibitor for dengue polymerase.

  16. A Survey of Plants with Anti-HIV Active Compounds and their Modes ...

    African Journals Online (AJOL)

    Administrator

    proteins, alkaloids, and biflavonoids inhibit various ... several plant families and species contain anti-HIV .... articles reviewed, only about a third were included .... membranes against free .... Pedersen, B.K. Low plasma level of adiponectin.

  17. New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity.

    Science.gov (United States)

    Romanucci, Valeria; Zarrelli, Armando; Liekens, Sandra; Noppen, Sam; Pannecouque, Christophe; Di Fabio, Giovanni

    2018-02-10

    The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV agents has been extensively reported in the literature over the last years. In the light of our recent results regarding the slow G-quadruplex folding kinetics of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV screening to investigate the impact of the G-quadruplex folding on their anti-HIV activity. In particular, varying the single stranded concentrations of ODNs, it has been tested a pool of ODN sample solutions with different G-quadruplex concentrations. The anti-HIV assays have been designed favouring the limited kinetics involved in the tetramolecular G4-association based on the d(TGGGAG) sequence. Aiming to determine the stoichiometry of G-quadruplex structures in the same experimental conditions of the anti-HIV assays, a native gel electrophoresis was performed. The gel confirmed the G-quadruplex formation for almost all sample solutions while showing the formation of high order G4 structures for the more concentrated ODNs solutions. The most significant result is the discovery of a potent anti-HIV activity of the G-quadruplex formed by the natural d(TGGGAG) sequence (IC 50  = 14 nM) that, until now, has been reported to be completely inactive against HIV infection. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  18. G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents.

    Science.gov (United States)

    Musumeci, Domenica; Riccardi, Claudia; Montesarchio, Daniela

    2015-09-22

    Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.

  19. Stability of the resistance to the thiosemicarbazone derived from 5,6-Dimethoxy-1-indanone, a non-nucleoside polymerase inhibitor of bovine viral diarrhea virus

    OpenAIRE

    Castro, Eliana Florencia; Campos, Rodolfo Hector; Cavallaro, Lucía Vicenta

    2017-01-01

    Bovine viral diarrhea virus (BVDV) is the prototype Pestivirus. BVDV infection is distributed worldwide and causes serious problems for the livestock industry. The thiosemicarbazone of 5,6-dimethoxy-1-indanone (TSC) is a non-nucleoside polymerase inhibitor (NNI) of BVDV. All TSC-resistant BVDV variants (BVDV-TSCr T1–5) present an N264D mutation in the NS5B gene (RdRp) whereas the variant BVDV-TSCr T1 also presents an NS5B A392E mutation. In the present study, we carried out twenty passages of...

  20. Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

    International Nuclear Information System (INIS)

    Shi Weiguo; Qi Zhi; Pan Chungen; Xue Na; Debnath, Asim K.; Qie Jiankun; Jiang Shibo; Liu Keliang

    2008-01-01

    The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins

  1. Accuracy of different thresholds for the anti-HIV avidity index

    Directory of Open Access Journals (Sweden)

    Claudio Galli

    2008-03-01

    Full Text Available Surveillance programs for human immunodeficiency virus (HIV infection are based on the reporting of newly diagnosed cases. In order to guarantee a more accurate estimate of the trends and behaviours of infected people, simple and reliable methods aimed at identifying recent (< 6 months HIV infections are needed. We evaluated the accuracy of the avidity index (AI of anti-HIV antibodies on 357 serum samples obtained from 127 subjects for whom an estimated date of seroconversion was calculated on the basis of the interval between the last negative and first positive anti-HIV test result.The ROC curve analysis performed at different thresholds of the AI showed that a cutoff of 0.80 (93.0% sensitivity and 98.5% specificity yields the best overall accuracy (95.8% and should be employed for surveillance purposes, whereas the application of the anti-HIV AI on individual cases is not recommended.

  2. Thiazoline peptides and a tris-phenethyl urea from Didemnum molle with anti-HIV activity.

    Science.gov (United States)

    Lu, Zhenyu; Harper, Mary Kay; Pond, Christopher D; Barrows, Louis R; Ireland, Chris M; Van Wagoner, Ryan M

    2012-08-24

    As part of our screening for anti-HIV agents from marine invertebrates, the MeOH extract of Didemnum molle was tested and showed moderate in vitro anti-HIV activity. Bioassay-guided fractionation of a large-scale extract allowed the identification of two new cyclopeptides, mollamides E and F (1 and 2), and one new tris-phenethyl urea, molleurea A (3). The absolute configurations were established using the advanced Marfey's method. The three compounds were evaluated for anti-HIV activity in both an HIV integrase inhibition assay and a cytoprotective cell-based assay. Compound 2 was active in both assays with IC(50) values of 39 and 78 μM, respectively. Compound 3 was active only in the cytoprotective cell-based assay, with an IC(50) value of 60 μM.

  3. Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

    Energy Technology Data Exchange (ETDEWEB)

    Giri, Namita; Oh, Byeongtaek; Lee, Chi H., E-mail: leech@umkc.edu [University of Missouri at Kansas City, Division of Pharmaceutical Sciences (United States)

    2016-05-15

    This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100{sup ®} (ES100{sup ®}), a pH-sensitive polymer. ES100{sup ®} NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100{sup ®} NPs. The morphology of the ES100{sup ®} NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100{sup ®} NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100{sup ®} NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100{sup ®} NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100{sup ®} NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100{sup ®} NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100{sup

  4. Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

    International Nuclear Information System (INIS)

    Giri, Namita; Oh, Byeongtaek; Lee, Chi H.

    2016-01-01

    This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100"® (ES100"®), a pH-sensitive polymer. ES100"® NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100"® NPs. The morphology of the ES100"® NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100"® NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100"® NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100"® NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100"® NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100"® NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100"® NPs were taken by vaginal epithelial cells through

  5. A Survey of Plants with Anti-HIV Active Compounds and their Modes ...

    African Journals Online (AJOL)

    Background: Several limitations of current antiretroviral therapy (ART) programmes will continue to push patients towards the use of plants to manage HIV/AIDS. However, evidence about the use of anti-HIV plants is anecdotal. Objectives: Search the literature for research articles that document plants with anti-HIV ...

  6. Photo-translocation of anti-HIV-1 drugs into TZM-bl cells

    CSIR Research Space (South Africa)

    Khanyile, T

    2013-04-01

    Full Text Available Targeted drug delivery into HIV-1 infected cells offers a reduction in toxicity and side effect. Using a femtosecond (fs) laser of different beam shapes anti-HIV-1 drugs are efficiently delivered into TZM-bl cells....

  7. Mechanism of anti-HIV activity of succinylated human serum albumin

    NARCIS (Netherlands)

    Kuipers, ME; Berg, HVD; Swart, PJ; Laman, Jon; Meijer, DKF; Kopelman, MHGM; Huisman, H

    1999-01-01

    In the present study, we described the interaction of succinylated human serum albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1 gp120 and in detail with the third variable domain of gp120 (V3 loop). To this end, different assay formats were tested in which gp120- and

  8. New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica

    DEFF Research Database (Denmark)

    Valsaraj, R; Pushpangadan, P; Smitt, U W

    1997-01-01

    A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit rind led to the isolation of two new lignans named termilignan (1) and thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and anolignan B (4). All four compounds possessed demonstrable anti-HIV-......, antimalarial, and antifungal activity in vitro....

  9. Estimation of Anti-HIV Activity of HEPT Analogues Using MLR, ANN, and SVM Techniques

    Directory of Open Access Journals (Sweden)

    Basheerulla Shaik

    2013-01-01

    value than those of MLR and SVM techniques. Rm2= metrics and ridge regression analysis indicated that the proposed four-variable model MATS5e, RDF080u, T(O⋯O, and MATS5m as correlating descriptors is the best for estimating the anti-HIV activity (log 1/C present set of compounds.

  10. Development of an anti-HIV vaccine eliciting broadly neutralizing antibodies.

    Science.gov (United States)

    Ahmed, Yousuf; Tian, Meijuan; Gao, Yong

    2017-09-12

    The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.

  11. 7,8-secolignans from Schisandra neglecta and their anti-HIV-1 activities

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xuemei; Mu, Huaixue; Hu, Qiufen, E-mail: huqiufena@yahoo.com.cn [Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan University of Nationalities (China); Wang, Ruirui; Yang, Liumeng; Zheng, Yongtang [Kunming Institute of Zoology, Chinese Academy of Sciences (China); Sun, Handong; Xiao, Weilie, E-mail: xwl@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China)

    2012-10-15

    Four new 7,8-secolignans (neglectahenols A-D), together with two known 7,8-secolignans, were isolated from leaves and stems of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive one and two dimension NMR (nuclear magnetic resonance) techniques. 7,8-Secolignans and neglectahenols A-D were also tested for their anti-HIV-1 (human immunodeficiency virus type 1) activities, and all of them showed modest activities. (author)

  12. Design and cellular kinetics of dansyl-labeled CADA derivatives with anti-HIV and CD4 receptor down-modulating activity.

    Science.gov (United States)

    Vermeire, Kurt; Lisco, Andrea; Grivel, Jean-Charles; Scarbrough, Emily; Dey, Kaka; Duffy, Noah; Margolis, Leonid; Bell, Thomas W; Schols, Dominique

    2007-08-15

    A new class of anti-retrovirals, cyclotriazadisulfonamide (CADA) and its derivatives, specifically down-regulate CD4, the main receptor of HIV, and prevent HIV infection in vitro. In this work, several CADA derivatives, chemically labeled with a fluorescent dansyl group, were evaluated for their biological features and cellular uptake kinetics. We identified a derivative KKD-016 with antiviral and CD4 down-modulating capabilities similar to those of the parental compound CADA. By using flow cytometry, we demonstrated that the dose-dependent cellular uptake of this derivative correlated with CD4 down-modulation. The uptake and activity of the dansyl-labeled compounds were not dependent on the level of expression of CD4 at the cell surface. Removal of the CADA compounds from the cell culture medium resulted in their release from the cells followed by a complete restoration of CD4 expression. The inability of several fluorescent CADA derivatives to down-modulate CD4 was not associated with their lower cellular uptake and was not reversed by facilitating their cell penetration by a surfactant. These results prove the successful integration of the dansyl fluorophore into the chemical structure of a CD4 down-modulating anti-HIV compound, and show the feasibility of tracking a receptor and its down-modulator simultaneously. These fluorescent CADA analogs with reversible CD4 down-regulating potency can now be applied in further studies on receptor modulation, and in the exploration of their potentials as preventive and therapeutic anti-HIV drugs.

  13. [Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir].

    Science.gov (United States)

    Cervero, Miguel; Torres, Rafael; Jusdado, Juan José; Pastor, Susana; Agud, Jose Luis

    2016-04-15

    To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876

    Energy Technology Data Exchange (ETDEWEB)

    McComas, Casey C.; Palani, Anandan; Chang, Wei; Holloway, M. Katharine; Lesburg, Charles A.; Li, Peng; Liverton, Nigel; Meinke, Peter T.; Olsen, David B.; Peng, Xuanjia; Soll, Richard M.; Ummat, Ajay; Wu, Jie; Wu, Jin; Zorn, Nicolas; Ludmerer, Steven W. (Merck); (WuXi App Tec)

    2017-07-25

    Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.

  15. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

    Science.gov (United States)

    Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

    2014-07-01

    Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

  16. Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

    Science.gov (United States)

    Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

    2015-01-01

    Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

  17. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  18. Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G.

    Science.gov (United States)

    Rose, Kristine M; Marin, Mariana; Kozak, Susan L; Kabat, David

    2005-07-01

    APOBEC3G and 3F (A3G and A3F) cytidine deaminases incorporate into retroviral cores where they lethally hypermutate nascent DNA reverse transcripts. As substantiated here, the viral infectivity factor (Vif) encoded by human immunodeficiency virus type-1 (HIV-1) binds A3G and A3F and induces their degradation, thereby precluding their incorporation into viral progeny. Previous evidence suggested that A3G is expressed in H9 and other nonpermissive cells that contain this antiviral defense but not in several permissive cells, and that overexpression of A3G or A3F makes permissive cells nonpermissive. Using a broader panel of cell lines, we confirmed a correlation between A3G and cellular abilities to inactivate HIV-1(Deltavif). However, there was a quantitative discrepancy because several cells with weak antiviral activities had similar amounts of wild-type A3G mRNA and protein compared to H9 cells. Antiviral activity of H9 cells was also attenuated in some conditions. These quantitative discrepancies could not be explained by the presence of A3F or other A3G paralogs in some of the cell lines. Thus, A3A, A3B, and A3C had weak but significant anti-HIV-1 activities and did not dominantly interfere with A3G or A3F antiviral functions. Control of A3G synthesis by the protein kinase C/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway was also similar in permissive and nonpermissive cells. A3G in highly permissive cells is degraded by Vif, suggesting that it is not in a sequestered site, and is specifically incorporated in low amounts into HIV-1(Deltavif). Although A3G and/or A3F inactivate HIV-1(Deltavif) and are neutralized by Vif, the antiviral properties of cell lines are also influenced by other cellular and viral factors.

  19. Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids

    DEFF Research Database (Denmark)

    Pedersen, Erik Bjerregaard; Nielsen, Jakob Toudahl; Nielsen, Claus

    2011-01-01

    Two G-quadruplex forming sequences, 50-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1......-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming...

  20. Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity

    Directory of Open Access Journals (Sweden)

    Ana I. S. Esteves

    2011-01-01

    Full Text Available The extraction, fractionation and HIV-1 inhibition potential of polysaccharides extracted from three species of marine sponges, Erylus discophorus, Cliona celata and Stelletta sp., collected in the Northeastern Atlantic, is presented in this work. The anti-HIV activity of 23 polysaccharide pellets and three crude extracts was tested. Crude extracts prepared from Erylus discophorus specimens were all highly active against HIV-1 (90 to 95% inhibition. Cliona celata pellets showed low polysaccharide content (bellow 38.5% and almost no anti-HIV activity (<10% inhibition. Stelletta sp. pellets, although quite rich in polysaccharide (up to 97.3%, showed only modest bioactivity (<36% HIV-1 inhibition. Erylus discophorus pellets were among the richest in terms of polysaccharide content (up to 98% and the most active against HIV-1 (up to 95% inhibition. Chromatographic fractionation of the polysaccharide pellet obtained from a specimen of Erylus discophorus (B161 yielded only modestly active fractions. However, we could infer that the active molecule is most probably a high molecular weight sulfated polysaccharide (>2000 kDa, whose mechanism is possibly preventing viral attachment and entry (fusion inhibitor.

  1. Characterization of Nanodiamond-based anti-HIV drug Delivery to the Brain.

    Science.gov (United States)

    Roy, Upal; Drozd, Vadym; Durygin, Andriy; Rodriguez, Jesse; Barber, Paul; Atluri, Venkata; Liu, Xiaohua; Voss, Thomas G; Saxena, Surendra; Nair, Madhavan

    2018-01-25

    Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the ineffective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature-making it a more efficient drug carrier than other carbon-based materials. Considering its potential and importance, we have characterized unmodified and surface-modified (-COOH and -NH 2 ) nanodiamond for its capacity to load the anti-HIV-1 drug efavirenz and cytotoxicity, in vitro. Overall, our study has established that unmodified nanodiamond conjugated drug formulation has significantly higher drug loading capacity than surface-modified nanodiamond with minimum toxicity. Further, this nanodrug formulation was characterized by its drug dissolution profile, transmigration through the BBB, and its therapeutic efficacy. The present biological characterizations provide a foundation for further study of in-vivo pharmacokinetics and pharmacodynamics of nanodiamond-based anti-HIV drugs.

  2. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Sulggi A Lee

    Full Text Available A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir". We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART.We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR; integrated DNA (Alu PCR; unspliced RNA (rtPCR, multiply-spliced RNA (TILDA, residual plasma HIV RNA (single copy PCR, and replication-competent virus (outgrowth assay. We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR. Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years, the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004 and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003. However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results.Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.

  3. Comparative pharmacokinetic, immunologic and hematologic studies on the anti-HIV-1/2 compounds aconitylated and succinylated HSA

    NARCIS (Netherlands)

    Swart, P J; Beljaars, E; Smit, C; Pasma, A; Schuitemaker, H; Meijer, D K

    1996-01-01

    Charge modification by succinylation or cis-aconitylation of the terminal epsilon NH2 functions of the amino acid lysine in human serum albumin, resulted in polyanionic compounds with an anti-HIV-1 activity in the low nanomolar concentration range. After iv injections in rats of the negatively

  4. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides

    NARCIS (Netherlands)

    Berkhout, Ben; van Wamel, Jeroen L. B.; Beljaars, Leonie; Meijer, Dirk K. F.; Visser, Servaas; Floris, René

    2002-01-01

    In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition

  5. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides

    NARCIS (Netherlands)

    Berkhout, B; van Wamel, JLB; Beljaars, L; Meijer, DKF; Visser, Servaas; Floris, R

    In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition

  6. Identification of anti-HIV active dicaffeoylquinic- and tricaffeoylquinic acids in Helichrysum populifolium by NMR-based metabolomic guided fractionation.

    Science.gov (United States)

    Heyman, Heino Martin; Senejoux, François; Seibert, Isabell; Klimkait, Thomas; Maharaj, Vinesh Jaichand; Meyer, Jacobus Johannes Marion

    2015-06-01

    South Africa being home to more than 35% of the world's Helichrysum species (c.a. 244) of which many are used in traditional medicine, is seen potentially as a significant resource in the search of new anti-HIV chemical entities. It was established that five of the 30 Helichrysum species selected for this study had significant anti-HIV activity ranging between 12 and 21 μg/mL (IC50) by using an in-house developed DeCIPhR method on a full virus model. Subsequent toxicity tests also revealed little or no toxicity for these active extracts. With the use of NMR-based metabolomics, the search for common chemical characteristics within the plant extract was conducted, which resulted in specific chemical shift areas identified that could be linked to the anti-HIV activity of the extracts. The NMR chemical shifts associated with the activity were identified to be 2.56-3.08 ppm, 5.24-6.28 ppm, 6.44-7.04 ppm and 7.24-8.04 ppm. This activity profile was then used to guide the fractionation process by narrowing down and focusing the fractionation and purification processes to speed up the putative identification of five compounds with anti-HIV activity in the most active species, Helichrysum populifolium. The anti-HIV compounds identified for the first time from H. populifolium were three dicaffeoylquinic acid derivatives, i.e. 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid as well as two tricaffeoylquinic acid derivatives i.e. 1,3,5-tricaffeoylquinic acid and either 5-malonyl-1,3,4-tricaffeoylquinic or 3-malonyl-1,4,5-tricaffeoylquinic acid, with the latter being identified for the first time in the genus. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

    Directory of Open Access Journals (Sweden)

    Silvana Pasetto

    Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

  8. A Novel Method for Determining the Inhibitory Potential of Anti-HIV Drugs

    Science.gov (United States)

    Shen, Lin; Rabi, S. Alireza; Siliciano, Robert F.

    2009-01-01

    In the absence of a cure, most HIV-1-infected individuals will require life-long treatment. It is therefore essential to optimize highly active antiretroviral therapy. Recent research has shown that the slope parameter or Hill coefficient, which describes the steepness of a dose-response curve, is a critical missing dimension in the evaluation of antiviral drug activity. Based on this finding, the instantaneous inhibitory potential (IIP) has been derived as a new measure of antiviral drug activity. IIP incorporates the slope parameter and thus is a more accurate pharmacodynamic measure of antiviral activity than current measures such as IC50 and inhibitory quotient. However, it remains important to determine how to use IIP to predict the in vivo efficacy of anti-HIV-1 drugs. This article discusses recent advances in in vitro measures of antiviral activity and the therapeutic implications of the dose-response curve slope and IIP. PMID:19837466

  9. [Asymmetry in international relations, industrial property rights and anti-HIV medication].

    Science.gov (United States)

    Costa-Couto, Maria Helena; Nascimento, Alvaro César

    2008-01-01

    This paper analyzes the asymmetry in the international relations as refers to the recognition of industrial property rights in the pharmaceutical industry. It focuses on the impact of such relations upon the access to ARV medication, an issue of worldwide interest due to its connection with the development of the nations. Clashing interests and the position taken by some countries in their patent laws point to a scenario less favorable for the access of peripheral countries to anti-HIV/AIDS medication. On the other hand, it seems that the success of the Brazilian STD/AIDS program in negotiating ARV prices will open new possibilities. The solution may be the internal strengthening of the National States and the active role played by the Agencies of the United Nations System in defense of the collective human interests.

  10. Stability of the resistance to the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone, a non-nucleoside polymerase inhibitor of bovine viral diarrhea virus.

    Science.gov (United States)

    Castro, Eliana F; Campos, Rodolfo H; Cavallaro, Lucía V

    2014-01-01

    Bovine viral diarrhea virus (BVDV) is the prototype Pestivirus. BVDV infection is distributed worldwide and causes serious problems for the livestock industry. The thiosemicarbazone of 5,6-dimethoxy-1-indanone (TSC) is a non-nucleoside polymerase inhibitor (NNI) of BVDV. All TSC-resistant BVDV variants (BVDV-TSCr T1-5) present an N264D mutation in the NS5B gene (RdRp) whereas the variant BVDV-TSCr T1 also presents an NS5B A392E mutation. In the present study, we carried out twenty passages of BVDV-TSCr T1-5 in MDBK cells in the absence of TSC to evaluate the stability of the resistance. The viral populations obtained (BVDV R1-5) remained resistant to the antiviral compound and conserved the mutations in NS5B associated with this phenotype. Along the passages, BVDV R2, R3 and R5 presented a delay in the production of cytopathic effect that correlated with a decrease in cell apoptosis and intracellular accumulation of viral RNA. The complete genome sequences that encode for NS2 to NS5B, Npro and Erns were analyzed. Additional mutations were detected in the NS5B of BVDV R1, R3 and R4. In both BVDV R2 and R3, most of the mutations found were localized in NS5A, whereas in BVDV R5, the only mutation fixed was NS5A V177A. These results suggest that mutations in NS5A could alter BVDV cytopathogenicity. In conclusion, the stability of the resistance to TSC may be due to the fixation of different compensatory mutations in each BVDV-TSCr. During their replication in a TSC-free medium, some virus populations presented a kind of interaction with the host cell that resembled a persistent infection: decreased cytopathogenicity and viral genome synthesis. This is the first report on the stability of antiviral resistance and on the evolution of NNI-resistant BVDV variants. The results obtained for BVDV-TSCr could also be applied for other NNIs.

  11. Stability of the resistance to the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone, a non-nucleoside polymerase inhibitor of bovine viral diarrhea virus.

    Directory of Open Access Journals (Sweden)

    Eliana F Castro

    Full Text Available Bovine viral diarrhea virus (BVDV is the prototype Pestivirus. BVDV infection is distributed worldwide and causes serious problems for the livestock industry. The thiosemicarbazone of 5,6-dimethoxy-1-indanone (TSC is a non-nucleoside polymerase inhibitor (NNI of BVDV. All TSC-resistant BVDV variants (BVDV-TSCr T1-5 present an N264D mutation in the NS5B gene (RdRp whereas the variant BVDV-TSCr T1 also presents an NS5B A392E mutation. In the present study, we carried out twenty passages of BVDV-TSCr T1-5 in MDBK cells in the absence of TSC to evaluate the stability of the resistance. The viral populations obtained (BVDV R1-5 remained resistant to the antiviral compound and conserved the mutations in NS5B associated with this phenotype. Along the passages, BVDV R2, R3 and R5 presented a delay in the production of cytopathic effect that correlated with a decrease in cell apoptosis and intracellular accumulation of viral RNA. The complete genome sequences that encode for NS2 to NS5B, Npro and Erns were analyzed. Additional mutations were detected in the NS5B of BVDV R1, R3 and R4. In both BVDV R2 and R3, most of the mutations found were localized in NS5A, whereas in BVDV R5, the only mutation fixed was NS5A V177A. These results suggest that mutations in NS5A could alter BVDV cytopathogenicity. In conclusion, the stability of the resistance to TSC may be due to the fixation of different compensatory mutations in each BVDV-TSCr. During their replication in a TSC-free medium, some virus populations presented a kind of interaction with the host cell that resembled a persistent infection: decreased cytopathogenicity and viral genome synthesis. This is the first report on the stability of antiviral resistance and on the evolution of NNI-resistant BVDV variants. The results obtained for BVDV-TSCr could also be applied for other NNIs.

  12. Aaptamine Derivatives with Antifungal and Anti-HIV-1 Activities from the South China Sea Sponge Aaptos aaptos

    Directory of Open Access Journals (Sweden)

    Hao-Bing Yu

    2014-12-01

    Full Text Available Five new alkaloids of aaptamine family, compounds (1–5 and three known derivatives (6–8, have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated by spectroscopic analyses, as well as by comparison with the literature data. Compounds 1–2 are characterized with triazapyrene lactam skeleton, whereas compounds 4–5 share an imidazole-fused aaptamine moiety. These compounds were evaluated in antifungal and anti-HIV-1 assays. Compounds 3, 7, and 8 showed antifungal activity against six fungi, with MIC values in the range of 4 to 64 μg/mL. Compounds 7–8 exhibited anti-HIV-1 activity, with inhibitory rates of 88.0% and 72.3%, respectively, at a concentration of 10 μM.

  13. Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide.

    Science.gov (United States)

    Yamamoto, Hidemi S; Xu, Qiang; Fichorova, Raina N

    2013-01-08

    moderately increased (SLPI). Similarly to MALP-2, colonization by L. jensenii WT activated NF-κB; however, unlike the synthetic TLR2/6 ligand, the live microorganisms did not induce significant changes in the secreted levels across all inflammation-associated proteins. The mCV-N production and function were confirmed by western blot and a HIV-1 gp120 binding assay, respectively. The bioengineered lactobacilli expressed mCV-N with anti-HIV activity preserved in the epithelial cell context and caused no significant immunoinflammatory changes as compared to the WT L. jensenii. These results highlight the translational value of the colonization model and justify further clinical investigation of the homeostatic and anti-HIV effectiveness of the L. jensenii derivates.

  14. Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.

    Science.gov (United States)

    Huang, Boshi; Kang, Dongwei; Zhan, Peng; Liu, Xinyong

    2015-12-01

    The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.

  15. A novel simple QSAR model for the prediction of anti-HIV activity using multiple linear regression analysis.

    Science.gov (United States)

    Afantitis, Antreas; Melagraki, Georgia; Sarimveis, Haralambos; Koutentis, Panayiotis A; Markopoulos, John; Igglessi-Markopoulou, Olga

    2006-08-01

    A quantitative-structure activity relationship was obtained by applying Multiple Linear Regression Analysis to a series of 80 1-[2-hydroxyethoxy-methyl]-6-(phenylthio) thymine (HEPT) derivatives with significant anti-HIV activity. For the selection of the best among 37 different descriptors, the Elimination Selection Stepwise Regression Method (ES-SWR) was utilized. The resulting QSAR model (R (2) (CV) = 0.8160; S (PRESS) = 0.5680) proved to be very accurate both in training and predictive stages.

  16. Fluorine Substituted 1,2,4-Triazinones as Potential Anti-HIV-1 and CDK2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Mohammed S. I. Makki

    2014-01-01

    Full Text Available Fluorine substituted 1,2,4-triazinones have been synthesized via alkylation, amination, and/or oxidation of 6-(2-amino-5-fluorophenyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H-one 1 and 4-fluoro-N-(4-fluoro-2-(5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-ylphenylbenzamide 5 as possible anti-HIV-1 and CDK2 inhibitors. Alkylation on positions 2 and 4 in 1,2,4-triazinone gave compounds 6–8. Further modification was performed by selective alkylation and amination on position 3 to form compounds 9–15. However oxidation of 5 yielded compounds 16–18. Structures of the target compounds have been established by spectral analysis data. Five compounds (5, 11, 14, 16, and 17 have shown very good anti-HIV activity in MT-4 cells. Similarly, five compounds (1, 3, and 14–16 have exhibited very significant CDK2 inhibition activity. Compounds 14 and 16 were found to have dual anti-HIV and anticancer activities.

  17. Plant-based anti-HIV-1 strategies: vaccine molecules and antiviral approaches.

    Science.gov (United States)

    Scotti, Nunzia; Buonaguro, Luigi; Tornesello, Maria Lina; Cardi, Teodoro; Buonaguro, Franco Maria

    2010-08-01

    The introduction of highly active antiretroviral therapy has drastically changed HIV infection from an acute, very deadly, to a chronic, long-lasting, mild disease. However, this requires continuous care management, which is difficult to implement worldwide, especially in developing countries. Sky-rocketing costs of HIV-positive subjects and the limited success of preventive recommendations mean that a vaccine is urgently needed, which could be the only effective strategy for the real control of the AIDS pandemic. To be effective, vaccination will need to be accessible, affordable and directed against multiple antigens. Plant-based vaccines, which are easy to produce and administer, and require no cold chain for their heat stability are, in principle, suited to such a strategy. More recently, it has been shown that even highly immunogenic, enveloped plant-based vaccines can be produced at a competitive and more efficient rate than conventional strategies. The high variability of HIV epitopes and the need to stimulate both humoral neutralizing antibodies and cellular immunity suggest the importance of using the plant system: it offers a wide range of possible strategies, from single-epitope to multicomponent vaccines, modulators of the immune response (adjuvants) and preventive molecules (microbicides), either alone or in association with plant-derived monoclonal antibodies, besides the potential use of the latter as therapeutic agents. Furthermore, plant-based anti-HIV strategies can be administered not only parenterally but also by the more convenient and safer oral route, which is a more suitable approach for possible mass vaccination.

  18. Structural insights into the anti-HIV activity of the Oscillatoria agardhii agglutinin homolog lectin family.

    Science.gov (United States)

    Koharudin, Leonardus M I; Kollipara, Sireesha; Aiken, Christopher; Gronenborn, Angela M

    2012-09-28

    Oscillatoria agardhii agglutinin homolog (OAAH) proteins belong to a recently discovered lectin family. All members contain a sequence repeat of ~66 amino acids, with the number of repeats varying among different family members. Apart from data for the founding member OAA, neither three-dimensional structures, information about carbohydrate binding specificities, nor antiviral activity data have been available up to now for any other members of the OAAH family. To elucidate the structural basis for the antiviral mechanism of OAAHs, we determined the crystal structures of Pseudomonas fluorescens and Myxococcus xanthus lectins. Both proteins exhibit the same fold, resembling the founding family member, OAA, with minor differences in loop conformations. Carbohydrate binding studies by NMR and x-ray structures of glycan-lectin complexes reveal that the number of sugar binding sites corresponds to the number of sequence repeats in each protein. As for OAA, tight and specific binding to α3,α6-mannopentaose was observed. All the OAAH proteins described here exhibit potent anti-HIV activity at comparable levels. Altogether, our results provide structural details of the protein-carbohydrate interaction for this novel lectin family and insights into the molecular basis of their HIV inactivation properties.

  19. Anti-HIV therapy with AZT prodrugs: AZT phosphonate derivatives, current state and prospects.

    Science.gov (United States)

    Khandazhinskaya, Anastasiya; Matyugina, Elena; Shirokova, Elena

    2010-06-01

    AIDS, a disease caused by human immunodeficiency virus, was called 'plague of the twentieth century'. 3'-Azido-3'-deoxythymidine (AZT), the first compound approved for the treatment of HIV, is still a mandatory component of treatment schemes. However, its toxicity stimulated a search for new agents. This review presents the history and current state of the design of AZT prodrugs based on its phosphonate derivatives. Although every effort was made to include as many AZT structures bearing phosphonate residues and demonstrate the variety they offer, we also concentrated on the studies performed in our laboratory. Special attention was also paid to AZT 5'-H-phosphonate (phosphazide, Nikavir) approved in the Russian Federation as a drug for the prevention and treatment of HIV infection. The prodrug strategy applied to AZT phosphonate derivatives enriched chemistry, biology and medicine not only with new knowledge, methods and structures, but also with a new anti-HIV drug Nikavir. Currently, study of another phosphonate, AZT 5'-aminocarbonylphosphonate, is underway. Slow release of AZT following oral administration and penetration into cells, decreased toxicity and the lack of cumulative properties make the compounds of this group promising as extended-release forms of AZT.

  20. HIV testing among pregnant women in Brazil: rates and predictors Prueba anti-HIV en mujeres embarazadas en Brasil: tasas y predictivos Testagem anti-HIV em mulheres grávidas no Brasil: taxas e preditores

    Directory of Open Access Journals (Sweden)

    Valdiléa G Veloso

    2008-10-01

    Full Text Available OBJECTIVE: To assess rates of offering and uptake of HIV testing and their predictors among women who attended prenatal care. METHODS: A population-based cross-sectional study was conducted among postpartum women (N=2,234 who attended at least one prenatal care visit in 12 cities. Independent and probabilistic samples were selected in the cities studied. Sociodemographic data, information about prenatal care and access to HIV prevention interventions during the current pregnancy were collected. Bivariate and multivariate analyses were carried out to assess independent effects of the covariates on offering and uptake of HIV testing. Data collection took place between November 1999 and April 2000. RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the current pregnancy. Offering of HIV testing was positively associated with: previous knowledge about prevention of mother-to-child transmission of HIV; higher number of prenatal care visits; higher level of education and being white. HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate that dissemination of information about prevention of mother-to-child transmission among women may contribute to increasing HIV testing coverage during pregnancy. Non-white women with lower level of education should be prioritized. Strategies to increase attendance of vulnerable women to prenatal care and to raise awareness among health care workers are of utmost importance.OBJETIVO: Estimar las tasas de oferta y realización de la prueba anti-HIV y sus predictivos entre mujeres que recibieron atención prenatal. MÉTODOS: Se realizó un estudio transversal, de base poblacional, con 2.234 puérperas en 12 ciudades de Brasil. Las muestras probabilísticas fueron seleccionadas independientemente por ciudad, entre puérperas que asistieron a por lo menos una visita prenatal. Se colectaron datos sociodemográficos, informaciones sobre cuidado prenatal y acceso a

  1. A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    2011-01-01

    Full Text Available Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development

  2. Anti-HIV and immunomodulation activities of cacao mass lignin-carbohydrate complex.

    Science.gov (United States)

    Sakagami, Hiroshi; Kawano, Michiyo; Thet, May Maw; Hashimoto, Ken; Satoh, Kazue; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Haishima, Yuji; Maeda, Yuuichi; Sakurai, Koji

    2011-01-01

    Recently, a prominent antiviral and macrophage stimulatory activity of cacao lignin-carbohydrate complex (LCC) has been reported. However, the solubility and sterility of LCC have not been considered yet. In the present study, complete solubilisation and sterilisation was achieved by autoclaving under mild alkaline conditions and the previously reported biological activities were re-examined. LCCs were obtained by 1% NaOH extraction and acid precipitation, and a repeated extraction-precipitation cycle. Nitric oxide (NO) and cytokine productions were assayed by the Griess method and ELISA, respectively. Inducible NO synthase (iNOS) expression was determined by Western blot analysis. Superoxide anion, hydroxyl radical and nitric oxide radical-scavenging activity was determined by ESR spectroscopy. Cacao mass LCC showed reproducibly higher anti-HIV activity than cacao husk LCC. Cacao mass LCC, up to 62.5 μg/ml, did not stimulate mouse macrophage-like cells (RAW264.7 and J774.1) to produce NO, nor did it induce iNOS protein, in contrast to lipopolysaccharide (LPS). Cacao mass LCC and LPS synergistically stimulated iNOS protein expression, suggesting a different point of action. Cacao mass LCC induced tumour necrosis factor-α production markedly less than LPS, and did not induce interleukin-1β, interferon-α or interferon-γ. ESR spectroscopy showed that cacao mass LCC, but not LPS, scavenged NO produced from NOC-7. This study demonstrated several new biological activities of LCCs distinct from LPS and further confirmed the promising antiviral and immunomodulating activities of LCCs.

  3. Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides.

    Science.gov (United States)

    das Neves, José; Sarmento, Bruno

    2015-05-01

    Polymeric nanoparticles (NPs) have the potential to provide effective and safe delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal microbicides. Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were produced by an emulsion-solvent evaporation method, optimized for colloidal properties using a 3-factor, 3-level Box-Behnken experimental design, and characterized for drug loading, production yield, morphology, thermal behavior, drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory potential. Also, drug permeability/membrane retention in well-established HEC-1-A and CaSki cell monolayer models as mediated by NPs was assessed in the absence or presence of mucin. Box-Behnken design allowed optimizing monodisperse 170nm drug-loaded NPs. Drug release experiments showed an initial burst effect up to 4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken up by different genital and macrophage cell lines as assessed by fluorescence microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as compared to the free drug, with up to around one-log increase in half-maximal cytotoxic concentration values. In all cases, no relevant changes in cell pro-inflammatory cytokine/chemokine production were observed. Dapivirine transport across cell monolayers was significantly decreased when mucin was present at the donor side with either NPs or the free drug, thus evidencing the influence of this natural glycoprotein in membrane permeability. Moreover, drug retention in cell monolayers was significantly higher for NPs in comparison with the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting technological and biological features that may contribute to their use as novel safe and effective vaginal microbicides. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

    Science.gov (United States)

    Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

    2018-04-12

    A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Synthesis of single- and double-chain fluorocarbon and hydrocarbon galactosyl amphiphiles and their anti-HIV-1 activity.

    Science.gov (United States)

    Faroux-Corlay, B; Clary, L; Gadras, C; Hammache, D; Greiner, J; Santaella, C; Aubertin, A M; Vierling, P; Fantini, J

    2000-07-24

    Galactosylceramide (GalCer) is an alternative receptor allowing HIV-1 entry into CD4(-)/GalCer(+) cells. This glycosphingolipid recognizes the V3 loop of HIV gp120, which plays a key role in the fusion of the HIV envelope and cellular membrane. To inhibit HIV uptake and infection, we designed and synthesized analogs of GalCer. These amphiphiles and bolaamphiphiles consist of single and double hydrocarbon and/or fluorocarbon chain beta-linked to galactose and galactosamine. They derive from serine (GalSer), cysteine (GalCys), and ethanolamine (GalAE). The anti-HIV activity and cytotoxicity of these galactolipids were evaluated in vitro on CEM-SS (a CD4(+) cell line), HT-29, a CD4(-) cell line expressing high levels of GalCer receptor, and/or HT29 genetically modified to express CD4. GalSer and GalAE derivatives, tested in aqueous medium or as part of liposome preparation, showed moderate anti-HIV-1 activities (IC50 in the 20-220 microM range), whereas none of the GalCys derivatives was found to be active. Moreover, only some of these anti-HIV active analogs inhibited the binding of [3H]suramin (a polysulfonyl compound which displays a high affinity for the V3 loop) to SPC3, a synthetic peptide which contains the conserved GPGRAF region of the V3 loop. Our results most likely indicate that the neutralization of the virion through masking of this conserved V3 loop region is not the only mechanism involved in the HIV-1 antiviral activity of our GalCer analogs.

