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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: Julian F. Guest; Jaime Esteban; Anton G. Manganelli; Andrea Novelli; +2 Authors

    Objective This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI. Methods Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. Results Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. Conclusion Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes.

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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/
    PLoS ONE
    Article . 2017 . Peer-reviewed
    License: CC BY
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    PLoS ONE
    Article . 2017
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      PLoS ONE
      Article . 2017 . Peer-reviewed
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      Article . 2017
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      PLoS ONE
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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
    Authors: Merja, Nurkkala; Lotta, Wassén; Inger, Nordström; Inger, Gustavsson; +3 Authors

    We have evaluated whether cholera toxin (CT) as a carrier/adjuvant can enhance human T-cell responses to a viral oncoprotein in vitro using dendritic cells (DCs) as antigen-presenting cells. Monocyte-derived DCs obtained from women with cervical dysplasia were pulsed with the HPV16 oncoprotein E7, either alone or conjugated to CT, and tested for their ability to induce antigen-specific activation of autologous T cells in vitro. CT-conjugation of E7 significantly improved the capacity of pulsed DCs to activate antigen-specific CD4+ T-cell proliferation and IFN-gamma secretion. The CT-E7-pulsed DCs also produced significantly more of the Th1-inducing cytokine IL-12 compared to DCs pulsed with E7 or CT alone. Furthermore, DCs pulsed with CT-conjugated HPV16 E7 caused a response in T cells from women with advanced disease (CIN III) as well as in T cells from women that were currently not infected with HPV16. These data show the potential of using CT-conjugated viral oncoproteins for DC-induced T-cell activation in humans.

    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 Vaccinearrow_drop_down
    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
    Vaccine
    Article . 2010 . Peer-reviewed
    License: Elsevier TDM
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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 Vaccinearrow_drop_down
      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
      Vaccine
      Article . 2010 . Peer-reviewed
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  • Authors: David Ellerman;

    Logical information theory is the quantitative version of the logic of partitions just as logical probability theory is the quantitative version of the dual Boolean logic of subsets. The resulting notion of information is about distinctions, differences, and distinguishability, and is formalized as the distinctions of a partition (a pair of points distinguished by the partition). All the definitions of simple, joint, conditional, and mutual entropy of Shannon information theory are derived by a uniform transformation from the corresponding definitions at the logical level. The purpose of this paper is to give the direct generalization to quantum logical information theory that similarly focuses on the pairs of eigenstates distinguished by an observable, i.e., qubits of an observable. The fundamental theorem for quantum logical entropy and measurement establishes a direct quantitative connection between the increase in quantum logical entropy due to a projective measurement and the eigenstates (cohered together in the pure superposition state being measured) that are distinguished by the measurement (decohered in the post-measurement mixed state). Both the classical and quantum versions of logical entropy have simple interpretations as "two-draw" probabilities. The conclusion is that quantum logical entropy is the simple and natural notion of information for a quantum information theory focusing on the distinguishing of quantum states.

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  • Authors: Axelsson, Hans;

