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  • Authors: Stephen Marsh; Yao Wang; Sylvie Noël; Lewis Robart; +1 Authors

    The Device Comfort methodology uses an enhanced notion of trust to enable a personal device to better reason about the state of interactions and actions between it, its owner, and the environment. This includes allowing a better understanding of how to manage information in fine-grained context as well as addressing the personal security of the user. As an information security methodology based on trust and thus context, it perfectly matches the growing security need for protecting users' medical data, stored as Electronic Health Records and/or partial medical data online or on device. In this paper, we present a threelevel information architecture for managing information access in healthcare that uses Device Comfort as an enabling methodology. We further discuss the interesting potentials for storage of information and how the Device Comfort model can assist in making trust-based sharing decisions regardless of the availability (or capacity) of its owner.

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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: Bernadette P, Luengo Kanacri; Concetta, Pastorelli; Nancy, Eisenberg; Antonio, Zuffianò; +2 Authors

    ABSTRACTThe goal of this study was to identify heterogenic longitudinal patterns of change in prosocial behavior from adolescence to early adulthood and their association with change in Big Five Factor (BFF) personality traits from adolescence until early adulthood. Participants were 573 Italian adolescents aged approximately 13 at the first assessment and 21 at the last assessment. Using growth mixture modeling, low increasing (LI; 18%), medium quadratic (MQ; 26%), and high quadratic (HQ; 54%) trajectories of prosocial behavior were distinguished. Generally, the LI trajectory group predicted an increase in Conscientiousness over time, whereas the HQ trajectory group predicted greater change in Agreeableness and Openness. In addition, positive changes in Conscientiousness, Agreeableness, and Openness between ages 13 and 21 predicted a higher probability of belonging to the HQ prosocial group. Findings support a malleable perspective on personality and identify longterm positive pathways for youths' prosocial development.

    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/ Repositorio ANID; LA...arrow_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
    Journal of Adolescence
    Article . 2014
    License: Wiley Online Library User Agreement
    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/ Repositorio ANID; LA...arrow_drop_down
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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 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 Adolescence
      Article . 2014
      License: Wiley Online Library User Agreement
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    Authors: Jordan L. Johnson; Ernesto Santoro; Roukia Zatout; Ana G. Petrovic; +5 Authors

    AbstractSesquitepenoids inuloxins A–D, belonging to different subgroups, were isolated from Dittrichia viscosa and showed potential biocontrol of some parasitic plants as Pelipanche, Orobanche, and Cuscuta species. The absolute configurations of the first three inuloxins A–C were previously determined by using experimental and computational chiroptical spectroscopic methods. The absolute configuration of inuloxin D remains to be established. The bioactive inuloxin E, closely related to inuloxin D, was recently isolated from the same plant organic extract. The same relative configuration of inuloxin D was assigned to inuloxin E by comparison of their NMR spectroscopic data. The absolute configurations of inuloxin D and inuloxin E are suggested in this work by analysis of the experimental and predicted chiroptical properties of the 4‐O‐acetyl derivative of inuloxin D.

    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/ Chiralityarrow_drop_down
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    Chirality
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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
    Chirality
    Article . 2021
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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/ Chiralityarrow_drop_down
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      Chirality
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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
      Chirality
      Article . 2021
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    Authors: Alessandro Zattoni; Michael A. Witt; William Q. Judge; Till Talaulicar; +13 Authors

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Prior evidence suggests that board independence may enhance financial performance, but this relationship has been tested almost exclusively for Anglo-American countries. To explore the boundary conditions of this prominent governance mechanism, we examine the impact of the formal and information institutions of 18 national business systems on the board independence-financial performance relationship. Our results show that while the direct effect of independence is weak, national-level institutions significantly moderate the independence-performance relationship. Our findings suggest that the efficacy of board structures is likely to be contingent on the specific national context, but the type of legal system is insignificant.