  6. Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi

    OpenAIRE

    Bashyal, Bharat P.; Wellensiek, Brian P.; Ramakrishnan, Rajesh; Faeth, Stanley H.; Ahmad, Nafees; Leslie Gunatilaka, A. A.

    2014-01-01

    Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, alterto...

  7. Broad anti-HIV activity of the Oscillatoria agardhii agglutinin homologue lectin family.

    Science.gov (United States)

    Férir, Geoffrey; Huskens, Dana; Noppen, Sam; Koharudin, Leonardus M I; Gronenborn, Angela M; Schols, Dominique

    2014-10-01

    Oscillatoria agardhii agglutinin homologue (OAAH) proteins belong to a recently discovered lectin family. The founding member OAA and a designed hybrid OAAH (OPA) recognize similar but unique carbohydrate structures of Man-9, compared with other antiviral carbohydrate-binding agents (CBAs). These two newly described CBAs were evaluated for their inactivating properties on HIV replication and transmission and for their potential as microbicides. Various cellular assays were used to determine antiviral activity against wild-type and certain CBA-resistant HIV-1 strains: (i) free HIV virion infection in human T lymphoma cell lines and PBMCs; (ii) syncytium formation assay using persistently HIV-infected T cells and non-infected CD4+ T cells; (iii) DC-SIGN-mediated viral capture; and (iv) transmission to uninfected CD4+ T cells. OAA and OPA were also evaluated for their mitogenic properties and potential synergistic effects using other CBAs. OAA and OPA inhibit HIV replication, syncytium formation between HIV-1-infected and uninfected T cells, DC-SIGN-mediated HIV-1 capture and transmission to CD4+ target T cells, thereby rendering a variety of HIV-1 and HIV-2 clinical isolates non-infectious, independent of their coreceptor use. Both CBAs competitively inhibit the binding of the Manα(1-2)Man-specific 2G12 monoclonal antibody (mAb) as shown by flow cytometry and surface plasmon resonance analysis. The HIV-1 NL4.3(2G12res), NL4.3(MVNres) and IIIB(GRFTres) strains were equally inhibited as the wild-type HIV-1 strains by these CBAs. Combination studies indicate that OAA and OPA act synergistically with Hippeastrum hybrid agglutinin, 2G12 mAb and griffithsin (GRFT), with the exception of OPA/GRFT. OAA and OPA are unique CBAs with broad-spectrum anti-HIV activity; however, further optimization will be necessary for microbicidal application. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights

  8. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina

    Directory of Open Access Journals (Sweden)

    Xiao-Liang ZHANG

    2016-07-01

    Full Text Available Northern pig-tailed macaques (NPMs, Macaca leonina are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.

  9. Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi.

    Science.gov (United States)

    Bashyal, Bharat P; Wellensiek, Brian P; Ramakrishnan, Rajesh; Faeth, Stanley H; Ahmad, Nafees; Gunatilaka, A A Leslie

    2014-11-01

    Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data. When tested in our cell-based assay at concentrations insignificantly toxic to T-cells, altertoxins V (1), I (3), II (4), and III (5) completely inhibited replication of the HIV-1 virus at concentrations of 0.50, 2.20, 0.30, and 1.50 μM, respectively. Our findings suggest that the epoxyperylene structural scaffold in altertoxins may be manipulated to produce potent anti-HIV therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. [Isolation, idetification and anti-HIV-1 integrase activity of culturable endophytic fungi from Tibetan medicinal plant Phlomis younghusbandii Mukerjee].

    Science.gov (United States)

    Zhang, Da-Wei; Zhao, Ming-Ming; Chen, Juan; Li, Chao; Guo, Shun-Xing

    2013-05-01

    A total of 52 endophytic fungi were isolated from roots and stems of Tibetan medicinal plant Phlomis younghusbandii Mukerjee. These fungal isolates were molecularly identified based on ITS sequnces and 28S sequences distributed to 12 genera, including Phoma, Chaetosphaeronema, Fusarium and Leptosphaeria, etc. Among them, the dominant genus was Phoma. Extracts of all strains were evaluated for anti-HIV-1 integrase activity by using soluable integrase expressed in E. coli BL21 (DE3). The results showed that seven samples from five fungal endophytes PHY-24, PHY-38, PHY-40, PHY-51, PHY-53, which belonged to genus Chaetosphaeronema, inhibited strand transfer reaction catalyzed by HIV-1 integrase with IC50 values, of 6.60, 5.20, 2.86, 7.86, 4.47, 4.56 and 3.23 microg x mL(-1) respectively. In conclusion, the endophytic fungi of Phlomis younghusbandii Mukerjee are valuable for further screening anti-HIV-1 integrase agents.

  11. Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm

    Directory of Open Access Journals (Sweden)

    Jones Maureen

    2010-07-01

    Full Text Available Abstract Background At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1 infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. Results Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC50 was ≤ 3.5 (0.8-3.5% and the TC50 ≤ 6.3 (1.0-6.3%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice

  12. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate...

  13. Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Mimi Ghosh

    2010-06-01

    Full Text Available We investigated the impact of antimicrobials in cervicovaginal lavage (CVL from HIV(+ and HIV(- women on target cell infection with HIV. Since female reproductive tract (FRT secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+ and (- women inhibit HIV infection.CVL from 32 HIV(+ healthy women with high CD4 counts and 15 healthy HIV(- women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+ women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(- controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3alpha indicated that each was present in CVL from HIV(+ and HIV(- women. HBD2 and MIP3alpha correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+ women.These findings indicate that CVL from healthy HIV(+ and HIV(- women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

  14. Detection of anti-HIV-1 IgG antibodies in whole saliva by GACELISA and Western blot assays.

    Science.gov (United States)

    Matee, M I; Lyamuya, E F; Simon, E; Mbena, E C; Kagoma, C; Samaranayake, L P; Scheutz, F

    1996-05-01

    The present study, based on 158 HIV seropositives and 167 HIV seronegatives, demonstrates that saliva collected with the Omni-SAL device and tested with GACELISA (an IgG antibody capture ELISA) is an effective non-invasive alternative to serum for anti-HIV IgG antibody screening. The study also shows that a conventional serum Western blot kit can be used, with slight modifications, for confirmatory testing of saliva specimens. Collecting saliva with the Omni-SAL device had a very good acceptance rate among Tanzanian subjects, and although this diagnostic method is not yet known by the general public, 65% of the study participants preferred to give saliva instead of blood for HIV testing.

  15. Screening of anti-HIV-1 inophyllums by HPLC-DAD of Calophyllum inophyllum leaf extracts from French Polynesia Islands.

    Science.gov (United States)

    Laure, Frédéric; Raharivelomanana, Phila; Butaud, Jean-François; Bianchini, Jean-Pierre; Gaydou, Emile M

    2008-08-22

    Various pyranocoumarins, calophyllolide, inophyllums B, C, G(1), G(2) and P, from Calophyllum inophyllum (Clusiaceae) leaves of French Polynesia (Austral, Marquesas, Society and Tuamotu archipelagos) have been determined in 136 leaf extracts using a high pressure liquid chromatography-UV-diode array detection (HPLC-UV-DAD) technique. Results show a wide range in chemical composition within trees growing on eighteen islands. The use of multivariate statistical analyses (PCA) shows geographical distribution of inophyllums and indicate those rich in HIV-1 active (+)-inophyllums. Inophyllum B and P contents (0.0-39.0 and 0.0-21.8 mg kg(-1), respectively) confirm the chemodiversity of this species within the large area of French Polynesia. The study suggests the presence of interesting chemotypes which could be used as plant source for anti-HIV-1 drugs.

  16. Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

    Science.gov (United States)

    Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Preparation and characterization of anti-HIV nanodrug targeted to microfold cell of gut-associated lymphoid tissue.

    Science.gov (United States)

    Roy, Upal; Ding, Hong; Pilakka-Kanthikeel, Sudheesh; Raymond, Andrea D; Atluri, Venkata; Yndart, Adriana; Kaftanovskaya, Elena M; Batrakova, Elena; Agudelo, Marisela; Nair, Madhavan

    2015-01-01

    The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host-pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz (EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the GALT. In this work, we have exploited this paracellular transport property of M-cells for targeted delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell-specific antibodies to the GALT (nanodrug). Preliminary characterization showed that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index, and the zeta potential of the particles was -19.38±2.2 mV. Further, drug dissolution study has shown a significantly improved sustained release over free drugs. Binding potential of nanodrug with M-cell was also confirmed with fluorescence microscopy and in vitro uptake and release studies. The anti-HIV activity of the nanodrug was also significantly higher compared to that of free drug. This novel formulation was able to show sustained release of EFV and inhibit the HIV-1 infection in the GALT compared to the free drug. The present study has potential for our in vivo targeted nanodrug delivery system by combining traditional enteric-coated capsule technique via oral administration.

  18. Effects of crystalline state and self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of the novel anti-HIV compound 6-benzyl-1-benzyloxymethyl-5-iodouracil in rats.

    Science.gov (United States)

    Lu, Ying-Yuan; Dai, Wen-Bing; Wang, Xin; Wang, Xiao-Wei; Liu, Jun-Yi; Li, Pu; Lou, Ya-Qing; Lu, Chuang; Zhang, Qiang; Zhang, Guo-Liang

    2018-02-01

    The objective of this study was to investigate the effect of crystalline state and a formulation of self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor, in rats. The crystalline states of W-1 were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The SNEDDS was formulated by medium-chain lipids, characterized by droplet particle size. The plasma concentrations of W-1 were measured by high performance liquid chromatography (HPLC). The results indicated that W-1 compound were presented as crystalline forms, A and B, the degree of crystallization in form B was higher than that in form A. The SNEDDS of W-1 displayed a significant increase in the dissolution rate than W-1 powder. Furthermore, after oral administration of W-1 (100 mg/kg), the pharmacokinetic parameters of form A, form B, and W-1 SNEDDS were as follows: AUC 0-t 526.4 ± 123.5, 305.1 ± 58.5 and 2297 ± 451 ng h/mL (p < .05, when W-1 SNEDDS were compared with either form A or form B), respectively. With SNEDDS formulation, the relative bioavailabilities were enhanced by 4.36-fold and 7.53-fold over the form A and form B of W-1, respectively. In conclusion, the present results suggested that the crystalline states of W-1 might lead to the lower oral bioavailability, and SNEDDS formulation is a promising strategy of improving bioavailability, in spite of that crystalline states usually carry small lot-to-lot variability.

  19. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

    Directory of Open Access Journals (Sweden)

    Paolo Monini

    Full Text Available Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs. Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

  20. Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity.

    Science.gov (United States)

    Regina, Giuseppe La; Coluccia, Antonio; Piscitelli, Francesco; Bergamini, Alberto; Sinistro, Anna; Cavazza, Antonella; Maga, Giovanni; Samuele, Alberta; Zanoli, Samantha; Novellino, Ettore; Artico, Marino; Silvestri, Romano

    2007-10-04

    Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. These compounds were highly effective against the 112 and the AB1 strains in lymphocytes and inhibited at nanomolar concentration the multiplication of the IIIBBa-L strain in macrophages. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations.

  1. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study.

    Science.gov (United States)

    Porter, Danielle P; Daeumer, Martin; Thielen, Alexander; Chang, Silvia; Martin, Ross; Cohen, Cal; Miller, Michael D; White, Kirsten L

    2015-12-07

    At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  2. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

    Directory of Open Access Journals (Sweden)

    Danielle P. Porter

    2015-12-01

    Full Text Available At Week 96 of the Single-Tablet Regimen (STaR study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF developed resistance mutations compared to those treated with efavirenz (EFV/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33, as well as baseline samples from control subjects with virologic response (n = 118. Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20% were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  3. ANN multiscale model of anti-HIV drugs activity vs AIDS prevalence in the US at county level based on information indices of molecular graphs and social networks.

    Science.gov (United States)

    González-Díaz, Humberto; Herrera-Ibatá, Diana María; Duardo-Sánchez, Aliuska; Munteanu, Cristian R; Orbegozo-Medina, Ricardo Alfredo; Pazos, Alejandro

    2014-03-24

    This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration the social determinants and activity/structure of anti-HIV drugs in preclinical assays. We trained different Artificial Neural Networks (ANNs) using as input information indices of social networks and molecular graphs. We used a Shannon information index based on the Gini coefficient to quantify the effect of income inequality in the social network. We obtained the data on AIDS prevalence and the Gini coefficient from the AIDSVu database of Emory University. We also used the Balaban information indices to quantify changes in the chemical structure of anti-HIV drugs. We obtained the data on anti-HIV drug activity and structure (SMILE codes) from the ChEMBL database. Last, we used Box-Jenkins moving average operators to quantify information about the deviations of drugs with respect to data subsets of reference (targets, organisms, experimental parameters, protocols). The best model found was a Linear Neural Network (LNN) with values of Accuracy, Specificity, and Sensitivity above 0.76 and AUROC > 0.80 in training and external validation series. This model generates a complex network of AIDS prevalence in the US at county level with respect to the preclinical activity of anti-HIV drugs in preclinical assays. To train/validate the model and predict the complex network we needed to analyze 43,249 data points including values of AIDS prevalence in 2,310 counties in the US vs ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4,856 protocols, and 10 possible experimental measures.

  4. Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity

    OpenAIRE

    Peng, Chunte Sam; Fedeles, Bogdan I.; Singh, Vipender; Li, Deyu; Amariuta, Tiffany; Essigmann, John M.; Tokmakoff, Andrei

    2015-01-01

    The anti-HIV drug KP1212 was designed to intentionally increase the mutation rate of HIV, thereby causing viral population collapse. Its mutagenicity and thus antiviral activity was proposed to be the result of tautomerization. We used 2D IR spectroscopy to identify rapidly interconverting tautomers under physiological conditions. The traditionally rare enol–imino tautomer for nucleobases was found to be the major species for KP1212, providing a structural support for the tautomer hypothesis....

  5. Challenges in integrating component level technology and system level information from Ayurveda: Insights from NMR phytometabolomics and anti-HIV potential of select Ayurvedic medicinal plants.

    Science.gov (United States)

    Jayasundar, Rama; Ghatak, Somenath; Makhdoomi, Muzamil Ashraf; Luthra, Kalpana; Singh, Aruna; Velpandian, Thirumurthy

    2018-01-03

    Information from Ayurveda meeting the analytical challenges of modern technology is an area of immense relevance. Apart from the cerebral task of bringing together two different viewpoints, the question at the pragmatic level remains 'who benefits whom'. The aim is to highlight the challenges in integration of information (Ayurvedic) and technology using test examples of Nuclear Magnetic Resonance (NMR) metabolomics and anti-HIV-1 potential of select Ayurvedic medicinal plants. The other value added objective is implications and relevance of such work for Ayurveda. Six medicinal plants (Azadirachta indica, Tinospora cordifolia, Swertia chirata, Terminalia bellerica, Zingiber officinale and Symplocos racemosa) were studied using high resolution proton NMR spectroscopy based metabolomics and also evaluated for anti-HIV-1 activity on three pseudoviruses (ZM53 M.PB12, ZM109F.PB4, RHPA 4259.7). Of the six plants, T.bellerica and Z.officinale showed minimum cell cytotoxicity and maximum anti-HIV-1 potential. T.bellerica was effective against all the three HIV-1 pseudoviruses. Untargeted NMR profiling and multivariate analyses demonstrated that the six plants, all of which had different Ayurvedic pharmacological properties, showed maximum differences in the aromatic region of the spectra. The work adds onto the list of potential plants for anti-HIV-1 drug molecules. At the same time, it has drawn attention to the different perspectives of Ayurveda and Western medicine underscoring the inherent limitations of conceptual bilinguism between the two systems, especially in the context of medicinal plants. The study has also highlighted the potential of NMR metabolomics in study of plant extracts as used in Ayurveda. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  6. Attitudes toward Shock Advertising of Western-European and Serbian University Students With Regard To Public Health Context (Anti-Smoking and Anti-HIV/AIDS Campaigns)

    OpenAIRE

    Krstic, Tamara

    2007-01-01

    The main objective of this dissertation is to examine attitudes toward shock advertising of western-European and Serbian university students with regard to public health context (anti-smoking and anti-HIV/AIDS campaigns). Although the use of shock advertising is widely adopted in practice, there has not been extensive research with regard to this topic. Public health context is of special interest in this dissertation as there is an urge for social marketing on Serbian market. The results of ...

  7. Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

    Science.gov (United States)

    Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

    2014-04-01

    Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

  8. Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity.

    Science.gov (United States)

    Agrahari, Vivek; Meng, Jianing; Ezoulin, Miezan Jm; Youm, Ibrahima; Dim, Daniel C; Molteni, Agostino; Hung, Wei-Ting; Christenson, Lane K; Youan, Bi-Botti C

    2016-11-01

    To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission. A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized in vitro/in vivo. A triggered drug release (87% w/w) from the engineered HA-SH-NFs (mean diameter ∼75 nm) occured within 1 h under the influence of seminal hyaluronidase enzyme. HA-SH-NFs were noncytotoxic, induced no damage on the C57BL/6 mice genital-tract and other organs. No significant CD45 cell-infiltration and changes in cytokines level in cervicovaginal tissues were observed. HA-SH-NFs significantly enhanced both TFV retention and bioavailability in vaginal tissue compared with the 1% TFV-gel. The anti-HIV activity of TFV (on pseudotyped virus followed by luciferase assay) was not adversely affected by the electrospinning process. HA-SH-NFs developed in this study could potentially serve as a safe nanotemplate for topical intravaginal delivery of HIV/AIDS microbicides.

  9. Amperometric sensing of anti-HIV drug zidovudine on Ag nanofilm-multiwalled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Rafati, Amir Abbas, E-mail: aa_rafati@basu.ac.ir; Afraz, Ahmadreza

    2014-06-01

    The zidovudine (ZDV) is the first drug approved for the treatment of HIV virus infection. The detection and determination of this drug are very importance in human serum because of its undesirable effects. A new ZDV sensor was fabricated on the basis of nanocomposite of silver nanofilm (Ag-NF) and multiwalled carbon nanotubes (MWCNTs) immobilized on glassy carbon electrode (GCE). The modified electrodes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry (CV), and linear sweep voltammetry (LSV) techniques. Results showed that the electrodeposited silver has a nanofilm structure and further electrochemical studies showed that the prepared nanocomposite has high electrocatalytic activity and is appropriate for using in sensors. The amperometric technique under optimal conditions is used for the determination of ZDV ranging from 0.1 to 400 ppm (0.37 μM–1.5 mM) with a low detection limit of 0.04 ppm (0.15 μM) (S/N = 3) and good sensitivity. The prepared sensor possessed accurate and rapid response to ZDV and shows an average recovery of 98.6% in real samples. - Highlights: • New anti-HIV drug sensor was fabricated on the basis of nanomaterials composite. • The GCE modified by prepared hydrophilic MWCNT silver nanoparticles. • Silver nanofilm electrodeposited on MWCNT/GCE and characterized by SEM, EDX, CV and LSV • Response of electrode to ZDV was thoroughly investigated by electrochemical techniques.

  10. Electrochemical studies of nevirapine, an anti-HIV drug, and its assay in tablets and biological samples

    Directory of Open Access Journals (Sweden)

    JALDAPPAGARI SEETHARAMAPPA

    2012-06-01

    Full Text Available The electrochemical oxidation of nevirapine, an anti-HIV drug, at a glassy carbon electrode has been studied by voltammetric techniques. Nevirapine showed one well defined irreversible oxidation peak with a potential of 0.749 V in phosphate buffer at pH 10. The effects of different electrolytes, pH and scan rate on the electrochemical behaviour of nevira¬pine were examined to determine the optimum reaction conditions. The oxidation peak current was found to vary linearly with the concentration of nevirapine in the range of 5.0 – 350 µM. The limit of detection and limit of quantification values were calculated and found to be 1.026 µM and 3.420 µM, respectively. The low relative standard deviation values of inter-day and intra-day assays highlighted the good reproducibility of the proposed m¬ethod for assay of nevirapine. Further, a sensitive and accurate differential pulse voltammetric method was developed for the determination of nevirapine concentrations in pharma¬ceutical formulations.

  11. Short communication: Anti-HIV-1 envelope immunoglobulin Gs in blood and cervicovaginal samples of Beninese commercial sex workers.

    Science.gov (United States)

    Batraville, Laurie-Anne; Richard, Jonathan; Veillette, Maxime; Labbé, Annie-Claude; Alary, Michel; Guédou, Fernand; Kaufmann, Daniel E; Poudrier, Johanne; Finzi, Andrés; Roger, Michel

    2014-11-01

    Characterization of the immune correlates of protection against HIV infection is crucial for the development of preventive strategies. This study examined HIV-1 envelope (Env) glycoproteins, specifically immunoglobulin G (IgG), in systemic and mucosal compartments of female Beninese commercial sex workers (CSWs). Samples of 23 HIV-1-positive and 20 highly exposed HIV-1-seronegative (HESN) CSWs were studied. HIV-1 Env-specific IgG detection in sera and cervicovaginal lavages (CVLs) from the study population was done by cell-based ELISA. The HIV neutralizing activity was evaluated with a neutralization assay. The HIV-1-specific antibody-dependent cellular cytotoxicity (ADCC) response of the cohort was measured with a FACS-based assay evaluating the ADCC-mediated elimination of gp120-coated target cells. No anti-HIV-1 Env-specific IgG neutralizing or ADCC activities were detected in samples from HESN CSWs. Samples from HIV-1-infected CSWs presented ADCC activity in both sera and CVLs. Anti-Env IgG from sera and CVLs from HIV-1-infected CSWs preferentially recognized Env in its CD4-bound conformation. HIV-1-infected CSWs have ADCC-mediating IgG that preferentially recognizes Env in its CD4-bound conformation at the mucosal site.

  12. In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

    Science.gov (United States)

    Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

    2012-11-01

    In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

    Directory of Open Access Journals (Sweden)

    Min-Hsuan Lin

    Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

  14. Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success.

    Science.gov (United States)

    Pillay, Viness; Mashingaidze, Felix; Choonara, Yahya E; Du Toit, Lisa C; Buchmann, Eckhart; Maharaj, Vinesh; Ndesendo, Valence M K; Kumar, Pradeep

    2012-06-01

    The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal microenvironmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties. Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus-target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately. Copyright © 2012 Wiley Periodicals, Inc.

  15. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

    Directory of Open Access Journals (Sweden)

    Lucianna Helene Santos

    2015-11-01

    Full Text Available Reverse transcriptase (RT is a multifunctional enzyme in the human immunodeficiency virus (HIV-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

  16. Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism.

    Science.gov (United States)

    Moonsamy, Suri; Bhakat, Soumendranath; Soliman, Mahmoud E S

    2015-01-01

    The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (∼1.5 Å), per-residue fluctuation (∼2 Å), C-alpha deviations (∼2 Å) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target.

  17. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody.

    Directory of Open Access Journals (Sweden)

    Frank Sainsbury

    2010-11-01

    Full Text Available The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product.To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER. Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO cell-produced 2G12.Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for

  18. Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages

    Science.gov (United States)

    Vieira, Marcos C; Zinder, Daniel; Cobey, Sarah

    2018-01-01

    Abstract High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable “hotspot” motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations. During the response, loss of mutational hotspots and changes in their distribution across CDRs and FRs are predicted to compromise the adaptability of B-cell receptors, yet the contributions of different mechanisms to gains and losses of hotspots remain unclear. We reconstructed changes in anti-HIV B-cell receptor sequences and show that mutability losses were ∼56% more frequent than gains in both CDRs and FRs, with the higher relative mutability of CDRs maintained throughout the response. At least 21% of the total mutability loss was caused by synonymous mutations. However, nonsynonymous substitutions caused most (79%) of the mutability loss in CDRs. Because CDRs also show strong positive selection, this result suggests that selection for mutations that increase binding affinity contributed to loss of mutability in antigen-binding regions. Although recurrent adaptation to evolving viruses could indirectly select for high mutation rates, we found no evidence of indirect selection to increase or retain hotspots. Our results suggest mutability losses are intrinsic to both the neutral and adaptive evolution of B-cell populations and might constrain their adaptation to rapidly evolving pathogens such as HIV and influenza. PMID:29688540

  19. Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.

    Science.gov (United States)

    Dosenovic, Pia; Kara, Ervin E; Pettersson, Anna-Klara; McGuire, Andrew T; Gray, Matthew; Hartweger, Harald; Thientosapol, Eddy S; Stamatatos, Leonidas; Nussenzweig, Michel C

    2018-04-16

    The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.

  20. Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon

    Science.gov (United States)

    Akiyama, Hisashi; Ramirez, Nora-Guadalupe Pina; Gibson, Gregory; Kline, Christopher; Watkins, Simon; Ambrose, Zandrea

    2017-01-01

    ABSTRACT A hallmark of human immunodeficiency virus type 1 (HIV-1) infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein, CD169, as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4+ T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4+ T cells in trans and thus offset antiviral effects of type I IFN. In support of this hypothesis, infection of HIV-1 or murine leukemia virus Env (MLV-Env)-pseudotyped HIV-1 particles was enhanced in IFN-α-treated THP-1 monocytoid cells, and this enhancement was primarily dependent on CD169-mediated enhancement at the virus entry step, a phenomenon phenocopied in HIV-1 infections of IFN-α-treated primary monocyte-derived macrophages (MDMs). Furthermore, expression of CD169, a marker of type I IFN-induced immune activation in vivo, was enhanced in lymph nodes from pigtailed macaques infected with simian immunodeficiency virus (SIV) carrying HIV-1 reverse transcriptase (RT-SHIV), compared to uninfected macaques, and interestingly, there was extensive colocalization of p27gag and CD169, suggesting productive infection of CD169+ myeloid cells in vivo. While cell-free HIV-1 infection of IFN-α-treated CD4+ T cells was robustly decreased, initiation of infection in trans via coculture with CD169+ IFN-α-treated DCs restored infection, suggesting that HIV-1 exploits CD169 in cis and in trans to attenuate a type I IFN-induced antiviral state. IMPORTANCE HIV-1 infection in humans causes immune activation characterized by elevated levels of proinflammatory cytokines, including type I interferons (IFN

  1. Synthesis of highly anti-HIV active sulfated poly- and oligo-saccharides and analysis of their action mechanisms by NMR [nuclear magnetic resonance] spectroscopy

    International Nuclear Information System (INIS)

    Uryu, Toshiyuki

    1998-01-01

    We have been synthesizing sulfated polysaccharides and oligosaccharides with highly anti-HIV (human immunodeficiency virus) activities. It has been known that sulfated polysaccharides such as dextran sulfate and pentosan polysulfate have biological activities such as anticoagulant activity and recently anti-HIV activity. Curdlan sulfate having 1,3-β-linked glucan backbone had high anti-HIV activity but low anticoagulant activity. Phase I/II test for the curdlan sulfate as an AIDS (acquired immunodeficiency syndrome) drug was carried out in the United States. In this study, regioselectivity sulfatec curdlan sulfates were prepared in order to study effects of sulfate groups and conformation of curdlan sulfates. In addition, action mechanisms of curdlan sulfate as anti-AIDS drug and of heparin as an anticoagulant were examined by means of NMR spectroscopy. 1. Structure dependence of anti-HIV and anticoagulant activities of sulfated polysaccharides. Curdlan with M n 9000 was regioselectively sulfated on its hydroxyl groups at 6, 4, and 2 positions. Those were a curdlan sulfate 62S in which 100% of 6-OH, and about 50% of 2-OH was sulfated, a curdlan sulfate 42S in which 4- and 2-OH's were sulfated, and a curdlan sulfate in which 6, 4, and 2-OH's were partially sulfated. All curdlan sulfates had very high anti-HIV activities exhibited by the drug concentration of 50% inhibition of infection, i.e., EC 50 of 0.04 - 0.25 μg/mL. However, there was almost no difference in the activity among the samples. Therefore, it was revealed that the degree of sulfation and putative conformation of the curdlan sulfates but not the position of sulfate groups have large effects on the anti-HIV activity. On the other hand, the anticoagulant activity increased with increasing molecular weight of the curdlan sulfates. As a result, it is assumed that the size of reaction sites of the virus protein reacting with curdlan sulfate is different from that of the proteins related to anticoagulant

  2. Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.

    Science.gov (United States)

    Abdel-Motal, U M; Harbison, C; Han, T; Pudney, J; Anderson, D J; Zhu, Q; Westmoreland, S; Marasco, W A

    2014-09-01

    Topical microbicides are a leading strategy for prevention of HIV mucosal infection to women; however, numerous pharmacokinetic limitations associated with coitally related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques (Rh) can provide prolonged expression of b12 minibodies in the cervical-vaginal secretions. Gene transfer studies demonstrated that, of various green fluorescent protein (GFP)-expressing AAV serotypes, AAV-6 most efficiently transduced freshly immortalized and primary genital epithelial cells (PGECs) of female Rh in vitro. In addition, AAV-6-b12 minibody transduction of Rh PGECs led to inhibition of SHIV162p4 transmigration and virus infectivity in vitro. AAV-6-GFP could also successfully transduce vaginal epithelial cells of Rh when applied intravaginally, including p63+ epithelial stem cells. Moreover, intravaginal application of AAV-6-b12 to female Rh resulted in prolonged minibody detection in their vaginal secretions throughout the 79-day study period. These data provide proof of principle that AAV-6-mediated delivery of anti-HIV broadly neutralizing antibody (BnAb) genes to the lower genital tract of female Rh results in persistent minibody detection for several months. This strategy offers promise that an anti-HIV-1 genetic microbicide strategy may be possible in which topical application of AAV vector, with periodic reapplication as needed, may provide sustained local BnAb expression and protection.

  3. Fatores associados à submissão ao teste rápido anti-HIV na assistência ao parto

    Directory of Open Access Journals (Sweden)

    Maria Inês Couto de Oliveira

    Full Text Available Resumo Os testes rápidos anti-HIV vêm sendo empregados nas maternidades com vistas à prevenção da transmissão vertical. O objetivo do estudo foi analisar os fatores associados à submissão ao teste rápido anti-HIV (desfecho. Estudo transversal, conduzido em 2009, em 15 hospitais do SUS do Rio de Janeiro/RJ, mediante entrevista a amostra representativa de 835 parturientes internadas e consulta a prontuários. Razões de prevalência ajustadas foram obtidas por regressão de Poisson, segundo modelo hierarquizado, permanecendo no modelo final as variáveis associadas ao desfecho (p ≤ 0,05. Segundo os prontuários (SP, 79,6% das mães foram submetidas ao teste rápido anti-HIV e, segundo as entrevistas (SE, 55,7%. No nível distal, a ausência de companheiro (SP, ter ≥ 6 moradores na residência (SP e a cor da pele não branca (SE se associaram a uma maior prevalência do desfecho. No nível intermediário, não dispor de sorologia negativa para o HIV do pré-natal (SP e SE se associou a uma maior prevalência do desfecho, bem como a realização de pré-natal na rede básica (SP e a não realização de pré-natal (SE. No nível proximal, o parto em hospital não certificado como amigo da criança se associou a uma maior prevalência do desfecho (SP e SE.

  4. A realização do teste anti-hiv no pré-natal: os significados para a gestante

    OpenAIRE

    Silva, Roberta Maria de Oliveira; Araújo, Carla Luzia França; Paz, Fatima Maria Trigo da

    2008-01-01

    O estudo teve por objetivo conhecer e analisar o significado da realização do teste anti-HIV no pré-natal para as gestantes. Trata-se de uma pesquisa com abordagem qualitativa e foi realizada em um Hospital Escola e em uma Maternidade do município do Rio de Janeiro. Como recurso técnico-metodológico utilizou-se o discurso do sujeito coletivo (DSC). Após a análise dos discursos verificamos que para as gestantes a realização do teste significa a possibilidade de prevenir a transmissão vertical ...

  5. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  6. The distribution of the anti-HIV drug, 2'3'-dideoxycytidine (ddC), across the blood-brain and blood-cerebrospinal fluid barriers and the influence of organic anion transport inhibitors.

    Science.gov (United States)

    Gibbs, J E; Thomas, S A

    2002-02-01

    The brain and CSF distribution of the HIV reverse transcriptase inhibitor, 2'3'-dideoxycytidine (ddC), was investigated by the in situ brain perfusion and isolated incubated choroid plexus methods in the guinea pig. Multiple-time brain perfusions indicated that the distribution of [3H]ddC to the brain and CSF was low and the unidirectional rate constant (K(in)) for the brain uptake of this nucleoside analogue (0.52 +/- 0.10 microL/min/g) was not significantly different to that for the vascular marker, [14C]mannitol (0.44 +/- 0.09 microL/min/g). The influence of unlabelled ddC, six organic anion transport inhibitors and 3'-azido 3'-deoxythymidine (AZT) on the CNS uptake of [3H]ddC was examined in situ and in vitro. ddC, probenecid and 2,4-dichlorophenoxyacetic acid altered the distribution of [3H]ddC into the brain and choroid plexuses, indicating that the limited distribution of [3H]ddC was a result of an organic anion efflux transporter, in addition to the low lipophilicity of this drug (octanol-saline partition coefficient, 0.047 +/- 0.001). The CNS distribution was also sensitive to p-aminohippurate and deltorphin II, but not digoxin, suggesting the involvement of organic anion transporters (OAT1/OAT3-like) and organic anion transporting polypeptides (OATP1/OATPA-like). AZT did not effect the accumulation of [3H]ddC, indicating that when these nucleoside analogues are used in anti-HIV combination therapy, the CNS distribution of ddC is unchanged.

  7. Synthesis and anti-HIV activity of novel 3-substituted phenyl-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues.

    Science.gov (United States)

    Ali, Mohamed A; Ismail, Rusli; Choon, Tan S; Yoon, Yeong K; Wei, Ang C; Pandian, Suresh; Samy, Jeyabalan G; De Clercq, Eric; Pannecouque, Christophe

    2011-01-01

    A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.

  8. The offer of the anti-HIV test to the users of the health basic net units: different aproaches of professionals

    Directory of Open Access Journals (Sweden)

    Sergio Corrêa Marques

    2015-01-01

    Full Text Available Objetivos: identificar e descrever as condutas dos profissionais de saúde na oferta do teste anti-HIV; analisar as práticas dos profissionais a partir dos relatos das usuárias dos serviços da rede básica de saúde. Método: é um estudo descritivo, qualitativo, com 40 mulheres assistidas em 08 Centros Municipais de Saúde. Resultados: a produção discursiva das entrevistas foi submetida ao programa Alceste, constituindo duas categorias de análise. A primeira contempla as abordagens no atendimento individual na rede de CMS do Rio de Janeiro descrevendo os três modos de conduta dos profissionais de saúde durante a oferta de teste anti-HIV. A segunda categoria refere-se às abordagens no atendimento coletivo, onde se observa que as atividades de aconselhamento não ocorrem de maneira uniforme. Conclusão: que os resultados apontam para uma prática que se desvirtua do que vem sendo preconizado pelos Programas oficiais em relação ao Aconselhamento.

  9. FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

    Science.gov (United States)

    Alcolea Palafox, M.; Kattan, D.; Afseth, N. K.

    2018-04-01

    A theoretical and experimental vibrational study of the anti-HIV d4T (stavudine or Zerit) nucleoside analogue was carried out. The predicted spectra in the three most stable conformers in the biological active anti-form of the isolated state were compared. Comparison of the conformers with those of the natural nucleoside thymidine was carried out. The calculated spectra were scaled by using different scaling procedures and three DFT methods. The TLSE procedure leads to the lowest error and is thus recommended for scaling. With the population of these conformers the IR gas-phase spectra were predicted. The crystal unit cell of the different polymorphism forms of d4T were simulated through dimer forms by using DFT methods. The scaled spectra of these dimer forms were compared. The FT-IR spectrum was recorded in the solid state in the 400-4000 cm-1 range. The respective vibrational bands were analyzed and assigned to different normal modes of vibration by comparison with the scaled vibrational values of the different dimer forms. Through this comparison, the polymorphous form of the solid state sample was identified. The study indicates that d4T exist only in the ketonic form in the solid state. The results obtained were in agreement with those determined in related anti-HIV nucleoside analogues.

  10. Zirconium phosphatidylcholine-based nanocapsules as an in vivo degradable drug delivery system of MAP30, a momordica anti-HIV protein.

    Science.gov (United States)

    Caizhen, Guo; Yan, Gao; Ronron, Chang; Lirong, Yang; Panpan, Chu; Xuemei, Hu; Yuanbiao, Qiao; Qingshan, Li

    2015-04-10

    An essential in vivo drug delivery system of a momordica anti-HIV protein, MAP30, was developed through encapsulating in chemically synthesized matrices of zirconium egg- and soy-phosphatidylcholines, abbreviated to Zr/EPC and Zr/SPC, respectively. Matrices were characterized by transmission electron microscopy and powder X-ray diffractometry studies. Zr/EPC granule at an approximate diameter of 69.43±7.78 nm was a less efficient encapsulator than the granule of Zr/SPC. Interlayer spacing of the matrices encapsulating MAP30 increased from 8.8 and 9.7 Å to 7.4 and 7.9 nm, respectively. In vivo kinetics on degradation and protein release was performed by analyzing the serum sampling of intravenously injected SPF chickens. The first order and biphasic variations were obtained for in vivo kinetics using equilibrium dialysis. Antimicrobial and anti-HIV assays yielded greatly decreased MIC50 and EC50 values of nanoformulated MAP30. An acute toxicity of MAP30 encapsulated in Zr/EPC occurred at a single intravenous dose above 14.24 mg/kg bw in NIH/KM/ICR mice. The folding of MAP30 from Zr/EPC sustained in vivo chickens for more than 8 days in high performance liquid chromatography assays. These matrices could protect MAP30 efficiently with strong structure retention, lowered toxicity and prolonged in vivo life. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. One-by-one imprinting in two eccentric layers of hollow core-shells: Sequential electroanalysis of anti-HIV drugs.