    Background and aim. Genes, proteins and pathways have been identified and suggested as potential targets in tumor angiogenesis, but current anti-angiogenic therapies have provided only modest benefits in survival of cancer patients. Therefore, further understanding of underlying mechanisms of tumor induced angiogenesis is mandatory in order to develop effective anti-angiogenic treatments in cancer disease. We have therefore focused on the role prostanoids may have to support tumor vasculature in progressive tumor growth of tumors. Methods. Two fundamentally different tumor models were used. MCG-101 tumors induced increased systemic levels of PGE2 and showed high sensitivity to COX inhibition, while K1735-M2 tumors did not produce PGE2 and were thus insensitive to COX inhibition regarding tumor growth in syngenic wild type mice. EP1- and EP3-receptor knockout tumor-bearing mice were also used. COX-inhibition was provided by indomethacin in the drinking water to block prostanoid synthesis in tumor and host tissues. Intravital microscopy was performed using a dorsal skin fold chamber technique for studies of early tumor growth and associated angiogenesis. Immunohistochemical and microarray analyses were applied. Results. Indomethacin reduced tumor growth and tumor related vascular area in wild type mice bearing MCG-101 tumors, but did not affect these parameters in K1735-M2 tumors. There was an unchanged relationship between the load of malignant cells and supportive vascular area among different tumor growth conditions. Unselective COX inhibition reduced tumor growth in EP3, but not in EP1 knockouts without significant alteration in tumor vascular density in EP3 knockouts. Indomethacin treatment influenced expression of a large number of genes (5% of >40 000 probes) responsible for important steps in carcinogenesis, inflammation, angiogenesis, apoptosis, cell cycle activity and proliferation, cell adhesion, carbohydrate & fatty acid metabolism and proteolysis in tumors on wild type mice. Affected genes were widely and uniformly distributed on chromosomes over the entire genome. Variation of COX-2 staining in MCG-101 tumors was significantly reduced following indomethacin treatment. Effects of altered prostanoid metabolism were significantly related to EGF-R expression in tumor tissue and transcripts of KRas, PI3K, JAK1, STAT3 and c-jun were down-regulated by indomethacin, while STAT1 and ELK1 did not show any such decline. Conclusion. Indomethacin treatment reduced tumor cell proliferation and increased tumor cell apoptosis in MCG-101 tumors with associated adaptive alterations in tumor vasculature. These effects were best predicted by alterations in EGF-R expression in tumor tissue with main downstream effects through KRas signaling.

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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: Raquel Cruz-Duarte; Cátia Rebelo de Almeida; Magda Negrão; Afonso Fernandes; +18 Authors

    Purpose: Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, about 60% of these patients show innate resistance to cetuximab. To increase cetuximab efficacy, it is crucial to successfully identify responder patients, as well as to develop new therapeutic approaches to overcome cetuximab resistance. Experimental design: We evaluated the value of EGFR effector phospholipase C gamma 1 (PLCγ1) in predicting cetuximab responses, by analyzing progression-free survival (PFS) of a multicentric retrospective cohort of 94 treated patients with mCRC (log-rank test and Cox regression model). Furthermore, we used in vitro and zebrafish xenotransplant models to identify and target the mechanism behind PLCγ1-mediated resistance to cetuximab. Results: In this study, levels of PLCγ1 were found increased in RAS WT tumors and were able to predict cetuximab responses in clinical samples and in vitro and in vivo models. Mechanistically, PLCγ1 expression was found to bypass cetuximab-dependent EGFR inhibition by activating ERK and AKT pathways. This novel resistance mechanism involves a noncatalytic role of PLCγ1 SH2 tandem domains in the propagation of downstream signaling via SH2-containing protein tyrosine phosphatase 2 (SHP2). Accordingly, SHP2 inhibition sensitizes PLCγ1-resistant cells to cetuximab. Conclusions: Our discoveries reveal the potential of PLCγ1 as a predictive biomarker for cetuximab responses and suggest an alternative therapeutic approach to circumvent PLCγ1-mediated resistance to cetuximab in patients with RAS WT mCRC. In this way, this work contributes to the development of novel strategies in the medical management and treatment of patients with mCRC. M. Martins' research was supported by Liga Portuguesa Contra o Cancro (LPCC): Terry Fox Fundation; Investigador FCT- Fundação para a Ciência e Technologia (IF/00409/2014) and IMM Bridge grant; RC-D research was supported by Fundação para a Ciência e Technologia (SFRH/BD/139138/2018). A. Fernandes was supported by LPCC-IMM BIOBANK; R. Fior was supported by Champalimaud Foundation and L. Costa was supported by Merck Serono. © 2022 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 International (CC BY-NC-ND)

