154 research outputs found

    The ODD protocol for describing agent-based and other simulation models: A second update to improve clarity, replication, and structural realism

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    © 2020, University of Surrey. All rights reserved. The Overview, Design concepts and Details (ODD) protocol for describing Individual-and Agent-Based Models (ABMs) is now widely accepted and used to document such models in journal articles. As a standardized document for providing a consistent, logical and readable account of the structure and dynamics of ABMs, some research groups also find it useful as a workflow for model design. Even so, there are still limitations to ODD that obstruct its more widespread adoption. Such limitations are discussed and addressed in this paper: the limited availability of guidance on how to use ODD; the length of ODD documents; limitations of ODD for highly complex models; lack of sufficient details of many ODDs to enable reimplementation without access to the model code; and the lack of provision for sections in the document structure covering model design ratio-nale, the model’s underlying narrative, and the means by which the model’s fitness for purpose is evaluated. We document the steps we have taken to provide better guidance on: structuring complex ODDs and an ODD summary for inclusion in a journal article (with full details in supplementary material; Table 1); using ODD to point readers to relevant sections of the model code; update the document structure to include sections on model rationale and evaluation. We also further advocate the need for standard descriptions of simulation experiments and argue that ODD can in principle be used for any type of simulation model. Thereby ODD would provide a lingua franca for simulation modelling

    First absolute measurements of fast-ion losses in the ASDEX Upgrade tokamak

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    A new diagnostic technique that allows to obtain absolute fluxes of fast-ion losses measured with absolutely calibrated scintillator based fast-ion loss detectors (FILD) is presented here. First absolute fluxes of fast-ion losses have been obtained in the ASDEX Upgrade tokamak. An instrument function that includes the scintillator efficiency, collimator geometry, optical transmission and camera efficiency has been constructed. The scintillator response to deuterium ions in the relevant energy range of fast-ions has been characterized using a tandem accelerator. Absolute flux of neutral beam injection (NBI) prompt losses has been obtained in magnetohydrodynamic quiescent plasmas. The temporal evolution of the heat load measured with FILD follows that measured at the FILD entrance obtained with an Infra-Red camera looking at the FILD detector head. ASCOT simulations are in good agreement with the absolute heat load of NBI prompt losses measured with FILD.Ministerio de EconomĂ­a, Industria y Competitividad RYC-2011-09152, FIS2015-69362-P, ENE2012-31087EUROfusion Consortium PCIG11-GA-2012- 321455Comunidad Europea de la EnergĂ­a AtĂłmica 63305

    Dependence on plasma shape and plasma fueling for small ELM regimes in TCV and ASDEX Upgrade

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    Within the EUROfusion MST1 Work Package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∌ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a Double Null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.EURATOM 63305

    The environmental impacts of land transformation in the coastal perimeter of the Mar Menor lagoon (Spain)

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    Assigned to WIT Press all rights under copyright that may exist in and to the Work and any associated written or multimedia components or other enhancements accompanying the Work.The distinctive environment of the lagoon has long been attractive for visitors. A surge in touristic activities has taken place in the area since the early 1960s, characterised by intense urban development along the lagoon s perimeter to accommodate the growing seasonal population. This phenomenon has particularly affected La Manga, a sandy bar which is 20 km in length. La Manga acts as a barrier between the lagoon and the Mediterranean Sea, crossed by five, more or less functional channels called golas . The urbanization process has changed the water flow system between the inside and seawater through the channels. The changes have affected coastal dynamics, the longitudinal profile of the coast and the lagoon s ecosystem. The coastal lagoon is also highly threatened by other pollution variables derived from agricultural lands. The water derived from the Tajo-Segura transfer generated a profound land transformation of the adjacent agricultural areas, which changed from extensive dry crop farming to intensively irrigated crops, disturbing the lagoon dramatically. This paper analyzes both land transformations around the coastal perimeter of the Mar Menor during the last 50 years and shows the environmental impact with its consequences on the ecosystem. Although numerous biological studies have been carried out in the Mar Menor, a better understanding of the consequences of land transformation in the perimeter of the lagoon is still necessary to understand the lagoon s situation. The results of territorial management in the Mar Menor lagoon need to be addressed in order to develop successful strategies in the area to protect this valuable ecosystem and its services.GarcĂ­a-Ayllon Veintimilla, S.; Miralles GarcĂ­a, JL. (2014). The environmental impacts of land transformation in the coastal perimeter of the Mar Menor lagoon (Spain). International Journal of Design and Nature and Ecodynamics. 9(2):109-128. doi:10.2495/DNE-V9-N2-109-128S1091289

    Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota)

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    In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV

    Front Matter

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    The carbohydrate Galα1-3GalÎČ1-(3)4GlcNAc-R (α-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against α-Gal. Anti-α-Gal IgE antibodies have been associated with tick-induced allergy (i.e. α-Gal syndrome) and anti-α-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The α-Gal on tick salivary proteins plays an important role in the etiology of the α-Gal syndrome. However, whether ticks are able to produce endogenous α-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of α-Gal. Heterologous gene expression in α-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in α-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased α-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous α-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of α-Gal syndrome in humans.This research was supported by the ConsejerĂ­a de EducaciĂłn, Cultura y Deportes, JCCM, Spain, project CCM17-PIC-036 (SBPLY/17/180501/000185). JJV was supported by Project FIT (Pharmacology, Immunotherapy, nanoToxicology), funded by the European Regional Development Fund.Peer Reviewe

    Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures

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    Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.Fan Wang for the kind gift of the Pi3kc3flox/flox mice. We thank Basant Abdulrahman and Hermann Schaetzl for providing the gene-edited Atg5 KO N2a cells. We are also grateful to Zhenyu Yue, Ralph Nixon, and Jean Gruenberg for the kind gift of anti-Atg14L, Cathepsin D, and BMP antibodies, respectively. We thank Thomas SĂŒdhof for sharing Cre recombinase lentiviruses. We thank the OCS Microscopy Core of New York University Langone Medical Center for the support of the EM work and Rocio Perez-Gonzalez and Efrat Levy of New York University for their support during optimization of the brain exosome isolation technique. We thank Elizabeta Micevska for the maintenance and genotyping of the animal colony and Bowen Zhou for the preliminary lipidomic analysis of conditional Pi3kc3 cKO mice. We also thank Rebecca Williams and Catherine Marquer for critically reading the manuscript. This work was supported by grants from the Fundação para a CiĂȘncia e Tecnologia (PD/BD/105915/2014 to A.M.M.); the National Institute of Health (R01 NS056049 to G.D.P., transferred to Ron Liem, Columbia University; T32-MH015174 to Rene Hen (Z.M.L.)). Z.M.L. and R.B.C. received pilot grants from ADRC grant P50 AG008702 to S.A.S.info:eu-repo/semantics/publishedVersio

    Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis

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    In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death
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