678 research outputs found

    Reflecting on PASUC Heritage Initiatives through Time, Positionality, and Place

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    This paper reports on heritage initiatives associated with a 12-year-long archaeology project in Yucatan, Mexico. Our work has involved both surprises and setbacks and in the spirit of adding to the repository of useful knowledge, we present these in a frank and transparent manner. Our findings are significant for a number of reasons. First, we show that the possibilities available to a heritage project facilitated by archaeologists depend not just on the form and focus of other stakeholders, but on the gender, sexuality, and class position of the archaeologists. Second, we provide a ground-level view of what approaches work well and which do not in terms of identifying aspects of cultural heritage that are relevant to a broad swath of stakeholders. Finally, we discuss ways in which heritage projects can overcome constraints to expanding community collaboration

    Demographic characteristics of exploited tropical lutjanids: a comparative analysis

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    Demographic parameters from seven exploited coral reef lutjanid species were compared as a case study of the implications of intrafamily variation in life histories for multispecies harvest management. Modal lengths varied by 4 cm among four species (Lutjanus fulviflamma, L. vitta, L. carponotatus, L. adetii), which were at least 6 cm smaller than the modal lengths of the largest species (L. gibbus, Symphorus nematophorus, Aprion virescens). Modal ages, indicating ages of full selection to fishing gear, were 10 years or less for all species, but maximum ages ranged from 12 (L. gibbus) to 36 years (S. nematophorus). Each species had a unique growth pattern, with differences in length-at-age and mean asymptotic fork length (L∞), but smaller species generally grew fast during the first 1–2 years of life and larger species grew more slowly over a longer period. Total mortality rates varied among species; L. gibbus had the highest mortality and L. fulviflamma, the lowest mortality. The variability in life history strategies of these tropical lutjanids makes generalizations about lutjanid life histories difficult, but the fact that all seven had characteristics that would make them particularly vulnerable to fishing indicates that harvest of tropical lutjanids should be managed with caution

    Semantic Annotation of Digital Objects by Multiagent Computing: Applications in Digital Heritage

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    Heritage organisations around the world are participating in broad scale digitisation projects, where traditional forms of heritage materials are being transcribed into digital representations in order to assist with their long-term preservation, facilitate cataloguing, and increase their accessibility to researchers and the general public. These digital formats open up a new world of opportunities for applying computational information retrieval techniques to heritage collections, making it easier than ever before to explore and document these materials. One of the key benefits of being able to easily share digital heritage collections is the strengthening and support of community memory, where members of a community contribute their perceptions and recollections of historical and cultural events so that this knowledge is not forgotten and lost over time. With the ever-growing popularity of digitally-native media and the high level of computer literacy in modern society, this is set to become a critical area for preservation in the immediate future

    Direct Genetics Referral Pathway for High-Grade Serous Ovarian Cancer Patients: The opt-Out Process

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    Purpose. In order to meet a clinical need for better pathways to access genetic testing for ovarian cancer patients, we implemented and reviewed an opt-out referral process for genetic consultation whereby a referral is automatically sent to genetics following a pathological diagnosis of HGSC. Methods. Following implementation of the opt-out referral process, each month a list of new cases of HGSC was generated from the synoptic pathology report and forwarded directly to the Cancer Genetics clinic. Using an advanced directive, patients were automatically referred for genetic counselling two months after surgery. If the patient declined genetic counselling (opted-out) after discussion with their surgeon within the two months after surgery, the Genetic Counsellor was informed and the patient was removed from the referral process. Results. Between January 1, 2015, and December 31, 2017, 168 women were diagnosed with HGSC, of whom 167 received a referral for genetic consultation. In only one case the referral was cancelled by the surgeon, resulting in a referral rate of 99.4%. By the end of the study period, 133 women attended a genetics consultation appointment and 125 (94%) agreed to proceed with genetic testing. Among those who completed genetic testing, 15% tested positive for a BRCA1 or BRCA2 gene mutation. Of the women who tested positive for a BRCA1/2 mutation, 56% had no family history of breast or ovarian cancer. Conclusions. The opt-out referral process described in this study is s a feasible, effective, and patient-centred approach to increase access to BRCA1/2 testing for patients with ovarian cancer

    FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance

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    International audienceAbstractBackgroundIrinotecan is a camptothecin analogue currently used in clinical practice to treat advanced colorectal cancer. However, acquired resistance mediated by the drug efflux pump ABCG2 is a recognized problem. We reported on a novel camptothecin analogue, FL118, which shows anticancer activity superior to irinotecan. In this study, we sought to investigate the potency of FL118 versus irinotecan or its active metabolite, SN-38, in both in vitro and in vivo models of human cancer with high ABCG2 activity. We also sought to assess the potency and ABCG2 affinity of several FL118 analogues with B-ring substitutions.MethodsColon and lung cancer cells with and without ABCG2 overexpression were treated with FL118 in the presence and absence of Ko143, an ABCG2-selective inhibitor, or alternatively by genetically modulating ABCG2 expression. Using two distinct in vivo human tumor animal models, we further assessed whether FL118 could extend time to progression in comparison with irinotecan. Lastly, we investigated a series of FL118 analogues with B-ring substitutions for ABCG2 sensitivity.ResultsBoth pharmacological inhibition and genetic modulation of ABCG2 demonstrated that, in contrast to SN-38, FL118 was able to bypass ABCG2-mediated drug resistance. FL118 also extended time to progression in both in vivo models by more than 50% compared with irinotecan. Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance.ConclusionsOur results suggest that in contrast to SN-38 and topotecan, FL118 is a poor substrate for ABCG2 and can effectively overcome ABCG2-mediated drug resistance. Our findings expand the uniqueness of FL118 and support continued development of FL118 as an attractive therapeutic option for patients with drug-refractory cancers resulting from high expression of ABCG2

