947 research outputs found

    Intense hurricane activity over the past 1500 years at South Andros Island, the Bahamas

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in E. J., Donnelly, J. P., van Hengstum, P. J., Wiman, C., Sullivan, R. M., Winkler, T. S., d'Entremont, N. E., Toomey, M., & Albury, N. Intense hurricane activity over the past 1500 years at South Andros Island, the Bahamas. Paleoceanography and Paleoclimatology, 34(11), (2019): 1761-1783, doi:10.1029/2019PA003665.Hurricanes cause substantial loss of life and resources in coastal areas. Unfortunately, historical hurricane records are too short and incomplete to capture hurricane‐climate interactions on multi‐decadal and longer timescales. Coarse‐grained, hurricane‐induced deposits preserved in blue holes in the Caribbean can provide records of past hurricane activity extending back thousands of years. Here we present a high resolution record of intense hurricane events over the past 1500 years from a blue hole on South Andros Island on the Great Bahama Bank. This record is corroborated by shorter reconstructions from cores collected at two nearby blue holes. The record contains coarse‐grained event deposits attributable to known historical hurricane strikes within age uncertainties. Over the past 1500 years, South Andros shows evidence of four active periods of hurricane activity. None of these active intervals occurred in the past 163 years. We suggest that Intertropical Convergence Zone position modulates hurricane activity on the island based on a correlation with Cariaco Basin titanium concentrations. An anomalous gap in activity on South Andros Island in the early 13th century corresponds to a period of increased volcanism. The patterns of hurricane activity reconstructed from South Andros Island closely match those from the northeastern Gulf of Mexico but are anti‐phased with records from New England. We suggest that either changes in local environmental conditions (e.g., SSTs) or a northeastward shift in storm tracks can account for the increased activity in the western North Atlantic when the Gulf of Mexico and southeastern Caribbean are less active.This work was funded by the National Science Foundation Graduate Research Fellowship (to E.J.W.), National Science Foundation grant OCE‐1356708 (to J.P.D. and P.J.vH.), the Dalio Explore Foundation and the USGS Land Change Science Program (M.R.T.). We are grateful to members of WHOI Coastal Systems Group, in particular Stephanie Madsen, for their help in the processing core samples. We thank two anonymous reviewers, Matthew Lachniet, Marci Robinson (USGS) and Miriam Jones (USGS) for their helpful feedback on earlier versions of this manuscript. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. The data are available on the National Climatic Data Center (http://www.ncdc.noaa.gov/dataaccess/paleoclimatology‐data) and WHOI Coastal Systems Group (https://web.whoi.edu/coastal‐group/) websites

    ELR510444 Inhibits Tumor Growth and Angiogenesis by Abrogating HIF Activity and Disrupting Microtubules in Renal Cell Carcinoma

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    Background: Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC. Principal Findings: ELR510444 decreased HIF-1a and HIF-2a levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. Conclusions: ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascula

    Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

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    Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

    Extended book review: Transnational trade unionism: dream and reality

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    Book review of : Reiner Tosstorff, The Red International of Labour Unions (RILU), 1920–1937, Leiden: Brill, 2016; 918 pp.: ISBN 9789004236646, (hbk); Chicago, IL: Haymarket Books, 2018; 918 pp.: ISBN 9781608468164, (pbk

    Racism, anti-racist practice and social work: articulating the teaching and learning experiences of Black social workers

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    In the mid 1990s a Black practice teacher programme was established in Manchester and Merseyside with the primary aim to increase the number of Black practice teachers in social work organisations, and in turn provide a supportive and encouraging learning environment for Black student social workers whilst on placement. In the north‐west of England research has been undertaken, to establish the quality of the practice teaching and student learning taking place with Black practice teachers and students. This paper is an exploration of the ideas generated within the placement process that particularly focused on the discourse of racism and ant‐racist practice. Black students and practice teachers explain their understanding of racism and anti‐racist practice within social work. From the research, the paper will critique some of the ideas concerning anti‐racism. In particular, it will question whether anti‐racist social work practice needs to be re‐evaluated in the light of a context with new migrants, asylum seekers and refugees. It will concluded, by arguing that whilst the terms anti‐racism, Black and Minority Ethnic have resonance as a form of political strategic essentialism, it is important to develop more positive representations in the future

    Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death

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    Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocyte-specific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF.These studies were supported by NIH grants R35 HL 161177 (to ACS), R01 HL 133864 (to ACS), R01 HL 128304 (to ACS), R41 HL15098 (to GS), R01 GM 122091 (to PHT), GM125944 (to FJS), R01 DK112854 (to FJS), R21 NS112787 (to MF), NS121706 (to YLW), EB023507 (to YLW), F31 HL149241 (to HMS), and F31 HL151173 (to JCG). Support was also provided by American Heart Association grants 19EIA34770095 (to ACS), AHA 18CDA34140024 (to YLW), and 19PRE34380152 (to NTC); the Spanish Ministry of Health (grant FIS PI17-01286); Junta de Andalucía BIO-177 and the FEDER Funding Program from the European Union and CIBERER (U729)-ISCIII (to PN); Department of Defense W81XWH1810070 (to YLW); and Vitalant. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Specifically, this work used the HTC cluster, which is supported by NIH award number S10OD028483.Peer reviewe

    Los lenguajes controlados y la documentación técnica : mejorando la traducibilidad

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    Los lenguajes controlados pueden suponer una estrategia efectiva para mejorar los procesos de traducción, modificando el texto origen para que se adapte a una serie de reglas que mejoran su traducibilidad. El artículo analiza el concepto de lenguaje controlado y revisa las diferentes áreas de control y su tipología, para después realizar un breve repaso al origen y evolución de estos si stemas lingüísticos. A continuación explora qué papel representan los lenguajes controlados en el proceso de redacción y traducción de documentación técnica. Por último, se centra en la relación entre lenguajes controlados y traducción y, más en concreto, la traducción automática, haciendo especial hincapié en las reglas más efectivas para la mejora de la traducibilidad.Els llenguatges controlats poden suposar una estratègia efectiva per a millorar els processos de traducció, modificant el text origen perquè s'adapte a una sèrie de regles que milloren la seua traduïbilitat. L'article analitza el concepte de llenguatge controlat i revisa les diferents àrees de control i la seua tipologia, per a després realitzar un breu repàs a l'origen i evolució d'estos sistemes lingüístics. A continuació explora quin paper representen els llenguatges controlats en el procés de redacció i traducció de documentació tècnica. Finalment, es centra en la relació entre llenguatges controlats i traducció i, més concretament, traducció autom àtica, fent especial insistència en les regles més efectives per a la millora de la traduïbilitat.Controlled languages can be an effective strategy to improve translation processes, pre-editing the source text to conform to a set of rules to improve its translatability. This article analyses the concept of controlled language and reviews the different control areas and their typology. Further, it reviews the origin and evolution of these linguistic systems and explores the role controlled languages play in the process of writing and translating technical documentation. Finally, it focuses on the relationship between controlled language and translation and, more specifically, machine translation, with particular emphasis on the rules aimed at improving translatability

    Being tolerated and being discriminated against:Links to psychological well-being through threatened social identity needs

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    We investigated whether and how the experience of being tolerated and of being discriminated against are associated with psychological well‐being in three correlational studies among three stigmatized groups in Turkey (LGBTI group members, people with disabilities, and ethnic Kurds, total N = 862). Perceived threat to social identity needs (esteem, meaning, belonging, efficacy, and continuity) was examined as a mediator in these associations. Structural equation models showed evidence for the detrimental role of both toleration and discrimination experiences on positive and negative psychological well‐being through higher levels of threatened social identity needs. A mini‐meta analysis showed small to moderate effect sizes and toleration was associated with lower positive well‐being through threatened needs among all three stigmatized groups

    Formal modeling and analysis of cognitive agent behavior

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    From an external perspective, cognitive agent behavior can be described by specifying (temporal) correlations of a certain complexity between stimuli (input states) and (re)actions (output states) of the agent. From an internal perspective the agent’s dynamics can be characterized by direct (causal) temporal relations between internal and mental states of the agent. The latter type of specifications can be represented in a relatively simple, executable format, which enables different types of analysis of the agent’s behavior. In particular, simulations of the agent’s behavior under different (environmental) circumstances can be explored. Furthermore, by applying verification techniques, automated analysis of the consequences of the agent’s behavior can be carried out. To enable such types of analysis when only given an external behavioral specification, this has to be transformed first into some type of executable format. An automated procedure for such a transformation is proposed in this paper. The application of the transformation procedure is demonstrated for a number of cases, showing examples of the types of analysis as mentioned for different forms of behavior
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