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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: F M Javed Mehedi Shamrat; Shamima Akter; Sami Azam; Asif Karim; +5 Authors
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    IEEE Access
    Article . 2023
    License: CC BY
    Data sources: Crossref
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      IEEE Access
      Article . 2023
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  • Authors: Robert J. Elliott; Tak Kuen Siu;

    Refereed/Peer-reviewed

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Elisa Conde Moreno; Alejandro Pascual; Daniel Prieto-Cuadra; Val F. Laza; +7 Authors

    microRNAs (miRNA) expression in colorectal (CR) primary tumours can facilitate a more precise molecular characterization. We identified and validated a miRNA profile associated with clinical and histopathological features that might be useful for patient stratification. In situ hybridization array using paraffin-embedded biopsies of CR primary tumours were used to screen 1436 miRNAs. 17 miRNAs were selected for validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 192) and were further correlated with clinical and histopathological data. We demonstrated that miRNAs associated to Colorectal Cancer (CRC) diagnosis age (over 50s and 60s) included miR-1-3p, miR-23b-3p, miR-27b-3p, miR-143-3p, miR-145-5p and miR-193b-5p. miR-23b-3p and miR-24-3p discriminated between Lynch Syndrome and sporadic CRC. miR-10a-5p, miR-20a-5p, miR-642b and Let-7a-5p were associated to stroma abundance. miR-642b and Let-7a-5p were associated with to peritumoral inflammation abundance. miR-1-3p, miR-143-3p and miR-145-5p correlated with mucinous component. miR-326 correlated with tumour location (right or left sided). miR-1-3p associated with tumour grade. miR-20a-5p, miR-193b-5p, miR-320a, miR-326 and miR-642b-3p associated to tumour stage and progression. Remarkably, we also demonstrated that miR-1-3p and miR-326 expression significantly associated with patient overall survival (OS). Hierarchical clustering and bioinformatics analysis indicated that selected miRNAs could re-classify the patients and work cooperatively, modulating common target genes involved in colorectal cancer key signalling pathways. In conclusion, molecular characterization of CR primary tumours based on miRNAs could lead to more accurate patient reclassification and may be useful for efficient patient management.

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    Cancers
    Other literature type . Article . 2019
    License: CC BY
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    Europe PubMed Central
    Article . 2019
    Data sources: PubMed Central
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    Cancers
    Article . 2019
    Data sources: DOAJ-Articles
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    Cancers
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    DOAJ
    Article . 2019
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      Cancers
      Other literature type . Article . 2019
      License: CC BY
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      Europe PubMed Central
      Article . 2019
      Data sources: PubMed Central
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Cancers
      Article . 2019
      Data sources: DOAJ-Articles
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      Cancers
      Article
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      DOAJ
      Article . 2019
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  • Authors: Dongvu Tonien; Reihaneh Safavi-Naini; Peter R. Wild;

    In this paper, we consider authentication codes where the adversary has access to a verification oracle. We formally study two attack games: offline attack and online attack. In an offline impersonation attack with verification query of order i, the adversary launches its attack through two stages. In the first stage — the query stage — the adversary can adaptively choose i distinct messages to query the verification oracle. The verification oracle will answer whether these queried messages are valid or invalid under the secret encoding rule agreed by the transmitter and the receiver. In the later stage — the spoofing stage — the adversary creates a fraudulent message which is different from all its queried messages and sends this message to the receiver. The adversary wins if the receiver accepts the fraudulent message as a valid message. In an online impersonation attack with verification query of order i, the adversary has i + 1 chances to query the verification oracle and wins as soon as one of the queries is a valid message. We make use of strategy trees, which allow optimal strategies in both attack games to be identified, to establish a number of relationships between the value of the two games. This allows us to formally prove a relationship between the value of the game when the adversary has i queries, and the one in which he does not have any. The relationship, though widely believed to be true, was only recently proved for computationally secure systems. Our result complements this latter work for the information theoretic setting.