    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/ NARCISarrow_drop_down
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    NARCIS
    Article . 2017
    Data sources: NARCIS
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    Journal of World Business
    Article
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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 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
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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/ NARCISarrow_drop_down
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      Article . 2017
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      Journal of World Business
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    Authors: LiteBIRD Collaboration; Allys, E.; Arnold, K.; Aumont, J.; +187 Authors

    This work is supported in Japan by ISAS/JAXA for Pre-Phase A2 studies, by the acceleration program of JAXA research and development directorate, by the World Premier International Research Center Initiative (WPI) of MEXT, by the JSPS Core-to-Core Program, and by JSPS KAKENHI. The Italian LiteBIRD phase A contribution is supported by the Italian Space Agency (ASI Grants No. 2020-9-HH.0 and 2016-24-H.1-2018), the National Institute for Nuclear Physics (INFN), the National Institute for Astrophysics (INAF), and a PGR grant from the Italian Ministry of Foreign Affairs and International Cooperation. The French LiteBIRD phase A contribution is supported by the Centre National d’Etudes Spatiale (CNES), by the Centre National de la Recherche Scientifique (CNRS), and by the Commissariat a l’Energie Atomique (CEA). The Canadian contribution is supported by the Canadian Space Agency. The US contribution is supported by NASA grant no. 80NSSC18K0132. Norwegian participation in LiteBIRD is supported by the Research Council of Norway (Grant No. 263011). The Spanish LiteBIRD phase A contribution is supported by the Spanish Agencia Estatal de Investigacion (AEI), project refs. PID2019-110610RBC21 and AYA2017-84185-P. Funds that support the Swedish contributions come from the Swedish National Space Agency (SNSA/Rymdstyrelsen) and the Swedish Research Council (Reg. no. 2019-03959). The German participation in LiteBIRD is supported in part by the Excellence Cluster ORIGINS, which is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (Grant No. EXC-2094- 390783311). LiteBIRD work has received funding from the European Research Council (ERC) under the Horizon 2020 Research and Innovation Programme. This research used resources of the Central Computing System owned and operated by the Computing Research Center at KEK, as well as resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy. LiteBIRD the Lite (Light) satellite for the study of B-mode polarization and Inflation from cosmic background Radiation Detection, is a space mission for primordial cosmology and fundamental physics. The Japan Aerospace Exploration Agency (JAXA) selected LiteBIRD in May 2019 as a strategic large-class (L-class) mission, with an expected launch in the late 2020s using JAXA’s H3 rocket. LiteBIRD is planned to orbit the Sun-Earth Lagrangian point L2, where it will map the cosmic microwave background (CMB) polarization over the entire sky for three years, with three telescopes in 15 frequency bands between 34 and 448 GHz, to achieve an unprecedented total sensitivity of 2.2 μK-arcmin, with a typical angular resolution of 0.5○ at 100 GHz. The primary scientific objective of LiteBIRD is to search for the signal from cosmic inflation, either making a discovery or ruling out well-motivated inflationary models. The measurements of LiteBIRD will also provide us with insight into the quantum nature of gravity and other new physics beyond the standard models of particle physics and cosmology. We provide an overview of the LiteBIRD project, including scientific objectives, mission and system requirements, operation concept, spacecraft and payload module design, expected scientific outcomes, potential design extensions and synergies with other projects. Subject Index LiteBIRD cosmic inflation, cosmic microwave background, B-mode polarization, primordial gravitational waves, quantum gravity, space telescope LiteBIRD Collaboration: et al. 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
    https://doi.org/10.48550/arxiv...
    Article . 2022
    License: arXiv Non-Exclusive Distribution
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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/ Archivio Istituziona...arrow_drop_down
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      https://doi.org/10.48550/arxiv...
      Article . 2022
      License: arXiv Non-Exclusive Distribution
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    Authors: Francesco Petrelli; Tamara Zehnder; Luca Pucci; Corrado Calì; +10 Authors

    AbstractAstrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).