    Science.gov (United States)

    Singh, Kislay; Jaiswal, Swadha; Singh, Richa; Fatma, Sana; Prasad, Bhim Bali

    2018-07-15

    Double layered one-by-one imprinted hollow core-shells@ pencil graphite electrode was fabricated for sequential sensing of anti-HIV drugs. For this, two eccentric layers were developed on the surface of vinylated silica nanospheres to obtain double layered one-by-one imprinted solid core-shells. This yielded hollow core-shells on treatment with hydrofluoric acid. The modified hollow core-shells (single layered dual imprinted) evolved competitive diffusion of probe/analyte molecules. However, the corresponding double layered one-by-one imprinted hollow core-shells (outer layer imprinted with Zidovudine, and inner layer with Lamivudine) were found relatively better owing to their bilateral diffusions into molecular cavities, without any competition. The entire work is based on differential pulse anodic stripping voltammetry at double layered one-by-one imprinted hollow core-shells. This resulted in indirect detection of electro inactive targets with limits of detection as low as 0.91 and 0.12 (aqueous sample), 0.94 and 0.13 (blood serum), and 0.99 and 0.20 ng mL -1 (pharmaceutics) for lamivudine and zidovudine, respectively in anti-HIV drug combination. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75

    International Nuclear Information System (INIS)

    Du Li; Zhao Yaxue; Chen, Jing; Yang Liumeng; Zheng Yongtang; Tang Yun; Shen Xu; Jiang Hualiang

    2008-01-01

    Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. Since LEDGF/p75 plays an important role in HIV integration, disruption of the LEDGF/p75 interaction with IN has provided a special interest for anti-HIV agent discovery. In this work, we reported that a benzoic acid derivative, 4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl) -1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)methyl]benzoic acid (D77) could potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution thus exhibiting antiretroviral activity. Molecular docking with site-directed mutagenesis analysis and surface plasmon resonance (SPR) binding assays has clarified possible binding mode of D77 against HIV-1 integrase. As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might supply useful structural information for further anti-HIV agent discovery

  13. FDA approves efavirenz. Food and Drug Administration.

    Science.gov (United States)

    Highleyman, L

    1998-10-01

    The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

  14. A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase - Structural and modeling insight into its functions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui-Guang [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States); Huang, Philip L. [American Biosciences, Boston, MA 02114 (United States); Zhang, Dawei; Sun, Yongtao [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States); Chen, Hao-Chia [Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 (United States); Zhang, John [Department of Chemistry, New York University, New York, NY 10003 (United States); Huang, Paul L. [Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114 (United States); Kong, Xiang-Peng, E-mail: xiangpeng.kong@med.nyu.edu [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States); Lee-Huang, Sylvia, E-mail: sylvia.lee-huang@med.nyu.edu [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States)

    2010-01-01

    We report here the high-resolution atomic structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5' overhanging adenosine ends, such as the 3'-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5' overhanging adenosine of the 3'-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third, GAP31 also removes the 5'-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA.

  15. In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.

    Science.gov (United States)

    Ndesendo, Valence M K; Choonara, Yahya E; Meyer, Leith C R; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

    2015-01-01

    The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.

  16. Genome-wide expression profiling analysis to identify key genes in the anti-HIV mechanism of CD4+ and CD8+ T cells.

    Science.gov (United States)

    Gao, Lijie; Wang, Yunqi; Li, Yi; Dong, Ya; Yang, Aimin; Zhang, Jie; Li, Fengying; Zhang, Rongqiang

    2018-07-01

    Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 + and CD8 + T cells. The numbers of CD4 + and CD8 + T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 + and CD8 + T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 + and CD8 + T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 + T cells counts and ratio of CD4 + /CD8 + T cells decreased while CD8 + T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 + and CD8 + T cells at acute and chronic stage with the criterial of P-value T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4 + T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4 + and CD8 + T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells. © 2018 Wiley Periodicals, Inc.

  17. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

    DEFF Research Database (Denmark)

    Worm, Signe Westring; Sabin, Caroline; Weber, Rainer

    2010-01-01

    BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients......% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI...

  18. Anti-staphylococcal, anti-HIV and cytotoxicity studies of four South African medicinal plants and isolation of bioactive compounds from Cassine transvaalensis (Burtt. Davy) codd.

    Science.gov (United States)

    Mthethwa, Ningy S; Oyedeji, Bola A O; Obi, Larry C; Aiyegoro, Olayinka A

    2014-12-18

    Medicinal plants represent an important opportunity to rural communities in Africa, as a source of affordable medicine and as a source of income. Increased patient awareness about safe usage is important as well as more training with regards to traditional medicine. The aim of this study was to evaluate the ethnomedicinal prowess of some indigenous South African plants commonly used in Eastern Cape Province of South Africa for the treatment of skin and respiratory tract infections, HIV and their toxicity potential. Cassine transvaalensis, Vangueria infausta, Croton gratissimus and Vitex ferruginea were tested for antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer disk diffusion and minimum inhibition concentration (MIC). Cytotoxic and anti-HIV-1 activities of plants were tested using MTT Assay (3- (Dimethylthiozole-2-yl-2,5-diphenyltetrazolium bromide)) and anti- HIV-1iib assay. In search of bioactive lead compounds, Cassine transvaalensis which was found to be the most active plant extract against the two Staphylocoous bacteria was subjected to various chromatographic. Thin layer chromatography, Column chromatography and Nuclear Magnetic Resonance (NMR), (1H-1H, 13C-13C, in DMSO_d6, Bruker 600 MHz) were used to isolate and characterize 3-Oxo-28-hydroxylbetuli-20(29)-ene and 3,28-dihydroxylbetuli-20(29)-ene bioactive compounds from C. transvaalensis. The four plants studied exhibited bioactive properties against the test isolates. The zones of inhibition ranged between 16 mm to 31 mm for multi-drug resistant staphylococci species. MIC values varied between 0.6 and 0.02 μg/ml. C. gratissimus and C. transvaalensis exhibited the abilities to inhibit HIV-1iib. Two bioactive compounds were isolated from C. transvaalensis. Data from this study reveals the use of these plant by traditional healers in the Eastern Cape. Furthermore, C. transvaalensis and C. gratissimus were found to be more active as against HIV-1iib

  19. Synthesis and Anti-HIV-1 Activity of New MKC-442 Analogues with an Alkynyl-Substituted 6-Benzyl Group

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo

    2007-01-01

    Synthesis and antiviral activities are reported of a series of 6-(3-alkynyl benzyl)-substituted analogues of MKC-442 (6-benzyl-1-(ethoxymethyl)-5-isopropyluracil), a highly potent agent against HIV. The 3-alkynyl group is assumed to give a better stacking of the substituted benzyl group to reverse...... transcriptase (RT) and this was believed to improve antiviral activity against HIV-1. The bromo derivatives, 5-alkyl-6-(3-bromo-benzyl)-1-ethoxymethyl derivatives 7a, b and 5-alkyl-6-(3-bromobenzyl)-1-allyloxymethyl derivatives 9a, b, showed activity against HIV on the same level as their corresponding...

  20. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  1. A realização do teste anti-hiv no pré-natal: os significados para a gestante El establecimiento de la lucha contra la prueba del vih en pre-navidad: significados para el embarazo The establishment of anti-hiv test in pre-natal: meanings for pregnancy

    Directory of Open Access Journals (Sweden)

    Roberta Maria de Oliveira Silva

    2008-12-01

    Full Text Available O estudo teve por objetivo conhecer e analisar o significado da realização do teste anti-HIV no pré-natal para as gestantes. Trata-se de uma pesquisa com abordagem qualitativa e foi realizada em um Hospital Escola e em uma Maternidade do município do Rio de Janeiro. Como recurso técnico-metodológico utilizou-se o discurso do sujeito coletivo (DSC. Após a análise dos discursos verificamos que para as gestantes a realização do teste significa a possibilidade de prevenir a transmissão vertical do HIV e como parte da assistência pré-natal. O pré-natal foi considerado pelas gestantes uma excelente oportunidade para a realização do teste anti HIV, para o conhecimento da condição sorológica e início precoce do tratamento. Conclui-se que o teste, para a maioria das gestantes, representa a possibilidade de proteger o filho do HIV, além de fazer parte da construção do papel materno a partir de um cuidado concreto com a saúde do bebê.El estudio que tenía para que el objetivo sepa y analice el significado de la realización del anti-VIH de la prueba en el prenatal para las mujeres embarazadas. Uno está sobre una investigación con acercamiento cualitativo y fue ejecutado en una escuela del hospital y una maternidad de la ciudad de Rio de Janeiro. Como recurso técnico-metodológico el discurso del ciudadano colectivo fue utilizado (DSC. Después de que el análisis de los discursos, nosotros verificamos que para las mujeres embarazadas la realización de la prueba significa la posibilidad para prevenir la transmisión vertical del VIH y como parte de la ayuda prenatal. El prenatal era considerado por las mujeres embarazadas una ocasión excelente para la realización del anti VIH de la prueba, para el conocimiento de la condición sorological y del principio precoz del tratamiento. Se concluye que la prueba, para la mayoría de las mujeres embarazadas, representa la posibilidad para proteger al hijo del VIH, más allá de ser

  2. Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein.

    Directory of Open Access Journals (Sweden)

    Ali Moghadam

    Full Text Available In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents.

  3. An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G.

    Science.gov (United States)

    Ejima, Tomohiko; Hirota, Mayuko; Mizukami, Tamio; Otsuka, Masami; Fujita, Mikako

    2011-10-01

    Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome. This finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that 5 µM SN-2 increases the expression of A3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. The proteasome inhibitor MG-132 increased the level of both A3G and Vif expression. These results demonstrate that A3G is ubiquitinated and degraded in the proteasome by a factor other than Vif, and that SN-2 selectively inhibits these processes. Furthermore, 5 µM SN-2 significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.

  4. Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

    Science.gov (United States)

    Pontikis, R; Benhida, R; Aubertin, A M; Grierson, D S; Monneret, C

    1997-06-06

    A series of 33 N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29 were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in which the N-1 side chain is rigidified by incorporation of an E-configured double bond, were obtained by palladium(0)-catalyzed coupling of several different 6-(arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13, 40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side chain, were found to be more potent than the known diphenyl-substituted HEPT analog BPT (2), two of them, 40c,d, being 10-fold more active.

  5. Formação, práticas e trajetórias de aconselhadores de centros de testagem anti-HIV do Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Claudia Mora

    2015-12-01

    Full Text Available Perante a importância do aconselhamento na testagem anti-HIV, analisamos as diretrizes institucionais, as competências privilegiadas no treinamento profissional e os saberes/práticas de aconselhadores. Trata-se de estudo qualitativo centrado na análise documental, observação e entrevista com aconselhadores de Centros de Testagem e Aconselhamento (CTA do estado do Rio de Janeiro. A análise foi orientada pela teoria de Pierre Bourdieu. Foi evidenciado que o habitus profissional dos aconselhadores resulta da articulação dos treinamentos, da graduação e de experiências e interesses pessoais. A operacionalização de competências, como a escuta ativa, é limitada pela rotina dos serviços e escassez de espaços de reflexão. Para incrementar a prática do aconselhamento, é importante desenvolver competências no treinamento, manter a educação continuada e fazer adequações na rotina do serviço. Tais ajustes podem fortalecer a passagem das diretrizes à ação e o aprimoramento da organização e gestão dos CTA.

  6. High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents

    Science.gov (United States)

    Malik, Ruchi; Bunkar, Devendra; Choudhary, Bhanwar Singh; Srivastava, Shubham; Mehta, Pakhuri; Sharma, Manish

    2016-10-01

    Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses. Several endogenous peptides present in semen, including a 39-amino acid fragments of prostatic acid phosphatase (PAP248-286) assemble into amyloid fibrils named as semen-derived enhancer of viral infection (SEVI) that promote virion attachment to target cells which dramatically enhance HIV virus infection by up to 105-fold. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound, is the major catechin found in green tea which disaggregates existing SEVI fibers, and inhibits the formation of SEVI fibers. The aim of this study was to screen a number of relevant polyphenols to develop a rational approach for designing PAP248-286 aggregation inhibitors as potential anti-HIV agents. The molecular docking based virtual screening results showed that polyphenolic compounds 2-6 possessed good docking score and interacted well with the active site residues of PAP248-286. Amino acid residues of binding site namely; Lys255, Ser256, Leu258 and Asn265 are involved in binding of these compounds. In silico ADMET prediction studies on these hits were also found to be promising. Polyphenolic compounds 2-6 identified as hits may act as novel leads for inhibiting aggregation of PAP248-286 into SEVI.

  7. Reverse Algols

    Science.gov (United States)

    Leung, K. C.

    1989-01-01

    Reverse Algols, binary systems with a semidetached configuration in which the more massive component is in contact with the critical equipotential surface, are examined. Observational evidence for reverse Algols is presented and the parameters of seven reverse Algols are listed. The evolution of Algols and reverse Algols is discussed. It is suggested that, because reverse Algols represent the premass-reversal semidetached phase of close binary evolution, the evolutionary time scale between regular and reverse Algols is the ratio of the number of confirmed systems of these two Algol types.

  8. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens D; Pedersen, Court

    2003-01-01

    BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ... the long-term consequences of triple class HAART regimens, including the development of broad drug resistance....

  9. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  10. Aconselhamento pós-teste anti-HIV: análise à luz de uma teoria humanística de Enfermagem Consejería pós test Anti-HIV: análisis a luz de una teoría humanistica de enfermería Anti-HIV after-test counselling: analysis at a light of a Nursing humanistic theory

    Directory of Open Access Journals (Sweden)

    Maria Alix Leite Araújo

    2006-12-01

    Full Text Available Este trabalho analisa o aconselhamento pós-teste anti-HIV em Unidades Básicas de Saúde. Trata-se de um estudo qualitativo desenvolvido em Unidades Básicas de Saúde da Família de Fortaleza (UBASF. O trabalho de campo ocorreu pela observação do atendimento de 12 enfermeiros em consultas de pré-natal. O referencial teórico de análise foi a Teoria Humanística de Enfermagem de Paterson e Zderad visto que a Enfermagem, segundo a teoria, implica um tipo especial de encontro entre seres humanos. A análise baseou-se no conceito de diálogo, tendo como variáveis seus elementos estruturais: o encontro, o relacionamento, a presença e o chamado, e a resposta. Observou-se que a assistência às gestantes não atingiu o relacionamento EU-TU, ou seja, o relacionamento sujeito-sujeito, com a presença do diálogo genuíno. Prevaleceu o relacionamento EU-ISSO, sujeito-objeto. As consultas eram rápidas e puramente mecânicas, levando esses profissionais, em certos momentos, a fugirem de uma assistência humanizada.Este trabajo analiza el pos test de consejería anti-HIV en las Unidades Básicas de Salud. Es un estudio cualitativo desarrollado en las Unidades Básicas de Salud de la Familia en la ciudad de Fortaleza (UBASF. El trabajo de campo sucedió por la observación de la asistencia de 12 enfermeros en las consultas de pré-natal. El referencial teórico de análisis fué la Teoría Humanistica de Paterson y Zderad de Enfermería, visto en la enfermería, según la teoría, implica en un tipo especial de encuentro entre los seres humanos. El análisis era basado en el concepto de diálogo, teniendo como las variables sus elementos estructurales: el encuentro, la relación, la presencia y el llamamiento y la respuesta. Fue observado que la ayuda a la embarazada no alcanzó la relación YO-USTED, en otros términos, el sujeto-sujeto de la relación, con la presencia del diálogo auténtico. La relación que prevaleció era el YO-AQUEL, sujeto

  11. Developing a community-level anti-HIV/AIDS stigma and homophobia intervention in new York city: The project CHHANGE model.

    Science.gov (United States)

    Frye, Victoria; Paige, Mark Q; Gordon, Steven; Matthews, David; Musgrave, Geneva; Kornegay, Mark; Greene, Emily; Phelan, Jo C; Koblin, Beryl A; Taylor-Akutagawa, Vaughn

    2017-08-01

    HIV/AIDS stigma and homophobia are associated with significant negative health and social outcomes among people living with HIV/AIDS (PLWHA) and those at risk of infection. Interventions to decrease HIV stigma have focused on providing information and education, changing attitudes and values, and increasing contact with people living with HIV/AIDS (PLWHA), activities that act to reduce stereotyped beliefs and prejudice, as well as acts of discrimination. Most anti-homophobia interventions have focused on bullying reduction and have been implemented at the secondary and post-secondary education levels. Few interventions address HIV stigma and homophobia and operate at the community level. Project CHHANGE, Challenge HIV Stigma and Homophobia and Gain Empowerment, was a community-level, multi-component anti-HIV/AIDS stigma and homophobia intervention designed to reduce HIV stigma and homophobia thus increasing access to HIV prevention and treatment access. The theory-based intervention included three primary components: workshops and trainings with local residents, businesses and community-based organizations (CBO); space-based events at a CBO-partner drop-in storefront and "pop-up" street-based events and outreach; and a bus shelter ad campaign. This paper describes the intervention design process, resultant intervention and the study team's experiences working with the community. We conclude that CHHANGE was feasible and acceptable to the community. Promoting the labeling of gay and/or HIV-related "space" as a non-stigmatized, community resource, as well as providing opportunities for residents to have contact with targeted groups and to understand how HIV stigma and homophobia relate to HIV/AIDS prevalence in their neighborhood may be crucial components of successful anti-stigma and discrimination programming. Copyright © 2017. Published by Elsevier Ltd.

  12. An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rγnull mice allows HIV replication and development of anti-HIV immune responses.

    Directory of Open Access Journals (Sweden)

    Maneesh Singh

    Full Text Available Cord blood hematopoietic progenitor cells (CB-HPCs transplanted immunodeficient NOD/LtsZ-scidIL2Rγ(null (NSG and NOD/SCID/IL2Rγ(null (NOG mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

  13. [Computational prediction of human immunodeficiency resistance to reverse transcriptase inhibitors].

    Science.gov (United States)

    Tarasova, O A; Filimonov, D A; Poroikov, V V

    2017-10-01

    Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and leads to over one million of deaths annually. Highly active antiretroviral treatment (HAART) is a gold standard in the HIV/AIDS therapy. Nucleoside and non-nucleoside inhibitors of HIV reverse transcriptase (RT) are important component of HAART, but their effect depends on the HIV susceptibility/resistance. HIV resistance mainly occurs due to mutations leading to conformational changes in the three-dimensional structure of HIV RT. The aim of our work was to develop and test a computational method for prediction of HIV resistance associated with the mutations in HIV RT. Earlier we have developed a method for prediction of HIV type 1 (HIV-1) resistance; it is based on the usage of position-specific descriptors. These descriptors are generated using the particular amino acid residue and its position; the position of certain residue is determined in a multiple alignment. The training set consisted of more than 1900 sequences of HIV RT from the Stanford HIV Drug Resistance database; for these HIV RT variants experimental data on their resistance to ten inhibitors are presented. Balanced accuracy of prediction varies from 80% to 99% depending on the method of classification (support vector machine, Naive Bayes, random forest, convolutional neural networks) and the drug, resistance to which is obtained. Maximal balanced accuracy was obtained for prediction of resistance to zidovudine, stavudine, didanosine and efavirenz by the random forest classifier. Average accuracy of prediction is 89%.

  14. Reverse Osmosis

    Indian Academy of Sciences (India)

    many applications, one of which is desalination of seawater. The inaugural Nobel Prize in Chemistry was awarded in 1901 to van 't Hoff for his seminal work in this area. The present article explains the principle of osmosis and reverse osmosis. Osmosis and Reverse Osmosis. As the name suggests, reverse osmosis is the ...

  15. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

    DEFF Research Database (Denmark)

    De Wit, Stephane; Sabin, Caroline A; Weber, Rainer

    2008-01-01

    OBJECTIVE: The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated...... with the onset of diabetes, and to identify possible mechanisms for any relationships found. RESEARCH DESIGN AND METHODS: D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes...

  16. Aconselhamento em DST/Aids às gestantes que realizaram o teste anti-HIV na admissão para o parto: os sentidos de uma prática

    Directory of Open Access Journals (Sweden)

    Patrícia de Lima Fonseca

    Full Text Available Foram analisadas as práticas e os sentidos do aconselhamento para gestantes submetidas ao teste anti-HIV na admissão para o parto, e para profissionais de saúde que atuam na assistência à maternidade em Salvador, Brasil. Foi realizado um estudo qualitativo em uma maternidade, com observação participante e entrevistas semiestruturadas com 13 puérperas sem diagnóstico prévio para o HIV e sete profissionais de saúde. Observou-se que o exame anti-HIV é realizado de forma compulsória, sem considerar a autonomia da gestante, e que o aconselhamento se limita a informar o diagnóstico e dar orientações no pós-teste somente àquelas cujos resultados foram positivos. Os sentidos que permeiam o exame, assim como o entendimento da experiência e os significados construídos pelas puérperas, sobretudo quando se descobrem positivas para o HIV, não são abordados pelos profissionais, que não se sentem capacitados para acolherem a subjetividade das pacientes.

  17. Aconselhamento em DST/Aids às gestantes que realizaram o teste anti-HIV na admissão para o parto: os sentidos de uma prática

    Directory of Open Access Journals (Sweden)

    Patrícia de Lima Fonseca

    2012-06-01

    Full Text Available Foram analisadas as práticas e os sentidos do aconselhamento para gestantes submetidas ao teste anti-HIV na admissão para o parto, e para profissionais de saúde que atuam na assistência à maternidade em Salvador, Brasil. Foi realizado um estudo qualitativo em uma maternidade, com observação participante e entrevistas semiestruturadas com 13 puérperas sem diagnóstico prévio para o HIV e sete profissionais de saúde. Observou-se que o exame anti-HIV é realizado de forma compulsória, sem considerar a autonomia da gestante, e que o aconselhamento se limita a informar o diagnóstico e dar orientações no pós-teste somente àquelas cujos resultados foram positivos. Os sentidos que permeiam o exame, assim como o entendimento da experiência e os significados construídos pelas puérperas, sobretudo quando se descobrem positivas para o HIV, não são abordados pelos profissionais, que não se sentem capacitados para acolherem a subjetividade das pacientes.

  18. 1,4-Bis(5-(naphthalen-1-yl)thiophen-2-yl)naphthalene, a small molecule, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular Lens epithelium-derived growth factor.

    Science.gov (United States)

    Gu, Wan-gang; Ip, Denis Tsz-Ming; Liu, Si-jie; Chan, Joseph H; Wang, Yan; Zhang, Xuan; Zheng, Yong-tang; Wan, David Chi-Cheong

    2014-04-25

    Translocation of viral integrase (IN) into the nucleus is a critical precondition of integration during the life cycle of HIV, a causative agent of Acquired Immunodeficiency Syndromes (AIDS). As the first discovered cellular factor to interact with IN, Lens epithelium-derived growth factor (LEDGF/p75) plays an important role in the process of integration. Disruption of the LEDGF/p75-IN interaction has provided a great interest for anti-HIV agent discovery. In this work, we reported that one small molecular compound, 1,4-bis(5-(naphthalen-1-yl)thiophen-2-yl)naphthalene(Compound 15), potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution at 1 μM. The putative binding mode of Compound 15 was constructed by a molecular docking simulation to provide structural insights into the ligand-binding mechanism. Compound 15 suppressed viral replication by measuring p24 antigen production in HIV-1IIIB acute infected C8166 cells with EC50 value of 11.19 μM. Compound 15 might supply useful structural information for further anti-HIV agent discovery. Copyright © 2014. Published by Elsevier Ireland Ltd.

  19. The history of antiretrovirals: key discoveries over the past 25 years.

    Science.gov (United States)

    De Clercq, Erik

    2009-09-01

    Within 25 years after zidovudine (3'-azido-2',3'-dideoxythymidine, AZT) was first described as an inhibitor of HIV replication, 25 anti-HIV drugs have been formally approved for clinical use in the treatment of HIV infections: seven nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; one nucleotide reverse transcriptase inhibitor (NtRTI): tenofovir [in its oral prodrug form: tenofovir disoproxil fumarate (TDF)]; four non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine, efavirenz and etravirine; ten protease inhibitors (PIs): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir; one fusion inhibitor (FI): enfuvirtide; one co-receptor inhibitor (CRI): maraviroc and one integrase inhibitor (INI): raltegravir. These compounds are used in various drug combination (some at fixed dose) regimens so as to achieve the highest possible benefit and tolerability, and to diminish the risk of virus-drug resistance development. (c) 2009 John Wiley & Sons, Ltd.

  20. Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    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

    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.

  1. Antitumor effect of combination of the inhibitors of two new oncotargets: proton pumps and reverse transcriptase.

    Science.gov (United States)

    Lugini, Luana; Sciamanna, Ilaria; Federici, Cristina; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Fais, Stefano

    2017-01-17

    Tumor therapy needs new approaches in order to improve efficacy and reduce toxicity of the current treatments. The acidic microenvironment and the expression of high levels of endogenous non-telomerase reverse transcriptase (RT) are common features of malignant tumor cells. The anti-acidic proton pump inhibitor Lansoprazole (LAN) and the non-nucleoside RT inhibitor Efavirenz (EFV) have shown independent antitumor efficacy. LAN has shown to counteract drug tumor resistance. We tested the hypothesis that combination of LAN and EFV may improve the overall antitumor effects. We thus pretreated human metastatic melanoma cells with LAN and then with EFV, both in 2D and 3D spheroid models. We evaluated the treatment effect by proliferation and cell death/apoptosis assays in classical and in pulse administration experiments. The action of EFV was negatively affected by the tumor microenvironmental acidity, and LAN pretreatment overcame the problem. LAN potentiated the cytotoxicity of EFV to melanoma cells and, when administered during the drug interruption period, prevented the replacement of tumor cell growth.This study supports the implementation of the current therapies with combination of Proton Pumps and Reverse Transcriptase inhibitors.

  2. Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kamata, Masakazu, E-mail: masa3k@ucla.edu [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Kim, Patrick Y. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ng, Hwee L. [Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O' Connor, Sean [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Yang, Otto O. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States); AIDS Healthcare Foundation, Los Angeles, CA (United States); Chen, Irvin S.Y. [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States)

    2015-07-31

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.

  3. Ectopic expression of anti-HIV-1 shRNAs protects CD8+ T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    International Nuclear Information System (INIS)

    Kamata, Masakazu; Kim, Patrick Y.; Ng, Hwee L.; Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O'Connor, Sean; Yang, Otto O.; Chen, Irvin S.Y.

    2015-01-01

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8 + T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8 + T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8 + T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24 Gag in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8 + T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8 + T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8 + T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8 + T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8 + T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8 + T cells from HIV-1 infection suppresses its cytopathic effect

  4. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study)

    DEFF Research Database (Denmark)

    Worm, Signe W; De Wit, Stephane; Weber, Rainer

    2009-01-01

    of DM and preexisting CHD on the development of a new CHD episode among 33,347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). METHODS AND RESULTS: Over 159,971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV...... transmission, ethnicity, family history of CHD, smoking, and calendar year, the rate of a CHD episode was 7.52 times higher (Poisson regression, 95% CI 6.02 to 9.39, P=0.0001) in those with preexisting CHD than in those without preexisting CHD, but it was only 2.41 times higher (95% CI 1.91 to 3.05, P=0...

  5. Development and validation of reversed-phase HPLC gradient method for the estimation of efavirenz in plasma.

    Directory of Open Access Journals (Sweden)

    Shweta Gupta

    Full Text Available Efavirenz is an anti-viral agent of non-nucleoside reverse transcriptase inhibitor category used as a part of highly active retroviral therapy for the treatment of infections of human immune deficiency virus type-1. A simple, sensitive and rapid reversed-phase high performance liquid chromatographic gradient method was developed and validated for the determination of efavirenz in plasma. The method was developed with high performance liquid chromatography using Waters X-Terra Shield, RP18 50 x 4.6 mm, 3.5 μm column and a mobile phase consisting of phosphate buffer pH 3.5 and Acetonitrile. The elute was monitored with the UV-Visible detector at 260 nm with a flow rate of 1.5 mL/min. Tenofovir disoproxil fumarate was used as internal standard. The method was validated for linearity, precision, accuracy, specificity, robustness and data obtained were statistically analyzed. Calibration curve was found to be linear over the concentration range of 1-300 μg/mL. The retention times of efavirenz and tenofovir disoproxil fumarate (internal standard were 5.941 min and 4.356 min respectively. The regression coefficient value was found to be 0.999. The limit of detection and the limit of quantification obtained were 0.03 and 0.1 μg/mL respectively. The developed HPLC method can be useful for quantitative pharmacokinetic parameters determination of efavirenz in plasma.

  6. Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre-exposure prophylaxis in colon and vagina tissues.

    Science.gov (United States)

    To, Elaine E; Hendrix, Craig W; Bumpus, Namandjé N

    2013-10-01

    Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Natural Plant Alkaloid (Emetine Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity

    Directory of Open Access Journals (Sweden)

    Ana Luiza Chaves Valadão

    2015-06-01

    Full Text Available Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V. Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.

  8. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  9. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Francesca Carlini

    Full Text Available BACKGROUND: Transposable Elements (TEs comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1 and Human Endogenous Retroviruses (HERVs that code for their own endogenous reverse transcriptase (RT. Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC, a nucleoside reverse transcription inhibitor (NRTI, on PC3 and LNCaP prostate cancer cell lines. PRINCIPAL FINDINGS: ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. CONCLUSIONS: Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications.

  10. Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strains.

    Science.gov (United States)

    Mai, Antonello; Artico, Marino; Rotili, Dante; Tarantino, Domenico; Clotet-Codina, Imma; Armand-Ugón, Mercedes; Ragno, Rino; Simeoni, Silvia; Sbardella, Gianluca; Nawrozkij, Maxim B; Samuele, Alberta; Maga, Giovanni; Esté, José A

    2007-11-01

    Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, we report here the synthesis and biological evaluation of a novel series of DABOs bearing a N,N-disubstituted amino group or a cyclic amine at the pyrimidine-C2 position, a hydrogen atom or a small alkyl group at C5 and/or at the benzylic position, and the favorable 2,6-difluorobenzyl moiety at the C6 position (F2-N,N-DABOs). The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. Such derivatives were more potent than S-DABOs, NH-DABOs, and nevirapine and efavirenz were chosen as reference drugs. The higher inhibitor adaptability to the HIV-1 RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs.

  11. Crystallographic Study of a Novel Sub-Nanomolar Inhibitor Provides Insight on the Binding Interactions of Alkenyldiarylmethanes with Human Immunodeficiency Virus-1 (HIV-1) Reverse Transcriptase†

    Science.gov (United States)

    Cullen, Matthew D.; Ho, William C.; Bauman, Joseph D.; Das, Kalyan; Arnold, Eddy; Hartman, Tracy L.; Watson, Karen M.; Buckheit, Robert W.; Pannecouque, Christophe; De Clercq, Erik; Cushman, Mark

    2009-01-01

    Two crystal structures have been solved for separate complexes of alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors (NNRTI) 3 and 4 with HIV-1 reverse transcriptase (RT). The structures reveal inhibitor binding is exclusively hydrophobic in nature and the shape of the inhibitor-bound NNRTI binding pocket is unique among other reported inhibitor-RT crystal structures. Primarily, ADAMs 3 and 4 protrude from a large gap in the backside of the binding pocket, placing portions of the inhibitors unusually close to the polymerase active site and allowing 3 to form a weak hydrogen bond with Lys223. The lack of additional stabilizing interactions, beyond the observed hydrophobic surface contacts, between 4 and RT is quite perplexing given the extreme potency of the compound (IC50 ≤ nM). ADAM 4 was designed to be hydrolytically stable in blood plasma, and an investigation of its hydrolysis in rat plasma demonstrated it has a significantly prolonged half-life in comparison to ADAM lead compounds 1 and 2. PMID:19775161

  12. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  13. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  14. Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide.

    Science.gov (United States)

    Woolfson, A David; Malcolm, R Karl; Morrow, Ryan J; Toner, Clare F; McCullagh, Stephen D

    2006-11-15

    TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients

  15. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  16. Tubal Ligation Reversal

    Science.gov (United States)

    ... seal off the fallopian tubes, such as the Essure or Adiana systems, generally aren't reversible. Why ... electrocautery). Some types of sterilization, such as the Essure or Adiana systems, aren't considered reversible. Risks ...

  17. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  18. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591: a novel HIV-1 reverse transcriptase translocation inhibitor.

    Science.gov (United States)

    Markowitz, Martin; Sarafianos, Stefan G

    2018-07-01

    4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a nucleoside reverse transcriptase inhibitor (NRTI) with a novel mechanism of action, unique structure, and amongst NRTIs, unparalleled anti-HIV-1 activity. We will summarize its structure and function, antiviral activity, resistance profile, and potential as an antiretroviral for use in the treatment and preexposure prophylaxis of HIV-1 infection. EFdA is active against wild-type (EC50 as low as 50 pmol/l) and most highly NRTI-resistant viruses. The active metabolite, EFdA-triphosphate, has been shown to have a prolonged intracellular half-life in human and rhesus (Rh) blood cells. As a result, single drug doses tested in simian immunodeficiency virus mac251-infected Rh macaques and HIV-1-infected individuals exhibited robust antiviral activity of 7-10 days duration. Preclinical studies of EFdA as preexposure prophylaxis in the Rh macaque/simian/human immunodeficiency virus low-dose intrarectal challenge model have shown complete protection when given in clinically relevant doses. EFdA is a novel antiretroviral with activity against both wild-type and NRTI-resistant viruses. As a result of the prolonged intracellular half-life of its active moiety, it is amenable to flexibility in dosing of at least daily to weekly and perhaps longer.

  19. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow...... operators. Reversible flowcharts are r- Turing-complete, meaning that they can simuluate reversible Turing machines without garbage data. We also demonstrate the injectivization of classical flowcharts into reversible flowcharts. The reversible flowchart computation model provides a theoretical...

  20. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  1. Reversibility of female sterilization.

    Science.gov (United States)

    Siegler, A M; Hulka, J; Peretz, A

    1985-04-01

    The discussion considers the current status of reversibility of sterilization in the US and describes clinical and experimental efforts for developing techniques designed for reversibility. It focuses on regret following sterilization, reversal potential of current sterilization techniques, patient selection, current reversal techniques, results of sterilization procedures, experimental approaches to reversal of current techniques of sterilization, and sterilization procedures devised for reversibility, in humans and in animals. Request is the 1st stage of reversal, but a request for sterilization reversal (SR) does not always mean regret for a decision made at the time. Frequently it is a wish to restore fertility because life circumstances have changed after a sterilization that was ppropriate at the time it was performed. Schwyhart and Kutner reviewed 22 studies published between 1949-69 in which they found that the percentage of patients regretting the procedure ranged from 1.3-15%. Requests for reversal remain low in most countries, but if sterilization becomes a more popular method of contraception, requests will also increase. The ideal operation considered as a reversaible method of sterilization should include an easy, reliable outpatient method of tubal occlusion with miniml risk or patient discomfort that subsequently could be reversed without the need for a major surgical intervention. Endoscopic methods have progressed toward the 1st objective. A recent search of the literature uncovered few series of SR of more than 50 cases. The 767 operations found were analyzed with regard to pregnancy outcome. The precent of live births varied from 74-78.8%, and the occurance of tubal pregnancies ranged from 1.7-6.5%. All of the confounding variables in patient selection and small numbers of reported procedures preclude any conclusion about the different techniques or the number of operations that give a surgeon a level of expertise. Few authors classify their

  2. Quantum reverse hypercontractivity

    Energy Technology Data Exchange (ETDEWEB)

    Cubitt, Toby [Department of Computer Science, University College London, London, United Kingdom and Centre for Quantum Information and Foundations, DAMTP, University of Cambridge, Cambridge (United Kingdom); Kastoryano, Michael [NBIA, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Montanaro, Ashley [School of Mathematics, University of Bristol, Bristol (United Kingdom); Temme, Kristan [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  3. Atrioventricular Pacemaker Lead Reversal

    Directory of Open Access Journals (Sweden)

    Mehmet K Aktas, MD

    2007-01-01

    Full Text Available During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal.

  4. An algebra of reversible computation.

    Science.gov (United States)

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  5. Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE.

    Science.gov (United States)

    Van Eygen, Veerle; Thys, Kim; Van Hove, Carl; Rimsky, Laurence T; De Meyer, Sandra; Aerssens, Jeroen; Picchio, Gaston; Vingerhoets, Johan

    2016-05-01

    Minority variants (1.0-25.0%) were evaluated by deep sequencing (DS) at baseline and virological failure (VF) in a selection of antiretroviral treatment-naïve, HIV-1-infected patients from the rilpivirine ECHO/THRIVE phase III studies. Linkage between frequently emerging resistance-associated mutations (RAMs) was determined. DS (llIumina®) and population sequencing (PS) results were available at baseline for 47 VFs and time of failure for 48 VFs; and at baseline for 49 responders matched for baseline characteristics. Minority mutations were accurately detected at frequencies down to 1.2% of the HIV-1 quasispecies. No baseline minority rilpivirine RAMs were detected in VFs; one responder carried 1.9% F227C. Baseline minority mutations associated with resistance to other non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 8/47 VFs (17.0%) and 7/49 responders (14.3%). Baseline minority nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs M184V and L210W were each detected in one VF (none in responders). At failure, two patients without NNRTI RAMs by PS carried minority rilpivirine RAMs K101E and/or E138K; and five additional patients carried other minority NNRTI RAMs V90I, V106I, V179I, V189I, and Y188H. Overall at failure, minority NNRTI RAMs and NRTI RAMs were found in 29/48 (60.4%) and 16/48 VFs (33.3%), respectively. Linkage analysis showed that E138K and K101E were usually not observed on the same viral genome. In conclusion, baseline minority rilpivirine RAMs and other NNRTI/NRTI RAMs were uncommon in the rilpivirine arm of the ECHO and THRIVE studies. DS at failure showed emerging NNRTI resistant minority variants in seven rilpivirine VFs who had no detectable NNRTI RAMs by PS. © 2015 Wiley Periodicals, Inc.

  6. Sex reversal in vertebrates

    OpenAIRE

    2016-01-01

    This special topic issue of Sexual Development gives an overview of sex reversal in vertebrates, from fishes naturally changing their sex, to rodents escaping the mammalian SRY-determining system. It offers eight up-to-date reviews on specific subjects in sex reversal, considering fishes, amphibians, reptiles, birds, marsupials, and placental mammals, including humans. The broad scope of represented animals makes this ideal for students and researchers, especially those interested in the...