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  • Authors: Roberto Aguilera; Roberto Aguilera;

    AbstractThe objective of this paper is to examine the effect of oil and gas prices on the development of tight and shale reservoirs including oil, gas and condensate.The methodology uses a variable shape distribution (VSD) model for examining past, present and futures prices of oil and gas. The VSD matches historical annual changes in oil and gas prices with coefficients of determination that are generally larger than 0.98. Contrary to several commentators and specialized organizations around the world that were forecasting continuous oil price escalation up to US$ 300/bbl (e.g. in 2008, when the oil price was around US$ 140/bbl), the VSD was used successfully to anticipate a significant drop in prices, leading to the on-record statement that the oil price was a bubble and was going to burst (June 13, 2008).The VSD was also used to build a case at LACPEC in 2014 (Aguilera and Aguilera, 2014) indicating that "with the vast global oil resource base and the significant technological advances being implemented by the industry, oil prices could actually decrease in the future". This is a painful fact being faced today by the oil and gas industry worldwide.In this paper, the VSD has been used with a global energy market (GEM) model to examine possible future outcomes of unconventional resources development in light of forecasted oil and gas demand and anticipated price-changes calculated with the VSD.The methodology provides a novel approach for examining some realistic possibilities regarding future development of unconventional oil, gas and condensate reservoirs.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Vijaya M, Musini; Kendra Ak, Lawrence; Patricia M, Fortin; Ken, Bassett; +1 Authors

    Background Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. Objectives To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension. To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. Selection criteria We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. Data collection and analysis This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available. Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. Main results 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias. Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes. Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Authors' conclusions Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

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    Europe PubMed Central
    Other literature type . 2017
    Data sources: PubMed Central
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      Europe PubMed Central
      Other literature type . 2017
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    Authors: Kathryn Janet Brooks; Dave Reid; Olivier Thebaud; Sophie Gourguet; +7 Authors

    Marine and coastal activities are closely interrelated, and conflicts among different sectors can undermine management and conservation objectives. Governance systems for fisheries, power generation, irrigation, aquaculture, marine biodiversity conservation, and other coastal and maritime activities are typically organized to manage conflicts within sectors, rather than across them. Based on the discussions around eight case studies presented at a workshop held in Brest in June 2019, this paper explores institutional approaches to move beyond managing conflicts within a sector. We primarily focus on cases where the groups and sectors involved are heterogeneous in terms of: the jurisdiction they fall under; their objectives; and the way they value ecosystem services. The paper first presents a synthesis of frameworks for understanding and managing cross-sectoral governance conflicts, drawing from social and natural sciences. We highlight commonalities but also conceptual differences across disciplines to address these issues. We then propose a novel analytical framework which we used to evaluate the eight case studies. Based on the main lessons learned from case studies, we then discuss the feasibility and key determinants of stakeholder collaboration as well as compensation and incentive schemes. The discussion concludes with future research needs to support policy development and inform integrated institutional regimes that consider the diversity of stakeholder interests and the potential benefits of cross-sectoral coordination.

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    Frontiers in Marine Science
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      Frontiers in Marine Science
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    Authors: Kristen K. Beck; Michael-Shawn Fletcher; Patricia Gadd; Henk Heijnis; +3 Authors

    AbstractCritical transitions in ecosystem states are often sudden and unpredictable. Consequently, there is a concerted effort to identify measurable early warning signals (EWS) for these important events. Aquatic ecosystems provide an opportunity to observe critical transitions due to their high sensitivity and rapid response times. Using palaeoecological techniques, we can measure properties of time series data to determine if critical transitions are preceded by any measurable ecosystem metrics, that is, identify EWS. Using a suite of palaeoenvironmental data spanning the last 2,400 years (diatoms, pollen, geochemistry, and charcoal influx), we assess whether a critical transition in diatom community structure was preceded by measurable EWS. Lake Vera, in the temperate rain forest of western Tasmania, Australia, has a diatom community dominated by Discostella stelligera and undergoes an abrupt compositional shift at ca. 820 cal yr BP that is concomitant with increased fire disturbance of the local vegetation. This shift is manifest as a transition from less oligotrophic acidic diatom flora (Achnanthidium minutissimum, Brachysira styriaca, and Fragilaria capucina) to more oligotrophic acidic taxa (Frustulia elongatissima, Eunotia diodon, and Gomphonema multiforme). We observe a marked increase in compositional variance and rate‐of‐change prior to this critical transition, revealing these metrics are useful EWS in this system. Interestingly, vegetation remains complacent to fire disturbance until after the shift in the diatom community. Disturbance taxa invade and the vegetation system experiences an increase in both compositional variance and rate‐of‐change. These trends imply an approaching critical transition in the vegetation and the probable collapse of the local rain forest system.