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    Hal-Diderot
    Preprint . 2021
    Data sources: Hal-Diderot
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    Authors: Federica Ganci; Claudio Pulito; Sara Valsoni; Andrea Sacconi; +17 Authors

    Abstract Purpose: Mutation of TP53 gene is a hallmark of head and neck squamous cell carcinoma (HNSCC) not yet exploited therapeutically. TP53 mutation frequently leads to the synthesis of mutant p53 proteins with gain-of-function activity, associated with radioresistance and high incidence of local recurrences in HNSCC. Experimental Design: Mutant p53–associated functions were investigated through gene set enrichment analysis in the Cancer Genome Atlas cohort of HNSCC and in a panel of 22 HNSCC cell lines. Mutant p53–dependent transcripts were analyzed in HNSCC cell line Cal27, carrying mutant p53H193L; FaDu, carrying p53R248L; and Detroit 562, carrying p53R175H. Drugs impinging on mutant p53-MYC–dependent signature were identified interrogating Connectivity Map (https://clue.io) derived from the Library of Integrated Network–based Cellular Signatures (LINCS) database (http://lincs.hms.harvard.edu/) and analyzed in HNSCC cell lines and patient-derived xenografts (PDX) models. Results: We identified a signature of transcripts directly controlled by gain-of-function mutant p53 protein and prognostic in HNSCC, which is highly enriched of MYC targets. Specifically, both in PDX and cell lines of HNSCC treated with the PI3Kα-selective inhibitor BYL719 (alpelisib) the downregulation of mutant p53/MYC-dependent signature correlates with response to this compound. Mechanistically, mutant p53 favors the binding of MYC to its target promoters and enhances MYC protein stability. Treatment with BYL719 disrupts the interaction of MYC, mutant p53, and YAP proteins with MYC target promoters. Of note, depletion of MYC, mutant p53, or YAP potentiates the effectiveness of BYL719 treatment. Conclusions: Collectively, the blocking of this transcriptional network is an important determinant for the response to BYL719 in HNSCC.

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    Clinical Cancer Research
    Article . 2020
    Data sources: Crossref
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    Authors: Georges Aad; S. Abdel Khalek; M. Abolins; Bobby Samir Acharya; +682 Authors

    A search for direct pair production of supersymmetric top squarks ((t) over tilde (1)) is presented, assuming the (t) over tilde (1) decays into a top quark and the lightest supersymmetric particle, (chi) over tilde (0)(1), and that both top quarks decay to purely hadronic final states. A total of 16 (4) events are observed compared to a predicted standard model background of 13.5(-3.6)(+3.7) (4.4(-1.3)(+1.7)) events in two signal regions based on integral Ldt = 4.7 fb(-1) of pp collision data taken at root s = 7 TeV with the ATLAS detector at the LHC. An exclusion region in the (t) over tilde (1) versus (chi) over tilde (0)(1) mass plane is evaluated: 370 1) 10) similar to 0 GeV while m((t) over tilde1) = 445 GeV is excluded for m((chi) over tilde 10) <= 50 GeV.

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    Physical Review Letters
    Article
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    Physical Review Letters
    Article . 2012
    License: CC BY
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      Physical Review Letters
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      Physical Review Letters
      Article . 2012
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    Authors: David, Tweats; David A, Eastmond; Anthony M, Lynch; Azeddine, Elhajouji; +6 Authors