  7. On thermodynamic and microscopic reversibility

    International Nuclear Information System (INIS)

    Crooks, Gavin E

    2011-01-01

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa

  8. Polyaza crown ether as non-nucleosidic building blocks in DNA-conjugates

    DEFF Research Database (Denmark)

    Jakobsen, Ulla; Rohr, Katja; Madsen, Rasmus K

    2007-01-01

    The synthesis of amphiphilic polyaza crown ether monomers X (palmityl-substituted), Y (cholesteryl-substituted) and Z (dipalmityl-subtituted) and their incorporation into oligonucleotides are described. Their effects on thermal duplex stability were investigated by UV melting curve analysis. Ther...

  9. In Vitro Antioxidant Properties, HIV-1 Reverse Transcriptase and Acetylcholinesterase Inhibitory Effects of Traditional Herbal Preparations Sold in South Africa

    Directory of Open Access Journals (Sweden)

    Johannes Van Staden

    2010-10-01

    Full Text Available The antioxidant potentials for fourteen multipurpose traditional herbal preparations sold in South Africa were determined using the DPPH radical scavenging, ferric reducing power and β-carotene-linoleic acid model system, the anti-HIV-1 reverse transcriptase (RT enzyme inhibitory effects using an ELISA kit and acetylcholinesterase (AChE enzyme inhibition using the microtitre plate assay. Nine of the herbal mixtures (Umzimba omubi, Umuthi wekukhwehlela ne zilonda, Mvusa ukunzi, Umpatisa inkosi, Imbiza ephuzwato, Vusa umzimba, Supreme one hundred, Sejeso herbal mixture Ingwe® and Ingwe® special muti exhibited higher antioxidant potentials, while only four (Imbiza ephuzwato, Ingwe® muthi mixture, Sejeso herbal mixture Ingwe® and African potato extractTM showed potent activity against the RT enzyme. Nine mixtures (Imbiza ephuzwato, Umpatisa inkosi, African potato extractTM, Sejeso herbal mixture Ingwe®, Vusa umzimba; Ingwe® muthi mixture, Ibhubezi™, Lion izifozonke Ingwe® and Ingwe® special muti showed AChE enzyme inhibitory activity greater than 50%. The observed activity exhibited by some of the herbal mixtures gives some credence to the manufacturers’ claims and goes part of the way towards validating their use against certain conditions such as oxidative stress, HIV/AIDS proliferation and some mental conditions. It is however, desirable to carry out further studies to determine the effects of mixing plant species/parts in one mixture on the antioxidant potency as well as isolating active constituents from the herbal mixtures.

  10. Molecular Docking Studies of Marine Diterpenes as Inhibitors of Wild-Type and Mutants HIV-1 Reverse Transcriptase

    Directory of Open Access Journals (Sweden)

    Alessandra M. T. de Souza

    2013-10-01

    Full Text Available AIDS is a pandemic responsible for more than 35 million deaths. The emergence of resistant mutations due to drug use is the biggest cause of treatment failure. Marine organisms are sources of different molecules, some of which offer promising HIV-1 reverse transcriptase (RT inhibitory activity, such as the diterpenes dolabelladienotriol (THD, IC50 = 16.5 µM, (6R-6-hydroxydichotoma-3,14-diene-1,17-dial (HDD, IC50 = 10 µM and (6R-6-acetoxydichotoma-3,14-diene-1,17-dial (ADD, IC50 = 35 µM, isolated from a brown algae of the genus Dictyota, showing low toxicity. In this work, we evaluated the structure-activity relationship (SAR of THD, HDD and ADD as anti HIV-1 RT, using a molecular modeling approach. The analyses of stereoelectronic parameters revealed a direct relationship between activity and HOMO (Highest Occupied Molecular Orbital-LUMO (Lowest Unoccupied Molecular Orbital gap (ELUMO–EHOMO, where antiviral profile increases with larger HOMO-LUMO gap values. We also performed molecular docking studies of THD into HIV-1 RT wild-type and 12 different mutants, which showed a seahorse conformation, hydrophobic interactions and hydrogen bonds with important residues of the binding pocket. Based on in vitro experiments and docking studies, we demonstrated that mutations have little influence in positioning and interactions of THD. Following a rational drug design, we suggest a modification of THD to improve its biological activity.

  11. Reversible Communicating Processes

    Directory of Open Access Journals (Sweden)

    Geoffrey Brown

    2016-02-01

    Full Text Available Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols, an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

  12. Synthesis and evaluation of "AZT-HEPT", "AZT-pyridinone", and "ddC-HEPT" conjugates as inhibitors of HIV reverse transcriptase.

    Science.gov (United States)

    Pontikis, R; Dollé, V; Guillaumel, J; Dechaux, E; Note, R; Nguyen, C H; Legraverend, M; Bisagni, E; Aubertin, A M; Grierson, D S; Monneret, C

    2000-05-18

    To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component (AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 microM anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC(50) = 0.45 microM) against HIV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.

  13. Economic impact of reversion

    International Nuclear Information System (INIS)

    2005-01-01

    Estimations of the Norwegian hydropower production and various reversion models' market value have been made. The value of the Norwegian hydropower production until 01.01.2007 is estimated to about Nok 289 billion after taxes, or about 2,42 Nok/kWh medium production, given an expected future electricity price of around 0,25 Nok/kWh and a discount rate at 6,5 percent in nominal terms after taxes. The estimate is slightly above the level of prices for Norwegian hydropower plants in the last 8-10 years. The value of reversion in private plants which today have a limited licence time is estimated to Nok 5,5 billion. The value of reversion in public-owned Norwegian hydropower plants are about Nok 21 billion with a 60 year licence period from 01.01.2007, and about 12 billion for 75 years (ml)

  14. Reversible deep disposal

    International Nuclear Information System (INIS)

    2009-10-01

    This presentation, given by the national agency of radioactive waste management (ANDRA) at the meeting of October 8, 2009 of the high committee for the nuclear safety transparency and information (HCTISN), describes the concept of deep reversible disposal for high level/long living radioactive wastes, as considered by the ANDRA in the framework of the program law of June 28, 2006 about the sustainable management of radioactive materials and wastes. The document presents the social and political reasons of reversibility, the technical means considered (containers, disposal cavities, monitoring system, test facilities and industrial prototypes), the decisional process (progressive development and blocked off of the facility, public information and debate). (J.S.)

  15. Thermosensory reversal effect quantified

    NARCIS (Netherlands)

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2008-01-01

    At room temperature, some materials feel colder than others due to differences in thermal conductivity, heat capacity and geometry. When the ambient temperature is well above skin temperature, the roles of 'cold' and 'warm' materials are reversed. In this paper, this effect is quantified by

  16. Thermosensory reversal effect quantified

    NARCIS (Netherlands)

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2008-01-01

    At room temperature, some materials feel colder than others due to differences in thermal conductivity, heat capacity and geometry. When the ambient temperature is well above skin temperature, the roles of ‘cold’ and ‘warm’ materials are reversed. In this paper, this effect is quantified by

  17. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  18. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  19. Sex Reversal in Birds.

    Science.gov (United States)

    Major, Andrew T; Smith, Craig A

    2016-01-01

    Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

  20. Elastomers with Reversible Nanoporosity

    DEFF Research Database (Denmark)

    Szewczykowski, Piotr Przemyslaw; Andersen, K.; Schulte, Lars

    2009-01-01

    nanostructure and displays liquid-filled cavities. Upon several cycles of swelling and drying the cavities open and close in a reversible fashion. When exposed to a nonsolvent, the material remains collapsed. This discriminating behavior of liquid-material interaction holds potential for the use...

  1. Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and RDDP functions.

    Science.gov (United States)

    Corona, Angela; Onnis, Valentina; Deplano, Alessandro; Bianco, Giulia; Demurtas, Monica; Distinto, Simona; Cheng, Yung-Chi; Alcaro, Stefano; Esposito, Francesca; Tramontano, Enzo

    2017-08-31

    In the continuous effort to identify new HIV-1 inhibitors endowed with innovative mechanisms, the dual inhibition of different viral functions would provide a significant advantage against drug-resistant variants. The HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) is the only viral-encoded enzymatic activity that still lacks an efficient inhibitor. We synthesized a library of 3,5-diamino-N-aryl-1H-pyrazole-4-carbothioamide and 4-amino-5-benzoyl-N-phenyl-2-(substituted-amino)-1H-pyrrole-3-carbothioamide derivatives and tested them against RNase H activity. We identified the pyrazolecarbothioamide derivative A15, able to inhibit viral replication and both RNase H and RNA-dependent DNA polymerase (RDDP) RT-associated activities in the low micromolar range. Docking simulations hypothesized its binding to two RT pockets. Site-directed mutagenesis experiments showed that, with respect to wt RT, V108A substitution strongly reduced A15 IC50 values (12.6-fold for RNase H inhibition and 4.7-fold for RDDP), while substitution A502F caused a 9.0-fold increase in its IC50 value for RNase H, not affecting the RDDP inhibition, reinforcing the hypothesis of a dual-site inhibition. Moreover, A15 retained good inhibition potency against three non-nucleoside RT inhibitor (NNRTI)-resistant enzymes, confirming a mode of action unrelated to NNRTIs and suggesting its potential as a lead compound for development of new HIV-1 RT dual inhibitors active against drug-resistant viruses. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. A new strategy to inhibit the excision reaction catalysed by HIV-1 reverse transcriptase: compounds that compete with the template–primer

    Science.gov (United States)

    Cruchaga, Carlos; Anso, Elena; Font, María; Martino, Virginia S.; Rouzaut, Ana; Martinez-Irujo, Juan J.

    2007-01-01

    Inhibitors of the excision reaction catalysed by HIV-1 RT (reverse transcriptase) represent a promising approach in the fight against HIV, because these molecules would interfere with the main mechanism of resistance of this enzyme towards chain-terminating nucleotides. Only a limited number of compounds have been demonstrated to inhibit this reaction to date, including NNRTIs (non-nucleoside RT inhibitors) and certain pyrophosphate analogues. We have found previously that 2GP (2-O-galloylpunicalin), an antiviral compound extracted from the leaves of Terminalia triflora, was able to inhibit both the RT and the RNase H activities of HIV-1 RT without affecting cell proliferation or viability. In the present study, we show that 2GP also inhibited the ATP- and PPi-dependent phosphorolysis catalysed by wild-type and AZT (3′-azido-3′-deoxythymidine)-resistant enzymes at sub-micromolar concentrations. Kinetic and direct-binding analysis showed that 2GP was a non-competitive inhibitor against the nucleotide substrate, whereas it competed with the binding of RT to the template–primer (Kd=85 nM). As expected from its mechanism of action, 2GP was active against mutations conferring resistance to NNRTIs and AZT. The combination of AZT with 2GP was highly synergistic when tested in the presence of pyrophosphate, indicating that the inhibition of RT-catalysed phosphorolysis was responsible for the synergy found. Although other RT inhibitors that compete with the template–primer have been described, this is the first demonstration that these compounds can be used to block the excision of chain terminating nucleotides, providing a rationale for their combination with nucleoside analogues. PMID:17355225

  3. Reversed field pinch diagnostics

    International Nuclear Information System (INIS)

    Weber, P.G.

    1986-01-01

    The Reversed Field Pinch (RFP) is a toroidal, axisymmetric magnetic confinement configuration characterized by a magnetic field configuration in which the toroidal magnetic field is of similar strength to the poloidal field, and is reversed at the edge compared to the center. The RFP routinely operates at high beta, and is a strong candidate for a compact fusion device. Relevant attributes of the configuration will be presented, together with an overview of present and planned experiments and their diagnostics. RFP diagnostics are in many ways similar to those of other magnetic confinement devices (such as tokamaks); these lectures will point out pertinent differences, and will present some diagnostics which provide special insights into unique attributes of the RFP

  4. Posterior Reversible Encephalopathy (PRES)

    International Nuclear Information System (INIS)

    Moron E, Fanny E; Diaz Marchan, Pedro

    2005-01-01

    The Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical Syndrome composed of cephalea, alteration in vision and convulsions, usually observed in patients with sudden elevation of arterial pressure. The imagenologic evidence shows reversible vasogenic brain edema without stroke. Its location is predominantly posterior; it affects the cortex and the subcortical white matter of the occipital, parietal and temporal lobes. The treatment with antihypertensive drugs and the removing of immunosupressor medication are generally associated with complete neurological recovery; this is reflected also in the images which return to their basal condition. The untreated hypertension, on the other side, can result in a progressive defect of the autoregulation system of the central nervous system with cerebral hemorrhage, irreversible brain stroke, coma and death

  5. Reversible infantile mitochondrial diseases.

    Science.gov (United States)

    Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

    2015-05-01

    Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.

  6. Positioning paper on reversibility

    International Nuclear Information System (INIS)

    2016-01-01

    After having recalled the legal framework adopted in 2006 for the deep geological storage of radioactive wastes, and briefly introduced the concept of reversibility, this publication presents the principle of geological storage, presents high and medium level and long life wastes, highlights the ethical necessity to deal with these radioactive wastes, outlines that geological storage is the generally admitted and adopted solution at the international level, and presents additional means implemented for radioactive waste management. It presents the Cigeo project as the technical answer to the issue of radioactive waste storage, describes the Cigeo development process, its current status and its development planning, and justifies the choice of this technical solution, notably from an ethical point of view. It addresses the issue of reversibility and proposes an overview of the various tools and means which aim at guaranteeing this reversibility. Appendices propose figures illustrating the Cigeo project and its development process, and a rather detailed Power Point presentation of the project by the ANDRA (history, object, planning, installations, and so on)

  7. Status of time reversal invariance

    International Nuclear Information System (INIS)

    Henley, E.M.

    1989-01-01

    Time Reversal Invariance is introduced, and theories for its violation are reviewed. The present experimental and theoretical status of Time Reversal Invariance and tests thereof will be presented. Possible future tests will be discussed. 30 refs., 2 figs., 1 tab

  8. Introduction to time reversal theory

    International Nuclear Information System (INIS)

    Henley, E.M.

    1987-01-01

    Theory and reaction mechanisms relevant to time reversal invariance are reviewed. Consequences of time reversal invariance are presented under the headings of CP tests, electromagnetic moments, weak emissions or absorptions, and scattering reactions. 8 refs., 4 figs

  9. The Causes of Preference Reversal.

    OpenAIRE

    Tversky, Amos; Slovic, Paul; Kahneman, Daniel

    1990-01-01

    Observed preference reversal cannot be adequately explained by violations of independence, the reduction axiom, or transitivity. The primary cause of preference reversal is the failure of procedure invariance, especially the overpricing of low-probability, high-payoff bets. This result violates regret theory and generalized (nonindependent) utility models. Preference reversal and a new reversal involving time preferences are explained by scale compatibility, which implies that payoffs are wei...

  10. Geomagnetic Field During a Reversal

    Science.gov (United States)

    Heirtzler, J. R.

    2003-01-01

    It has frequently been suggested that only the geomagnetic dipole, rather than higher order poles, reverse during a geomagnetic field reversal. Under this assumption the geomagnetic field strength has been calculated for the surface of the Earth for various steps of the reversal process. Even without an eminent a reversal of the field, extrapolation of the present secular change (although problematic) shows that the field strength may become zero in some geographic areas within a few hundred years.

  11. A Study on Reverse Logistics

    OpenAIRE

    Reddy, Dhananjaya

    2011-01-01

    In the competitive world of manufacturing, companies are often searching for new ways to improve their process, customer satisfaction and stay ahead in the game with their competitors. Reverse logistics has been considered a strategy to bring these things to life for the past decade or so. This thesis work tries to shed some light on the basics of reverse logistics and how reverse logistics can be used as a management strategy. This paper points out the fundamentals of reverse logistics and l...

  12. Geomagnetic Reversals during the Phanerozoic.

    Science.gov (United States)

    McElhinny, M W

    1971-04-09

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency.

  13. Reversal Strategies for NOACs

    DEFF Research Database (Denmark)

    Husted, Steen; Verheugt, Freek; Comuth, Willemijn

    2015-01-01

    , coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific...... antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants...

  14. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  15. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  16. Reversible posterior leukoencephalopathy syndrome

    International Nuclear Information System (INIS)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won; Song, Chang Joon; Song, Soon-Young; Koo, Ja Hong; Kim, Man Deuk

    2001-01-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  17. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  18. Reverse osmosis application studies

    International Nuclear Information System (INIS)

    Golomb, A.

    1982-02-01

    To assess the feasibility of applying reverse osmosis (RO) and ultrafiltration (UF) for effective treatment of process and waste streams from operations at Ontario Hydro's thermal and nuclear stations, an extensive literature survey has been carried out. It is concluded that RO is not at present economic for pretreatment of Great Lakes water prior to ion exchange demineralization for boiler makeup. Using both conventional and novel commercial membrane modules, RO pilot studies are recommended for treatment of boiler cleaning wastes, fly ash leachates, and flue gas desulphurization scrubber discharges for removal of heavy metals. Volume reduction and decontamination of nuclear station low-level active liquid waste streams by RO/UF also appear promising. Research programmes are proposed

  19. Reverse photoacoustic standoff spectroscopy

    Science.gov (United States)

    Van Neste, Charles W [Kingston, TN; Senesac, Lawrence R [Knoxville, TN; Thundat, Thomas G [Knoxville, TN

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  20. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  1. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  2. Sex Reversal in Amphibians.

    Science.gov (United States)

    Flament, Stéphane

    2016-01-01

    Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species. © 2016 S. Karger AG, Basel.

  3. High-throughput screening using pseudotyped lentiviral particles: a strategy for the identification of HIV-1 inhibitors in a cell-based assay.

    Science.gov (United States)

    Garcia, Jean-Michel; Gao, Anhui; He, Pei-Lan; Choi, Joyce; Tang, Wei; Bruzzone, Roberto; Schwartz, Olivier; Naya, Hugo; Nan, Fa-Jun; Li, Jia; Altmeyer, Ralf; Zuo, Jian-Ping

    2009-03-01

    Two decades after its discovery the human immunodeficiency virus (HIV) is still spreading worldwide and killing millions. There are 25 drugs formally approved for HIV currently on the market, but side effects as well as the emergence of HIV strains showing single or multiple resistances to current drug-therapy are causes for concern. Furthermore, these drugs target only 4 steps of the viral cycle, hence the urgent need for new drugs and also new targets. In order to tackle this problem, we have devised a cell-based assay using lentiviral particles to look for post-entry inhibitors of HIV-1. We report here the assay development, validation as well as confirmation of the hits using both wild-type and drug-resistant HIV-1 viruses. The screening was performed on an original library, rich in natural compounds and pure molecules from Traditional Chinese Medicine pharmacopoeia, which had never been screened for anti-HIV activity. The identified hits belong to four chemical sub-families that appear to be all non-nucleoside reverse transcriptase inhibitors (NNRTIs). Secondary tests with live viruses showed that there was good agreement with pseudotyped particles, confirming the validity of this approach for high-throughput drug screens. This assay will be a useful tool that can be easily adapted to screen for inhibitors of viral entry.

  4. Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention.

    Science.gov (United States)

    Dezzutti, Charlene S; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R; Rohan, Lisa C

    2015-11-01

    Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm(2)/min(1/2)), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm(2)/min(1/2)). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention.

  5. Performance comparison of the 4th generation Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA on the EVOLIS™ automated system versus Abbott ARCHITECT HIV Ag/Ab Combo, Ortho Anti-HIV 1+2 EIA on Vitros ECi and Siemens HIV-1/O/2 enhanced on Advia Centaur.

    Science.gov (United States)

    Mitchell, Elizabeth O; Stewart, Greg; Bajzik, Olivier; Ferret, Mathieu; Bentsen, Christopher; Shriver, M Kathleen

    2013-12-01

    A multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1+2 EIA and Siemens HIV 1/O/2 was also evaluated. Study objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels. Analytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels. GS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41 IU/mL versus 1.2 IU/mL (WHO) and 12.7 pg/mL versus 20.1 pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7-11 days earlier than the 3rd generation HIV antibody only EIAs. Both 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7-11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. 49 CFR 230.89 - Reverse gear.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse gear...

  7. Diabetes mellitus in HIV-infected patients receiving antiretroviral ...

    African Journals Online (AJOL)

    Primary analysis using conditional logistic regression was employed to estimate univariate .... Refers to first-line regimen in Botswana – either non-nucleoside reverse transcriptase inhibitor-based regimen (NVP or. EFV) or .... Public Health.

  8. Docking mode of delvardine and its analogues into the p66 domain ...

    Indian Academy of Sciences (India)

    SEARCHU

    Delvardine and its structural derivatives are important non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs). .... [PDB ID:1REV] was taken from the Protein Data Bank ... Water molecules were removed and H atoms were added.

  9. TropJrnal Vol 32 No 1

    African Journals Online (AJOL)

    Mr Olusoji

    On logistic regression, factors that retained an ... used was a non-nucleoside reverse transcriptase (NNRTI) based HAART. Preterm births were .... Approval was obtained from the joint UI/ ... Package for Social Sciences (SPSS Inc, Chicago, Ill).

  10. Field reversal experiments (FRX)

    International Nuclear Information System (INIS)

    Linford, R.K.; Armstrong, W.T.; Platts, D.A.; Sherwood, E.G.

    1978-01-01

    The equilibrium, confinement, and stability properties of the reversed-field configuration (RFC) are being studied in two theta-pinch facilities. The RFC is an elongated toroidal plasma confined in a purely poloidal field geometry. The open field lines of the linear theta pinch support the closed-field RFC much like the vertical field centers the toroidal plasma in a tokamak. Depending on stability and confinement properties, the RFC might be used to greatly reduce the axial losses in linear fusion devices such as mirrors, theta pinches, and liners. The FRX systems produce RFC's with a major radius R = 2-6 cm, minor radius a approximately 2 cm, and a total length l approximately 35 cm. The observed temperatures are T/sub e/ approximately 100 eV and T/sub i/ = 150-350 eV with a peak density n approximately 2 x 10 15 cm -3 . After the plasma reaches equilibrium, the RFC remains stable for up to 30 μs followed by the rapid growth of the rotational m = 2 instability, which terminates the confinement. During the stable equilibrium, the particle and energy confinement times are more than 10 times longer than in an open-field system. The behavior of the m = 2 mode qualitatively agrees with the theoretically predicted instability for rotational velocities exceeding some critical value

  11. Field reversal experiments (FRX)

    International Nuclear Information System (INIS)

    Linford, R.K.; Armstrong, W.T.; Platts, D.A.; Sherwood, E.G.

    1979-01-01

    The equilibrium, confinement, and stability properties of the reversed-field configuration (RFC) are being studied in two theta-pinch facilities. The RFC is an elongated toroidal plasma confined in a purely poloidal field geometry. The open field lines of the linear theta pinch support the closed-field RFC much like the vertical field centres the toroidal plasma in a tokamak. Depending on stability and confinement properties, the RFC might be used to greatly reduce the axial losses in linear fusion devices such as mirrors, theta pinches, and liners. The FRX systems produce RFCs with a major radius R=2-6cm, a minor radius a approximately 2cm, and a total length l approximately 35cm. The observed temperatures are Tsub(e) approximately 100eV and Tsub(i)=150-350eV with a peak density n approximately 2x10 15 cm -3 . After the plasma has reached equilibrium, the RFC remains stable for up to 30μs, followed by the rapid growth of the rotational m=2 instability, which terminates the confinement. During the stable equilibrium, the particle and energy confinement times are more than 10 times longer than in an open-field system. The behaviour of the m=2 mode agrees qualitatively with the theoretically predicted instability for rotational velocities exceeding some critical value. (author)

  12. Towards a reversible functional language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    /equality operator also simplifies inverse computation and program inversion. We discuss the advantages of a reversible functional language using example programs, including run-length encoding. Program inversion is seen to be as lightweight as for imperative reversible languages and realized by recursive descent...

  13. Reverse engineering of RFID devices

    NARCIS (Netherlands)

    Bokslag, W.

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID

  14. How decision reversibility affects motivation

    NARCIS (Netherlands)

    Bullens, L.; van Harreveld, F.; Förster, J.; Higgins, T.E.

    2014-01-01

    The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making,

  15. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.

    1984-01-01

    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.
    In Chapter 1 the present knowledge about reversed micelles and

  16. Reversible networks in supramolecular polymers

    NARCIS (Netherlands)

    Havermans - van Beek, D.J.M.

    2007-01-01

    Non–covalent interactions between low molecular weight polymers form the basis of supramolecular polymers. The material properties of such polymers are determined by the strength and lifetime of the non–covalent reversible interactions. Due to the reversibility of the interactions between the low

  17. Reverse genetics of avian metapneumoviruses

    Science.gov (United States)

    An overview of avian metapneumovirus (aMPV) infection in turkeys and development of a reverse genetics system for aMPV subgroup C (aMPV-C) virus will be presented. By using reverse genetics technology, we generated recombinant aMPV-C viruses containing a different length of glycoprotein (G) gene or...

  18. MODELS OF PROJECT REVERSE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Віктор Володимирович ІВАНОВ

    2017-03-01

    Full Text Available Reverse engineering decided important scientific and technical problems of increasing the cost of the existing technical product by transforming it into a product with other features or design. Search ideas of the new application of existing products on the base of heuristic analysis were created. The concept of reverse engineering and its division into three types: conceptual, aggregate and complete was expanded. The use of heuristic methods for reverse engineering concept was showed. The modification model of Reverse engineering based on the model of РМВОК was developed. Our model includes two new phases: identification and transformation. At the identification phase, technical control is made. At the transformation phase, search heuristic idea of the new applied existing technical product was made. The model of execution phase that included heuristic methods, metrological equipment, and CAD/CAM/CAE program complex was created. The model that connected economic indicators of reverse engineering project was developed.

  19. What do reversible programs compute?

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    Reversible computing is the study of computation models that exhibit both forward and backward determinism. Understanding the fundamental properties of such models is not only relevant for reversible programming, but has also been found important in other fields, e.g., bidirectional model...... transformation, program transformations such as inversion, and general static prediction of program properties. Historically, work on reversible computing has focussed on reversible simulations of irreversible computations. Here, we take the viewpoint that the property of reversibility itself should...... are not strictly classically universal, but that they support another notion of universality; we call this RTM-universality. Thus, even though the RTMs are sub-universal in the classical sense, they are powerful enough as to include a self-interpreter. Lifting this to other computation models, we propose r...

  20. Fundamentals of reversible flowchart languages

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2016-01-01

    Abstract This paper presents the fundamentals of reversible flowcharts. They are intended to naturally represent the structure and control flow of reversible (imperative) programming languages in a simple computation model, in the same way classical flowcharts do for conventional languages......, structured reversible flowcharts are as expressive as unstructured ones, as shown by a reversible version of the classic Structured Program Theorem. We illustrate how reversible flowcharts can be concretized with two example programming languages, complete with syntax and semantics: a low-level unstructured...... language and a high-level structured language. We introduce concrete tools such as program inverters and translators for both languages, which follow the structure suggested by the flowchart model. To further illustrate the different concepts and tools brought together in this paper, we present two major...

  1. The Geomagnetic Field During a Reversal

    Science.gov (United States)

    Heirtzler, James R.

    2003-01-01

    By modifying the IGRF it is possible to learn what may happen to the geomagnetic field during a geomagnetic reversal. If the entire IGRF reverses then the declination and inclination only reverse when the field strength is zero. If only the dipole component of the IGRF reverses a large geomagnetic field remains when the dipole component is zero and he direction of the field at the end of the reversal is not exactly reversed from the directions at the beginning of the reversal.

  2. How decision reversibility affects motivation.

    Science.gov (United States)

    Bullens, Lottie; van Harreveld, Frenk; Förster, Jens; Higgins, Tory E

    2014-04-01

    The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed.

  3. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  4. Reverse engineering for quality systems

    International Nuclear Information System (INIS)

    Nolan, A.J.

    1995-01-01

    When the age of software engineering began, many companies were faced with a problem of how to support the older, pre-software-engineering, programs. The techniques of reverse engineering and re-engineering were developed to bridge the gap between the past and the present. Although reverse engineering can be used for generating missing documentation, it can also be used as a means to demonstrate quality in these older programs. This paper presents, in the form of a case study, how Rolls-Royce and Associates Limited addressed the quality issues of reverse engineering and re-engineering. (author)

  5. Field reversal in mirror machines

    International Nuclear Information System (INIS)

    Pearlstein, L.D.; Anderson, D.V.; Boozer, A.H.

    1978-01-01

    This report discusses some of the physics issues anticipated in field-reversed mirrors. The effect of current cancellation due to electrons is described. An estimate is made of the required impurity level to maintain a field-reversed configuration. The SUPERLAYER code is used to simulate the high-β 2XIIB results, and favorable comparisons require inclusion of quasilinear RF turbulence. Impact of a quadrupole field on field-line closure and resonant transport is discussed. A simple self-consistent model of ion currents is presented. Conditions for stability of field-reversed configurations to E x B driven rotations are determined

  6. Zero field reversal probability in thermally assisted magnetization reversal

    Science.gov (United States)

    Prasetya, E. B.; Utari; Purnama, B.

    2017-11-01

    This paper discussed about zero field reversal probability in thermally assisted magnetization reversal (TAMR). Appearance of reversal probability in zero field investigated through micromagnetic simulation by solving stochastic Landau-Lifshitz-Gibert (LLG). The perpendicularly anisotropy magnetic dot of 50×50×20 nm3 is considered as single cell magnetic storage of magnetic random acces memory (MRAM). Thermally assisted magnetization reversal was performed by cooling writing process from near/almost Curie point to room temperature on 20 times runs for different randomly magnetized state. The results show that the probability reversal under zero magnetic field decreased with the increase of the energy barrier. The zero-field probability switching of 55% attained for energy barrier of 60 k B T and the reversal probability become zero noted at energy barrier of 2348 k B T. The higest zero-field switching probability of 55% attained for energy barrier of 60 k B T which corespond to magnetif field of 150 Oe for switching.

  7. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng

    2015-01-01

    secondary market introduction, this study expands the espoused definition of reverse innovation beyond its market-introduction focus with reversals in the flow of innovation in the ideation and product development phases. Recognizing that each phase can take place in different geographical locations...... taking place in an emerging country. This analytical framework allows recasting of current research at the intersection between innovation and international business. Of the 10 reverse innovation flows, six are new and have not been covered in the literature to date. The study addresses questions......’s portfolio of global innovation competence and capability. The implications for management are concerned with internal and external resistance to reverse innovation. Most significantly, while greater recognition and power of innovation in formerly subordinate organizational units is inconvenient to some...

  8. Evaluation of enzyme-linked immunosorbent and alternative assays for detection of HIV antibodies using panels of Brasilian sera Avaliação de testes sorológicos para a detecção de anticorpos anti-HIV em painéis de soros de brasileiros

    Directory of Open Access Journals (Sweden)

    Jairo Ivo-Dos-Santos

    1990-04-01

    Full Text Available Sera from 472 Brazilian subjects, confirmed to be either positive or negative for HIV antibodies and comprising the total clinical spectrum of HIV infection, were utilized in the evaluation of six commercially available enzyme-linked immunosorbent assays (ELISA, as well as of four alternative assays, namely indirect immunofluorescence (IIF, passive hemagglutination (PHA, dot blot and Karpas AIDS cell test. The sensitivities ranged from 100% (Abbott and Roche ELISA to 84.2% (PHA and the specificities ranged from 99.3% (IIF to 80.2% (PHA. The sensitivity and specificity of the PHA and the sensitivity of the Karpas cell test were significantly lower than those of the other tests. Although the IFF and dot blot had good sensitivities and specificities, the six ELISA were more attractive than those tests when other parameters such as ease of reading and duration of assay were considered.Os soros de 472 brasileiros, confirmados como sendo positivos ou negativos em relação à presença de anticorpos anti-HIV e compreendendo todo o espectro clínico da infecção, foram utilizados na avaliação de seis ensaios imunoenzimáticos comerciais (ELISA, bem como de quatro testes alternativos tais como imunofluorescência indireta (IFI, hemaglutinação passiva (HP, dot blot e Karpas AIDS cell test. As sensibilidades variaram de 100% (ELISA Abbott e Roche a 84,2% (HP e as especificidades variaram de 99,3% (IFI a 80,2% (HP. A sensibilidade e especificidade da HP e a sensibilidade do Karpas AIDS cell test foram significativamente menores que os outros ensaios. Embora a IFI e o dot blot tivessem apresentado uma boa sensibilidade e especificidade, os ensaios imunoenzimáticos (ELISA foram mais adequados para serem utilizados em triagem quando outros parâmetros tais como facilidade de leitura e interpretação dos resultados e duração dos ensaios foram considerados.

  9. Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

    Science.gov (United States)

    Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

    2016-04-01

    The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories ( 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

  10. Spontaneous direct and reverse osmosis

    International Nuclear Information System (INIS)

    Valitov, N.Kh.

    1996-01-01

    It has been ascertained experimentally that in the course of separation of CsCl, KCl, NaCl aqueous solutions by semi-permeable membrane from distilled water the direct and then reverse osmosis are observed. The same sequence is observed in case of separation of CsCl aqueous solutions from NaCl of different concentrations. The reason for the direct and reverse osmosis has been explained. 5 refs.; 3 figs. 1 tab

  11. Garbage collection for reversible functional languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2015-01-01

    Reversible languages are programming languages where all programs can run both forwards and backwards. Reversible functional languages have been proposed that use symmetric pattern matching and data construction. To be reversible, these languages require linearity: Every variable must be used...

  12. The anti-HIV-1 effect of scutellarin

    International Nuclear Information System (INIS)

    Zhang Gaohong; Wang Qian; Chen Jijun; Zhang Xuemei; Tam, S.-C.; Zheng Yongtang

    2005-01-01

    Scutellarin was purified from the plant Erigeron breviscapus (Vant.) Hand.-Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-1 IIIB ), drug-resistant virus (HIV-1 74V ), and low-passage clinical isolated virus (HIV-1 KM018 ). From syncytia inhibition study, the EC 50 of scutellarin against HIV-1 IIIB direct infection in C8166 cells was 26 μM with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC 50 reduced to 15 μM. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-1 74V (EC 50 253 μM) and HIV-1 KM018 (EC 50 136 μM) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433 μM, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54 μM. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication

  13. Voltammetric determination of wedelolactone, an anti-HIV herbal ...

    Indian Academy of Sciences (India)

    -wave and cyclic ... ing in charge transfer resistance at the boron-doped diamond electrode as compared to the glassy carbon elec- ... The effect of concentration on the peak currents of ... has low charge carrier activation energy of 0.37 eV,42.

  14. AIDS: Anti-HIV Agents, Therapies, and Vaccines

    Science.gov (United States)

    1990-12-26

    Rabson, T. F. Smith & F. Wong-Staal, Eds. Theoretical Biology and Biophysics Group T-10. Los Alamos, New Mexico . 146 ANNALS NEW YORK ACADEMY OV SCIENCES...delayed-type hypersensitivity (DTH) responses to a 10 tg intradermal injection of purified protein derivative (PPD) of My"cobacterium tuberculosis ...8217t, & G. M SIt-ARt R. 1989. J. Clin. Invest. 84" 1892- 1899, I. M\\i R\\ K., Q. N. 1982 AdN . Exp. Med. iliol. 155:649 57. 17. MOORi. V L, Q N. MNRVIK

  15. Clinical outcomes in clinical trials of anti-HIV treatment

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; J, Neaton

    2007-01-01

    Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

  16. Plant made anti-HIV microbicides: a field of opportunity

    CSIR Research Space (South Africa)

    Lotter-Stark, HCT

    2012-11-01

    Full Text Available -HIV microbicides- a field of opportunity Hester C.T. Lotter-Stark1*, Edward P. Rybicki2 and Rachel K. Chikwamba1 1 Council for Scientific and Industrial Research (CSIR), Biosciences, Pretoria, South Africa. 2 Institute of Infectious Disease and Molecular... efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant 2 population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate...

  17. Latest animal models for anti-HIV drug discovery.

    Science.gov (United States)

    Sliva, Katja

    2015-02-01

    HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

  18. Contribution of the anti HIV/AIDS community conversation programs ...

    African Journals Online (AJOL)

    admin

    group facilitators), Likert-type rating scale (questionnaire) administered to a sample of 200 participants (half of them .... that are virtually cross-cutting the various interventions ... and ability to effect positive change in attitudes related to.

  19. Clinical outcomes in clinical trials of anti-HIV treatment

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; J, Neaton

    2007-01-01

    Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

  20. Evaluation Of Algorithms Of Anti- HIV Antibody Tests

    Directory of Open Access Journals (Sweden)

    Paranjape R.S

    1997-01-01

    Full Text Available Research question: Can alternate algorithms be used in place of conventional algorithm for epidemiological studies of HIV infection with less expenses? Objective: To compare the results of HIV sero- prevalence as determined by test algorithms combining three kits with conventional test algorithm. Study design: Cross â€" sectional. Participants: 282 truck drivers. Statistical analysis: Sensitivity and specificity analysis and predictive values. Results: Three different algorithms that do not include Western Blot (WB were compared with the conventional algorithm, in a truck driver population with 5.6% prevalence of HIV â€"I infection. Algorithms with one EIA (Genetic Systems or Biotest and a rapid test (immunocomb or with two EIAs showed 100% positive predictive value in relation to the conventional algorithm. Using an algorithm with EIA as screening test and a rapid test as a confirmatory test was 50 to 70% less expensive than the conventional algorithm per positive scrum sample. These algorithms obviate the interpretation of indeterminate results and also give differential diagnosis of HIV-2 infection. Alternate algorithms are ideally suited for community based control programme in developing countries. Application of these algorithms in population with low prevalence should also be studied in order to evaluate universal applicability.

  1. Vasectomy reversal: a clinical update

    Directory of Open Access Journals (Sweden)

    Abhishek P Patel

    2016-01-01

    Full Text Available Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.

  2. Reverse Knowledge Transfer in MNEs

    DEFF Research Database (Denmark)

    Mudambi, Ram; Piscitello, Lucia; Rabbiosi, Larissa

    2014-01-01

    a positive correlation with the extent of reverse knowledge transfers to the parent MNE. Relying on the headquarters-subsidiary view of the MNE, we argue that, beyond a point, increasing subsidiary innovativeness will be associated with lower reverse knowledge transfers. Further, we argue......It is now well recognized that multinational enterprises (MNEs) are differentiated networks wherein subsidiaries vary in terms of their ability to create new knowledge and competencies for their parent groups. In much of this theory, it is taken for granted that subsidiary innovativeness has...... that this relationship is sensitive to the subsidiary entry mode. Using data from a sample of 293 Italian subsidiaries, we find strong support for our hypotheses. In particular, our results confirm that the effect of subsidiary innovativeness on reverse knowledge transfers displays an inverted-U shape...