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    Journal of Geophysical Research Biogeosciences
    Article . 2018
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      Journal of Geophysical Research Biogeosciences
      Article . 2018
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    Authors: Marika A. Schulhof; Andrew E. Allen; Eric E. Allen; Natalie Mladenov; +7 Authors

    AbstractWarming, eutrophication (nutrient fertilization) and brownification (increased loading of allochthonous organic matter) are three global trends impacting lake ecosystems. However, the independent and synergistic effects of resource addition and warming on autotrophic and heterotrophic microorganisms are largely unknown. In this study, we investigate the independent and interactive effects of temperature, dissolved organic carbon (DOC, both allochthonous and autochthonous) and nitrogen (N) supply, in addition to the effect of spatial variables, on the composition, richness, and evenness of prokaryotic and eukaryotic microbial communities in lakes across elevation and N deposition gradients in the Sierra Nevada mountains of California, USA. We found that both prokaryotic and eukaryotic communities are structured by temperature, terrestrial (allochthonous) DOC and latitude. Prokaryotic communities are also influenced by total and aquatic (autochthonous) DOC, while eukaryotic communities are also structured by nitrate. Additionally, increasing N availability was associated with reduced richness of prokaryotic communities, and both lower richness and evenness of eukaryotes. We did not detect any synergistic or antagonistic effects as there were no interactions among temperature and resource variables. Together, our results suggest that (a) organic and inorganic resources, temperature, and geographic location (based on latitude and longitude) independently influence lake microbial communities; and (b) increasing N supply due to atmospheric N deposition may reduce richness of both prokaryotic and eukaryotic microbes, probably by reducing niche dimensionality. Our study provides insight into abiotic processes structuring microbial communities across environmental gradients and their potential roles in material and energy fluxes within and between ecosystems.

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    Molecular Ecology
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    Molecular Ecology
    Article . 2020
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      Molecular Ecology
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      Molecular Ecology
      Article . 2020
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    Authors: Vanessa M, Howieson; Elisa, Tran; Annabelle, Hoegl; Han Ling, Fam; +5 Authors

    ABSTRACT The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo . In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC 50 s) of ∼50 nM, and three others have submicromolar IC 50 s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [ 14 C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.

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    Europe PubMed Central
    Other literature type . 2016
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    Antimicrobial Agents and Chemotherapy
    Article . 2016
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Antimicrobial Agents and Chemotherapy
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91,204 Research products
  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: F M Javed Mehedi Shamrat; Shamima Akter; Sami Azam; Asif Karim; +5 Authors
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    IEEE Access
    Article . 2023
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  • Authors: Robert J. Elliott; Tak Kuen Siu;

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    Authors: Elisa Conde Moreno; Alejandro Pascual; Daniel Prieto-Cuadra; Val F. Laza; +7 Authors

    microRNAs (miRNA) expression in colorectal (CR) primary tumours can facilitate a more precise molecular characterization. We identified and validated a miRNA profile associated with clinical and histopathological features that might be useful for patient stratification. In situ hybridization array using paraffin-embedded biopsies of CR primary tumours were used to screen 1436 miRNAs. 17 miRNAs were selected for validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 192) and were further correlated with clinical and histopathological data. We demonstrated that miRNAs associated to Colorectal Cancer (CRC) diagnosis age (over 50s and 60s) included miR-1-3p, miR-23b-3p, miR-27b-3p, miR-143-3p, miR-145-5p and miR-193b-5p. miR-23b-3p and miR-24-3p discriminated between Lynch Syndrome and sporadic CRC. miR-10a-5p, miR-20a-5p, miR-642b and Let-7a-5p were associated to stroma abundance. miR-642b and Let-7a-5p were associated with to peritumoral inflammation abundance. miR-1-3p, miR-143-3p and miR-145-5p correlated with mucinous component. miR-326 correlated with tumour location (right or left sided). miR-1-3p associated with tumour grade. miR-20a-5p, miR-193b-5p, miR-320a, miR-326 and miR-642b-3p associated to tumour stage and progression. Remarkably, we also demonstrated that miR-1-3p and miR-326 expression significantly associated with patient overall survival (OS). Hierarchical clustering and bioinformatics analysis indicated that selected miRNAs could re-classify the patients and work cooperatively, modulating common target genes involved in colorectal cancer key signalling pathways. In conclusion, molecular characterization of CR primary tumours based on miRNAs could lead to more accurate patient reclassification and may be useful for efficient patient management.