    Aneuploidy is regarded as a hallmark of cancer, however, its role is complex with both pro- and anti-carcinogenic effects evident. In this IWGT review, we consider the role of aneuploidy in cancer biology; cancer risk associated with constitutive aneuploidy; rodent carcinogenesis with known chemical aneugens; and chemotherapy-related malignant neoplasms. Aneuploidy is seen at various stages in carcinogenesis. However, the relationship between induced aneuploidy occurring after exposure and clonal aneuploidy present in tumours is not clear. Recent evidence indicates that the induction of chromosomal instability (CIN), may be more important than aneuploidy per se, in the carcinogenic process. Down Syndrome, trisomy 21, is associated with altered hematopoiesis in utero which, in combination with subsequent mutations, results in an increased risk for acute megakaryoblastic and lymphoblastic leukemias. In contrast, there is reduced cancer risk for most solid tumours in Down Syndrome. Mouse models with high levels of aneuploidy are also associated with increased cancer risk for particular tumours with long latencies, but paradoxically other types of tumour often show decreased incidence. The aneugens reviewed that induce cancer in humans and animals all possess other carcinogenic properties, such as mutagenicity, clastogenicity, cytotoxicity, organ toxicities, hormonal and epigenetic changes which likely account for, or interact with aneuploidy, to cause carcinogenesis. Although the role that aneuploidy plays in carcinogenesis has not been fully established, in many cases, it may not play a primary causative role. Tubulin-disrupting aneugens that do not possess other properties linked to carcinogenesis, were not carcinogenic in rodents. Similarly, in humans, for the tubulin-disrupting aneugens colchicine and albendazole, there is no reported association with increased cancer risk. There is a need for further mechanistic studies on agents that induce aneuploidy, particularly by mechanisms other than tubulin disruption and to determine the role of aneuploidy in pre-neoplastic events and in early and late stage neoplasia.

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    ENEA Open Archive
    Article . 2019
    Data sources: ENEA Open Archive
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    ENEA Open Archive
    Article . 2019
    Data sources: ENEA Open Archive
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      Article . 2019
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      ENEA Open Archive
      Article . 2019
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  • Authors: Franck Morschhauser; Paula Marlton; Umberto Vitolo; Ola Lindén; +10 Authors

    Abstract Background: Ocrelizumab is a new humanised anti-CD20 antibody with the potential for enhanced efficacy in non-Hodgkin’s lymphoma (NHL) compared with rituximab due to increased binding affinity for the low-affinity variants of the FcγRIIIa receptor. An open-label, multicentre, dose-escalation study was conducted to evaluate the safety, efficacy, pharmacokinetics and pharmacogenetics of ocrelizumab in patients (pts) with relapsed/refractory follicular NHL following prior rituximab-containing therapy. Methods: A total of 47 pts with a response (complete response [CR], unconfirmed CR [CRu], partial response [PR]) or stable disease (SD) of ≥6 months’ duration following prior rituximab-containing treatment were enrolled into 3 sequential dose cohorts. Pts received infusions of ocrelizumab q3w at 200 mg/m2 (cohort A), 375 mg/m2 (cohort B) and 750 mg/m2 (cohort C) for up to 8 doses. Response was assessed after 4 doses and after the end of treatment. Results: Fifteen pts were enrolled in cohort A, 16 in cohort B and 16 in cohort C; 60% were male; mean age was 57 years; 78% had stage III/IV disease. At study entry 30%, 50% and 67% had intermediate or high FLIPI score in cohorts A, B and C, respectively. Median number of prior therapies was 2 (range 1–7); time to progression after last rituximab-containing therapy of <12 months: 47% (cohort A), 31% (cohort B) and 62% (cohort C) of pts. The majority of pts reported ≥1 adverse event (AE) [80–100%, cohorts A-C]; most of these were grade 1/2, with only 6 pts experiencing a grade 3 AE and no grade 4 AEs observed. The most common AEs were infusion-related reactions (IRR; 73%, 75% and 69% in cohorts A, B and C, respectively); only one was grade 3. Two pts discontinued treatment due to toxicity (dyspnoea, IRR). A total of 17 pts responded to ocrelizumab for a response rate (RR) of 36% (13% CR/CRu) across all cohorts. RR by cohort was 27% (13% CR/CRu) for A, 50% (25% CR/CRu) for B and 31% (no CR/CRu) for C. In pts relapsing after prior response (CR/PR) to rituximab-containing therapy (n=40), RRs were 23% (15% CR/CRu), 62% (31% CR/CRu) and 33% (no CR/CRu) in cohorts A, B and C, respectively. Of 6 pts with SD after prior rituximab-containing therapy, 1 pt had a PR, 4 pts had SD and 1 pt progressed. Conclusion: Ocrelizumab is well tolerated at doses up to 750 mg/m2 given q3w; AEs consist mainly of grade 1/2 IRRs. Severe IRRs (grade 3/4) following ocrelizumab occur less frequently than with rituximab. In this heavily and rituximab-pretreated pt population, the RR of 36% is encouraging.