  3. Ice ages and geomagnetic reversals

    Science.gov (United States)

    Wu, Patrick

    1992-01-01

    There have been speculations on the relationship between climatic cooling and polarity reversals of the earth's magnetic field during the Pleistocene. Two of the common criticisms on this relationship have been the reality of these short duration geomagnetic events and the accuracy of their dates. Champion et al. (1988) have reviewed recent progress in this area. They identified a total of 10 short-duration polarity events in the last 1 Ma and 6 of these events have been found in volcanic rocks, which also have K-Ar dates. Supposing that the speculated relationship between climatic cooling and geomagnetic reversals actually exist, two mechanisms that assume climatic cooling causes short period magnetic reversals will be investigated. These two methods are core-mantle boundary topography and transfer of the rotational energy to the core.

  4. Reverse innovation in maternal health.

    Science.gov (United States)

    Firoz, Tabassum; Makanga, Prestige Tatenda; Nathan, Hannah L; Payne, Beth; Magee, Laura A

    2017-09-01

    Reverse innovation, defined as the flow of ideas from low- to high-income settings, is gaining traction in healthcare. With an increasing focus on value, investing in low-cost but effective and innovative solutions can be of mutual benefit to both high- and low-income countries. Reverse innovation has a role in addressing maternal health challenges in high-income countries by harnessing these innovative solutions for vulnerable populations especially in rural and remote regions. In this paper, we present three examples of 'reverse innovation' for maternal health: a low-cost, easy-to-use blood pressure device (CRADLE), a diagnostic algorithm (mini PIERS) and accompanying mobile app (PIERS on the Move), and a novel method for mapping maternal outcomes (MOM).

  5. Reverse Transfection Using Gold Nanoparticles

    Science.gov (United States)

    Yamada, Shigeru; Fujita, Satoshi; Uchimura, Eiichiro; Miyake, Masato; Miyake, Jun

    Reverse transfection from a solid surface has the potential to deliver genes into various types of cell and tissue more effectively than conventional methods of transfection. We present a method for reverse transfection using a gold colloid (GC) as a nanoscaffold by generating nanoclusters of the DNA/reagentcomplex on a glass surface, which could then be used for the regulation of the particle size of the complex and delivery of DNA into nuclei. With this method, we have found that the conjugation of gold nanoparticles (20 nm in particle size) to the pEGFP-N1/Jet-PEI complex resulted in an increase in the intensity of fluorescence of enhanced green fluorescent protein (EGFP) (based on the efficiency of transfection) from human mesenchymal stem cells (hMSCs), as compared with the control without GC. In this manner, we constructed a method for reverse transfection using GC to deliver genes into the cells effectively.

  6. Designing the Reverse Supply Chain

    DEFF Research Database (Denmark)

    Gobbi, Chiara

    2011-01-01

    Purpose – The purpose of this paper is to explore the impact of the product residual value (PRV) and the loss of value over time of returned products in the reverse supply chain configuration. It also examines whether or not the distinction of Fisher's functional and innovative products holds...... that allows for recapturing most of the PRV. These notions have then been tested by analyzing two reverse supply chains with a case study research methodology. Findings – The findings show that low PRV is associated with second-class recovery options (recycling and energy recovery) and that high PRV...... is associated with first-class recovery options (reconditioning and remarketing). When the recovery option is recycling, time is not relevant, the primary objective is cost reduction (efficiency), the chain is centralized, and actors and phases of the reverse chain are determined by the specificity...

  7. Reverse genetics with animal viruses. NSV reverse genetics

    International Nuclear Information System (INIS)

    Mebatsion, T.

    2005-01-01

    New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus in 1994. Since then, reverse genetic systems have been established for several pathogens of medical and veterinary importance. Based on the reverse genetics technique, it is now possible to design safe and more effective live attenuated vaccines against important viral agents. In addition, genetically tagged recombinant viruses can be designed to facilitate serological differentiation of vaccinated animals from infected animals. The approach of delivering protective immunogens of different pathogens using a single vector was made possible with the introduction of the reverse genetics system, and these novel broad-spectrum vaccine vectors have potential applications in improving animal health in developing countries. (author)

  8. Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing.

    Directory of Open Access Journals (Sweden)

    Dieter Hoffmann

    Full Text Available Simple and cost-effective approaches for HIV drug-resistance testing are highly desirable for managing increasingly expanding HIV-1 infected populations who initiate antiretroviral therapy (ART, particularly in resource-limited settings. Non-nucleoside reverse trancriptase inhibitor (NNRTI-based regimens with an NRTI backbone containing lamivudine (3TC or emtricitabine (FTC are preferred first ART regimens. Failure with these drug combinations typically involves the selection of NNRTI- and/or 3TC/FTC-resistant viruses. Therefore, the availability of simple assays to measure both types of drug resistance is critical. We have developed a high throughput screening test for assessing enzymatic resistance of the HIV-1 RT in plasma to 3TC/FTC and NNRTIs. The test uses the sensitive "Amp-RT" assay with a newly-developed real-time PCR format to screen biochemically for drug resistance in single reactions containing either 3TC-triphosphate (3TC-TP or nevirapine (NVP. Assay cut-offs were defined based on testing a large panel of subtype B and non-subtype B clinical samples with known genotypic profiles. Enzymatic 3TC resistance correlated well with the presence of M184I/V, and reduced NVP susceptibility was strongly associated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. The sensitivity and specificity for detecting resistance were 97.0% and 96.0% in samples with M184V, and 97.4% and 96.2% for samples with NNRTI mutations, respectively. We further demonstrate the utility of an HIV capture method in plasma by using magnetic beads coated with CD44 antibody that eliminates the need for ultracentifugation. Thus our results support the use of this simple approach for distinguishing WT from NNRTI- or 3TC/FTC-resistant viruses in clinical samples. This enzymatic testing is subtype-independent and can assist in the clinical management of diverse populations particularly in resource-limited settings.

  9. Marburg Virus Reverse Genetics Systems

    Directory of Open Access Journals (Sweden)

    Kristina Maria Schmidt

    2016-06-01

    Full Text Available The highly pathogenic Marburg virus (MARV is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  10. Reverse Zymography: Overview and Pitfalls.

    Science.gov (United States)

    Sharma, Kanika; Bhattacharyya, Debasish

    2017-01-01

    Reverse zymography is a technique by which protease inhibitor(s) in a sample could be electrophoretically separated in a substrate-impregnated acrylamide gel and their relative abundance could be semi-quantified. The gel after electrophoresis is incubated with a protease when the impregnated substrate and all other proteins of the sample are degraded into small peptides except the inhibitor(s) that show clear bands against a white background. Since reverse zymography cannot distinguish between a protease inhibitor and a protein that is resistant against proteolysis, the results should be confirmed from inhibition of protease activity by solution state assay.

  11. Reverse hybrid total hip arthroplasty

    DEFF Research Database (Denmark)

    Wangen, Helge; Havelin, Leif I.; Fenstad, Anne M

    2017-01-01

    Background and purpose - The use of a cemented cup together with an uncemented stem in total hip arthroplasty (THA) has become popular in Norway and Sweden during the last decade. The results of this prosthetic concept, reverse hybrid THA, have been sparsely described. The Nordic Arthroplasty....... Patients and methods - From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk...

  12. Reference counting for reversible languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2014-01-01

    inverses: Freeing a block of memory is done by running the allocation procedure backwards. Axelsen and Glück use this heap manager to sketch implementation of a simple reversible functional language where pattern matching a constructor is the inverse of construction, so pattern-matching implies......Modern programming languages and operating systems use heap memory that allows allocation and deallocation of memory to be decoupled, so they don't follow a stack discipline. Axelsen and Glück have presented a reversible heap manager where allocation and deallocation are each other's logical...

  13. A functional language for describing reversible logic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal

    2012-01-01

    Reversible logic is a computational model where all gates are logically reversible and combined in circuits such that no values are lost or duplicated. This paper presents a novel functional language that is designed to describe only reversible logic circuits. The language includes high....... Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...... circuits. The flow relies on a reversible combinator language as an intermediate language....

  14. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    Science.gov (United States)

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  15. Time reversal and parity tests

    International Nuclear Information System (INIS)

    Terwilliger, K.

    1975-01-01

    A recent review by Henley discusses the present status of Time Reversal and Parity symmetry violations, and comments on the implications for high energy hadron scattering. This note will briefly summarize the situation with particular attention to the sizes of possible effects, relating them to experimental accuracy available or reasonably possible at the ZGS

  16. A Framework for Reverse Logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2003-01-01

    textabstractReverse Logistics has been stretching out worldwide, involving all the layers of supply chains in various industry sectors. While some actors in the chain have been forced to take products back, others have pro-actively done so, attracted by the value in used products One way or the

  17. Reverse ventilation--perfusion mismatch

    International Nuclear Information System (INIS)

    Palmaz, J.C.; Barnett, C.A.; Reich, S.B.; Krumpe, P.E.; Farrer, P.A.

    1984-01-01

    Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients

  18. Reverse amblyopia with atropine treatment.

    Science.gov (United States)

    Hainline, Bryan C; Sprunger, Derek C; Plager, David A; Neely, Daniel E; Guess, Matthew G

    2009-01-01

    Occlusion, pharmacologic pernalization and combined therapy have been documented in controlled studies to effectively treat amblyopia with few complications. However, there remain concerns about the effectiveness and complications when, as in this case, there are not standardized treatment protocols. A retrospective chart review of 133 consecutive patients in one community based ophthalmology practice treated for amblyopia was performed. Treatments evaluated were occlusion only, atropine penalization, and combination of occlusion and atropine. Reverse amblyopia was defined as having occured when the visual acuity of the sound eye was 3 LogMar units worse than visual acuity of the amblyopia eye after treatment. Improvement in vision after 6 months and 1 year of amblyopia therapy was similar among all three groups: 0.26 LogMar lines and 0.30 in the atropine group, 0.32 and 0.34 in the occlusion group, and 0.24 and 0.32 in the combined group. Eight (6%) patients demonstrated reverse amblyopia. The mean age of those who developed reverse amblyopia was 3.5 years, 1.5 years younger than the mean age of the study population, 7/8 had strabismic amblyopia, 6/8 were on daily atropine and had a mean refractive error of +4.77 diopters in the amblyopic eye and +5.06 diopters in the sound eye. Reverse amblyopia did not occur with occlusion only therapy. In this community based ophthalmology practice, atropine, patching, and combination therapy appear to be equally effective modalities to treat ambyopia. Highly hyperopic patients under 4 years of age with dense, strabismic amblyopia and on daily atropine appeared to be most at risk for development of reverse amblyopia.

  19. Prediction of the binding mode and resistance profile for a dual-target pyrrolyl diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated ribonuclease H.

    Science.gov (United States)

    Yang, Fengyuan; Zheng, Guoxun; Fu, Tingting; Li, Xiaofeng; Tu, Gao; Li, Ying Hong; Yao, Xiaojun; Xue, Weiwei; Zhu, Feng

    2018-06-27

    The rapid emergence of drug-resistant variants is one of the most common causes of highly active antiretroviral therapeutic (HAART) failure in patients infected with HIV-1. Compared with the existing HAART, the recently developed pyrrolyl diketo acid scaffold targeting both HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) is an efficient approach to counteract the failure of anti-HIV treatment due to drug resistance. However, the binding mode and potential resistance profile of these inhibitors with important mechanistic principles remain poorly understood. To address this issue, an integrated computational method was employed to investigate the binding mode of inhibitor JMC6F with HIV-1 IN and RNase H. By using per-residue binding free energy decomposition analysis, the following residues: Asp64, Thr66, Leu68, Asp116, Tyr143, Gln148 and Glu152 in IN, Asp443, Glu478, Trp536, Lys541 and Asp549 in RNase H were identified as key residues for JMC6F binding. And then computational alanine scanning was carried to further verify the key residues. Moreover, the resistance profile of the currently known major mutations in HIV-1 IN and 2 mutations in RNase H against JMC6F was predicted by in silico mutagenesis studies. The results demonstrated that only three mutations in HIV-1 IN (Y143C, Q148R and N155H) and two mutations in HIV-1 RNase H (Y501R and Y501W) resulted in a reduction of JMC6F potency, thus indicating their potential role in providing resistance to JMC6F. These data provided important insights into the binding mode and resistance profile of the inhibitors with a pyrrolyl diketo acid scaffold in HIV-1 IN and RNase H, which would be helpful for the development of more effective dual HIV-1 IN and RNase H inhibitors.

  20. Reversal agents in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Nibedita Pani

    2015-01-01

    Full Text Available Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice.

  1. Reverse osmosis water purification system

    Science.gov (United States)

    Ahlstrom, H. G.; Hames, P. S.; Menninger, F. J.

    1986-01-01

    A reverse osmosis water purification system, which uses a programmable controller (PC) as the control system, was designed and built to maintain the cleanliness and level of water for various systems of a 64-m antenna. The installation operates with other equipment of the antenna at the Goldstone Deep Space Communication Complex. The reverse osmosis system was designed to be fully automatic; with the PC, many complex sequential and timed logic networks were easily implemented and are modified. The PC monitors water levels, pressures, flows, control panel requests, and set points on analog meters; with this information various processes are initiated, monitored, modified, halted, or eliminated as required by the equipment being supplied pure water.

  2. Trend towards reverse leach process

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The South African gold mining industry is making notable strides in improving recovery methods for both gold and uranium with significant additions to profits because of higher efficiencies and reductions in costs in the recovery processes. The most notable step on the gold side recently is the adoption of the reverse leach process at Buffelsfontein and Western Deep Levels. This process was pioneered at Hartebeesfontein as far back as 1975 and when introduced there resulted in a two and a half per cent improvement in recovery efficiencies. The essence of reverse leaching under which the uranium is recovered before the gold is the fact that the gold partly coated with iron oxide or locked in uranite, is exposed to be recovered later by cyanidation

  3. Reversible evolution of charged ergoregions

    Energy Technology Data Exchange (ETDEWEB)

    Kokkotas, K.; Spyrou, N.

    1987-07-01

    The reversible evolution of a charged rotating ergoregion, due to the injection into it of particles with mass-energy and angular momentum, is studied systematically. As in the uncharged case, a bulge always forms on the outer boundary of the ergoregion due to the latter's angular momentum. The behavior of the bulge's position, relative to the black hole's rotation axis and equatorial plane, is studied, on the basis of the cosmic censorship hypothesis, during the ergoregion's reversible evolution. The range of the permitted values of the ergoregion's linear dimensions along the rotation axis and perpendicular to it is specified. Finally the differences with the evolution of an uncharged ergoregion are pointed out and discussed.

  4. Malware analysis and reverse engineering

    OpenAIRE

    Šváb, Martin

    2014-01-01

    Focus of this thesis is reverse engineering in information technology closely linked with the malware analysis. It explains fundamentals of IA-32 processors architecture and basics of operating system Microsoft Windows. Main part of this thesis is dedicated to the malware analysis, including description of creating a tool for simplification of static part of the analysis. In Conclusion various approaches to the malware analysis, which were described in previous part of the thesis, are practic...

  5. How to play Reverse Hex

    DEFF Research Database (Denmark)

    Toft, Bjarne; Hayward, Ryan B.; Henderson, Philip

    2012-01-01

    We present new results on how to play Reverse Hex, also known as Rex, or Misère Hex, on n × n boards. We give new proofs – and strengthened versions – of Lagarias and Sleator’s theorem (for n × n boards, each player can prolong the game until the board is full, so the first/second player can alwa...

  6. Theory of field reversed configurations

    International Nuclear Information System (INIS)

    Steinhauer, L.C.

    1990-01-01

    This final report surveys the results of work conducted on the theory of field reversed configurations. This project has spanned ten years, beginning in early 1980. During this period, Spectra Technology was one of the leading contributors to the advances in understanding FRC. The report is organized into technical topic areas, FRC formation, equilibrium, stability, and transport. Included as an appendix are papers published in archival journals that were generated in the course of this report. 33 refs

  7. Reverse engineering of integrated circuits

    Science.gov (United States)

    Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

    2003-01-01

    Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

  8. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

    Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

    2017-01-01

    This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

  9. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2013-12-01

    Full Text Available As the power of consumers is growing, the product return for customer service and customer retention has become a common practice in the competitive market, which propels the recent practice of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle. Reverse logistics is the flow and management of products, packaging, components and information from the point of consumption to the point of origin. It is a collection of practices similar to those of supply chain management, but in the opposite direction, from downstream to upstream. It involves activities such as reuse, repair, remanufacture, refurbish, reclaim and recycle. For the conventional forward logistics systems, the flow starts upstream as raw materials, later as manufactured parts and components to be assembled and continues downstream to reach customers as final products to be disposed once they reach their economic or useful lives. In reverse logistics, the disposed products are pushed upstream to be repaired, remanufactured, refurbished, and disassembled into components to be reused or as raw material to be recycled for later use.

  10. SELECTED PROBLEMS OF REVERSE LOGISTICS IN POLAND

    OpenAIRE

    Agata Mesjasz-Lech

    2009-01-01

    This paper presents the essence of reverse logistics and directions of physical and information flows between logistic network partners. It also analyses effects of implementation of the principles of reverse logistics in Poland in the years 2004-2007

  11. Periodicity and Immortality in Reversible Computing

    OpenAIRE

    Kari , Jarkko; Ollinger , Nicolas

    2008-01-01

    Additional material available on the web at http://www.lif.univ-mrs.fr/~nollinge/rec/gnirut/; We investigate the decidability of the periodicity and the immortality problems in three models of reversible computation: reversible counter machines, reversible Turing machines and reversible one-dimensional cellular automata. Immortality and periodicity are properties that describe the behavior of the model starting from arbitrary initial configurations: immortality is the property of having at le...

  12. r-Universal reversible logic gates

    International Nuclear Information System (INIS)

    Vos, A de; Storme, L

    2004-01-01

    Reversible logic plays a fundamental role both in ultra-low power electronics and in quantum computing. It is therefore important to know which reversible logic gates can be used as building block for the reversible implementation of an arbitrary boolean function and which cannot

  13. THEORETICAL FRAMES FOR DESIGNING REVERSE LOGISTICS PROCESSES

    OpenAIRE

    Janusz K. Grabara; Sebastian Kot

    2009-01-01

    Logistics processes of return flow became more and more important in present business practice. Because of better customer satisfaction, environmental and financial aspects many enterprises deal with reverse logistics performance. The paper is a literature review focused on the design principles of reverse logistics processes Keywords: reverse logistics, designing.

  14. Prefix reversals on binary and ternary strings

    NARCIS (Netherlands)

    Hurkens, C.A.J.; van Iersel, L.J.J.; Keijsper, J.C.M.; Kelk, S.M.; Stougie, L.; Tromp, J.T.

    2007-01-01

    Given a permutation $\\pi$, the application of prefix reversal $f^{(i)}$ to $\\pi$ reverses the order of the first $i$ elements of $\\pi$. The problem of sorting by prefix reversals (also known as pancake flipping), made famous by Gates and Papadimitriou (Discrete Math., 27 (1979), pp. 47–57), asks

  15. Prefix reversals on binary and ternary strings

    NARCIS (Netherlands)

    Hurkens, C.A.J.; Iersel, van L.J.J.; Keijsper, J.C.M.; Kelk, S.M.; Stougie, L.; Tromp, J.T.

    2007-01-01

    Given a permutation $\\pi$, the application of prefix reversal $f^{(i)}$ to $\\pi$ reverses the order of the first $i$ elements of $\\pi$. The problem of sorting by prefix reversals (also known as pancake flipping), made famous by Gates and Papadimitriou (Discrete Math., 27 (1979), pp. 47–57), asks for

  16. Remote Whispering Applying Time Reversal

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Brian Eric [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-16

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wires and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.

  17. Repeatable Reverse Engineering with PANDA

    Science.gov (United States)

    2015-12-08

    necessary layout information for the Android 2.3 and 4.2 SDK kernels. See Section IV-C for an example of the kind of deep reverse engineering of Android apps ...code re-use and simplifying complex analysis development. We demonstrate PANDA’s effectiveness via a number of use cases, including enabling an old but...continue to function. 2) Identify critical vulnerabilities . 3) Understand the true purpose and actions of code. It is common for legacy code to stop

  18. Corrosion protected reversing heat exchanger

    International Nuclear Information System (INIS)

    Zawierucha, R.

    1984-01-01

    A reversing heat exchanger of the plate and fin type having multiple aluminum parting sheets in a stacked arrangement with corrugated fins separating the sheets to form multiple flow paths, means for closing the ends of the sheets, an input manifold arrangement of headers for the warm end of of the exchanger and an output manifold arrangement for the cold end of the exchanger with the input air feed stream header and the waste gas exhaust header having an alloy of zinc and aluminum coated on the inside surface for providing corrosion protection to the stack

  19. Presbycusis: reversible with anesthesia drugs?

    Science.gov (United States)

    Kocher, Carl A

    2009-02-01

    Age-related hearing impairment, or presbycusis, is a degenerative condition not currently treatable by medication. It is therefore significant that the author, as a patient, experienced a reversal of high-frequency hearing loss during a 2-day period following abdominal surgery with general anesthesia. This report documents the surgery and the subsequent restoration of hearing, which was bilateral and is estimated to have exceeded 50dB at 4kHz. A possible role is noted for anesthetic agents such as lidocaine, propofol, or fentanyl. This experience may hold a clue for research toward the development of medical treatments for presbycusis.

  20. Field-reversed mirror reactor

    International Nuclear Information System (INIS)

    Carlson, G.A.

    1978-01-01

    The reactor design is a multicell arrangement wherein a series of field-reversed plasma layers are arranged along the axis of a long superconducting solenoid which provides the background magnetic field. Normal copper mirror coils and Ioffe bars placed at the first wall radius provide shallow axial and radial magnetic wells for each plasma layer. Each of 11 plasma layers requires the injection of 3.6 MW of 200 keV deuterium and tritium and produces 20 MW of fusion power. The reactor has a net electric output of 74 MWe and an estimated direct capital cost of $1200/kWe

  1. Development and validation of a HPLC method for the assay of dapivirine in cell-based and tissue permeability experiments.

    Science.gov (United States)

    das Neves, José; Sarmento, Bruno; Amiji, Mansoor; Bahia, Maria Fernanda

    2012-12-12

    Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is being currently used for the development of potential anti-HIV microbicide formulations and delivery systems. A new high-performance liquid chromatography (HPLC) method with UV detection was developed for the assay of this drug in different biological matrices, namely cell lysates, receptor media from permeability experiments and homogenates of mucosal tissues. The method used a reversed-phase C18 column with a mobile phase composed of trifluoroacetic acid solution (0.1%, v/v) and acetonitrile in a gradient mode. Injection volume was 50μL and the flow rate 1mL/min. The total run time was 12min and UV detection was performed at 290nm for dapivirine and the internal standard (IS) diphenylamine. A Box-Behnken experimental design was used to study different experimental variables of the method, namely the ratio of the mobile phase components and the gradient time, and their influence in responses such as the retention factor, tailing factor, and theoretical plates for dapivirine and the IS, as well as the peak resolution between both compounds. The optimized method was further validated and its usefulness assessed for in vitro and ex vivo experiments using dapivirine or dapivirine-loaded nanoparticles. The method showed to be selective, linear, accurate and precise in the range of 0.02-1.5μg/mL. Other chromatographic parameters, namely carry-over, lower limit of quantification (0.02μg/mL), limit of detection (0.006μg/mL), recovery (equal or higher than 90.7%), and sample stability at different storage conditions, were also determined and found adequate for the intended purposes. The method was successfully used for cell uptake assays and permeability studies across cell monolayers and pig genital mucosal tissues. Overall, the proposed method provides a simple, versatile and reliable way for studying the behavior of dapivirine in different biological matrices and assessing its potential as an anti-HIV

  2. Kinematic reversal schemes for the geomagnetic dipole.

    Science.gov (United States)

    Levy, E. H.

    1972-01-01

    Fluctuations in the distribution of cyclonic convective cells, in the earth's core, can reverse the sign of the geomagnetic field. Two kinematic reversal schemes are discussed. In the first scheme, a field maintained by cyclones concentrated at low latitude is reversed by a burst of cyclones at high latitude. Conversely, in the second scheme, a field maintained predominantly by cyclones in high latitudes is reversed by a fluctuation consisting of a burst of cyclonic convection at low latitude. The precise fluid motions which produce the geomagnetic field are not known. However, it appears that, whatever the details are, a fluctuation in the distribution of cyclonic cells over latitude can cause a geomagnetic reversal.

  3. N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance.

    Directory of Open Access Journals (Sweden)

    Soo-Huey Yap

    2007-12-01

    Full Text Available The catalytically active 66-kDa subunit of the human immunodeficiency virus type 1 (HIV-1 reverse transcriptase (RT consists of DNA polymerase, connection, and ribonuclease H (RNase H domains. Almost all known RT inhibitor resistance mutations identified to date map to the polymerase domain of the enzyme. However, the connection and RNase H domains are not routinely analysed in clinical samples and none of the genotyping assays available for patient management sequence the entire RT coding region. The British Columbia Centre for Excellence in HIV/AIDS (the Centre genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance.The prevalence of N348I in clinical isolates, the time taken for it to emerge under selective drug pressure, and its association with changes in viral load, specific drug treatment, and known drug resistance mutations was analysed from genotypes, viral loads, and treatment histories from the Centre's database. N348I increased in prevalence from below 1% in 368 treatment-naïve individuals to 12.1% in 1,009 treatment-experienced patients (p = 7.7 x 10(-12. N348I appeared early in therapy and was highly associated with thymidine analogue mutations (TAMs M41L and T215Y/F (p < 0.001, the lamivudine resistance mutations M184V/I (p < 0.001, and non-nucleoside RTI (NNRTI resistance mutations K103N and Y181C/I (p < 0.001. The association with TAMs and NNRTI resistance mutations was consistent with the selection of N348I in patients treated with regimens that included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval 1.43-4.81. The appearance of N348I was associated with a significant increase in viral load (p < 0.001, which

  4. Theta, time reversal and temperature

    Energy Technology Data Exchange (ETDEWEB)

    Gaiotto, Davide [Perimeter Institute for Theoretical Physics,Waterloo, Ontario, N2L 2Y5 (Canada); Kapustin, Anton [Walter Burke Institute for Theoretical Physics, California Institute of Technology,Pasadena, CA 91125 (United States); Komargodski, Zohar [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 76100 (Israel); Seiberg, Nathan [School of Natural Sciences, Institute for Advanced Study,Princeton, NJ 08540 (United States)

    2017-05-17

    SU(N) gauge theory is time reversal invariant at θ=0 and θ=π. We show that at θ=π there is a discrete ’t Hooft anomaly involving time reversal and the center symmetry. This anomaly leads to constraints on the vacua of the theory. It follows that at θ=π the vacuum cannot be a trivial non-degenerate gapped state. (By contrast, the vacuum at θ=0 is gapped, non-degenerate, and trivial.) Due to the anomaly, the theory admits nontrivial domain walls supporting lower-dimensional theories. Depending on the nature of the vacuum at θ=π, several phase diagrams are possible. Assuming area law for space-like loops, one arrives at an inequality involving the temperatures at which CP and the center symmetry are restored. We also analyze alternative scenarios for SU(2) gauge theory. The underlying symmetry at θ=π is the dihedral group of 8 elements. If deconfined loops are allowed, one can have two O(2)-symmetric fixed points. It may also be that the four-dimensional theory around θ=π is gapless, e.g. a Coulomb phase could match the underlying anomalies.

  5. Exercise prescription to reverse frailty.

    Science.gov (United States)

    Bray, Nick W; Smart, Rowan R; Jakobi, Jennifer M; Jones, Gareth R

    2016-10-01

    Frailty is a clinical geriatric syndrome caused by physiological deficits across multiple systems. These deficits make it challenging to sustain homeostasis required for the demands of everyday life. Exercise is likely the best therapy to reverse frailty status. Literature to date suggests that pre-frail older adults, those with 1-2 deficits on the Cardiovascular Health Study-Frailty Phenotype (CHS-frailty phenotype), should exercise 2-3 times a week, for 45-60 min. Aerobic, resistance, flexibility, and balance training components should be incorporated but resistance and balance activities should be emphasized. On the other hand, frail (CHS-frailty phenotype ≥ 3 physical deficits) older adults should exercise 3 times per week, for 30-45 min for each session with an emphasis on aerobic training. During aerobic, balance, and flexibility training, both frail and pre-frail older adults should work at an intensity equivalent to a rating of perceived exertion of 3-4 ("somewhat hard") on the Borg CR10 scale. Resistance-training intensity should be based on a percentage of 1-repetition estimated maximum (1RM). Program onset should occur at 55% of 1RM (endurance) and progress to higher intensities of 80% of 1RM (strength) to maximize functional gains. Exercise is the medicine to reverse or mitigate frailty, preserve quality of life, and restore independent functioning in older adults at risk of frailty.

  6. Theta, time reversal and temperature

    International Nuclear Information System (INIS)

    Gaiotto, Davide; Kapustin, Anton; Komargodski, Zohar; Seiberg, Nathan

    2017-01-01

    SU(N) gauge theory is time reversal invariant at θ=0 and θ=π. We show that at θ=π there is a discrete ’t Hooft anomaly involving time reversal and the center symmetry. This anomaly leads to constraints on the vacua of the theory. It follows that at θ=π the vacuum cannot be a trivial non-degenerate gapped state. (By contrast, the vacuum at θ=0 is gapped, non-degenerate, and trivial.) Due to the anomaly, the theory admits nontrivial domain walls supporting lower-dimensional theories. Depending on the nature of the vacuum at θ=π, several phase diagrams are possible. Assuming area law for space-like loops, one arrives at an inequality involving the temperatures at which CP and the center symmetry are restored. We also analyze alternative scenarios for SU(2) gauge theory. The underlying symmetry at θ=π is the dihedral group of 8 elements. If deconfined loops are allowed, one can have two O(2)-symmetric fixed points. It may also be that the four-dimensional theory around θ=π is gapless, e.g. a Coulomb phase could match the underlying anomalies.

  7. Optimized reversible binary-coded decimal adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert

    2008-01-01

    Abstract Babu and Chowdhury [H.M.H. Babu, A.R. Chowdhury, Design of a compact reversible binary coded decimal adder circuit, Journal of Systems Architecture 52 (5) (2006) 272-282] recently proposed, in this journal, a reversible adder for binary-coded decimals. This paper corrects and optimizes...... their design. The optimized 1-decimal BCD full-adder, a 13 × 13 reversible logic circuit, is faster, and has lower circuit cost and less garbage bits. It can be used to build a fast reversible m-decimal BCD full-adder that has a delay of only m + 17 low-power reversible CMOS gates. For a 32-decimal (128-bit....... Keywords: Reversible logic circuit; Full-adder; Half-adder; Parallel adder; Binary-coded decimal; Application of reversible logic synthesis...

  8. Kinetic Line Voronoi Operations and Their Reversibility

    DEFF Research Database (Denmark)

    Mioc, Darka; Anton, François; Gold, Christopher

    2010-01-01

    In Geographic Information Systems the reversibility of map update operations has not been explored yet. In this paper we are using the Voronoi based Quad-edge data structure to define reversible map update operations. The reversibility of the map operations has been formalised at the lowest level...... mechanisms and dynamic map visualisations. In order to use the reversibility within the kinetic Voronoi diagram of points and open oriented line segments, we need to assure that reversing the map commands will produce exactly the changes in the map equivalent to the previous map states. To prove...... that reversing the map update operations produces the exact reverse changes, we show an isomorphism between the set of complex operations on the kinetic Voronoi diagram of points and open oriented line segments and the sets of numbers of new / deleted Voronoi regions induced by these operations, and its...

  9. Reversal of diaschisis by zolpidem

    International Nuclear Information System (INIS)

    Claus, R.P.; Nel, H.W.; Sathekge, M.

    2004-01-01

    Full text: Introduction: Recent literature has reported on clinical improvement after zolpidem, a GABAergic anti insomnia drug, in brain injury and stroke patients. In this study, the effect of zolpidem on crossed cerebellar diaschisis was investigated in such patients. Method: Four patients with crossed cerebellar diaschisis after brain injury or stroke were investigated before and after application of 10 mg zolpidem by 99mTc HMPAO brain SPECT. Result: Apart from clinical improvements, 99mTc HMPAO brain SPECT studies showed reversal of the crossed cerebellar diaschisis and improvement of perfusion defects after zolpidem. Conclusion: 99mTc HMPAO brain SPECT may have a role to pre-select brain injury and stroke patients who will benefit clinically from zolpidem therapy. (author)

  10. Model of reverse steam generator

    International Nuclear Information System (INIS)

    Malasek, V.; Manek, O.; Masek, V.; Riman, J.

    1987-01-01

    The claim of Czechoslovak discovery no. 239272 is a model designed for the verification of the properties of a reverse steam generator during the penetration of water, steam-water mixture or steam into liquid metal flowing inside the heat exchange tubes. The design may primarily be used for steam generators with a built-in inter-tube structure. The model is provided with several injection devices configured in different heat exchange tubes, spaced at different distances along the model axis. The design consists in that between the pressure and the circumferential casings there are transverse partitions and that in one chamber consisting of the circumferential casings, pressure casing and two adjoining partitions there is only one passage of the injection device through the inter-tube space. (Z.M.). 1 fig

  11. Reversible arithmetic logic unit for quantum arithmetic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert; Axelsen, Holger Bock

    2010-01-01

    This communication presents the complete design of a reversible arithmetic logic unit (ALU) that can be part of a programmable reversible computing device such as a quantum computer. The presented ALU is garbage free and uses reversible updates to combine the standard reversible arithmetic...... and logical operations in one unit. Combined with a suitable control unit, the ALU permits the construction of an r-Turing complete computing device. The garbage-free ALU developed in this communication requires only 6n elementary reversible gates for five basic arithmetic-logical operations on two n......-bit operands and does not use ancillae. This remarkable low resource consumption was achieved by generalizing the V-shape design first introduced for quantum ripple-carry adders and nesting multiple V-shapes in a novel integrated design. This communication shows that the realization of an efficient reversible...

  12. Principles of a reversible programming language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    The principles of reversible programming languages are explicated and illustrated with reference to the design of a high-level imperative language, Janus. The fundamental properties for such languages include backward as well as forward determinism and reversible updates of data. The unique design...... languages, and demonstrate this for Janus. We show the practicality of the language by implementation of a reversible fast Fourier transform. Our results indicate that the reversible programming paradigm has fundamental properties that are relevant to many different areas of computer science....... features of the language include explicit post-condition assertions, direct access to an inverse semantics and the possibility of clean (i.e., garbage-free) computation of injective functions. We suggest the clean simulation of reversible Turing machines as a criterion for computing strength of reversible...

  13. Securing Biometric Images using Reversible Watermarking

    OpenAIRE

    Thampi, Sabu M.; Jacob, Ann Jisma

    2011-01-01

    Biometric security is a fast growing area. Protecting biometric data is very important since it can be misused by attackers. In order to increase security of biometric data there are different methods in which watermarking is widely accepted. A more acceptable, new important development in this area is reversible watermarking in which the original image can be completely restored and the watermark can be retrieved. But reversible watermarking in biometrics is an understudied area. Reversible ...

  14. Combining or Separating Forward and Reverse Logistics

    DEFF Research Database (Denmark)

    Herbert-Hansen, Zaza Nadja Lee; Larsen, Samuel; Nielsen, Anders

    2018-01-01

    Purpose – While forward logistics handles and manages the flow of goods downstream in the supply chain from suppliers to customers, reverse logistics (RL) manages the flow of returned goods upstream. A firm can combine reverse logistics with forward logistics, keep the flows separated, or choose......-research addresses intra-RL issues while the relationship between forward and reverse logistics is under-researched. This paper contributes to RL-theory by identifying the contextual factors that determine the most advantageous relationship between forward and reverse logistics, and proposes a novel decision making...

  15. Time reversal and the neutron

    International Nuclear Information System (INIS)

    Chupp, T. E.; Cooper, R. L.; Coulter, K. P.; Freedman, S. J.; Fujikawa, B. K.; Jones, G. L.; Garcia, A.; Mumm, H. P.; Nico, J. S.; Thompson, A. K.; Trull, C.; Wietfeldt, F. E.; Wilkerson, J. F.

    2013-01-01

    We have measured the triple correlation D n >/J n ·(β e x p-hat ν ) with a polarized cold-neutron beam (Mumm et al., Phys Rev Lett 107:102301, 2011; Chupp et al., Phys Rev C 86:035505, 2012). A non-zero value of D can arise due to parity-even-time-reversal-odd interactions that imply CP violation. Final-state effects also contribute to D at the level of 10  − 5 and can be calculated with precision of 1 % or better. The D coefficient is uniquely sensitive to the imaginary part of the ratio of axial-vector and vector beta-decay amplitudes as well as to scalar and tensor interactions that could arise due to beyond-Standard-Model physics. Over 300 million proton-electron coincidence events were used in a blind analysis with the result D = [ − 0.94±1.89 (stat)±0.97(sys)]×10  − 4 . Assuming only vector and axial vector interactions in beta decay, our result can be interpreted as a measure of the phase of the axial-vector coupling relative to the vector coupling, φ AV = 180.012 ° ± 0.028 °. This result also improves constrains on certain non-VA interactions.

  16. Reverse transcriptase inhibitors as microbicides.

    Science.gov (United States)

    Lewi, Paul; Heeres, Jan; Ariën, Kevin; Venkatraj, Muthusamy; Joossens, Jurgen; Van der Veken, Pieter; Augustyns, Koen; Vanham, Guido

    2012-01-01

    The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.

  17. Reversible hypothyroidism and Whipple's disease

    Directory of Open Access Journals (Sweden)

    Tran Huy A

    2006-05-01

    Full Text Available Abstract Background The major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease. Case presentation A 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipple's disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipple's disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipple's disease. Conclusion This is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipple's disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.