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    Cancers
    Other literature type . Article . 2019
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    Europe PubMed Central
    Article . 2019
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    Cancers
    Article . 2019
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    Cancers
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    Article . 2019
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      Cancers
      Other literature type . Article . 2019
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      Europe PubMed Central
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      Cancers
      Article . 2019
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      Cancers
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  • Authors: Dongvu Tonien; Reihaneh Safavi-Naini; Peter R. Wild;

    In this paper, we consider authentication codes where the adversary has access to a verification oracle. We formally study two attack games: offline attack and online attack. In an offline impersonation attack with verification query of order i, the adversary launches its attack through two stages. In the first stage — the query stage — the adversary can adaptively choose i distinct messages to query the verification oracle. The verification oracle will answer whether these queried messages are valid or invalid under the secret encoding rule agreed by the transmitter and the receiver. In the later stage — the spoofing stage — the adversary creates a fraudulent message which is different from all its queried messages and sends this message to the receiver. The adversary wins if the receiver accepts the fraudulent message as a valid message. In an online impersonation attack with verification query of order i, the adversary has i + 1 chances to query the verification oracle and wins as soon as one of the queries is a valid message. We make use of strategy trees, which allow optimal strategies in both attack games to be identified, to establish a number of relationships between the value of the two games. This allows us to formally prove a relationship between the value of the game when the adversary has i queries, and the one in which he does not have any. The relationship, though widely believed to be true, was only recently proved for computationally secure systems. Our result complements this latter work for the information theoretic setting.

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  • Authors: Roberto Aguilera; Roberto Aguilera;

    AbstractThe objective of this paper is to examine the effect of oil and gas prices on the development of tight and shale reservoirs including oil, gas and condensate.The methodology uses a variable shape distribution (VSD) model for examining past, present and futures prices of oil and gas. The VSD matches historical annual changes in oil and gas prices with coefficients of determination that are generally larger than 0.98. Contrary to several commentators and specialized organizations around the world that were forecasting continuous oil price escalation up to US$ 300/bbl (e.g. in 2008, when the oil price was around US$ 140/bbl), the VSD was used successfully to anticipate a significant drop in prices, leading to the on-record statement that the oil price was a bubble and was going to burst (June 13, 2008).The VSD was also used to build a case at LACPEC in 2014 (Aguilera and Aguilera, 2014) indicating that "with the vast global oil resource base and the significant technological advances being implemented by the industry, oil prices could actually decrease in the future". This is a painful fact being faced today by the oil and gas industry worldwide.In this paper, the VSD has been used with a global energy market (GEM) model to examine possible future outcomes of unconventional resources development in light of forecasted oil and gas demand and anticipated price-changes calculated with the VSD.The methodology provides a novel approach for examining some realistic possibilities regarding future development of unconventional oil, gas and condensate reservoirs.

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    Authors: Vijaya M, Musini; Kendra Ak, Lawrence; Patricia M, Fortin; Ken, Bassett; +1 Authors

    Background Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. Objectives To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension. To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. Selection criteria We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. Data collection and analysis This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available. Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. Main results 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias. Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes. Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Authors' conclusions Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

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    Europe PubMed Central
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      Europe PubMed Central
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    Authors: Kathryn Janet Brooks; Dave Reid; Olivier Thebaud; Sophie Gourguet; +7 Authors

    Marine and coastal activities are closely interrelated, and conflicts among different sectors can undermine management and conservation objectives. Governance systems for fisheries, power generation, irrigation, aquaculture, marine biodiversity conservation, and other coastal and maritime activities are typically organized to manage conflicts within sectors, rather than across them. Based on the discussions around eight case studies presented at a workshop held in Brest in June 2019, this paper explores institutional approaches to move beyond managing conflicts within a sector. We primarily focus on cases where the groups and sectors involved are heterogeneous in terms of: the jurisdiction they fall under; their objectives; and the way they value ecosystem services. The paper first presents a synthesis of frameworks for understanding and managing cross-sectoral governance conflicts, drawing from social and natural sciences. We highlight commonalities but also conceptual differences across disciplines to address these issues. We then propose a novel analytical framework which we used to evaluate the eight case studies. Based on the main lessons learned from case studies, we then discuss the feasibility and key determinants of stakeholder collaboration as well as compensation and incentive schemes. The discussion concludes with future research needs to support policy development and inform integrated institutional regimes that consider the diversity of stakeholder interests and the potential benefits of cross-sectoral coordination.