    Bloodarrow_drop_down
    Blood
    Article . 2007
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      Article . 2007
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  • Authors: Stephen Marsh; Yao Wang; Sylvie Noël; Lewis Robart; +1 Authors

    The Device Comfort methodology uses an enhanced notion of trust to enable a personal device to better reason about the state of interactions and actions between it, its owner, and the environment. This includes allowing a better understanding of how to manage information in fine-grained context as well as addressing the personal security of the user. As an information security methodology based on trust and thus context, it perfectly matches the growing security need for protecting users' medical data, stored as Electronic Health Records and/or partial medical data online or on device. In this paper, we present a threelevel information architecture for managing information access in healthcare that uses Device Comfort as an enabling methodology. We further discuss the interesting potentials for storage of information and how the Device Comfort model can assist in making trust-based sharing decisions regardless of the availability (or capacity) of its owner.

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    Authors: Bernadette P, Luengo Kanacri; Concetta, Pastorelli; Nancy, Eisenberg; Antonio, Zuffianò; +2 Authors

    ABSTRACTThe goal of this study was to identify heterogenic longitudinal patterns of change in prosocial behavior from adolescence to early adulthood and their association with change in Big Five Factor (BFF) personality traits from adolescence until early adulthood. Participants were 573 Italian adolescents aged approximately 13 at the first assessment and 21 at the last assessment. Using growth mixture modeling, low increasing (LI; 18%), medium quadratic (MQ; 26%), and high quadratic (HQ; 54%) trajectories of prosocial behavior were distinguished. Generally, the LI trajectory group predicted an increase in Conscientiousness over time, whereas the HQ trajectory group predicted greater change in Agreeableness and Openness. In addition, positive changes in Conscientiousness, Agreeableness, and Openness between ages 13 and 21 predicted a higher probability of belonging to the HQ prosocial group. Findings support a malleable perspective on personality and identify longterm positive pathways for youths' prosocial development.

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    Journal of Adolescence
    Article . 2014
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      Journal of Adolescence
      Article . 2014
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    Authors: Jordan L. Johnson; Ernesto Santoro; Roukia Zatout; Ana G. Petrovic; +5 Authors

    AbstractSesquitepenoids inuloxins A–D, belonging to different subgroups, were isolated from Dittrichia viscosa and showed potential biocontrol of some parasitic plants as Pelipanche, Orobanche, and Cuscuta species. The absolute configurations of the first three inuloxins A–C were previously determined by using experimental and computational chiroptical spectroscopic methods. The absolute configuration of inuloxin D remains to be established. The bioactive inuloxin E, closely related to inuloxin D, was recently isolated from the same plant organic extract. The same relative configuration of inuloxin D was assigned to inuloxin E by comparison of their NMR spectroscopic data. The absolute configurations of inuloxin D and inuloxin E are suggested in this work by analysis of the experimental and predicted chiroptical properties of the 4‐O‐acetyl derivative of inuloxin D.

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    Chirality
    Article . 2021
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      Article . 2021
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    Authors: Alessandro Zattoni; Michael A. Witt; William Q. Judge; Till Talaulicar; +13 Authors

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Prior evidence suggests that board independence may enhance financial performance, but this relationship has been tested almost exclusively for Anglo-American countries. To explore the boundary conditions of this prominent governance mechanism, we examine the impact of the formal and information institutions of 18 national business systems on the board independence-financial performance relationship. Our results show that while the direct effect of independence is weak, national-level institutions significantly moderate the independence-performance relationship. Our findings suggest that the efficacy of board structures is likely to be contingent on the specific national context, but the type of legal system is insignificant.