  18. Time reversal and the neutron

    Energy Technology Data Exchange (ETDEWEB)

    Chupp, T. E., E-mail: chupp@umich.edu; Cooper, R. L.; Coulter, K. P. [Univeristy of Michigan (United States); Freedman, S. J.; Fujikawa, B. K. [University of California and Lawrence Berkeley Laboratory (United States); Jones, G. L. [Hamilton College (United States); Garcia, A. [University of Washington (United States); Mumm, H. P.; Nico, J. S.; Thompson, A. K. [National Institute of Standards and Technology (United States); Trull, C.; Wietfeldt, F. E. [Tulane University (United States); Wilkerson, J. F. [University of North Carolina (United States); Collaboration: emiT II Collaboration

    2013-03-15

    We have measured the triple correlation D/J{sub n}{center_dot}({beta}{sub e} x p-hat{sub {nu}}) with a polarized cold-neutron beam (Mumm et al., Phys Rev Lett 107:102301, 2011; Chupp et al., Phys Rev C 86:035505, 2012). A non-zero value of D can arise due to parity-even-time-reversal-odd interactions that imply CP violation. Final-state effects also contribute to D at the level of 10{sup - 5} and can be calculated with precision of 1 % or better. The D coefficient is uniquely sensitive to the imaginary part of the ratio of axial-vector and vector beta-decay amplitudes as well as to scalar and tensor interactions that could arise due to beyond-Standard-Model physics. Over 300 million proton-electron coincidence events were used in a blind analysis with the result D = [ - 0.94{+-}1.89 (stat){+-}0.97(sys)] Multiplication-Sign 10{sup - 4}. Assuming only vector and axial vector interactions in beta decay, our result can be interpreted as a measure of the phase of the axial-vector coupling relative to the vector coupling, {phi}{sub AV} = 180.012 Degree-Sign {+-} 0.028 Degree-Sign . This result also improves constrains on certain non-VA interactions.

  19. 5-Hydroxypyrido[2,3-b]pyrazin-6(5H)-one derivatives as novel dual inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H and integrase.

    Science.gov (United States)

    Sun, Lin; Gao, Ping; Dong, Guanyu; Zhang, Xujie; Cheng, Xiqiang; Ding, Xiao; Wang, Xueshun; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Menéndez-Arias, Luis; Zhan, Peng; Liu, Xinyong

    2018-06-18

    We reported herein the design, synthesis and biological evaluation of a series of 5-hydroxypyrido[2,3-b]pyrazin-6(5H)-one derivatives as HIV-1 reverse transcriptase (RT) ribonuclease H (RNase H) inhibitors using a privileged structure-guided scaffold refining strategy. In view of the similarities between the pharmacophore model of RNase H and integrase (IN) inhibitors as well as their catalytic sites, we also performed IN inhibition assays. Notably, the majority of these derivatives inhibited RNase H and IN at micromolar concentrations. Among them, compound 7a exhibited similar inhibitory activity against RNase H and IN (IC 50 RNase H  = 1.77 μM, IC 50 IN  = 1.18 μM, ratio = 1.50). To the best of our knowledge, this is the first reported dual HIV-1 RNase H-IN inhibitor based on a 5-hydroxypyrido[2,3-b]pyrazin-6(5H)-one structure. Molecular modeling has been used to predict the binding mode of 7a in complex with the catalytic cores of HIV-1 RNase H and IN. Taken together these results strongly support the feasibility of developing HIV-1 dual inhibitors from analog-based optimization of divalent metal ion chelators. Recently, the identification of dual inhibitors proved to be a highly effective strategy for novel antivirals discovery. Therefore, these compounds appear to be useful leads that can be further modified to develop more valuable anti-HIV-1 molecules with suitable drug profiles. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Multiple reversal olfactory learning in honeybees

    Directory of Open Access Journals (Sweden)

    Theo Mota

    2010-07-01

    Full Text Available In multiple reversal learning, animals trained to discriminate a reinforced from a non-reinforced stimulus are subjected to various, successive reversals of stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-. This protocol is useful to determine whether or not animals learn to learn and solve successive discriminations faster (or with fewer errors with increasing reversal experience. Here we used the olfactory conditioning of proboscis extension reflex to study how honeybees Apis mellifera perform in a multiple reversal task. Our experiment contemplated four consecutive differential conditioning phases involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+. We show that bees in which the weight of reinforced or non-reinforced stimuli was similar mastered the multiple olfactory reversals. Bees which failed the task exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus being unable to rapidly reverse stimulus contingencies. Efficient reversers did not improve their successive discriminations but rather tended to generalize their choice to both odors at the end of conditioning. As a consequence, both discrimination and reversal efficiency decreasedalong experimental phases. This result invalidates a learning-to-learn effect and indicates that bees do not only respond to the actual stimulus contingencies but rather combine these with an average of past experiences with the same stimuli.  

  1. Online Reverse Auctions for Procurement of Services

    NARCIS (Netherlands)

    U.L. Radkevitch (Uladzimir)

    2008-01-01

    textabstractOnline reverse auctions, in which a buyer seeks to select a supplier and suppliers compete for contracts by bidding online, revolutionized corporate procurement early this century. Shortly after they had been pioneered by General Electric, many companies rushed to adopt reverse auctions

  2. Vibrational dynamics of ice in reverse micelles

    NARCIS (Netherlands)

    Dokter, A.M.; Petersen, C.; Woutersen, S.; Bakker, H.J.

    2008-01-01

    he ultrafast vibrational dynamics of HDO:D2O ice at 180 K in anionic reverse micelles is studied by midinfrared femtosecond pump-probe spectroscopy. Solutions containing reverse micelles are cooled to low temperatures by a fast-freezing procedure. The heating dynamics of the micellar solutions is

  3. Reversible logic gates on Physarum Polycephalum

    International Nuclear Information System (INIS)

    Schumann, Andrew

    2015-01-01

    In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum

  4. Magnetic reversals from planetary dynamo waves.

    Science.gov (United States)

    Sheyko, Andrey; Finlay, Christopher C; Jackson, Andrew

    2016-11-24

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines by columnar convection. Here we present an example of another class of reversing-geodynamo model, which operates in a regime of comparatively low viscosity and high magnetic diffusivity. This class does not fit into the paradigm of reversal regimes that are dictated by the value of the local Rossby number (the ratio of advection to Coriolis force). Instead, stretching of the magnetic field by a strong shear in the east-west flow near the imaginary cylinder just touching the inner core and parallel to the axis of rotation is crucial to the reversal mechanism in our models, which involves a process akin to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.

  5. Reverse engineering of the robot base platform

    International Nuclear Information System (INIS)

    Anwar A Rahman; Azizul Rahman A Aziz; Mohd Arif Hamzah; Muhd Nor Atan; Fadil Ismail; Rosli Darmawan

    2009-01-01

    The robot base platform used to place the robotic arm version 2 was imported through a local company. The robot base platform is used as a reference for reverse egineering development for a smaller size robot. The paper will discuss the reverse engineering design process and parameters involved in the development of the robot base platform. (Author)

  6. Reverse logistics: A review of case studies

    NARCIS (Netherlands)

    Brito, de M.P.; Dekker, Rommert; Flapper, S.D.P.; Fleischmann, B.; Klose, A.

    2004-01-01

    This paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In addition we compare

  7. Reversal of laryngotracheal separation in paediatric patients.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    OBJECTIVE: Laryngotracheal separation (LTS) is an effective and reliable definitive treatment for intractable aspiration. A major advantage of this treatment for intractable aspiration is its\\' potential reversibility. Should the underlying disorder improve, a reversal of the procedure may be attempted. This has been successfully achieved in the adult population. To our knowledge, no previous cases have been reported of successful reversal of LTS in children. METHODS: A retrospective review from 2003 to 2010 identified four cases of intractable aspiration treated with LTS in our department. Two of these patients displayed objective evidence of sufficient recovery of their underlying aspiration to consider reversal. Patient selection for reversal was dependent upon successful oral intake for 9 months along with videofluoroscopic evidence of normal or minimally impaired swallow. RESULTS: Two children who were successfully treated for intractable aspiration with LTS demonstrated objective evidence of recovery sufficient to attempt reversal. Both children underwent successful surgical reversal of LTS using a cricotracheal resection with end-to-end anastamosis, similar to that used in treatment of subglottic stenosis. Both children can now tolerate oral diet and their speech and language development is in line with their overall developmental level. CONCLUSIONS: Laryngotracheal separation is an effective and reliable definitive treatment for intractable aspiration facilitating protection of the airway and allowing safe swallowing with unimpeded respiration, but with the major drawback of loss of phonation. To our knowledge, we document the first two cases of successful LTS reversal in children.

  8. Observation of the reversed current effect

    International Nuclear Information System (INIS)

    Jones, I.R.; Silawatshananai, C.

    1979-05-01

    The paper describes an observation of the reversed current effect, and its consequences, in a 'stabilized' Z-pinch. Magnetic probe measurements and holographic interferometry were used to follow the development of a reversed current layer and to pinpoint its location in the outer region of the pinched plasma column. The subsequent ejection of the outer plasma layer was observed using fast photography

  9. Magnetic reversals from planetary dynamo waves

    DEFF Research Database (Denmark)

    Sheyko, Andrey; Finlay, Chris; Jackson, Andrew

    2016-01-01

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes ...... to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.......A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes...... place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines...

  10. Kronisk ileus efter iatrogen reversering af tyndtarmen

    DEFF Research Database (Denmark)

    Pedersen, Mark Ellebaek; Rahr, Hans B; Mahdi, Bassam

    2010-01-01

    We report a case of inadvertent reversal of the entire small intestine leading to severe complications and long-standing ileus. The clinical diagnosis was confirmed by magnetic resonance imaging and laparotomy. The patient was cured by surgical re-reversal of the bowel. Care should be taken to ma...... the bowel ends when multiple simultaneous bowel resections are performed....

  11. Probabilistic Reversible Automata and Quantum Automata

    OpenAIRE

    Golovkins, Marats; Kravtsev, Maksim

    2002-01-01

    To study relationship between quantum finite automata and probabilistic finite automata, we introduce a notion of probabilistic reversible automata (PRA, or doubly stochastic automata). We find that there is a strong relationship between different possible models of PRA and corresponding models of quantum finite automata. We also propose a classification of reversible finite 1-way automata.

  12. Designing Novel Quaternary Quantum Reversible Subtractor Circuits

    Science.gov (United States)

    Haghparast, Majid; Monfared, Asma Taheri

    2018-01-01

    Reversible logic synthesis is an important area of current research because of its ability to reduce energy dissipation. In recent years, multiple valued logic has received great attention due to its ability to reduce the width of the reversible circuit which is a main requirement in quantum technology. Subtractor circuits are between major components used in quantum computers. In this paper, we will discuss the design of a quaternary quantum reversible half subtractor circuit using quaternary 1-qudit, 2-qudit Muthukrishnan-Stroud and 3-qudit controlled gates and a 2-qudit Generalized quaternary gate. Then a design of a quaternary quantum reversible full subtractor circuit based on the quaternary half subtractor will be presenting. The designs shall then be evaluated in terms of quantum cost, constant input, garbage output, and hardware complexity. The proposed quaternary quantum reversible circuits are the first attempt in the designing of the aforementioned subtractor.

  13. Parkinson’s disease managing reversible neurodegeneration

    Science.gov (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

  14. Estimation and uncertainty of reversible Markov models.

    Science.gov (United States)

    Trendelkamp-Schroer, Benjamin; Wu, Hao; Paul, Fabian; Noé, Frank

    2015-11-07

    Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta-stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software--http://pyemma.org--as of version 2.0.

  15. Drift reversal capability in helical systems

    International Nuclear Information System (INIS)

    Yokoyama, M.; Itoh, K.; Okamura, S.

    2002-10-01

    The maximum-J (J is the second adiabatic invariant) capability, i.e., the drift reversal capability, is examined in quasi-axisymmetric (QAS) stellarators and quasi-poloidally symmetric (QPS) stellarators as a possible mechanism for turbulent transport suppression. Due to the existence of non-axisymmetry of the magnetic field strength in QAS configurations, a local maximum of J is created to cause the drift reversal. The increase of magnetic shear in finite beta equilibria also has favorable effect in realizing the drift reversal. The radial variation of the uniform magnetic field component plays a crucial role for the drift reversal in a QPS configuration. Thus, the drift reversal capability and its external controllability are demonstrated for QAS and QPS stellarators, by which the impact of magnetic configuration on turbulent transport can be studied in experiments. (author)

  16. Drift reversal capability in helical systems

    International Nuclear Information System (INIS)

    Yokoyama, M.; Itoh, K.; Okamura, S.; Matsuoka, K.; Nakajima, N.; Itoh, S.-I.; Neilson, G.H.; Zarnstorff, M.C.; Rewoldt, G.

    2003-01-01

    The maximum-J (J is the second adiabatic invariant) capability, i.e., the drift reversal capability, is examined in quasi-axisymmetric (QAS) stellarators and quasi-poloidally symmetric (QPS) stellarators as a possible mechanism for turbulent transport suppression. Due to the existence of non-axisymmetry of the magnetic field strength in QAS configurations, a local maximum of J is created to cause the drift reversal. The increase of magnetic shear in finite beta equilibria also has favorable effect in realizing the drift reversal. The radial variation of the uniform magnetic field component plays a crucial role for the drift reversal in a QPS configuration. Thus, the drift reversal capability and its external controllability are demonstrated for QAS and QPS stellarators, by which the impact of magnetic configuration on turbulent transport can be studied in experiments. (author)

  17. Reversed field pinch ignition requirements

    International Nuclear Information System (INIS)

    Werley, K.A.

    1991-01-01

    Plasma models are described and used to calculated numerically the transport confinement (nτ E ) requirements and steady state operation points for both the reversed field pinch (RFP) and the tokamak. The models are used to examine the CIT tokamak ignition conditions and the RFP experimental and ignition conditions. Physics differences between RFPs and tokamaks and their consequences for a D-T ignition machine are discussed. Compared with a tokamak, the ignition RFP has many physics advantages, including Ohmic heating to ignition (no need for auxiliary heating systems), higher beta, lower ignition current, less sensitivity of ignition requirements to impurity effects, no hard disruptions (associated with beta or density limits) and successful operation with high radiation fractions (f RAD ∼ 0.95). These physics advantages, coupled with important engineering advantages associated with lower external magnetic field, larger aspect ratios and smaller plasma cross-sections, translate to significant cost reductions for both ignition and reactor applications. The primary drawback of the RFP is the uncertainty that the present scaling will extrapolate to reactor regimes. Devices that are under construction should go a long way toward resolving this scaling uncertainty. The 4 MA ZTH is expected to extend the nτ E transport scaling data by three orders of magnitude above the results of ZT-40M, and, if the present scaling holds, ZTH is expected to achieve a D-T equivalent scientific energy breakeven, Q = 1. A base case RFP ignition point is identified with a plasma current of 8.1 MA and no auxiliary heating. (author). 19 refs, 11 figs, 3 tabs

  18. Reversibility: An Engineer's Point of View

    Energy Technology Data Exchange (ETDEWEB)

    Berest, Pierre [LMS, ecole Polytechnique (France)

    2012-07-01

    Reversibility is the most consistent option in a democratic country. However reversibility may also have several drawbacks which must be identified and mitigated. Reversibility of a geological repository is a relatively new idea in France. The 1991 law dedicated to nuclear waste management considered reversibility as a possible option. Fifteen years later, the 2006 law mandated that a deep repository must be reversible and that the exact content of this notion should be defined by a new law to be discussed by the Parliament in 2015. Reversibility was not a concern put forward by engineers. It clearly originated from a societal demand sponsored and formulated by the Parliament. Since 1991, the exact meaning of this mandate progressively became more precise. In the early days, reversibility meant the technical and financial capability to retrieve the wastes from the repository, at least for some period of time after being emplaced. Progressively, a broader definition, suggested by Andra, was accepted: reversibility also means that a disposal facility should be operated in such a way that a stepwise decision-making process is possible. At each step, society must be able to decide to proceed to the next step, to pause or to reverse a step. Several benefits can be expected from a reversible repository. Some technical safety concerns may be only recognised after waste emplacement. Radioactive wastes may become a resource whose recoverability is desirable. Regulations may change, alternative waste treatment or better disposal techniques may be developed, or the need to modify a component of the facility may arise. Looking back at how chemical or domestic wastes were managed some 50 years ago easily underscores that it is not unreasonable to hope for significant advances in the future. For scientists and engineers, reversibility proves to have several other merits. To design and build a good repository, time is needed. The operator of a mine or of an oil field knows that

  19. Chemical reactions in reverse micelle systems

    Science.gov (United States)

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.

    1993-08-24

    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.

  20. Reversible Lithium Neurotoxicity: Review of the Literature

    Science.gov (United States)

    Netto, Ivan

    2012-01-01

    Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. Data Sources: A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. Study Selection: A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. Data Extraction: The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Data Synthesis: Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Conclusions: Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate

  1. Reversible lithium neurotoxicity: review of the literatur.

    Science.gov (United States)

    Netto, Ivan; Phutane, Vivek H

    2012-01-01

    Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of

  2. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    The design of fast arithmetic logic circuits is an important research topic for reversible and quantum computing. A special challenge in this setting is the computation of standard arithmetical functions without the generation of \\emph{garbage}. Here, we present a novel parallelization scheme...... wherein $m$ parallel $k$-bit reversible ripple-carry adders are combined to form a reversible $mk$-bit \\emph{ripple-block carry adder} with logic depth $\\mathcal{O}(m+k)$ for a \\emph{minimal} logic depth $\\mathcal{O}(\\sqrt{mk})$, thus improving on the $mk$-bit ripple-carry adder logic depth $\\mathcal...

  3. Reverse logistics in the Brazilian construction industry.

    Science.gov (United States)

    Nunes, K R A; Mahler, C F; Valle, R A

    2009-09-01

    In Brazil most Construction and Demolition Waste (C&D waste) is not recycled. This situation is expected to change significantly, since new federal regulations oblige municipalities to create and implement sustainable C&D waste management plans which assign an important role to recycling activities. The recycling organizational network and its flows and components are fundamental to C&D waste recycling feasibility. Organizational networks, flows and components involve reverse logistics. The aim of this work is to introduce the concepts of reverse logistics and reverse distribution channel networks and to study the Brazilian C&D waste case.

  4. Reversible perspective and splitting in time.

    Science.gov (United States)

    Hart, Helen Schoenhals

    2012-01-01

    The element of time--the experience of it and the defensive use of it--is explored in conjunction with the use of reversible perspective as a psychotic defense. Clinical material from a long analysis illustrates how a psychotic patient used the reversible perspective, with its static splitting, to abolish the experience of time. When he improved and the reversible perspective became less effective for him, he replaced it with a more dynamic splitting mechanism using time gaps. With further improvement, the patient began to experience the passage of time, and along with it the excruciating pain of separation, envy, and loss.

  5. Performance of the reverse Helmbold universal portfolio

    Science.gov (United States)

    Tan, Choon Peng; Kuang, Kee Seng; Lee, Yap Jia

    2017-04-01

    The universal portfolio is an important investment strategy in a stock market where no stochastic model is assumed for the stock prices. The zero-gradient set of the objective function estimating the next-day portfolio which contains the reverse Kullback-Leibler order-alpha divergence is considered. From the zero-gradient set, the explicit, reverse Helmbold universal portfolio is obtained. The performance of the explicit, reverse Helmbold universal portfolio is studied by running them on some stock-price data sets from the local stock exchange. It is possible to increase the wealth of the investor by using these portfolios in investment.

  6. Time reversibility in the quantum frame

    Energy Technology Data Exchange (ETDEWEB)

    Masot-Conde, Fátima [Escuela Superior Ingenieros, Dpt. Física Aplicada III, Universidad de Sevilla Isla Mágica, 41092- Sevilla (Spain)

    2014-12-04

    Classic Mechanics and Electromagnetism, conventionally taken as time-reversible, share the same concept of motion (either of mass or charge) as the basis of the time reversibility in their own fields. This paper focuses on the relationship between mobile geometry and motion reversibility. The goal is to extrapolate the conclusions to the quantum frame, where matter and radiation behave just as elementary mobiles. The possibility that the asymmetry of Time (Time’s arrow) is an effect of a fundamental quantum asymmetry of elementary particles, turns out to be a consequence of the discussion.

  7. Refractory reverse amblyopia with atropine penalization

    Directory of Open Access Journals (Sweden)

    Preeti Ajit Patil

    2010-01-01

    Full Text Available Pharmacological penalization with atropine has been shown to be equally effective as conventional occlusion therapy in the treatment of amblyopia in children. Reverse amblyopia of the sound eye with atropine penalization has been reported before, but is more common in cases where the effect is augmented with optical penalization and is mostly reversible. We report a case of reverse amblyopia with atropine penalization, in a 4-year-old girl, which was refractory to treatment. This report highlights the need for strict monitoring of the vision in the sound eye and regular follow-up in children undergoing amblyopia treatment.

  8. Reversible machine code and its abstract processor architecture

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert; Yokoyama, Tetsuo

    2007-01-01

    A reversible abstract machine architecture and its reversible machine code are presented and formalized. For machine code to be reversible, both the underlying control logic and each instruction must be reversible. A general class of machine instruction sets was proven to be reversible, building...

  9. Constraining the reversing and non-reversing modes of the geodynamo. New insights from magnetostratigraphy.

    Science.gov (United States)

    Gallet, Y.; Pavlov, V.; Shatsillo, A.; Hulot, G.

    2015-12-01

    Constraining the evolution in the geomagnetic reversal frequency over hundreds of million years is not a trivial matter. Beyond the fact that there are long periods without reversals, known as superchrons, and periods with many reversals, the way the reversal frequency changes through time during reversing periods is still debated. A smooth evolution or a succession of stationary segments have both been suggested to account for the geomagnetic polarity time scale since the Middle-Late Jurassic. Sudden changes from a reversing mode to a non-reversing mode of the geodynamo may also well have happened, the switch between the two modes having then possibly been controlled by the thermal conditions at the core-mantle boundary. There is, nevertheless, a growing set of magnetostratigraphic data, which could help decipher a proper interpretation of the reversal history, in particular in the early Paleozoic and even during the Precambrian. Although yielding a fragmentary record, these data reveal the occurrence of both additional superchrons and periods characterized by extremely high, not to say extraordinary, magnetic reversal frequencies. In this talk, we will present a synthesis of these data, mainly obtained from Siberia, and discuss their implication for the magnetic reversal behavior over the past billion years.

  10. Long-acting reversible hormonal contraception

    African Journals Online (AJOL)

    Abstract. Long-acting reversible hormonal contraceptives are effective methods of birth control that provide contraception for an extended ... The World Health Organization (WHO) has online tools available .... trials and marketing experience.

  11. Reversal of target-specific oral anticoagulants

    Science.gov (United States)

    Siegal, D.M.; Cuker, Adam

    2014-01-01

    Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

  12. Magnetization reversal mechanisms under oblique magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Ntallis, N.; Efthimiadis, K.G., E-mail: kge@auth.gr

    2017-03-01

    In this work finite element micromagnetic simulations were performed in order to study the reversal mechanisms of spherical ferromagnetic particles with uniaxial magnetocrystalline anisotropy, when they are magnetized along an oblique direction with respect to the anisotropy axis. Magnetization loops are taken in different directions of external magnetic field, at different anisotropy constants and particle sizes. In the simulation results, the three reversal mechanisms (coherent, curling and domains) are observed and new phenomena arise due to the action of oblique magnetic fields. Moreover, the dependence of the critical fields with respect to the angle of the external field is presented. - Highlights: • Finite element micromagnetic simulation of the three different reversal mechanisms. • For the curling mechanism, the new phenomenon is the rotation of the vortex. • In the domain reversal mechanism, the formed domain wall is smaller than 180°. • In soft ferromagnetic particles a rearrangement of the magnetic domains is observed.

  13. Medical abortion reversal: science and politics meet.

    Science.gov (United States)

    Bhatti, Khadijah Z; Nguyen, Antoinette T; Stuart, Gretchen S

    2018-03-01

    Medical abortion is a safe, effective, and acceptable option for patients seeking an early nonsurgical abortion. In 2014, medical abortion accounted for nearly one third (31%) of all abortions performed in the United States. State-level attempts to restrict reproductive and sexual health have recently included bills that require physicians to inform women that a medical abortion is reversible. In this commentary, we will review the history, current evidence-based regimen, and regulation of medical abortion. We will then examine current proposed and existing abortion reversal legislation. The objective of this commentary is to ensure physicians are armed with rigorous evidence to inform patients, communities, and policy makers about the safety of medical abortion. Furthermore, given the current paucity of evidence for medical abortion reversal, physicians and policy makers can dispel bad science and misinformation and advocate against medical abortion reversal legislation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Stability of the field-reversed mirror

    International Nuclear Information System (INIS)

    Morse, E.C.

    1979-01-01

    The stability of a field reversed mirror plasma configuration is studied with an energy principle derived from the Vlasov equation. Because of finite orbit effects, the stability properties of a field-reversed mirror are different from the stability properties of similar magnetohydrodynamic equilibria. The Vlasov energy principle developed here is applied to a computer simulation of an axisymmetric field-reversed mirror state. It has been possible to prove that the l = 0 modes, called tearing modes, satisfy a sufficient condition for stability. Precessional modes, with l = 1, 2, are found to be unstable at low growth rate. This suggests possible turbulent behavior (Bohm confinement) in the experimental devices aiming at field reversal. Techniques for suppressing these instabilities are outlined, and the applicability of the Vlasov energy principle to more complicated equilibrium models is shown

  15. Modified and reverse radiometric flow injection analysis

    Energy Technology Data Exchange (ETDEWEB)

    Myint, U; Ba, H; Khin, M M; Aung, K; Thida, [Yangon Univ. (Myanmar). Dept. of Chemistry; Toelgyessy, J [Slovak Technical Univ., Bratislava (Slovakia). Dept. of Environmental Science

    1994-06-01

    Determination of [sup 137]Cs and [sup 60]Co by using modified and reverse radiometric flow injection analysis is described. Two component RFIA was also realized using [sup 60]Co and [sup 137]Cs radionuclides. (author) 2 refs.; 5 figs.

  16. Reverse-osmosis membranes by plasma polymerization

    Science.gov (United States)

    Hollahan, J. R.; Wydeven, T.

    1972-01-01

    Thin allyl amine polymer films were developed using plasma polymerization. Resulting dry composite membranes effectively reject sodium chloride during reverse osmosis. Films are 98% sodium chloride rejective, and 46% urea rejective.

  17. Reverse-symmetry waveguides: Theory and fabrication

    DEFF Research Database (Denmark)

    Horvath, R.; Lindvold, Lars René; Larsen, N.B.

    2002-01-01

    We present an extensive theoretical analysis of reverse-symmetry waveguides with special focus on their potential application as sensor components in aqueous media and demonstrate a novel method for fabrication of such waveguides. The principle of reverse symmetry is based on making the refractive...... index of the waveguide substrate less than the refractive index of the medium covering the waveguiding film (n(water) = 1.33). This is opposed to the conventional waveguide geometry, where the substrate is usually glass or polymers with refractive indices of approximate to1.5. The reverse configuration...... are combined with air-grooved polymer supports to form freestanding single-material polymer waveguides of reverse symmetry capable of guiding light....

  18. Time reversibility, computer simulation, algorithms, chaos

    CERN Document Server

    Hoover, William Graham

    2012-01-01

    A small army of physicists, chemists, mathematicians, and engineers has joined forces to attack a classic problem, the "reversibility paradox", with modern tools. This book describes their work from the perspective of computer simulation, emphasizing the author's approach to the problem of understanding the compatibility, and even inevitability, of the irreversible second law of thermodynamics with an underlying time-reversible mechanics. Computer simulation has made it possible to probe reversibility from a variety of directions and "chaos theory" or "nonlinear dynamics" has supplied a useful vocabulary and a set of concepts, which allow a fuller explanation of irreversibility than that available to Boltzmann or to Green, Kubo and Onsager. Clear illustration of concepts is emphasized throughout, and reinforced with a glossary of technical terms from the specialized fields which have been combined here to focus on a common theme. The book begins with a discussion, contrasting the idealized reversibility of ba...

  19. Optical reversible programmable Boolean logic unit.

    Science.gov (United States)

    Chattopadhyay, Tanay

    2012-07-20

    Computing with reversibility is the only way to avoid dissipation of energy associated with bit erase. So, a reversible microprocessor is required for future computing. In this paper, a design of a simple all-optical reversible programmable processor is proposed using a polarizing beam splitter, liquid crystal-phase spatial light modulators, a half-wave plate, and plane mirrors. This circuit can perform 16 logical operations according to three programming inputs. Also, inputs can be easily recovered from the outputs. It is named the "reversible programmable Boolean logic unit (RPBLU)." The logic unit is the basic building block of many complex computational operations. Hence the design is important in sense. Two orthogonally polarized lights are defined here as two logical states, respectively.

  20. Elastic least-squares reverse time migration

    KAUST Repository

    Feng, Zongcai; Schuster, Gerard T.

    2016-01-01

    Elastic least-squares reverse time migration (LSRTM) is used to invert synthetic particle-velocity data and crosswell pressure field data. The migration images consist of both the P- and Svelocity perturbation images. Numerical tests on synthetic and field data illustrate the advantages of elastic LSRTM over elastic reverse time migration (RTM). In addition, elastic LSRTM images are better focused and have better reflector continuity than do the acoustic LSRTM images.

  1. SLE local martingales, reversibility and duality

    Energy Technology Data Exchange (ETDEWEB)

    Kytoelae, Kalle; Kemppainen, Antti [Department of Mathematics and Statistics, PO Box 68, FIN-00014 University of Helsinki (Finland)

    2006-11-17

    We study Schramm-Loewner evolutions (SLEs) reversibility and duality using the Virasoro structure of the space of local martingales. For both problems we formulate a setup where the questions boil down to comparing two processes at a stopping time. We state algebraic results showing that local martingales for the processes have enough in common. When one has in addition integrability, the method gives reversibility and duality for any polynomial expected value. (letter to the editor)

  2. SLE local martingales, reversibility and duality

    International Nuclear Information System (INIS)

    Kytoelae, Kalle; Kemppainen, Antti

    2006-01-01

    We study Schramm-Loewner evolutions (SLEs) reversibility and duality using the Virasoro structure of the space of local martingales. For both problems we formulate a setup where the questions boil down to comparing two processes at a stopping time. We state algebraic results showing that local martingales for the processes have enough in common. When one has in addition integrability, the method gives reversibility and duality for any polynomial expected value. (letter to the editor)

  3. Geomagnetic reversal in brunhes normal polarity epoch.

    Science.gov (United States)

    Smith, J D; Foster, J H

    1969-02-07

    The magnetic stratigraphly of seven cores of deep-sea sediment established the existence of a short interval of reversed polarity in the upper part of the Brunches epoch of normal polarity. The reversed zone in the cores correlates well with paleontological boundaries and is named the Blake event. Its boundaries are estimated to be 108,000 and 114,000 years ago +/- 10 percent.

  4. How the geomagnetic field vector reverses polarity

    Science.gov (United States)

    Prevot, M.; Mankinen, E.A.; Gromme, C.S.; Coe, R.S.

    1985-01-01

    A highly detailed record of both the direction and intensity of the Earth's magnetic field as it reverses has been obtained from a Miocene volcanic sequence. The transitional field is low in intensity and is typically non-axisymmetric. Geomagnetic impulses corresponding to astonishingly high rates of change of the field sometimes occur, suggesting that liquid velocity within the Earth's core increases during geomagnetic reversals. ?? 1985 Nature Publishing Group.

  5. Boosting reversible pushdown machines by preprocessing

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Kutrib, Martin; Malcher, Andreas

    2016-01-01

    languages, whereas for reversible pushdown automata the accepted family of languages lies strictly in between the reversible deterministic context-free languages and the real-time deterministic context-free languages. Moreover, it is shown that the computational power of both types of machines...... is not changed by allowing the preprocessing sequential transducer to work irreversibly. Finally, we examine the closure properties of the family of languages accepted by such machines....

  6. Elastic least-squares reverse time migration

    KAUST Repository

    Feng, Zongcai

    2016-09-06

    Elastic least-squares reverse time migration (LSRTM) is used to invert synthetic particle-velocity data and crosswell pressure field data. The migration images consist of both the P- and Svelocity perturbation images. Numerical tests on synthetic and field data illustrate the advantages of elastic LSRTM over elastic reverse time migration (RTM). In addition, elastic LSRTM images are better focused and have better reflector continuity than do the acoustic LSRTM images.

  7. Post-partum posterior reversible encephalopathy syndrome

    OpenAIRE

    B. V. Triveni; Salman Mohammed Sheikh; Deepak Shedde

    2014-01-01

    Posterior Reversible Encephalopathy Syndrome (PRES) is a clinicopathological syndrome associated with various clinical conditions presenting with headache, encephalopathy, seizure and cortical visual disturbances. Radiological findings in PRES are thought to be due to vasogenic edema predominantly in posterior cerebral hemispheres and are reversible with appropriate management. We present a case of post partum PRES,A 29 year old primigravida of 33 weeks 3 days period of gestation who prese...

  8. DIC-CAM recipe for reverse engineering

    Science.gov (United States)

    Romero-Carrillo, P.; Lopez-Alba, E.; Dorado, R.; Diaz-Garrido, F. A.

    2012-04-01

    Reverse engineering (RE) tries to model and manufacture an object from measurements one of a reference object. Modern optical measurement systems and computer aided engineering software have improved reverse engineering procedures. We detail the main RE steps from 3D digitalization by Digital Image Correlation to manufacturing. The previous description is complemented with an application example, which portrays the performance of RE. The differences between original and manufactured objects are less than 2 mm (close to the tool radius).

  9. Central structure preservation of the reversal sign

    International Nuclear Information System (INIS)

    Chen, C.J.

    1999-01-01

    We report serial changes of central structure preservation of the reversal sign in a case of child abuse. The serial CT images show that the relatively spared attenuation at the basal ganglia, thalami, and posterior fossa develops before the occurrence of transtentorial herniation. This finding makes the theory that central preservation of the reversal sign is due to pressure relief after transtentorial herniation less convincible. (orig.)

  10. Modified Borohydrides for Reversible Hydrogen Storage (2)

    International Nuclear Information System (INIS)

    Ming Au

    2006-01-01

    This paper reports the results in the effort to destabilize lithium borohydride for reversible hydrogen storage. A number of metals, metal hydrides, metal chlorides and complex hydrides were selected and evaluated as the destabilization agents for reducing de-hydriding temperature and generating de-hydriding-re-hydriding reversibility. It is found that some additives are effective. The Raman spectroscopic analysis shows the change of B-H binding nature. (authors)

  11. Central structure preservation of the reversal sign

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C.J. [Dept. of Diagnostic Radiology, Chang Gung Memorial Hospital, Taipei (Taiwan)

    1999-12-01

    We report serial changes of central structure preservation of the reversal sign in a case of child abuse. The serial CT images show that the relatively spared attenuation at the basal ganglia, thalami, and posterior fossa develops before the occurrence of transtentorial herniation. This finding makes the theory that central preservation of the reversal sign is due to pressure relief after transtentorial herniation less convincible. (orig.)

  12. Turbulent transport in reversed field pinches

    International Nuclear Information System (INIS)

    Christiansen, J.P.; Roberts, K.V.

    1976-01-01

    MHD stability of the Reversed Field Pinch (RFP) relies on reversal of the toroidal field component in the outer plasma region. Interest in this configuration comes from its potential economic advantages as a thermonuclear reactor, since compared to a Tokamak the RFP supports a higher value of β, the ratio between plasma and total magnetic pressure. Results of computations on the time-evolution of the RFP using a 1D MHD model are reported. (orig./GG) [de

  13. Rotating Reverse-Osmosis for Water Purification

    Science.gov (United States)

    Lueptow, RIchard M.

    2004-01-01

    A new design for a water-filtering device combines rotating filtration with reverse osmosis to create a rotating reverse- osmosis system. Rotating filtration has been used for separating plasma from whole blood, while reverse osmosis has been used in purification of water and in some chemical processes. Reverse- osmosis membranes are vulnerable to concentration polarization a type of fouling in which the chemicals meant not to pass through the reverse-osmosis membranes accumulate very near the surfaces of the membranes. The combination of rotating filtration and reverse osmosis is intended to prevent concentration polarization and thereby increase the desired flux of filtered water while decreasing the likelihood of passage of undesired chemical species through the filter. Devices based on this concept could be useful in a variety of commercial applications, including purification and desalination of drinking water, purification of pharmaceutical process water, treatment of household and industrial wastewater, and treatment of industrial process water. A rotating filter consists of a cylindrical porous microfilter rotating within a stationary concentric cylindrical outer shell (see figure). The aqueous suspension enters one end of the annulus between the inner and outer cylinders. Filtrate passes through the rotating cylindrical microfilter and is removed via a hollow shaft. The concentrated suspension is removed at the end of the annulus opposite the end where the suspension entered.

  14. Ascorbyl radical disproportionation in reverse micellar systems

    Science.gov (United States)

    Gębicki, J. L.; Szymańska-Owczarek, M.; Pacholczyk-Sienicka, B.; Jankowski, S.

    2018-04-01

    Ascorbyl radical was generated by the pulse radiolysis method and observed with the fast kinetic spectrophotometry within reverse micelles stabilized by AOT in n-heptane or by Igepal CO-520 in cyclohexane at different water to surfactant molar ratio, w0. Rate constants for the disproportionation of the ascorbyl radicals were smaller than those for intermicellar exchange for both type of reverse micelles and slower than those in homogeneous aqueous solutions. However, they increased with increasing w0 for AOT/n-heptane system, while they decreased for Igepal CO-520 system. The absorption spectra of ascorbic acid AOT/n-heptane reverse micellar system showed that the "pH" sensed by this molecule is lower than that in respective homogeneous aqueous solutions. The obtained results were rationalized taking into account three main factors (i) preferential location of ascorbic acid molecules in the interfacial region of the both types of reverse micelles; (ii) postulate that the pH of the interface is lower than that of the water pool of reverse micelles and (iii) different structure of the interface of the reverse micelles made by AOT in n-heptane and those formed by Igepal CO-520 I cyclohexane. Some possible consequences of these findings are discussed.