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    Clinical Cancer Research
    Article . 2022 . Peer-reviewed
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    Universidade de Lisboa: Repositório.UL
    Other literature type . 2022
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    Clinical Cancer Research
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    Hal-Diderot
    Article . 2022
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      Clinical Cancer Research
      Article . 2022 . Peer-reviewed
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      Universidade de Lisboa: Repositório.UL
      Other literature type . 2022
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      Clinical Cancer Research
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  • Authors: A, Lith; C, Lindstrand; H-G, Gröndahl;

    To assess, in a young population (age 6-19) managed by a restrictive attitude to radiography and operative intervention, prevalence of patients with posterior caries and/or fillings, probabilities of new proximal dentine lesions given different caries experience, correlation between radiographic intervals and caries experience, and prevalence of endodontic treatment.Bitewing radiographs, taken between age 6 through 19 in 285 patients, were analysed in succession. Occlusal and proximal surfaces were coded for caries depth (0-4) and presence of fillings (5). Simple regression analysis was used to determine relations between radiographic intervals and caries experience. Significance testings of probability estimates were made with chi(2)- and t-tests, when applicable adjusted by the Bonferroni-Holm correction for mass-significance.The prevalence of patients with/ or =1 fillings/dentine lesions in occlusal surfaces increased from 6-78% and in proximal ones from 1-38%. The probability of developing new proximal dentine lesions/fillings over different time periods was significantly lower among caries-free patients than among those with enamel or dentine lesions. There was a poor correlation between radiographic intervals (mean=16 months, range=6-33) and accumulated caries experience. Endodontic treatment had been made in a total of six teeth in six patients.A restrictive attitude both to the frequency with which radiographs are taken and to operative treatment of proximal caries seems to be possible in young populations with low caries prevalence.

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    Authors: Alves, C. J. S.; Martins, N. F. M.;

    In this work we consider the inverse problem of detecting inclusions or cavities in an elastic body, using a single boundary measurement on an external boundary. We discuss the identifiability questions on shape reconstruction, presenting counterexamples for Robin boundary conditions or with additional unknown Lame parameters. Using the method of fundamental solutions (MFS) we adapt a method introduced twenty years ago by Andreas Kirsch and Rainer Kress [17] (in the context of an exterior problem in acoustic scattering) to this inverse problem in a bounded domain. We prove density results that justify the reconstruction of the solution from the Cauchy data using the MFS. We also establish some connections between this linear part of the KirschKress method and the direct MFS, through matrices of boundary layer integrals. Several numerical examples are presented, showing that with noisy data we were able to retrieve a fairly good reconstruction of the shape (or of its convex hull) with this MFS version of the Kirsch-Kress method.

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    Journal of Integral Equations and Applications
    Article . 2009 . Peer-reviewed
    License: implied-oa
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    Project Euclid
    Other literature type . 2009
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      Journal of Integral Equations and Applications
      Article . 2009 . Peer-reviewed
      License: implied-oa
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      Project Euclid
      Other literature type . 2009
      Data sources: Project Euclid
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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

    This article investigates the responses of intersectional activists to the political opportunity spaces made for them by international organisations at the European transnational level. To do so, it uses Romani women’s activism and the Council of Europe as case studies, and develops a heuristic tool – the (Un)Safeness Response Line – that builds on five categories of analysis: compliance, compromise, contestation from within, opposition and denial. Mostly based on semi-structured and unstructured expert interviews conducted in 2016 and 2017, this study observes that Romnja activists have been mostly compliant with the political agendas of international organisations. Yet, they have not always perceived the opportunity spaces created for them as safe spaces. This has manifested in negotiating safeness and accepting compromises, as well as in strong opposition. This article shows that opportunity spaces for intersectional activisms are not enough, and that the quality of such spaces matters. Thus, it fosters a more critical approach to the study of contemporary social movements.