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    Article . 2017
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    Journal of World Business
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      Journal of World Business
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    Authors: LiteBIRD Collaboration; Allys, E.; Arnold, K.; Aumont, J.; +187 Authors

    This work is supported in Japan by ISAS/JAXA for Pre-Phase A2 studies, by the acceleration program of JAXA research and development directorate, by the World Premier International Research Center Initiative (WPI) of MEXT, by the JSPS Core-to-Core Program, and by JSPS KAKENHI. The Italian LiteBIRD phase A contribution is supported by the Italian Space Agency (ASI Grants No. 2020-9-HH.0 and 2016-24-H.1-2018), the National Institute for Nuclear Physics (INFN), the National Institute for Astrophysics (INAF), and a PGR grant from the Italian Ministry of Foreign Affairs and International Cooperation. The French LiteBIRD phase A contribution is supported by the Centre National d’Etudes Spatiale (CNES), by the Centre National de la Recherche Scientifique (CNRS), and by the Commissariat a l’Energie Atomique (CEA). The Canadian contribution is supported by the Canadian Space Agency. The US contribution is supported by NASA grant no. 80NSSC18K0132. Norwegian participation in LiteBIRD is supported by the Research Council of Norway (Grant No. 263011). The Spanish LiteBIRD phase A contribution is supported by the Spanish Agencia Estatal de Investigacion (AEI), project refs. PID2019-110610RBC21 and AYA2017-84185-P. Funds that support the Swedish contributions come from the Swedish National Space Agency (SNSA/Rymdstyrelsen) and the Swedish Research Council (Reg. no. 2019-03959). The German participation in LiteBIRD is supported in part by the Excellence Cluster ORIGINS, which is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (Grant No. EXC-2094- 390783311). LiteBIRD work has received funding from the European Research Council (ERC) under the Horizon 2020 Research and Innovation Programme. This research used resources of the Central Computing System owned and operated by the Computing Research Center at KEK, as well as resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy. LiteBIRD the Lite (Light) satellite for the study of B-mode polarization and Inflation from cosmic background Radiation Detection, is a space mission for primordial cosmology and fundamental physics. The Japan Aerospace Exploration Agency (JAXA) selected LiteBIRD in May 2019 as a strategic large-class (L-class) mission, with an expected launch in the late 2020s using JAXA’s H3 rocket. LiteBIRD is planned to orbit the Sun-Earth Lagrangian point L2, where it will map the cosmic microwave background (CMB) polarization over the entire sky for three years, with three telescopes in 15 frequency bands between 34 and 448 GHz, to achieve an unprecedented total sensitivity of 2.2 μK-arcmin, with a typical angular resolution of 0.5○ at 100 GHz. The primary scientific objective of LiteBIRD is to search for the signal from cosmic inflation, either making a discovery or ruling out well-motivated inflationary models. The measurements of LiteBIRD will also provide us with insight into the quantum nature of gravity and other new physics beyond the standard models of particle physics and cosmology. We provide an overview of the LiteBIRD project, including scientific objectives, mission and system requirements, operation concept, spacecraft and payload module design, expected scientific outcomes, potential design extensions and synergies with other projects. Subject Index LiteBIRD cosmic inflation, cosmic microwave background, B-mode polarization, primordial gravitational waves, quantum gravity, space telescope LiteBIRD Collaboration: et al. Peer reviewed

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    https://doi.org/10.48550/arxiv...
    Article . 2022
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      https://doi.org/10.48550/arxiv...
      Article . 2022
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    Authors: Francesco Petrelli; Tamara Zehnder; Luca Pucci; Corrado Calì; +10 Authors

    AbstractAstrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).