  15. Reversal modes in asymmetric Ni nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Leighton, B.; Pereira, A. [Departamento de Fisica, Universidad de Santiago de Chile (USACH), Avda. Ecuador 3493, 917-0124 Santiago (Chile); Escrig, J., E-mail: jescrigm@gmail.com [Departamento de Fisica, Universidad de Santiago de Chile (USACH), Avda. Ecuador 3493, 917-0124 Santiago (Chile); Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Avda. Ecuador 3493, 917-0124 Santiago (Chile)

    2012-11-15

    We have investigated the evolution of the magnetization reversal mechanism in asymmetric Ni nanowires as a function of their geometry. Circular nanowires are found to reverse their magnetization by the propagation of a vortex domain wall, while in very asymmetric nanowires the reversal is driven by the propagation of a transverse domain wall. The effect of shape asymmetry of the wire on coercivity and remanence is also studied. Angular dependence of the remanence and coercivity is also addressed. Tailoring the magnetization reversal mechanism in asymmetric nanowires can be useful for magnetic logic and race-track memory, both of which are based on the displacement of magnetic domain walls. Finally, an alternative method to detect the presence of magnetic drops is proposed. - Highlights: Black-Right-Pointing-Pointer Asymmetry strongly modifies the magnetic behavior of a wire. Black-Right-Pointing-Pointer Very asymmetric nanowires reverse their magnetization by a transverse domain wall. Black-Right-Pointing-Pointer An alternative method to detect the presence of magnetic drops is proposed. Black-Right-Pointing-Pointer Tailoring the reversal mode in asymmetric nanowires can be useful for potential applications.

  16. (3,4-dihydroisoquinolin-2(1H)-yl)

    Indian Academy of Sciences (India)

    Administrator

    HIV-1 reverse transcriptase (HIV-1 RT); non-nucleoside reverse transcriptase inhibitor. (NNRTI); docking; autodock; 1,2,3,4-tetrahydroisoquinoline. 1. Introduction. Acquired immuno deficiency syndrome (AIDS) is one of the most serious pandemic public health chal- lenges since 1981. 1. Human immuno deficiency virus.

  17. NEW DRUGS NEW TARGETS AND NOVEL ANTIRETROVIRALS

    African Journals Online (AJOL)

    2005-11-02

    Nov 2, 2005 ... Highly active antiretroviral therapy (HAART) has to date been based on use of a triple combination of drugs chosen from three classes of antiretrovirals (ARVs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).

  18. New targets and novel antiretrovirals | Wood | Southern African ...

    African Journals Online (AJOL)

    Highly active antiretroviral therapy (HAART) has to date been based on use of a triple combination of drugs chosen from three classes of antiretrovirals (ARVs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). These ARV classes ...

  19. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

    Directory of Open Access Journals (Sweden)

    Ru-Yin Tsai

    2016-06-01

    Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

  20. The misconception of mean-reversion

    International Nuclear Information System (INIS)

    Eliazar, Iddo I; Cohen, Morrel H

    2012-01-01

    The notion of random motion in a potential well is elemental in the physical sciences and beyond. Quantitatively, this notion is described by reverting diffusions—asymptotically stationary diffusion processes which are simultaneously (i) driven toward a reversion level by a deterministic force, and (ii) perturbed off the reversion level by a random white noise. The archetypal example of reverting diffusions is the Ornstein–Uhlenbeck process, which is mean-reverting. In this paper we analyze reverting diffusions and establish that: (i) if the magnitude of the perturbing noise is constant then the diffusion's stationary density is unimodal and the diffusion is mode-reverting; (ii) if the magnitude of the perturbing noise is non-constant then, in general, neither is the diffusion's stationary density unimodal, nor is the diffusion mode-reverting. In the latter case we further establish a result asserting when unimodality and mode-reversion do hold. In particular, we demonstrate that the notion of mean-reversion, which is fundamental in economics and finance, is a misconception—as mean-reversion is an exception rather than the norm. (fast track communication)

  1. Reverse logistics in the construction industry.

    Science.gov (United States)

    Hosseini, M Reza; Rameezdeen, Raufdeen; Chileshe, Nicholas; Lehmann, Steffen

    2015-06-01

    Reverse logistics in construction refers to the movement of products and materials from salvaged buildings to a new construction site. While there is a plethora of studies looking at various aspects of the reverse logistics chain, there is no systematic review of literature on this important subject as applied to the construction industry. Therefore, the objective of this study is to integrate the fragmented body of knowledge on reverse logistics in construction, with the aim of promoting the concept among industry stakeholders and the wider construction community. Through a qualitative meta-analysis, the study synthesises the findings of previous studies and presents some actions needed by industry stakeholders to promote this concept within the real-life context. First, the trend of research and terminology related with reverse logistics is introduced. Second, it unearths the main advantages and barriers of reverse logistics in construction while providing some suggestions to harness the advantages and mitigate these barriers. Finally, it provides a future research direction based on the review. © The Author(s) 2015.

  2. Parkinson’s disease managing reversible neurodegeneration

    Directory of Open Access Journals (Sweden)

    Hinz M

    2016-04-01

    Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole,3 Beth McDougall,4 Mark Westaway5 1Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, 2Stein Orthopedic Associates, Plantation, FL, 3Cole Center for Healing, Cincinnati, OH, 4CLEARCenter of Health, Mill Valley, CA, USA; 5Four Pillars Health, Brendale, QLD, Australia Abstract: Traditionally, the Parkinson’s disease (PD symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. Keywords: Parkinson’s disease, L-dopa, carbidopa, B6, neurodegeneration

  3. AN OVERVIEW ON RETAIL REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2014-07-01

    Full Text Available This article is a theoretical approach on retail reverse logistics. Environmental concern and the current marketing strategy have spurred retailers to implement strategies to facilitate product returns from end customers. Reverse logistics, indicating the process of this return flow, encompasses such activities as the movement of returned products, facilities to accommodate returned items, and overall remedy process for returned items. The retail industry, under great competitive pressure, has used return policies as a competitive weapon. Grocery retailers were the first to begin to focus serious attention on the problem of returns and to develop reverse logistics innovations. Grocery retailers first developed innovations such as reclamation centers. Reclamation centers, in turn, led to the establishment of centralized return centers. Centralizing returns has led to significant benefits for most firms that have implemented them. Over the last several years, retailers have consolidated. Now, more than ever, reverse logistics is seen as being important. This reverse distribution activity can be crucial to the survival of companies, because the permanent goodwill of the company is at stake. Businesses succeed because they respond to both external and internal changes and adjust in an effective manner to remain competitive.

  4. Pattern-reversal electroretinograms in unilateral glaucoma.

    Science.gov (United States)

    Wanger, P; Persson, H E

    1983-06-01

    Pattern-reversal and flash electroretinograms (ERG) and oscillatory potentials (OP) were recorded from 11 patients with unilateral glaucoma. All glaucomatous eyes had reduced amplitudes both compared to the opposite eye in the same patient and to reference values. In 10 of the 11 cases this reduction was below the level of normal variation. The difference in pattern-reversal ERG amplitude means from glaucomatous and opposite eyes was statistically significant. No differences were observed in flash ERGs or OPs. The histopathologic correlate to the visual field defects in glaucoma is retinal ganglion cell degeneration. The present electrophysiologic findings support the view, based on results from animal experiments, that the pattern-reversal ERG reflects ganglion cell activity.

  5. Medulla Oblongata Hemorrhage and Reverse Takotsubo Cardiomyopathy.

    Science.gov (United States)

    Gobeske, Kevin T; Sarano, Maurice E; Fugate, Jennifer E; Wijdicks, Eelco F

    2017-12-19

    Acute brain injury with strong surges of adrenergic outflow has resulted in takotsubo cardiomyopathy, but there are surprisingly few reports of takotsubo cardiomyopathy after intracranial hemorrhage, and none have been described from hemorrhage within the brainstem. We describe a patient with reverse and reversible cardiomyopathy following a hemorrhage in the lateral medulla oblongata. While it is limited in size, the location of the hemorrhage caused acute systolic failure with left ventricular ejection fraction of 27% and vasopressor requirement for cardiogenic shock and pulmonary edema. There was full recovery after 7 days. Detailed case report. Hemorrhage into medulla oblongata pressor centers may result in acute, reversible, stress-induced cardiomyopathy, affirming the adrenergic origin of this condition.

  6. Neutrophil Reverse Migration Becomes Transparent with Zebrafish

    Directory of Open Access Journals (Sweden)

    Taylor W. Starnes

    2012-01-01

    Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

  7. Time in Science: Reversibility vs. Irreversibility

    Science.gov (United States)

    Pomeau, Yves

    To discuss properly the question of irreversibility one needs to make a careful distinction between reversibility of the equations of motion and the choice of the initial conditions. This is also relevant for the rather confuse philosophy of the wave packet reduction in quantum mechanics. The explanation of this reduction requires also to make precise assumptions on what initial data are accessible in our world. Finally I discuss how a given (and long) time record can be shown in an objective way to record an irreversible or reversible process. Or: can a direction of time be derived from its analysis? This leads quite naturally to examine if there is a possible spontaneous breaking of the time reversal symmetry in many body systems, a symmetry breaking that would be put in evidence objectively by looking at certain specific time correlations.

  8. Fuel bundle movement due to reverse flow

    Energy Technology Data Exchange (ETDEWEB)

    Wahba, N N; Akalin, O [Ontario Hydro, Toronto, ON (Canada)

    1996-12-31

    When a break occurs in the inlet feeder or inlet header, the rapid depressurization will cause the channel flow to reverse forcing the string of bundles to accelerate and impact with upstream shield plug. A model has been developed to predict the bundle motion due to the channel flow reversal. The model accounts for various forces acting on the bundle. A series of five reverse flow, bundle acceleration experiments have been conducted simulating a break in the inlet feeder of a CANDU fuel channel. The model has been validated against the experiments. The predicted impact velocities are in good agreement with the measured values. It is demonstrated that the model may be successfully used in predicting bundle relocation timing following a large LOCA (loss of coolant). (author). 7 refs., 3 tabs., 11 figs.

  9. Reversible Carnot cycle outside a black hole

    International Nuclear Information System (INIS)

    Xi-Hao, Deng; Si-Jie, Gao

    2009-01-01

    A Carnot cycle outside a Schwarzschild black hole is investigated in detail. We propose a reversible Carnot cycle with a black hole being the cold reservoir. In our model, a Carnot engine operates between a hot reservoir with temperature T 1 and a black hole with Hawking temperature T H . By naturally extending the ordinary Carnot cycle to the black hole system, we show that the thermal efficiency for a reversible process can reach the maximal efficiency 1 – T H /T 1 . Consequently, black holes can be used to determine the thermodynamic temperature by means of the Carnot cycle. The role of the atmosphere around the black hole is discussed. We show that the thermal atmosphere provides a necessary mechanism to make the process reversible. (general)

  10. REVERSIBLE VENTILATION SYSTEM FOR ADMINISTRATIVE BUILDINGS

    Directory of Open Access Journals (Sweden)

    Valery Yu. Kravchuk

    2017-01-01

    Full Text Available Abstract. Objectives To consider the possibility of applying the principle of reversing air flows for a centralised ventilation system; to develop a specific scheme for air exchange reversible ventilation, which will take into account the peculiarities of the microclimate of administrative buildings; to select the type of filling of the air-permeable element and justify this choice; to determine the conditions for changing the direction of air movement in the ventilation system and the area of its application; to form a list of equipment necessary for the operation of such a system; to consider the influence of supply and exhaust devices on the heat and humidity regime of claddings. Methods  To achieve this goal, the published thematic material was reviewed and a patent search carried out using Russian and European databases. Data on mathematical modelling of filtration in porous media and experimental results were used. A method for ventilating rooms in administrative building using the reversal of movement of supply and exhaust air streams along the same channels was applied. Results  Schemas for reversible ventilation systems are presented and their modes of operation considered. It is established that the idea of reversing ventilation flows has not yet been applied in the development of centralised ventilation systems. Based on these published materials, it was concluded that the proposed design of supply and exhaust devices can be used in practice. An original air exchange scheme for the ventilation of administrative buildings and design of supply and exhaust devices for this system are proposed. The conditions for changing the operating modes of the system and the scope of its application are determined. Conclusion The use of the proposed ventilation system allows normative air exchange to be provided without using a supply unit during the cold season. This application of airflow reversal allows the potential of natural forces to be used

  11. Post-partum posterior reversible encephalopathy syndrome

    DEFF Research Database (Denmark)

    Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with vasogenic subcortical oedema caused by hypertension. Oedema is often seen on magnetic resonance imaging. The wide clinical spectrum ranges from headaches to vision loss and even death. Early diagnosis...... and treatment is important for the reversibility of the condition. In this case report we emphasize the importance of blood pressure control in a post-partum woman, who had a rather complicated pregnancy. The symptoms of PRES were not recognized immediately because of failure to use and acknowledge a blood...

  12. Research regarding reverse engineering for aircraft components

    Directory of Open Access Journals (Sweden)

    Udroiu Razvan

    2017-01-01

    Full Text Available Reverse engineering is a useful technique used in manufacturing and design process of new components. In aerospace industry new components can be developed, based on existing components without technical Computer Aided Design (CAD data, in order to reduce the development cycle of new products. This paper proposes a methodology wherein the CAD model of turbine blade can be build using computer aided reverse engineering technique utilising a 5 axis Coordinate Measuring Machine (CMM. The proposed methodology uses a scanning strategy by features, followed by a design methodology for 3D modelling of complex shapes.

  13. A simple statistical model for geomagnetic reversals

    Science.gov (United States)

    Constable, Catherine

    1990-01-01

    The diversity of paleomagnetic records of geomagnetic reversals now available indicate that the field configuration during transitions cannot be adequately described by simple zonal or standing field models. A new model described here is based on statistical properties inferred from the present field and is capable of simulating field transitions like those observed. Some insight is obtained into what one can hope to learn from paleomagnetic records. In particular, it is crucial that the effects of smoothing in the remanence acquisition process be separated from true geomagnetic field behavior. This might enable us to determine the time constants associated with the dominant field configuration during a reversal.

  14. Reverse preferential spread in complex networks

    Science.gov (United States)

    Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

    2012-08-01

    Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

  15. Post-partum posterior reversible encephalopathy syndrome

    DEFF Research Database (Denmark)

    Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder

    2015-01-01

    and treatment is important for the reversibility of the condition. In this case report we emphasize the importance of blood pressure control in a post-partum woman, who had a rather complicated pregnancy. The symptoms of PRES were not recognized immediately because of failure to use and acknowledge a blood......Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with vasogenic subcortical oedema caused by hypertension. Oedema is often seen on magnetic resonance imaging. The wide clinical spectrum ranges from headaches to vision loss and even death. Early diagnosis...

  16. [Post-partum posterior reversible encephalopathy syndrome].

    Science.gov (United States)

    Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder; Bülow, Hans Henrik

    2015-11-23

    Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with vasogenic subcortical oedema caused by hypertension. Oedema is often seen on magnetic resonance imaging. The wide clinical spectrum ranges from headaches to vision loss and even death. Early diagnosis and treatment is important for the reversibility of the condition. In this case report we emphasize the importance of blood pressure control in a post-partum woman, who had a rather complicated pregnancy. The symptoms of PRES were not recognized immediately because of failure to use and acknowledge a blood pressure test.

  17. Reversed Extension Flow of Polymer melts

    DEFF Research Database (Denmark)

    Rasmussen, Henrik K.; Nielsen, Jens Kromann

    2007-01-01

    The measurement of the startup of uni axial elongational flow (potentially until steady state) followed by reversed bi axial flow, both with a constant elongational rate was made possible using a Filament Stretching Rheometer (FSR). The filament stretching rheometer rheometer is surrounded...... by a thermostated environment and allows measurements on polymeric melts and liquids from room temperatures until 200 °C. In the experiments the Hencky strain at which the stress becomes zero (the recovery strain) of the reversed flow can be identified....

  18. Reversible computing fundamentals, quantum computing, and applications

    CERN Document Server

    De Vos, Alexis

    2010-01-01

    Written by one of the few top internationally recognized experts in the field, this book concentrates on those topics that will remain fundamental, such as low power computing, reversible programming languages, and applications in thermodynamics. It describes reversible computing from various points of view: Boolean algebra, group theory, logic circuits, low-power electronics, communication, software, quantum computing. It is this multidisciplinary approach that makes it unique.Backed by numerous examples, this is useful for all levels of the scientific and academic community, from undergr

  19. Contextual influences on reverse knowledge transfer

    DEFF Research Database (Denmark)

    Søberg, Peder Veng

    2010-01-01

    Further development of theories about how contextual factors influence the beneficial reverse knowledge transfer from subsidiary to head quarters in disparate national country contexts, is the aim of our study. Earlier studies do not fully capture the different effects national country cultures can....... A proposition model is developed where the dependent variable is beneficial reverse knowledge transfer. The independent variables are: higher relative knowledge level in subsidiaty than in HQ, authority respect, activity fit with contextual learning preference. The conclusion suggest that different contexts...

  20. Microscopic reversibility and the information contained in the composition vector

    CERN Document Server

    Luetich, J J

    2001-01-01

    The microscopic level of observation is the level where every (hypothetical) transformation is reversible. As during reversible processes no composition information is generated by the system, when transforming composition variables, microscopic reversibility is the other side of the coin. This paper is the fourth member of a tetralogy conceived to give insight into the concept of microscopic reversibility.

  1. Design of a novel quantum reversible ternary up-counter

    Science.gov (United States)

    Houshmand, Pouran; Haghparast, Majid

    2015-08-01

    Reversible logic has been recently considered as an interesting and important issue in designing combinational and sequential circuits. The combination of reversible logic and multi-valued logic can improve power dissipation, time and space utilization rate of designed circuits. Only few works have been reported about sequential reversible circuits and almost there are no paper exhibited about quantum ternary reversible counter. In this paper, first we designed 2-qutrit and 3-qutrit quantum reversible ternary up-counters using quantum ternary reversible T-flip-flop and quantum reversible ternary gates. Then we proposed generalized quantum reversible ternary n-qutrit up-counter. We also introduced a new approach for designing any type of n-qutrit ternary and reversible counter. According to the results, we can conclude that applying second approach quantum reversible ternary up-counter is better than the others.

  2. END-OF-USE PRODUCTS IN REVERSE LOGISTICS

    OpenAIRE

    Marta Starostka-Patyk

    2007-01-01

    Reverse logistics is a very useful tool for enterprises which have to deal with end-of-use products. Forward logistics is not able to manage them, because they show up on the beginning of reverse supply chain. That is the reason for growing importance of reverse flows. Reverse logistics is quite new logistics system. This paper presents the idea of reverse logistics and end-of-use products problems.

  3. Energy drift in reversible time integration

    International Nuclear Information System (INIS)

    McLachlan, R I; Perlmutter, M

    2004-01-01

    Energy drift is commonly observed in reversible integrations of systems of molecular dynamics. We show that this drift can be modelled as a diffusion and that the typical energy error after time T is O(√T). (letter to the editor)

  4. Predicting flux decline of reverse osmosis membranes

    NARCIS (Netherlands)

    Schippers, J.C.; Hanemaayer, J.H.; Smolders, C.A.; Kostense, A.

    1981-01-01

    A mathematical model predicting flux decline of reverse osmosis membranes due to colloidal fouling has been verified. This mathema- tical model is based on the theory of cake or gel filtration and the Modified Fouling Index (MFI). Research was conducted using artificial colloidal solutions and a

  5. Multiples least-squares reverse time migration

    KAUST Repository

    Zhang, Dongliang; Zhan, Ge; Dai, Wei; Schuster, Gerard T.

    2013-01-01

    To enhance the image quality, we propose multiples least-squares reverse time migration (MLSRTM) that transforms each hydrophone into a virtual point source with a time history equal to that of the recorded data. Since each recorded trace is treated

  6. "At Sea": Reversibility in Teaching and Learning

    Science.gov (United States)

    Cavicchi, Elizabeth Mary

    2018-01-01

    An equal-armed balance at equilibrium--the bar is horizontal--tips into disequilibrium upon displacing a weight. Equilibrium is restored by reversing that move--putting the weight back where it was, or doing the same on the other side. Piaget adopted the idea of equilibration to describe how the intellect, in relating to the world, develops.…

  7. Reverse Logistics: RFID the key to optimality

    Directory of Open Access Journals (Sweden)

    Rezwan Asif

    2011-07-01

    Full Text Available Purpose: The purpose of this paper is to find ways to reduce uncertainties in Reverse logistic supply chain (RLSC through the use of Radio-frequency identification (RFID technology.Design/methodology/approach: This paper reviews literature and builds model to relate RFID with uncertainties in order to optimize Reverse Logistics. Findings: RFID is really efficient to determine and detect quantity, variety and cycle times of returns; however it's not as convenient to determine quality of the returns. The collected information from RFID can be used to standardize the RLSC.Research limitations: Though it’s several and unique advantages some limitations of RFID have been identified in quality and processing sequence, collecting points and different standards, and in global usage.Originality/value: Previous studies in the area of Reverse Logistics and RFID don’t cover all impacts of this technology on RLSC. This review paper has investigated these impacts and offers a model for optimizing the Reverse Logistics Supply Chain.

  8. Kinetin Reversal of NaCl Effects

    Science.gov (United States)

    Katz, Adriana; Dehan, Klara; Itai, Chanan

    1978-01-01

    Leaf discs of Nicotiana rustica L. were floated on NaCl in the presence of kinetin or abscisic acid. On the 5th day 14CO2 fixation, [3H]leucine incorporation, stomatal conductance, and chlorophyll content were determined. Kinetin either partially or completely reversed the inhibitory effects of NaCl while ABA had no effect. PMID:16660618

  9. Sustainable reverse logistics for household plastic waste

    NARCIS (Netherlands)

    Bing, X.

    2014-01-01

    Summary of the thesis titled “Sustainable Reverse Logistics for Household Plastic Waste”

    PhD Candidate: Xiaoyun Bing

    Recycled plastic can be used in the manufacturing of plastic products to reduce the use of virgin plastics material. The cost of recycled plastics is usually lower

  10. Reverse ray tracing for transformation optics.

    Science.gov (United States)

    Hu, Chia-Yu; Lin, Chun-Hung

    2015-06-29

    Ray tracing is an important technique for predicting optical system performance. In the field of transformation optics, the Hamiltonian equations of motion for ray tracing are well known. The numerical solutions to the Hamiltonian equations of motion are affected by the complexities of the inhomogeneous and anisotropic indices of the optical device. Based on our knowledge, no previous work has been conducted on ray tracing for transformation optics with extreme inhomogeneity and anisotropicity. In this study, we present the use of 3D reverse ray tracing in transformation optics. The reverse ray tracing is derived from Fermat's principle based on a sweeping method instead of finding the full solution to ordinary differential equations. The sweeping method is employed to obtain the eikonal function. The wave vectors are then obtained from the gradient of that eikonal function map in the transformed space to acquire the illuminance. Because only the rays in the points of interest have to be traced, the reverse ray tracing provides an efficient approach to investigate the illuminance of a system. This approach is useful in any form of transformation optics where the material property tensor is a symmetric positive definite matrix. The performance and analysis of three transformation optics with inhomogeneous and anisotropic indices are explored. The ray trajectories and illuminances in these demonstration cases are successfully solved by the proposed reverse ray tracing method.

  11. Detecting A Botnet By Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Oesman Hendra Kelana

    2013-06-01

    Full Text Available Abstract— Botnet malware is a malicious program. Botnet that infects computers, called bots, will be controlled by a botmaster to do various things such as: spamming, phishing, keylogging Distributed Denial of Service (DDoS and other activities that are generally profitable to the owner of the bot (botmaster or those who use botnet services. The problem is that many computers have been controlled by botnets without the knowledge of the computer owner.  There are many ways to examine botnets, for example by studying the traffic from the botnet network, studying how botnets communicate to each, studying how each robot receives orders to do something, and so forth. Of the many methods, the most frequently and commonly used is the reverse engineering, where researchers study how a botnet works by botnet debugging. In this study the author tries to understand or research botnets by taking a type of botnet, namely Agobot, using reverse engineering.  One of the result of the research is that malware program files in general and in particular botnet has a technique to obscure the way that research using reverse engineering. Another result also shows that the botnet Agobot runs on computers by using the Windows service, and by changing the Windows registry so that every time the computer starts, Agobot always actively works in the computer memory. Keywords— Malware, Bot, Botnet, Botmaster, Agobot, Spam, Distributed Denial of Services, Identity Theft, Computer Security, Reverse Engineering, Debug, Windows Service, the Registry.

  12. Purchasing Power Parity and Heterogeneous Mean Reversion

    NARCIS (Netherlands)

    C.G. Koedijk (Kees); B. Tims (Ben); M.A. van Dijk (Mathijs)

    2005-01-01

    textabstractThis paper analyzes the properties of multivariate tests of purchasing power parity (PPP) that fail to take heterogeneity in the speed of mean reversion across real exchange rates into account. We compare the performance of homogeneous and heterogeneous unit root testing methodologies.

  13. Survey of methods for rapid spin reversal

    International Nuclear Information System (INIS)

    McKibben, J.L.

    1980-01-01

    The need for rapid spin reversal technique in polarization experiments is discussed. The ground-state atomic-beam source equipped with two rf transitions for hydrogen can be reversed rapidly, and is now in use on several accelerators. It is the optimum choice provided the accelerator can accept H + ions. At present all rapid reversal experiments using H - ions are done with Lamb-shift sources; however, this is not a unique choice. Three methods for the reversal of the spin of the atomic beam within the Lamb-shift source are discussed in order of development. Coherent intensity and perhaps focus modulation seem to be the biggest problems in both types of sources. Methods for reducing these modulations in the Lamb-shift source are discussed. The same Lamb-shift apparatus is easily modified to provide information on the atomic physics of quenching of the 2S/sub 1/2/ states versus spin orientation, and this is also discussed. 2 figures

  14. Reverse Logistics in Food Supply Chains

    NARCIS (Netherlands)

    Zeimpekis, V.; Bloemhof, J.M.; Bourlakis, M.

    2014-01-01

    Reverse logistics can be defined as the process of planning, implementing, and controlling the flow of raw materials, in-process inventory, and finished goods from the point of consumption to the point of origin for the purpose of recapturing value or proper disposal. In environmental and economic

  15. Bayesian analysis for reversible Markov chains

    NARCIS (Netherlands)

    Diaconis, P.; Rolles, S.W.W.

    2006-01-01

    We introduce a natural conjugate prior for the transition matrix of a reversible Markov chain. This allows estimation and testing. The prior arises from random walk with reinforcement in the same way the Dirichlet prior arises from Pólya’s urn. We give closed form normalizing constants, a simple

  16. Reversibility of continuous-variable quantum cloning

    International Nuclear Information System (INIS)

    Filip, Radim; Marek, Petr; Fiurasek, Jaromir

    2004-01-01

    We analyze a reversibility of optimal Gaussian 1→2 quantum cloning of a coherent state using only local operations on the clones and classical communication between them and propose a feasible experimental test of this feature. Performing Bell-type homodyne measurement on one clone and anticlone, an arbitrary unknown input state (not only a coherent state) can be restored in the other clone by applying appropriate local unitary displacement operation. We generalize this concept to a partial reversal of the cloning using only local operations and classical communication (LOCC) and we show that this procedure converts the symmetric cloner to an asymmetric cloner. Further, we discuss a distributed LOCC reversal in optimal 1→M Gaussian cloning of coherent states which transforms it to optimal 1→M ' cloning for M ' < M. Assuming the quantum cloning as a possible eavesdropping attack on quantum communication link, the reversibility can be utilized to improve the security of the link even after the attack

  17. Reverse electrodialysis : evaluation of suitable electrode systems

    NARCIS (Netherlands)

    Veerman, J.; Saakes, M.; Metz, S. J.; Harmsen, G. J.

    Reverse electrodialysis (RED) is a method for directly extracting electrical energy from salinity gradients, especially from sea and river water. For the commercial implementation of RED, the electrode system is a key component. In this paper, novel electrode systems for RED were compared with

  18. Female genital mutilation reversal: a general approach.

    Science.gov (United States)

    Anand, Mallika; Stanhope, Todd J; Occhino, John A

    2014-07-01

    Female genital mutilation (FGM) is a violation of human rights; yet, more than 100 million females are estimated to have undergone the procedure worldwide. There is an increased need for physician education in treating FGM. Female pelvic surgeons have a unique opportunity to treat this population of patients. Here, we depict the classification of FGM and a general approach to FGM reversal. We specifically address the procedure of type III FGM reversal, or defibulation. In this video, we first highlight the importance of the problem of FGM. Next, we present the classification of FGM using an original, simple, schematic diagram highlighting they key anatomic structures involved in the four types of FGM. We then present a simple case of reversal of type III FGM, a procedure also known as defibulation. After depicting the surgical procedure, we discuss clinical results and summarize key principles of the defibulation procedure. Our patient was a 25-year-old woman who had undergone type III FGM as a child in Somalia. She desired restoration of vaginal function. We performed a reversal, and her postoperative course was uncomplicated. By 6 weeks postoperatively, she was able to engage in sexual intercourse without dyspareunia. FGM is a problem at the doorsteps of female pelvic medicine and reconstructive surgery. Our video demonstrates a basic surgical approach that can be applied to simple cases of type III FGM presenting to the female pelvic surgeon.

  19. Adiabatic process reversibility: microscopic and macroscopic views

    International Nuclear Information System (INIS)

    Anacleto, Joaquim; Pereira, Mario G

    2009-01-01

    The reversibility of adiabatic processes was recently addressed by two publications. In the first (Miranda 2008 Eur. J. Phys. 29 937-43), an equation was derived relating the initial and final volumes and temperatures for adiabatic expansions of an ideal gas, using a microscopic approach. In that relation the parameter r accounts for the process reversibility, ranging between 0 and 1, which corresponds to the free and reversible expansion, respectively. In the second (Anacleto and Pereira 2009 Eur. J. Phys. 30 177-83), the authors have shown that thermodynamics can effectively and efficiently be used to obtain the general law for adiabatic processes carried out by an ideal gas, including compressions, for which r≥1. The present work integrates and extends the aforementioned studies, providing thus further insights into the analysis of the adiabatic process. It is shown that Miranda's work is wholly valid for compressions. In addition, it is demonstrated that the adiabatic reversibility coefficient given in terms of the piston velocity and the root mean square velocity of the gas particles is equivalent to the macroscopic description, given just by the quotient between surroundings and system pressure values. (letters and comments)

  20. Garbageless reversible implementation of integer linear transformations

    DEFF Research Database (Denmark)

    Burignat, Stéphane; Vermeirsch, Kenneth; De Vos, Alexis

    2013-01-01

    inputs. The resulting reversible circuit is able to perform both the forward transform and the inverse transform. Which of the two computations that actually is performed, simply depends on the orientation of the circuit when it is inserted in a computer board (if one takes care to provide...

  1. Flow reversal power limit for the HFBR

    International Nuclear Information System (INIS)

    Cheng, L.Y.; Tichler, P.R.

    1997-01-01

    The High Flux Beam Reactor (HFBR) is a pressurized heavy water moderated and cooled research reactor that began operation at 40 MW. The reactor was subsequently upgraded to 60 MW and operated at that level for several years. The reactor undergoes a buoyancy-driven reversal of flow in the reactor core following certain postulated accidents. Questions which were raised about the afterheat removal capability during the flow reversal transition led to a reactor shutdown and subsequent resumption of operation at a reduced power of 30 MW. An experimental and analytical program to address these questions is described in this report. The experiments were single channel flow reversal tests under a range of conditions. The analytical phase involved simulations of the tests to benchmark the physical models and development of a criterion for dryout. The criterion is then used in simulations of reactor accidents to determine a safe operating power level. It is concluded that the limit on the HFBR operating power with respect to the issue of flow reversal is in excess of 60 MW. Direct use of the experimental results and an understanding of the governing phenomenology supports this conclusion

  2. Reversible thermal gelation in soft spheres

    DEFF Research Database (Denmark)

    Kapnistos, M.; Vlassopoulos, D.; Fytas, G.

    2000-01-01

    Upon heating, concentrated solutions of star polymers and block copolymer micelles in a good solvent, representing soft spheres, undergo a reversible gelation. This phenomenon is attributed to the formation of clusters causing a partial dynamic arrest of the swollen interpenetrating spheres at hi...

  3. Returnable containers: an example of reverse logistics

    NARCIS (Netherlands)

    L.G. Kroon (Leo); G.M.C. Vrijens

    1996-01-01

    textabstractConsiders the application of returnable containers as an example of reverse logistics. A returnable container is a type of secondary packaging that can be used several times in the same form, in contrast with traditional cardboard boxes. For this equipment to be used, a system for the

  4. Remendable Polymeric Materials Using Reversible Covalent Bonds

    Science.gov (United States)

    2008-12-01

    response in poly(ethylene-co-methacrylic acid ) copolymers. Journal of The Royal Society Interface, 4, 405-411. Kavitha, A. A., and N. K. Singha...2007: A tailor-made polymethacrylate bearing a reactive diene in reversible diels-alder reaction. J. Polym. Sci. A Polym. Chem., 45, 4441-4449

  5. Strong and Reversible Monovalent Supramolecular Protein Immobilization

    NARCIS (Netherlands)

    Young, Jacqui F.; Nguyen, Hoang D.; Yang, Lanti; Huskens, Jurriaan; Jonkheijm, Pascal; Brunsveld, Luc

    2010-01-01

    Proteins with an iron clasp: Site-selective incorporation of a ferrocene molecule into a protein allows for easy, strong, and reversible supramolecular protein immobilization through a selective monovalent interaction of the ferrocene with a cucurbit[7]uril immobilized on a gold surface. The

  6. Long acting reversible contraception | Kluge | Obstetrics and ...

    African Journals Online (AJOL)

    Long acting reversible contraception (LARC) has great potential in reducing these pregnancies as they are highly effective and do not rely a great deal on compliance and correct use. They have better continuation rates than short term hormonal contraception and as per definition require administration less than once per ...

  7. Time reversal technique for gas leakage detection.

    Science.gov (United States)

    Maksimov, A O; Polovinka, Yu A

    2015-04-01

    The acoustic remote sensing of subsea gas leakage traditionally uses sonars as active acoustic sensors and hydrophones picking up the sound generated by a leak as passive sensors. When gas leaks occur underwater, bubbles are produced and emit sound at frequencies intimately related to their sizes. The experimental implementation of an acoustic time-reversal mirror (TRM) is now well established in underwater acoustics. In the basic TRM experiment, a probe source emits a pulse that is received on an array of sensors, time reversed, and re-emitted. After time reversal, the resulting field focuses back at the probe position. In this study, a method for enhancing operation of the passive receiving system has been proposed by using it in the regime of TRM. Two factors, the local character of the acoustic emission signal caused by the leakage and a resonant nature of the bubble radiation at their birth, make particularly effective scattering with the conjugate wave (CW). Analytical calculations are performed for the scattering of CW wave on a single bubble when CW is formed by bubble birthing wail received on an array, time reversed, and re-emitted. The quality of leakage detection depends on the spatio-temporal distribution of ambient noise.

  8. Posterior reversible encephalopathy syndrome in patient

    African Journals Online (AJOL)

    abp

    2015-05-26

    May 26, 2015 ... reversible Posterior leukoencephalopathy syndrome [1, 2]. The. PRES is a clinical and radiological entity associating varying degrees, headaches, impaired consciousness, seizures and visual disturbances to neurological and radiological abnormalities of the parietal-occipital white matter [3]. PRES has a ...

  9. Compound nucleus studies withy reverse kinematics

    International Nuclear Information System (INIS)

    Moretto, L.G.

    1985-06-01

    Reverse kinematics reactions are used to demonstrate the compound nucleus origin of intermediate mass particles at low energies and the extension of the same mechanism at higher energies. No evidence has appeared in our energy range for liquid-vapor equilibrium or cold fragmentation mechanisms. 11 refs., 12 figs

  10. Muscular activation during reverse and non-reverse chewing cycles in unilateral posterior crossbite.

    Science.gov (United States)

    Piancino, Maria Grazia; Farina, Dario; Talpone, Francesca; Merlo, Andrea; Bracco, Pietro

    2009-04-01

    The aim of this study was to characterize the kinematics and masseter muscle activation in unilateral posterior crossbite. Eighty-two children (8.6 +/- 1.3 yr of age) with unilateral posterior crossbite and 12 children (8.9 +/- 0.6 yr of age) with normal occlusion were selected for the study. Electromyography (EMG) and kinematics were concurrently recorded during mastication of a soft bolus and a hard bolus. The percentage of reverse cycles in the group of patients was 59.0 +/- 33.1% (soft bolus) and 69.7 +/- 29.7% (hard bolus) when chewing on the crossbite side. When chewing on the non-affected side, the number of reverse cycles was 16.7 +/- 24.5% (soft bolus) and 16.7 +/- 22.3% (hard bolus). The reverse cycles on the crossbite side were narrower with respect to the cycles on the non-affected side. Although both types of cycles in patients resulted in lower EMG activity of the masseter of the crossbite side than of the contralateral masseter, the activity of the non-affected side was larger for reverse than for non-reverse cycles. It was concluded that when chewing on the crossbite side, the masseter activity is reduced on the mastication side (crossbite) and is unaltered (non-reverse cycles) or increased (reverse) on the non-affected side.

  11. Dynamical similarity of geomagnetic field reversals.

    Science.gov (United States)

    Valet, Jean-Pierre; Fournier, Alexandre; Courtillot, Vincent; Herrero-Bervera, Emilio

    2012-10-04

    No consensus has been reached so far on the properties of the geomagnetic field during reversals or on the main features that might reveal its dynamics. A main characteristic of the reversing field is a large decrease in the axial dipole and the dominant role of non-dipole components. Other features strongly depend on whether they are derived from sedimentary or volcanic records. Only thermal remanent magnetization of lava flows can capture faithful records of a rapidly varying non-dipole field, but, because of episodic volcanic activity, sequences of overlying flows yield incomplete records. Here we show that the ten most detailed volcanic records of reversals can be matched in a very satisfactory way, under the assumption of a common duration, revealing common dynamical characteristics. We infer that the reversal process has remained unchanged, with the same time constants and durations, at least since 180 million years ago. We propose that the reversing field is characterized by three successive phases: a precursory event, a 180° polarity switch and a rebound. The first and third phases reflect the emergence of the non-dipole field with large-amplitude secular variation. They are rarely both recorded at the same site owing to the rapidly changing field geometry and last for less than 2,500 years. The actual transit between the two polarities does not last longer than 1,000 years and might therefore result from mechanisms other than those governing normal secular variation. Such changes are too brief to be accurately recorded by most sediments.