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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
    European Journal of Politics and Gender
    Article . 2021 . Peer-reviewed
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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
      European Journal of Politics and Gender
      Article . 2021 . Peer-reviewed
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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
    Authors: Borut, Poljsak; Peter, Raspor;

    AbstractThe antioxidant and pro‐oxidant properties of ascorbic acid (vitamin C) and the water‐soluble analogue of α‐tocopherol (trolox) were compared. Trolox has advantages over α‐tocopherol, the latter being only lipid‐soluble due to the presence of a carboxyl group in lieu of a phytol chain which imparts trolox with water solubility. Trolox is used as a standard antioxidant in biochemical studies against which the antioxidant capacity of compounds is compared. Although ascorbic acid and tocopherols possess strong antioxidant properties, they might also exhibit pro‐oxidant properties in the presence of free transition metals. Thus, reactions detailed in this study were performed in the presence of Cr(VI) in an effort to investigate the potential of ascorbic acid and trolox to generate hydroxyl radicals in a Fenton‐like reaction. Results obtained were derived from reactions containing the same concentration of ascorbic acid and trolox under identical experimental conditions. Hydroxyl radical formation was observed in the reaction of Cr(VI) with ascorbic acid resulting from ascorbic acid auto‐oxidation and H2O2 formation. Hydroxyl radical formation was only detected in the reaction mixture containing Cr(VI) and trolox following the addition of H2O2. Copyright © 2007 John Wiley & Sons, Ltd.

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    Journal of Applied Toxicology
    Article . 2007 . Peer-reviewed
    License: Wiley Online Library User Agreement
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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
      Journal of Applied Toxicology
      Article . 2007 . Peer-reviewed
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    Authors: Guido, Ferraro; Björn, Baschek; Geraldine, de Montpellier; Ove, Njoten; +2 Authors

    Satellite services that deliver information about possible oil spills at sea currently use different labels of "confidence" to describe the detections based on radar image processing. A common approach is to use a classification differentiating between low, medium and high levels of confidence. There is an ongoing discussion on the suitability of the existing classification systems of possible oil spills detected by radar satellite images with regard to the relevant significance and correspondence to user requirements. This paper contains a basic analysis of user requirements, current technical possibilities of satellite services as well as proposals for a redesign of the classification system as an evolution towards a more structured alert system. This research work offers a first review of implemented methodologies for the categorisation of detected oil spills, together with the proposal of explorative ideas evaluated by the European Group of Experts on satellite Monitoring of sea-based oil Pollution (EGEMP).

    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 Open Marine Archivearrow_drop_down
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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
    Marine Pollution Bulletin
    Article . 2010 . Peer-reviewed
    License: Elsevier TDM
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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
      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
      Marine Pollution Bulletin
      Article . 2010 . Peer-reviewed
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    Authors: Suhua Wei; Chuixiang Yi; George R. Hendrey; Timothy T. Eaton; +17 Authors

    Several lines of evidence suggest that the warming climate plays a vital role in driving certain types of extreme weather. The impact of this warming and extreme weather on forest carbon assimilation capacity is poorly known. Filling this knowledge gap is critical towards understanding changing the amount of carbon that forests can hold. Here, we used a perfect-deficit approach to identify forest canopy photosynthetic capacity (CPC) deficits and analyze how they correlate to climate extremes, based on data measured by the eddy covariance method at 26 forest sites integrating 146 site-years. We found that droughts severely affect the carbon assimilation capacities of evergreen broadleaf forest and deciduous broadleaf forest. In addition, the carbon assimilation capacities of Mediterranean forests are highly sensitive to climate extremes, while marine forest climates tend to be insensitive to climate extremes. Our estimates suggest an average global reduction of forest canopy photosynthetic capacity of 6.3petagramsof carbon per growing season over 2001-2010, with evergreen broadleaf forests contributing 51.7% of the total reduction. JRC.H.7-Climate Risk Management

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    Other literature type . Article . 2014
    License: CC BY
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    Environmental Research Letters
    Article . 2014 . Peer-reviewed
    License: CC BY
    Data sources: Crossref; NARCIS
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      Other literature type . Article . 2014
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      Environmental Research Letters
      Article . 2014 . Peer-reviewed
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    Authors: Della Pia, A.; Luo, D.; Blackwell, R.; Costantini, G.; +1 Authors