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    Hal-Diderot
    Preprint . 2021
    Data sources: Hal-Diderot
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    Authors: Federica Ganci; Claudio Pulito; Sara Valsoni; Andrea Sacconi; +17 Authors

    Abstract Purpose: Mutation of TP53 gene is a hallmark of head and neck squamous cell carcinoma (HNSCC) not yet exploited therapeutically. TP53 mutation frequently leads to the synthesis of mutant p53 proteins with gain-of-function activity, associated with radioresistance and high incidence of local recurrences in HNSCC. Experimental Design: Mutant p53–associated functions were investigated through gene set enrichment analysis in the Cancer Genome Atlas cohort of HNSCC and in a panel of 22 HNSCC cell lines. Mutant p53–dependent transcripts were analyzed in HNSCC cell line Cal27, carrying mutant p53H193L; FaDu, carrying p53R248L; and Detroit 562, carrying p53R175H. Drugs impinging on mutant p53-MYC–dependent signature were identified interrogating Connectivity Map (https://clue.io) derived from the Library of Integrated Network–based Cellular Signatures (LINCS) database (http://lincs.hms.harvard.edu/) and analyzed in HNSCC cell lines and patient-derived xenografts (PDX) models. Results: We identified a signature of transcripts directly controlled by gain-of-function mutant p53 protein and prognostic in HNSCC, which is highly enriched of MYC targets. Specifically, both in PDX and cell lines of HNSCC treated with the PI3Kα-selective inhibitor BYL719 (alpelisib) the downregulation of mutant p53/MYC-dependent signature correlates with response to this compound. Mechanistically, mutant p53 favors the binding of MYC to its target promoters and enhances MYC protein stability. Treatment with BYL719 disrupts the interaction of MYC, mutant p53, and YAP proteins with MYC target promoters. Of note, depletion of MYC, mutant p53, or YAP potentiates the effectiveness of BYL719 treatment. Conclusions: Collectively, the blocking of this transcriptional network is an important determinant for the response to BYL719 in HNSCC.

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    Clinical Cancer Research
    Article . 2020
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    Authors: Georges Aad; S. Abdel Khalek; M. Abolins; Bobby Samir Acharya; +682 Authors

    A search for direct pair production of supersymmetric top squarks ((t) over tilde (1)) is presented, assuming the (t) over tilde (1) decays into a top quark and the lightest supersymmetric particle, (chi) over tilde (0)(1), and that both top quarks decay to purely hadronic final states. A total of 16 (4) events are observed compared to a predicted standard model background of 13.5(-3.6)(+3.7) (4.4(-1.3)(+1.7)) events in two signal regions based on integral Ldt = 4.7 fb(-1) of pp collision data taken at root s = 7 TeV with the ATLAS detector at the LHC. An exclusion region in the (t) over tilde (1) versus (chi) over tilde (0)(1) mass plane is evaluated: 370 1) 10) similar to 0 GeV while m((t) over tilde1) = 445 GeV is excluded for m((chi) over tilde 10) <= 50 GeV.

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    Physical Review Letters
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    Physical Review Letters
    Article . 2012
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      Physical Review Letters
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      Physical Review Letters
      Article . 2012
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    Authors: David, Tweats; David A, Eastmond; Anthony M, Lynch; Azeddine, Elhajouji; +6 Authors

    Aneuploidy is regarded as a hallmark of cancer, however, its role is complex with both pro- and anti-carcinogenic effects evident. In this IWGT review, we consider the role of aneuploidy in cancer biology; cancer risk associated with constitutive aneuploidy; rodent carcinogenesis with known chemical aneugens; and chemotherapy-related malignant neoplasms. Aneuploidy is seen at various stages in carcinogenesis. However, the relationship between induced aneuploidy occurring after exposure and clonal aneuploidy present in tumours is not clear. Recent evidence indicates that the induction of chromosomal instability (CIN), may be more important than aneuploidy per se, in the carcinogenic process. Down Syndrome, trisomy 21, is associated with altered hematopoiesis in utero which, in combination with subsequent mutations, results in an increased risk for acute megakaryoblastic and lymphoblastic leukemias. In contrast, there is reduced cancer risk for most solid tumours in Down Syndrome. Mouse models with high levels of aneuploidy are also associated with increased cancer risk for particular tumours with long latencies, but paradoxically other types of tumour often show decreased incidence. The aneugens reviewed that induce cancer in humans and animals all possess other carcinogenic properties, such as mutagenicity, clastogenicity, cytotoxicity, organ toxicities, hormonal and epigenetic changes which likely account for, or interact with aneuploidy, to cause carcinogenesis. Although the role that aneuploidy plays in carcinogenesis has not been fully established, in many cases, it may not play a primary causative role. Tubulin-disrupting aneugens that do not possess other properties linked to carcinogenesis, were not carcinogenic in rodents. Similarly, in humans, for the tubulin-disrupting aneugens colchicine and albendazole, there is no reported association with increased cancer risk. There is a need for further mechanistic studies on agents that induce aneuploidy, particularly by mechanisms other than tubulin disruption and to determine the role of aneuploidy in pre-neoplastic events and in early and late stage neoplasia.