    Optimization of the Lucy Interplanetary Trajectory via Two-Point Direct Shooting

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    Lucy is NASAs next Discovery-class mission and will explore the Trojan asteroids in the Sun-Jupiter L4 and L5 regions. This paper details the design of Lucys interplanetary trajectory using a two-point direct shooting transcription, nonlinear programming, and monotonic basin hopping. These techniques are implemented in the Evolutionary Mission Trajectory Generator (EMTG), a trajectory optimization tool developed at NASA Goddard Space Flight Center. We present applications to the baseline trajectory design, Monte Carlo analysis, and operations

    Integrating Sequence Capture and Restriction Site-Associated DNA Sequencing to resolve Recent Radiations of Pelagic Seabirds

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    The diversification of modern birds has been shaped by a number of radiations. Rapid diversification events make reconstructing the evolutionary relationships among taxa challenging due to the convoluted effects of incomplete lineage sorting (ILS) and introgression. Phylogenomic datasets have the potential to detect patterns of phylogenetic incongruence, and to address their causes. However, the footprints of ILS and introgression on sequence data can vary between different phylogenomic markers at different phylogenetic scales depending on factors such as their evolutionary rates or their selection pressures. We show that combining phylogenomic markers that evolve at different rates, such as paired-end double-digest restriction site-associated DNA (PE-ddRAD) and ultraconserved elements (UCEs), allows a comprehensive exploration of the causes of phylogenetic discordance associated with short internodes at different timescales. We used thousands of UCE and PE-ddRAD markers to produce the first well-resolved phylogeny of shearwaters, a group of medium-sized pelagic seabirds that are among the most phylogenetically controversial and endangered bird groups. We found that phylogenomic conflict was mainly derived from high levels of ILS due to rapid speciation events. We also documented a case of introgression, despite the high philopatry of shearwaters to their breeding sites, which typically limits gene flow. We integrated state-of-the-art concatenated and coalescent-based approaches to expand on previous comparisons of UCE and RAD-Seq datasets for phylogenetics, divergence time estimation and inference of introgression, and we propose a strategy to optimise RAD-Seq data for phylogenetic analyses. Our results highlight the usefulness of combining phylogenomic markers evolving at different rates to understand the causes of phylogenetic discordance at different timescales

    Integrating Sequence Capture and Restriction Site-Associated DNA Sequencing to Resolve Recent Radiations of Pelagic Seabirds

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    The diversification of modern birds has been shaped by a number of radiations. Rapid diversification events make reconstructing the evolutionary relationships among taxa challenging due to the convoluted effects of incomplete lineage sorting (ILS) and introgression. Phylogenomic data sets have the potential to detect patterns of phylogenetic incongruence, and to address their causes. However, the footprints of ILS and introgression on sequence data can vary between different phylogenomic markers at different phylogenetic scales depending on factors such as their evolutionary rates or their selection pressures. We show that combining phylogenomic markers that evolve at different rates, such as paired-end double-digest restriction site-associated DNA (PE-ddRAD) and ultraconserved elements (UCEs), allows a comprehensive exploration of the causes of phylogenetic discordance associated with short internodes at different timescales. We used thousands of UCE and PE-ddRAD markers to produce the first well-resolved phylogeny of shearwaters, a group of medium-sized pelagic seabirds that are among the most phylogenetically controversial and endangered bird groups. We found that phylogenomic conflict was mainly derived from high levels of ILS due to rapid speciation events. We also documented a case of introgression, despite the high philopatry of shearwaters to their breeding sites, which typically limits gene flow. We integrated state- of-the-art concatenated and coalescent-based approaches to expand on previous comparisons of UCE and RAD-Seq data sets for phylogenetics, divergence time estimation, and inference of introgression, and we propose a strategy to optimize RAD-Seq data for phylogenetic analyses. Our results highlight the usefulness of combining phylogenomic markers evolving at different rates to understand the causes of phylogenetic discordance at different timescales.

    Palaeoceanographic changes in the late Pliocene promoted rapid diversification in pelagic seabirds

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    Aim: Palaeoceanographic changes can act as drivers of diversification and speciation, even in highly mobile marine organisms. Shearwaters are a group of globally distributed and highly mobile pelagic seabirds. Despite a recent well-resolved phylogeny, shearwaters have controversial species limits, and show periods of both slow and rapid diversification. Here, we explore the role of palaeoceanographic changes on shearwaters' diversification and speciation. We investigate shearwater biogeography and the evolution of a key phenotypic trait, body size, and we assess the validity of their current taxonomy
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