    Self-assembly of three related molecules – terephthalic acid and its hydroxylated analogues – at liquid/solid interfaces (graphite/heptanoic acid and graphite/1-phenyloctane) has been studied using a combination of scanning tunnelling microscopy and molecular mechanics and molecular dynamics calculations. Brickwork-like patterns typical for terephthalic acid self-assembly have been observed for all three molecules. However, several differences became apparent: (i) formation or lack of adsorbed monolayers (self-assembled monolayers formed in all systems, with one notable exception of terephthalic acid at the graphite/1-phenyloctane interface where no adsorption was observed), (ii) the size of adsorbate islands (large islands at the interface with heptanoic acid and smaller ones at the interface with 1-phenyloctane), and (iii) polymorphism of the hydroxylated terephthalic acids’ monolayers, dependent on the molecular structure and/or solvent. To rationalise this behaviour, molecular mechanics and molecular dynamics calculations have been performed, to analyse the three key aspects of the energetics of self-assembly: intermolecular, substrate–adsorbate and solvent–solute interactions. These energetic characteristics of self-assembly were brought together in a Born–Haber cycle, to obtain the overall energy effects of formation of self-assembled monolayers at these liquid/solid interfaces.\ud \ud

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    Authors: Jesper, Sundell; Emile, Bienvenu; David, Janzén; Sofia, Birgersson; +2 Authors

    Tuberculosis is the most common cause of death in HIV‐infected patients. Isoniazid is used as a first‐line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co‐infected patients is therefore critical. Plasma levels of isoniazid, acetyl‐isoniazid, and isonicotinic acid from 63 patients co‐infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed‐effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz‐based antiretroviral therapy or HIV treatment naïve. Clearances of isoniazid were 1.3‐fold and 2.3‐fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz‐based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl‐isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment naïve. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid‐related toxicity and treatment failure is presented.

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    Clinical Pharmacology & Therapeutics
    Article . 2020 . Peer-reviewed
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    Clinical Pharmacology & Therapeutics
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      Clinical Pharmacology & Therapeutics
      Article . 2020 . Peer-reviewed
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      Clinical Pharmacology & Therapeutics
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    Authors: Valeria Mereghetti; Bessem Chouaia; Lidia Limonta; Daria Patrizia Locatelli; +1 Authors

    AbstractDiversity and composition of lepidopteran microbiotas are poorly investigated, especially across the different developmental stages. To improve this knowledge, we characterize the microbiota among different developmental stages of the Indian meal moth, Plodia interpunctella, which is considered one of the major pest of commodities worldwide. Using culture‐independent approach based on Illumina 16S rRNA gene sequencing we characterized the microbiota of four developmental stages: eggs, first‐, and last‐instar larvae, and adult. A total of 1022 bacterial OTUs were obtained, showing a quite diversified microbiota associated to all the analyzed stages. The microbiotas associated with P. interpunctella resulted almost constant throughout the developmental stages, with approximately 77% of bacterial OTUs belonging to the phylum of Proteobacteria. The dominant bacterial genus is represented by Burkholderia (∼64%), followed by Propionibacterium, Delftia, Pseudomonas, and Stenotrophomonas. A core bacterial community, composed of 139 OTUs, was detected in all the developmental stages, among which 112 OTUs were assigned to the genus Burkholderia. A phylogenetic reconstruction, based on the 16S rRNA, revealed that our Burkholderia OTUs clustered with Burkholderia cepacia complex, in the same group of those isolated from the hemipterans Gossyparia spuria and Acanthococcus aceris. The functional profiling, predicted on the base of the bacterial 16S rRNA, indicates differences in the metabolic pathways related to metabolism of amino acids between preimaginal and adult stages. We can hypothesize that bacteria may support the insect host during preimaginal stages.

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    Insect Science
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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
    Insect Science
    Article . 2017 . Peer-reviewed
    License: Wiley Online Library User Agreement
    Data sources: Crossref
    Insect Science
    Article . 2017
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