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    Frontiers in Marine Science
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    Authors: Kristen K. Beck; Michael-Shawn Fletcher; Patricia Gadd; Henk Heijnis; +3 Authors

    AbstractCritical transitions in ecosystem states are often sudden and unpredictable. Consequently, there is a concerted effort to identify measurable early warning signals (EWS) for these important events. Aquatic ecosystems provide an opportunity to observe critical transitions due to their high sensitivity and rapid response times. Using palaeoecological techniques, we can measure properties of time series data to determine if critical transitions are preceded by any measurable ecosystem metrics, that is, identify EWS. Using a suite of palaeoenvironmental data spanning the last 2,400 years (diatoms, pollen, geochemistry, and charcoal influx), we assess whether a critical transition in diatom community structure was preceded by measurable EWS. Lake Vera, in the temperate rain forest of western Tasmania, Australia, has a diatom community dominated by Discostella stelligera and undergoes an abrupt compositional shift at ca. 820 cal yr BP that is concomitant with increased fire disturbance of the local vegetation. This shift is manifest as a transition from less oligotrophic acidic diatom flora (Achnanthidium minutissimum, Brachysira styriaca, and Fragilaria capucina) to more oligotrophic acidic taxa (Frustulia elongatissima, Eunotia diodon, and Gomphonema multiforme). We observe a marked increase in compositional variance and rate‐of‐change prior to this critical transition, revealing these metrics are useful EWS in this system. Interestingly, vegetation remains complacent to fire disturbance until after the shift in the diatom community. Disturbance taxa invade and the vegetation system experiences an increase in both compositional variance and rate‐of‐change. These trends imply an approaching critical transition in the vegetation and the probable collapse of the local rain forest system.

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    Journal of Geophysical Research Biogeosciences
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      Journal of Geophysical Research Biogeosciences
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    Authors: Marika A. Schulhof; Andrew E. Allen; Eric E. Allen; Natalie Mladenov; +7 Authors

    AbstractWarming, eutrophication (nutrient fertilization) and brownification (increased loading of allochthonous organic matter) are three global trends impacting lake ecosystems. However, the independent and synergistic effects of resource addition and warming on autotrophic and heterotrophic microorganisms are largely unknown. In this study, we investigate the independent and interactive effects of temperature, dissolved organic carbon (DOC, both allochthonous and autochthonous) and nitrogen (N) supply, in addition to the effect of spatial variables, on the composition, richness, and evenness of prokaryotic and eukaryotic microbial communities in lakes across elevation and N deposition gradients in the Sierra Nevada mountains of California, USA. We found that both prokaryotic and eukaryotic communities are structured by temperature, terrestrial (allochthonous) DOC and latitude. Prokaryotic communities are also influenced by total and aquatic (autochthonous) DOC, while eukaryotic communities are also structured by nitrate. Additionally, increasing N availability was associated with reduced richness of prokaryotic communities, and both lower richness and evenness of eukaryotes. We did not detect any synergistic or antagonistic effects as there were no interactions among temperature and resource variables. Together, our results suggest that (a) organic and inorganic resources, temperature, and geographic location (based on latitude and longitude) independently influence lake microbial communities; and (b) increasing N supply due to atmospheric N deposition may reduce richness of both prokaryotic and eukaryotic microbes, probably by reducing niche dimensionality. Our study provides insight into abiotic processes structuring microbial communities across environmental gradients and their potential roles in material and energy fluxes within and between ecosystems.

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    Molecular Ecology
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    Authors: Vanessa M, Howieson; Elisa, Tran; Annabelle, Hoegl; Han Ling, Fam; +5 Authors

    ABSTRACT The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo . In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC 50 s) of ∼50 nM, and three others have submicromolar IC 50 s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [ 14 C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2016
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Antimicrobial Agents and Chemotherapy
    Article . 2016
    License: ASM Journals Non-Commercial TDM
    Data sources: Crossref
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2016
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Antimicrobial Agents and Chemotherapy
      Article . 2016
      License: ASM Journals Non-Commercial TDM
      Data sources: Crossref
      addClaim

      This Research product is the result of merged Research products in OpenAIRE.

      You have already added works in your ORCID record related to the merged Research product.