  12. Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

    Directory of Open Access Journals (Sweden)

    Chelis Leonidas

    2012-10-01

    Full Text Available Abstract Background The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. Case report We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. Conclusion In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and

  13. Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

    International Nuclear Information System (INIS)

    Chelis, Leonidas; Kakolyris, Stylianos; Souftas, Vasilios; Amarantidis, Kiriakos; Xenidis, Nikolaos; Chamalidou, Eleni; Dimopoulos, Prokopios; Michailidis, Prodromos; Christakidis, Evagelos; Prassopoulos, Panagiotis

    2012-01-01

    The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse effect, if untreated, that should

  14. Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

    Science.gov (United States)

    Mbuagbaw, Lawrence; Mursleen, Sara; Irlam, James H; Spaulding, Alicen B; Rutherford, George W; Siegfried, Nandi

    2016-12-10

    The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure

  15. Flux trapping during field reversal in a field reversed theta pinch

    International Nuclear Information System (INIS)

    Milroy, R.D.; Hoffman, A.L.; Slough, J.T.; Harding, D.G.

    1983-01-01

    In this paper we present new results from both numerical and experimental studies of the formation of the conducting sheath near the tube wall and its effectiveness in trapping bias flux during field reversal

  16. A Reverse Shock in GRB 160509A

    Science.gov (United States)

    Laskar, Tanmoy; Alexander, Kate D.; Berger, Edo; Fong, Wen-fai; Margutti, Raffaella; Shivvers, Isaac; Williams, Peter K. G.; Kopač, Drejc; Kobayashi, Shiho; Mundell, Carole; Gomboc, Andreja; Zheng, WeiKang; Menten, Karl M.; Graham, Melissa L.; Filippenko, Alexei V.

    2016-12-01

    We present the second multi-frequency radio detection of a reverse shock in a γ-ray burst. By combining our extensive radio observations of the Fermi-Large Area Telescope γ-ray burst 160509A at z = 1.17 up to 20 days after the burst with Swift X-ray observations and ground-based optical and near-infrared data, we show that the afterglow emission comprises distinct reverse shock and forward shock contributions: the reverse shock emission dominates in the radio band at ≲10 days, while the forward shock emission dominates in the X-ray, optical, and near-infrared bands. Through multi-wavelength modeling, we determine a circumburst density of {n}0≈ {10}-3 {{cm}}-3, supporting our previous suggestion that a low-density circumburst environment is conducive to the production of long-lasting reverse shock radiation in the radio band. We infer the presence of a large excess X-ray absorption column, N H ≈ 1.5 × 1022 {{cm}}-2, and a high rest-frame optical extinction, A V ≈ 3.4 mag. We identify a jet break in the X-ray light curve at {t}{jet}≈ 6 {days}, and thus derive a jet opening angle of {θ }{jet}≈ 4^\\circ , yielding a beaming-corrected kinetic energy and radiated γ-ray energy of {E}{{K}}≈ 4× {10}50 erg and {E}γ ≈ 1.3× {10}51 erg (1-104 keV, rest frame), respectively. Consistency arguments connecting the forward shocks and reverse shocks suggest a deceleration time of {t}{dec} ≈ 460 s ≈ T 90, a Lorentz factor of {{Γ }}({t}{dec})≈ 330, and a reverse-shock-to-forward-shock fractional magnetic energy density ratio of {R}{{B}}\\equiv {ɛ }{{B},{RS}}/{ɛ }{{B},{FS}}≈ 8. Our study highlights the power of rapid-response radio observations in the study of the properties and dynamics of γ-ray burst ejecta.

  17. Dendritic cells used in anti-HIV immunotherapy showed different modulation in anti-HIV genes expression: New concept for the improvement of patients' selection criteria

    Directory of Open Access Journals (Sweden)

    Alessandra Pontillo

    2016-11-01

    Conclusions: These results suggest that the actual selection of HIV+ individual for immunotherapy, based on clinical features, did not ensure the same DC product, and that less “activated/exhausted” DC could positively affect the outcome of immunotherapy.

  18. ‘Picking People to Hate’: Reversible reversals in stand-up comedy

    DEFF Research Database (Denmark)

    Keisalo, Marianna Päivikki

    2017-01-01

    Generally speaking, ritual reversals mean switching to the opposite of what is considered ‘the normal order’. Such reversals can occur, for example, in terms of social hierarchies in rites of passage, in action in carnival, or in the framing of action as ritual or performance. For comedic figures...... cultural grounds and show how the study of comedic performance can offer insights into the semiotics of performance more broadly....

  19. Reverse micelles as a tool for probing solvent modulation of protein dynamics: Reverse micelle encapsulated hemoglobin☆

    OpenAIRE

    Roche, Camille J.; Dantsker, David; Heller, Elizabeth R.; Sabat, Joseph E.; Friedman, Joel M.

    2013-01-01

    Hydration waters impact protein dynamics. Dissecting the interplay between hydration waters and dynamics requires a protein that manifests a broad range of dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve this objective because the water content can be manipulated. Hemoglobin is an appropriate tool with which to probe hydration effects. We describe both a protocol for hemoglobin encapsulation in reverse micelles and a facile method using PEG and cosolvents to mani...

  20. Reverse logistics policy – differences between conservative and innovative reverse logistics management

    Directory of Open Access Journals (Sweden)

    Alena Klapalová

    2013-01-01

    Full Text Available One of the of the key barriers that hampers effective and efficient management of reverse flows detected within a number of empirical surveys and case studies focused on reverse logistics and/or return management is business (organisational policy, specifically lack of policy, deficiency in existing policy or inferior policy. Despite this fact, there is a gap in literature which would show some evidence from practice that innovative reverse logistics policy both can pay off and is associated with certain aspects of reverse logistics management. Such proof can have several implications. It can support the call for better understanding and more research of the linkages of reverse logistics with other corporate functions, promote the acceptation of strategic character of reverse logistics and stress the role of RL policy within the rest of overall corporate management.The aim of this paper is to contribute and to enrich the existing body of knowledge concerning the above-mentioned gap through presentation of survey results that was realized in 2012 among managers of 244 Czech firms. The results demonstrate the statistically significant association between the innovativeness of RL policy and profitability of firms, quality of RL planning, perception of RL importance, level of RL knowledge and perception of product innovation importance for firms’ competitiveness and frequency of product innovation. They also reveal statistically significant differences between firms with conservative and innovative RL policy and the perceived existence of some barriers to manage RL.

  1. Dissaving of the Past via Reverse Mortgages

    Directory of Open Access Journals (Sweden)

    Ana Luiza Champloni

    Full Text Available We build a simple two-period general equilibrium model with incomplete markets which incorporates reverse market mortgages without appealing to the complicated framework required by the infinite horizon models. Two types of agents are considered: elderly agents and investors. The former are owners of physical assets (for instance housing who will want to sell them to investors. For that end the elderly agents, who are assumed to not have any bequest motive, issue claims against physical assets they own. One of the claims issued will be interpreted as reverse mortgage (loan for seniors and the other one as a call option written on the value of housing equity. By assuming that both the elderly agents and the investors are price takers, and by applying the generalized game approach, we show that the equilibrium in this economy always exists, providing the usual conditions on utilities and initial endowments are satisfied. We end with a remark on efficiency of the quilibrium.

  2. Posterior reversible encephalopathy syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Kostić Dejan

    2015-01-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by the following symptoms: seizures, impaired consciousness and/or vision, vomiting, nausea, and focal neurological signs. Diagnostic imaging includes examination by magnetic resonance (MR and computed tomography (CT, where brain edema is visualized bi-laterally and symmetrically, predominantly posteriorly, parietally, and occipitally. Case report. We presented a 73-year-old patient with the years-long medical history of hipertension and renal insufficiency, who developed PRES with the symptomatology of the rear cranium. CT and MR verified changes in the white matter involving all lobes on both sides of the brain. After a two-week treatment (antihypertensive, hypolipemic and rehydration therapy clinical improvement with no complications occurred, with complete resolution of changes in the white matter observed on CT and MR. Conclusion. PRES is a reversible syndrome in which the symptoms withdraw after several days to several weeks if early diagnosis is made and appropriate treatment started without delay.

  3. Time-Reversal Generation of Rogue Waves

    Science.gov (United States)

    Chabchoub, Amin; Fink, Mathias

    2014-03-01

    The formation of extreme localizations in nonlinear dispersive media can be explained and described within the framework of nonlinear evolution equations, such as the nonlinear Schrödinger equation (NLS). Within the class of exact NLS breather solutions on a finite background, which describe the modulational instability of monochromatic wave trains, the hierarchy of rational solutions localized in both time and space is considered to provide appropriate prototypes to model rogue wave dynamics. Here, we use the time-reversal invariance of the NLS to propose and experimentally demonstrate a new approach to constructing strongly nonlinear localized waves focused in both time and space. The potential applications of this time-reversal approach include remote sensing and motivated analogous experimental analysis in other nonlinear dispersive media, such as optics, Bose-Einstein condensates, and plasma, where the wave motion dynamics is governed by the NLS.

  4. Heavy metal removal using reverse osmosis

    Directory of Open Access Journals (Sweden)

    Lucia Gajdošová

    2009-12-01

    Full Text Available The aim of this work was to study reverse osmosis characteristics for copper, nickel and zinc removal from technological aqueoussolutions. Reverse osmosis (RO is a separation process that uses pressure to force a solution through a membrane that retainsthe solute on one side and allows the pure solvent to pass to the other side. A polyamide thin-film composite membrane TW30-1812-50was used. The difference in flux decline is significant. There is a significant difference in flux decline depending on the anions of usedheavy metal salts. The heavy metal concentration also has a significant influence on the membrane separation. There is alsoa significant difference in flux decline depending on the transmembrane pressure.

  5. Time reversal tests in polarized neutron reactions

    International Nuclear Information System (INIS)

    Asahi, Koichiro; Bowman, J.D.; Crawford, B.

    1998-01-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). In recent years the nuclear weak interaction has been studied in the compound nucleus via parity violation. The observed parity-violating effects are strongly enhanced by nuclear structure. The predictions are that the interaction of polarized neutrons with polarized nuclear targets could be also used to perform sensitive tests of time-reversal-violation because of the nuclear enhancements. The author has designed experiments to search for time-reversal violation in neutron-nucleus interactions. He has also developed techniques to polarize neutrons with laser-polarized 3 He gas targets. Using the polarized 3 He neutron spin filter, he has performed two experiments at LANSCE: an absolute neutron beam polarization measurement with an accuracy of 0.2--0.3% and a neutron spin-rotation measurement on a 139 La sample

  6. Microscopic theory of ultrafast spin linear reversal

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, G P, E-mail: gpzhang@indstate.edu [Department of Physics, Indiana State University, Terre Haute, IN 47809 (United States)

    2011-05-25

    A recent experiment (Vahaplar et al 2009 Phys. Rev. Lett. 103 117201) showed that a single femtosecond laser can reverse the spin direction without spin precession, or spin linear reversal (SLR), but its microscopic theory has been missing. Here we show that SLR does not occur naturally. Two generic spin models, the Heisenberg and Hubbard models, are employed to describe magnetic insulators and metals, respectively. We find analytically that the spin change is always accompanied by a simultaneous excitation of at least two spin components. The only model that has prospects for SLR is the Stoner single-electron band model. However, under the influence of the laser field, the orbital angular momenta are excited and are coupled to each other. If a circularly polarized light is used, then all three components of the orbital angular momenta are excited, and so are their spins. The generic spin commutation relation further reveals that if SLR exists, it must involve a complicated multiple state excitation.

  7. Reverse osmosis membrane allows in situ regeneration

    International Nuclear Information System (INIS)

    Bonhomme, N.; Menjeaud, C.; Poyet, C.

    1989-01-01

    The use of mineral membranes on metallic supports has provided a novel solution to the problem of filtration by the reverse osmosis process. A new reverse osmosis membrane is described which is capable of resisting high operational temperatures (120 0 C), fluctuations in pH(3 to 12) and high pressure (100 bar), as well as significant chlorine concentrations. In addition, the membrane can be regenerated in-situ on the same porous metal support. Numerous membranes can thus be used over the multi-year life of the porous support. Moreover, accidental damage to the membrane is of no great consequence as the membrane itself can be easily replaced. The life of the installation can thus be extended and the overall cost of filtration reduced. The membrane's various applications include water and effluent treatment in the nuclear power industry. (author)

  8. Cranial MR finding of reversible eclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Seok Ho; Hwang, Mi Young; Kim, Kyu Hwa; Kim, Seon Goo; Lee, Sung Moon; Kim, Hong; Joo, Yang Goo; Suh, Soo Ji [College of Medicine, Keimyung University, Daegu (Korea, Republic of)

    1994-05-15

    To evaluate clinical usefulness of cranial magnetic resonance imaging(MRI) in diagnosis and for follow-up of reversible eclampsia. Cranial MRI was performed on four consecutive pregnant patients(ante-partum 3 cases, postpartum 1 cases), who had generalized tonic-clonic seizure caused by eclampsia. One of the four patients underwent follow-up MRI. Cranial MRI typically demonstrated bilateral hyperintense lesions on T2-weighted images and iso-to hypointense lesions on T1-weighted images. MRI abnormalities were most commonly located in the distribution of the posterior cerebral artery circulation and were associated with symptoms of visual disturbance. Most cranial lesions of eclampsia demonstrated in MRI were reversible. MRI with its capability to detect even subtle abnormalities in the brain that are not visible on CT, and may be the technique of choice for evaluating the cerebral the pathology of pregnant women with eclampsia.

  9. Crystallization features of ternary reversible reciprocal systems

    International Nuclear Information System (INIS)

    Tomashik, V.N.; Shcherbak, L.P.; Fejchuk, P.I.; Grytsiv, V.I.

    2006-01-01

    Some features of the primary crystallization of phases in ternary reversible reciprocal system are considered and discussed. The diagonal join CdTe-GeSe of the CdTe + GeSe = CdSe + GeTe ternary reciprocal system is studied to show that the features in primary and secondary heating and cooling curves in such systems under fully equilibrium conditions are not reproduced upon consecutive heating and cooling sessions, because of the existence of different amounts of the reagents and the reaction products in the mixture; the temperatures of each transformation lie in a range. Those who experimentally investigate other ternary and more complex reversible reciprocal systems should take this fact into account [ru

  10. Quantum vertex model for reversible classical computing.

    Science.gov (United States)

    Chamon, C; Mucciolo, E R; Ruckenstein, A E; Yang, Z-C

    2017-05-12

    Mappings of classical computation onto statistical mechanics models have led to remarkable successes in addressing some complex computational problems. However, such mappings display thermodynamic phase transitions that may prevent reaching solution even for easy problems known to be solvable in polynomial time. Here we map universal reversible classical computations onto a planar vertex model that exhibits no bulk classical thermodynamic phase transition, independent of the computational circuit. Within our approach the solution of the computation is encoded in the ground state of the vertex model and its complexity is reflected in the dynamics of the relaxation of the system to its ground state. We use thermal annealing with and without 'learning' to explore typical computational problems. We also construct a mapping of the vertex model into the Chimera architecture of the D-Wave machine, initiating an approach to reversible classical computation based on state-of-the-art implementations of quantum annealing.

  11. Antiproton Production beam and Reverse Injection System

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, G.

    1981-08-16

    The objectives of this project are two fold: (1) To extract high energy protons from the Main Ring (MR) and target them to produce antiprotons which are subsequently captured in the existing Booster accelerator; and (2) to provide a channel for injecting either protons or antiprotons into the MR from the booster in a direction opposite to that of the normal proton acceleration as colliding beams can be created. The present design, therefore, is in support of two separate larger projects, viz., the collisions of protons in the Tevatron (normal circulation direction) with 'reverse injected' protons in the MR, and the collision of normal direction protons with reverse injected antiprotons either in the MR or in the Tevatron. Figure 1 shows the layout of the project area. It spans the shortest distance between possible injection/ejection points in the existing accelerator structures, hence minimizing costs. The tunnel will lie underground at the level of the MR and booster.

  12. Laser heating of field-reversed configurations

    International Nuclear Information System (INIS)

    Carson, R.S.; Vlases, G.C.

    1983-01-01

    The experimental facility is a 21-cm-long solenoid with a 5.5-cm bore. The 4-cm ID quartz tube is filled with slowly flowing H 2 to 0.5-3.0 torr. Fields up to 6.5 T in 3.7 μsec are produced, with reverse-bias fields up -1.9 T. Preionization is by 40kA axial discharge 4.5 μsec before field-reversal is begun. The CO 2 laser used produces 300 to 400 J in 2 μsec, in an annular beam that can be defocused for preheating the outer edges of the plasma, or focused tightly for central-column heating and beam propagation during formation. The focusing system includes a return mirror for multiple passing of the laser energy. Diagnostics include compensated, diamagnetic flux loops, internal field probes, cross-tube and axial interferometers, fast photography, and spectroscopy

  13. Plutonium decontamination studies using Reverse Osmosis

    International Nuclear Information System (INIS)

    Plock, C.E.; Travis, T.N.

    1980-01-01

    Water in batches of 45 gallons each, from a creek crossing the Rocky Flats Plant, was transferred to the Reverse Osmosis (RO) laboratory for experimental testing. The testing involved using RO for plutonium decontamination. For each test, the water was spiked with plutonium, had its pH adjusted, and was then processed by RO. At a water recovery level of 87%, the plutonium decontamination factors ranged from near 100 to 1200, depending on the pH of the processed water

  14. A Reverse Stroop Task with Mouse Tracking

    Science.gov (United States)

    Yamamoto, Naohide; Incera, Sara; McLennan, Conor T.

    2016-01-01

    In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed—for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants’ responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants’ performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse’s approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID:27199881

  15. Variable Cycle Intake for Reverse Core Engine

    Science.gov (United States)

    Suciu, Gabriel L (Inventor); Chandler, Jesse M (Inventor); Staubach, Joseph B (Inventor)

    2016-01-01

    A gas generator for a reverse core engine propulsion system has a variable cycle intake for the gas generator, which variable cycle intake includes a duct system. The duct system is configured for being selectively disposed in a first position and a second position, wherein free stream air is fed to the gas generator when in the first position, and fan stream air is fed to the gas generator when in the second position.

  16. Computational methods for reversed-field equilibrium

    International Nuclear Information System (INIS)

    Boyd, J.K.; Auerbach, S.P.; Willmann, P.A.; Berk, H.L.; McNamara, B.

    1980-01-01

    Investigating the temporal evolution of reversed-field equilibrium caused by transport processes requires the solution of the Grad-Shafranov equation and computation of field-line-averaged quantities. The technique for field-line averaging and the computation of the Grad-Shafranov equation are presented. Application of Green's function to specify the Grad-Shafranov equation boundary condition is discussed. Hill's vortex formulas used to verify certain computations are detailed. Use of computer software to implement computational methods is described

  17. Reversible thyristor converters of brushless synchronous compensators

    Directory of Open Access Journals (Sweden)

    А.М.Galynovskiy

    2013-12-01

    Full Text Available Behavior of models of three-phase-to-single-phase rotary reversible thyristor converters of brushless synchronous compensators in a circuit simulation system is analyzed. It is shown that combined control mode of opposite-connected thyristors may result in the exciter armature winding short circuits both at the thyristor feed-forward and lagging current delay angles. It must be taken into consideration when developing brushless compensator excitation systems.

  18. Forward and reverse mutagenesis in C. elegans

    Science.gov (United States)

    Kutscher, Lena M.; Shaham, Shai

    2014-01-01

    Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

  19. Particle transort in field-reversed configurations

    Energy Technology Data Exchange (ETDEWEB)

    Tuszewski, M.; Linford, R.K.; Lipson, J.; Sgro, A.G.

    1981-01-01

    A field reversed configuration (FRC) is a compact toroid that contains no toroidal field. These plasmas are observed to be grossly stable for about 10-100 ..mu..sec. The lifetimes appear limited by an n = 2 rotational instability which may be caused by particle loss. Particle transport is therefore an important issue for these configurations. We investigate particle loss with a steady-state, 1-D model which approximates the experimental observation of elongated FRC equilibrium with about constant separatrix radius.

  20. On the design of reversible QDCA systems.

    Energy Technology Data Exchange (ETDEWEB)

    DeBenedictis, Erik P.; Frank, Michael P. (Florida State University, Tallahassee, FL); Ottavi, Marco; Frost-Murphy, Sarah E. (University of Notre Dame, Notre Dame, IN)

    2006-10-01

    This work is the first to describe how to go about designing a reversible QDCA system. The design space is substantial, and there are many questions that a designer needs to answer before beginning to design. This document begins to explicate the tradeoffs and assumptions that need to be made and offers a range of approaches as starting points and examples. This design guide is an effective tool for aiding designers in creating the best quality QDCA implementation for a system.

  1. Evaluating Reverse Supply Chain Efficiency: Manufacturer's Perspective

    DEFF Research Database (Denmark)

    Kumar, M.; Tiwari, M. K.; Wong, K. Y.

    2014-01-01

    The paper aims to illustrate the use of fuzzy data envelopment analysis (DEA) in analyzing reverse supply chain (RSC) performance from the manufacturer's perspective. By using an alternative alpha-cut approach, the fuzzy DEA model was converted into a crisp linear programming problem, thereby...... usually ensures an environmentally friendly supply chain network, companies which have implemented RSC techniques since a longer duration do not necessarily have a more efficient supply chain in general....

  2. Clinical Applications of Reverse Panoramic Radiography

    Directory of Open Access Journals (Sweden)

    Sujatha S Reddy

    2011-09-01

    Full Text Available The essence of oral and maxil-lofacial radiology is not only to be an important tool in the diagnostic assessment of dental patients but also to equip the clinician with the ability to interpret images of certain maxillocraniofacial structures of importance to dental, medical and surgical practices. Although combinations of several conven-tional x-ray projections can be adequate in a number of clinical situations, radiographic assessment of certain craniofacial structures some-times needs to be facilitated by other imaging modalities. A not-so-recent development called reverse panoramic radiography may be a useful adjuvant to such a situation, at least in the near future. It is essentially a technique where the patient is placed backwards in the panoramic machine in a reverse position in such a way that x-ray beam is directed through the patient’s face and the exit beam then passes through the patient’s head on the opposite side where it is captured on the receptor. The following manuscript is an attempt to throw light on this technique and the impact it may have on dental, medical and surgical practices. The advantages and disadvantages of reverse panoramic radiography and it’s comparison to conventional panoramic radiographs and other skull views are also dis-cussed.

  3. Earth's magnetic field is probably not reversing.

    Science.gov (United States)

    Brown, Maxwell; Korte, Monika; Holme, Richard; Wardinski, Ingo; Gunnarson, Sydney

    2018-04-30

    The geomagnetic field has been decaying at a rate of [Formula: see text]5% per century from at least 1840, with indirect observations suggesting a decay since 1600 or even earlier. This has led to the assertion that the geomagnetic field may be undergoing a reversal or an excursion. We have derived a model of the geomagnetic field spanning 30-50 ka, constructed to study the behavior of the two most recent excursions: the Laschamp and Mono Lake, centered at 41 and 34 ka, respectively. Here, we show that neither excursion demonstrates field evolution similar to current changes in the geomagnetic field. At earlier times, centered at 49 and 46 ka, the field is comparable to today's field, with an intensity structure similar to today's South Atlantic Anomaly (SAA); however, neither of these SAA-like fields develop into an excursion or reversal. This suggests that the current weakened field will also recover without an extreme event such as an excursion or reversal. The SAA-like field structure at 46 ka appears to be coeval with published increases in geomagnetically modulated beryllium and chlorine nuclide production, despite the global dipole field not weakening significantly in our model during this time. This agreement suggests a greater complexity in the relationship between cosmogenic nuclide production and the geomagnetic field than is commonly assumed.

  4. Domino model for geomagnetic field reversals.

    Science.gov (United States)

    Mori, N; Schmitt, D; Wicht, J; Ferriz-Mas, A; Mouri, H; Nakamichi, A; Morikawa, M

    2013-01-01

    We solve the equations of motion of a one-dimensional planar Heisenberg (or Vaks-Larkin) model consisting of a system of interacting macrospins aligned along a ring. Each spin has unit length and is described by its angle with respect to the rotational axis. The orientation of the spins can vary in time due to spin-spin interaction and random forcing. We statistically describe the behavior of the sum of all spins for different parameters. The term "domino model" in the title refers to the interaction among the spins. We compare the model results with geomagnetic field reversals and dynamo simulations and find strikingly similar behavior. The aggregate of all spins keeps the same direction for a long time and, once in a while, begins flipping to change the orientation by almost 180 degrees (mimicking a geomagnetic reversal) or to move back to the original direction (mimicking an excursion). Most of the time the spins are aligned or antialigned and deviate only slightly with respect to the rotational axis (mimicking the secular variation of the geomagnetic pole with respect to the geographic pole). Reversals are fast compared to the times in between and they occur at random times, both in the model and in the case of the Earth's magnetic field.

  5. Navigation of the autonomous vehicle reverse movement

    Science.gov (United States)

    Rachkov, M.; Petukhov, S.

    2018-02-01

    The paper presents a mathematical formulation of the vehicle reverse motion along a multi-link polygonal trajectory consisting of rectilinear segments interconnected by nodal points. Relevance of the problem is caused by the need to solve a number of tasks: to save the vehicle in the event of а communication break by returning along the trajectory already passed, to avoid a turn on the ground in constrained obstacles or dangerous conditions, or a partial return stroke for the subsequent bypass of the obstacle and continuation of the forward movement. The method of navigation with direct movement assumes that the reverse path is elaborated by using landmarks. To measure landmarks on board, a block of cameras is placed on a vehicle controlled by the operator through the radio channel. Errors in estimating deviation from the nominal trajectory of motion are determined using the multidimensional correlation analysis apparatus based on the dynamics of a lateral deviation error and a vehicle speed error. The result of the experiment showed a relatively high accuracy in determining the state vector that provides the vehicle reverse motion relative to the reference trajectory with a practically acceptable error while returning to the start point.

  6. Preference reversal in quantum decision theory

    Directory of Open Access Journals (Sweden)

    Vyacheslav I. Yukalov

    2015-10-01

    Full Text Available We consider the psychological effect of preference reversal and showthat it finds a natural explanation in the frame of quantum decisiontheory. When people choose between lotteries with non-negative payoffs, they prefer a more certain lottery because of uncertainty aversion. But when people evaluate lottery prices, e.g. for selling to others the right to play them, they do this more rationally, being less subject to behavioral biases. This difference can be explained bythe presence of the attraction factors entering the expression of quantumprobabilities. Only the existence of attraction factors can explain why,considering two lotteries with close utility factors, a decision maker prefers one of them when choosing, but evaluates higher the other one when pricing. We derive a general quantitative criterion for the preference reversal to occur that relates the utilities of the two lotteries to the attraction factors under choosing versus pricing and test successfully its application on experiments by Tversky et al.We also show that the planning paradox can be treated as a kind of preference reversal.

  7. Alfven eigenmodes in shear reversed plasmas

    International Nuclear Information System (INIS)

    Breizman, B.N.; Berk, H.L.; Pekker, M.S.; Sharapov, S.E.; Hawkes, N.C.; Borba, D.N.; Pinches, S.D.

    2003-01-01

    Experiments on JT-60U and JET have shown that plasma configurations with shear reversal are prone to the excitation of unusual Alfven Eigenmodes by energetic particles. These modes emerge outside the TAE frequency gap, where one might expect them to be strongly damped. The modes often appear in bunches and they exhibit a quasi-periodic pattern of predominantly upward frequency sweeping (Alfven Cascades) as the safety factor q changes in time. This work presents a theory that explains the key features of the observed unusual modes including their connection to TAE's as well as the modifications of TAE's themselves near the shear reversal point. The developed theory has been incorporated into a reduced numerical model and verified with full geometry codes. JET experimental data on Alfven spectroscopy have been simulated to infer the mode numbers and the evolution of q min in the discharge. This analysis confirms the values of q that characterize the internal transport barrier triggering in reversed shear plasmas. (author)

  8. Model of reversible vesicular transport with exclusion

    International Nuclear Information System (INIS)

    Bressloff, Paul C; Karamched, Bhargav R

    2016-01-01

    A major question in neurobiology concerns the mechanics behind the motor-driven transport and delivery of vesicles to synaptic targets along the axon of a neuron. Experimental evidence suggests that the distribution of vesicles along the axon is relatively uniform and that vesicular delivery to synapses is reversible. A recent modeling study has made explicit the crucial role that reversibility in vesicular delivery to synapses plays in achieving uniformity in vesicle distribution, so called synaptic democracy (Bressloff et al 2015 Phys. Rev. Lett. 114 168101). In this paper we generalize the previous model by accounting for exclusion effects (hard-core repulsion) that may occur between molecular motor-cargo complexes (particles) moving along the same microtubule track. The resulting model takes the form of an exclusion process with four internal states, which distinguish between motile and stationary particles, and whether or not a particle is carrying vesicles. By applying a mean field approximation and an adiabatic approximation we reduce the system of ODEs describing the evolution of occupation numbers of the sites on a 1D lattice to a system of hydrodynamic equations in the continuum limit. We find that reversibility in vesicular delivery allows for synaptic democracy even in the presence of exclusion effects, although exclusion does exacerbate nonuniform distributions of vesicles in an axon when compared with a model without exclusion. We also uncover the relationship between our model and other models of exclusion processes with internal states. (paper)

  9. Magnetization reversal in single molecule magnets

    Science.gov (United States)

    Bokacheva, Louisa

    2002-09-01

    I have studied the magnetization reversal in single molecule magnets (SMMs). SMMs are Van der Waals crystals, consisting of identical molecules containing transition metal ions, with high spin and large uniaxial magnetic anisotropy. They can be considered as ensembles of identical, iso-oriented nanomagnets. At high temperature, these materials behave as superparamagnets and their magnetization reversal occurs by thermal activation. At low temperature they become blocked, and their magnetic relaxation occurs via thermally assisted tunneling or pure quantum tunneling through the anisotropy barrier. We have conducted detailed experimental studies of the magnetization reversal in SMM material Mn12-acetate (Mn12) with S = 10. Low temperature measurements were conducted using micro-Hall effect magnetometry. We performed hysteresis and relaxation studies as a function of temperature, transverse field, and magnetization state of the sample. We identified magnetic sublevels that dominate the tunneling at a given field, temperature and magnetization. We observed a crossover between thermally assisted and pure quantum tunneling. The form of this crossover depends on the magnitude and direction of the applied field. This crossover is abrupt (first-order) and occurs in a narrow temperature interval (tunneling mechanisms in Mn12.

  10. Reversal of multidrug resistance by surfactants.

    Science.gov (United States)

    Woodcock, D. M.; Linsenmeyer, M. E.; Chojnowski, G.; Kriegler, A. B.; Nink, V.; Webster, L. K.; Sawyer, W. H.

    1992-01-01

    Cremophor EL, a pharmacologically inactive solubilising agent, has been shown to reverse multidrug resistance (MDR). Using flow cytometric evaluation of equilibrium intracellular levels of daunorubicin (DNR), we found that eight other surface active agents will also reverse MDR. All the active detergents contain polyethoxylated moieties but have no similarities in their hydrophobic components. The properties of three polyethoxylated surfactants that showed the lowest toxicities, Cremophor, Tween 80 and Solutol HS15, were examined in more detail. The concentrations of Tween 80 and Solutol required to reverse DNR exclusion were 10-fold lower than for Cremophor. However while concentrations greater than or equal to 1:10(2) of the former two surfactants resulted in breakdown of cells, even 1:10 of Cremophor did not lyse cells. Studies of the effects of Cremophor on the uptake and efflux of DNR in normal and MDR cell types showed that Cremophor increases intracellular DNR primarily by locking the rapid efflux from the cells. This blockage of drug efflux may be mediated by a substantial alteration in the fluidity of cell membranes induced by Cremophor, as shown by decreased fluorescence anisotropy of a membrane probe. Consistent with these data, coinjection of adriamycin plus Cremophor into mice carrying a multidrug resistant P388 transplantable tumour significantly increased the survival time of the mice compared with adriamycin treatment alone. PMID:1637678

  11. Preference reversal in quantum decision theory

    Science.gov (United States)

    Yukalov, Vyacheslav I.; Sornette, Didier

    2015-01-01

    We consider the psychological effect of preference reversal and show that it finds a natural explanation in the frame of quantum decision theory. When people choose between lotteries with non-negative payoffs, they prefer a more certain lottery because of uncertainty aversion. But when people evaluate lottery prices, e.g., for selling to others the right to play them, they do this more rationally, being less subject to behavioral biases. This difference can be explained by the presence of the attraction factors entering the expression of quantum probabilities. Only the existence of attraction factors can explain why, considering two lotteries with close utility factors, a decision maker prefers one of them when choosing, but evaluates higher the other one when pricing. We derive a general quantitative criterion for the preference reversal to occur that relates the utilities of the two lotteries to the attraction factors under choosing vs. pricing and test successfully its application on experiments by Tversky et al. We also show that the planning paradox can be treated as a kind of preference reversal. PMID:26500592

  12. Reversible logic synthesis methodologies with application to quantum computing

    CERN Document Server

    Taha, Saleem Mohammed Ridha

    2016-01-01

    This book opens the door to a new interesting and ambitious world of reversible and quantum computing research. It presents the state of the art required to travel around that world safely. Top world universities, companies and government institutions  are in a race of developing new methodologies, algorithms and circuits on reversible logic, quantum logic, reversible and quantum computing and nano-technologies. In this book, twelve reversible logic synthesis methodologies are presented for the first time in a single literature with some new proposals. Also, the sequential reversible logic circuitries are discussed for the first time in a book. Reversible logic plays an important role in quantum computing. Any progress in the domain of reversible logic can be directly applied to quantum logic. One of the goals of this book is to show the application of reversible logic in quantum computing. A new implementation of wavelet and multiwavelet transforms using quantum computing is performed for this purpose. Rese...

  13. Photonics of dyes molecules in reverse micellar solution

    International Nuclear Information System (INIS)

    Ibragimova, M.R.; Laurinas, V.Ch.

    2001-01-01

    Spectral luminescent characteristics of the dye acridine orange and eosin has been studied in reverse micellar solutions of sodium bis(2-ethyl-hexyl)sulfosuccinate. It was shown that the increase of the nucleus volume of reverse micelles. (author)

  14. Long-acting reversible hormonal contraception | Dahan-Farkas ...

    African Journals Online (AJOL)

    Long-acting reversible hormonal contraceptives are effective methods of birth control that provide contraception for an extended period without requiring user action. Long-acting reversible hormonal contraceptives include progesterone only injectables, subdermal implants and the levonorgestrel intrauterine system.

  15. The Role of Reverse Logistics on the European Market

    OpenAIRE

    Irina Tobosaru; Irina Nicolau

    2009-01-01

    The Council of Logistics Management has published the first definition of reverse logistics in 1992: “The term reverse logistics refers to the role of logistics in recycling waste, in the distribution and the handling of dangerous materials. A broader definition includes in the reverse logistics, activities that have the purpose of reducing the resources, of recycling, replacing, reusing the materials and relocating them”. Reverse logistics can be also defined using as standard the definition...

  16. Reversible and non-reversible enlargement of cerebral spinal fluid spaces in anorexia nervosa

    International Nuclear Information System (INIS)

    Artmann, H.; Grau, H.; Adelmann, M.; Schleiffer, R.

    1985-01-01

    Brain CT studies of 35 patients with anoxia nervosa confirmed the observations of other authors: cerebral dystrophic changes correlate with weight loss and the reversibility of these changes also correlates with the normalization of body weight. Other corroborated facts are: the most numerous and most pronounced enlargements are of the cortical sulci and the interhemispheric fissure, moderate widening affects the ventricles and the rarest and most insignificant changes are those of the cerebellum. The reversibility of the changes showed a parallel to the extent of the changes themselves and to the duration of improvement of the body weight. The reversibility of the enlargement of the cortical sulci and of the distances between the frontal horns of the lateral ventricles was more often significant than that of the abnormal measurements of the cella media. This difference is based on minimal early acquired brain damage which occurs in 60% of our patients. This high incidence of early acquired minimal brain disease in patients with anorexia nervosa is here discussed as a nonspecific predisposing factor. Although there is no exact explanation of the etiology of the reversible enlargement of cerenral spinal fluid (CSF) spaces in anorexia nervosa, the changes resemble those in alcoholics. The mechanisms of brain changes in alcoholism, as shown experimentally, seem to us to throw light on the probable mechanism of reversible dystrophic brain changes in anorexia nervosa. (orig.)

  17. Reversible and non-reversible enlargement of cerebral spinal fluid spaces in anorexia nervosa

    Energy Technology Data Exchange (ETDEWEB)

    Artmann, H.; Grau, H.; Adelmann, M.; Schleiffer, R.

    1985-07-01

    Brain CT studies of 35 patients with anoxia nervosa confirmed the observations of other authors: cerebral dystrophic changes correlate with weight loss and the reversibility of these changes also correlates with the normalization of body weight. Other corroborated facts are: the most numerous and most pronounced enlargements are of the cortical sulci and the interhemispheric fissure, moderate widening affects the ventricles and the rarest and most insignificant changes are those of the cerebellum. The reversibility of the changes showed a parallel to the extent of the changes themselves and to the duration of improvement of the body weight. The reversibility of the enlargement of the cortical sulci and of the distances between the frontal horns of the lateral ventricles was more often significant than that of the abnormal measurements of the cella media. This difference is based on minimal early acquired brain damage which occurs in 60% of our patients. This high incidence of early acquired minimal brain disease in patients with anorexia nervosa is here discussed as a nonspecific predisposing factor. Although there is no exact explanation of the etiology of the reversible enlargement of cerenral spinal fluid (CSF) spaces in anorexia nervosa, the changes resemble those in alcoholics. The mechanisms of brain changes in alcoholism, as shown experimentally, seem to us to throw light on the probable mechanism of reversible dystrophic brain changes in anorexia nervosa.

  18. Rethinking the risk-benefit ratio of efavirenz in HIV-infected children

    NARCIS (Netherlands)

    Wijer, L van de; Schellekens, A.F.A.; Burger, D.M.; Homberg, J.R.; Mast, Q. de; Ven, A.J.A.M. van der

    2016-01-01

    The non-nucleoside reverse transcriptase inhibitor efavirenz is part of the WHO guidelines for preferred first-line treatment of HIV-1-infected adults, pregnant and lactating women, and children. Efavirenz is well known to cause CNS toxicity. Although good data for CNS toxicity are available for

  19. Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

    2008-01-01

    OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

  20. Efficacy and durability of nevirapine in antiretroviral drug naive patients

    NARCIS (Netherlands)

    Lange, Joep M. A.

    2003-01-01

    Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) naive patients. Four key studies have