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    ENEA Open Archive
    Article . 2019
    Data sources: ENEA Open Archive
    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
    ENEA Open Archive
    Article . 2019
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      ENEA Open Archive
      Article . 2019
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      ENEA Open Archive
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  • Authors: Franck Morschhauser; Paula Marlton; Umberto Vitolo; Ola Lindén; +10 Authors

    Abstract Background: Ocrelizumab is a new humanised anti-CD20 antibody with the potential for enhanced efficacy in non-Hodgkin’s lymphoma (NHL) compared with rituximab due to increased binding affinity for the low-affinity variants of the FcγRIIIa receptor. An open-label, multicentre, dose-escalation study was conducted to evaluate the safety, efficacy, pharmacokinetics and pharmacogenetics of ocrelizumab in patients (pts) with relapsed/refractory follicular NHL following prior rituximab-containing therapy. Methods: A total of 47 pts with a response (complete response [CR], unconfirmed CR [CRu], partial response [PR]) or stable disease (SD) of ≥6 months’ duration following prior rituximab-containing treatment were enrolled into 3 sequential dose cohorts. Pts received infusions of ocrelizumab q3w at 200 mg/m2 (cohort A), 375 mg/m2 (cohort B) and 750 mg/m2 (cohort C) for up to 8 doses. Response was assessed after 4 doses and after the end of treatment. Results: Fifteen pts were enrolled in cohort A, 16 in cohort B and 16 in cohort C; 60% were male; mean age was 57 years; 78% had stage III/IV disease. At study entry 30%, 50% and 67% had intermediate or high FLIPI score in cohorts A, B and C, respectively. Median number of prior therapies was 2 (range 1–7); time to progression after last rituximab-containing therapy of <12 months: 47% (cohort A), 31% (cohort B) and 62% (cohort C) of pts. The majority of pts reported ≥1 adverse event (AE) [80–100%, cohorts A-C]; most of these were grade 1/2, with only 6 pts experiencing a grade 3 AE and no grade 4 AEs observed. The most common AEs were infusion-related reactions (IRR; 73%, 75% and 69% in cohorts A, B and C, respectively); only one was grade 3. Two pts discontinued treatment due to toxicity (dyspnoea, IRR). A total of 17 pts responded to ocrelizumab for a response rate (RR) of 36% (13% CR/CRu) across all cohorts. RR by cohort was 27% (13% CR/CRu) for A, 50% (25% CR/CRu) for B and 31% (no CR/CRu) for C. In pts relapsing after prior response (CR/PR) to rituximab-containing therapy (n=40), RRs were 23% (15% CR/CRu), 62% (31% CR/CRu) and 33% (no CR/CRu) in cohorts A, B and C, respectively. Of 6 pts with SD after prior rituximab-containing therapy, 1 pt had a PR, 4 pts had SD and 1 pt progressed. Conclusion: Ocrelizumab is well tolerated at doses up to 750 mg/m2 given q3w; AEs consist mainly of grade 1/2 IRRs. Severe IRRs (grade 3/4) following ocrelizumab occur less frequently than with rituximab. In this heavily and rituximab-pretreated pt population, the RR of 36% is encouraging.

    Bloodarrow_drop_down
    Blood
    Article . 2007
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      Blood
      Article . 2007
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