1,721,099 research outputs found
RGS2 is a novel mediator of hypoxia-induced pulmonary artery constriction
No full textPulmonary hypertension (PH) is characterized by an increase in blood pressure in the pulmonary vasculature associated with excessive vasoconstriction of pulmonary arteries and vascular remodeling. Pulmonary vasoconstriction is controlled by endogenous mediators, including those that act by stimulating G protein-coupled receptors (GPCRs). Vasoconstrictors such as serotonin (5-HT), endothelin-1 (ET-1) and thromboxane signal via GPCRs coupled to the G protein Gq. Gq activates signaling cascades in vascular smooth muscle that cause vasoconstriction. Regulators of G Protein Signaling 2 (RGS2) proteins turn off Gq signaling and thus inhibit the downstream pathways that cause vasoconstriction. Inhibition of RGS2 increases Gq-coupled GPCR vasoconstriction caused by many endogenous vasoconstrictors, including those implicated in PH.|Hypoxia is a key factor in the development of PH. Acute hypoxia causes hypoxic pulmonary vasoconstriction (HPV), which regulates ventilation by diverting blood flow away from poorly oxygenated regions of the lung. HPV is associated with an increase in calcium (Ca2+) mobilization, initially due to Ca2+ release from intracellular stores and followed by a sustained increase in Ca2+ influx through voltage-gated Ca2+ channels. Chronic hypoxia causes PH, in part, by enhanced Ca2+ mobilization contributing to HPV. Thus I hypothesized that hypoxia reduces RGS2 in pulmonary arteries, causing increased calcium mobilization and excessive vasoconstriction that may contribute to the development of PH. My objectives were:|1. To characterize the effects of RGS2 on Gq-coupled GPCR agonistmediated constriction and Ca2+ signaling in human pulmonary arterial smooth muscle (HPASM) cells. RGS2 protein was knocked-down (KD) in HPASM cells using RGS2 siRNA. I measured Gq-coupled GPCRmediated Ca2+ mobilization and contraction in RGS2 KD and scrambled HPASM cells.|2. To determine the effects of RGS2 on mouse pulmonary artery vasoconstriction activated by Gq-coupled GPCR agonists. I prepared precision cut lung slices (lung slices) from RGS2 KO and WT mice and assessed Gq-coupled GPCR agonist-mediated constriction concentrationresponse curves.|3. To determine the effects of hypoxia on mouse pulmonary artery vasoconstriction activated by Gq-coupled GPCR agonists. RGS2 KO and WT lung slices were incubated in hypoxia for 48 h and concentrationresponse curves for 5-HT and U46619 (thromboxane A2 mimetic) were analyzed.|4. To determine whether hypoxia enhancement of Gq-coupled GPCR agonist-mediated Ca2+ signaling and pulmonary arterial constriction is caused by down-regulation of RGS2 expression, HPASM cells were incubated in hypoxia (1% O2) or normoxia (21% O2) for 1-48 h and RGS2 expression was measured by western blotting. HPASM cells were also cultured for 48 h in hypoxia and Ca2+ mobilization and contraction of HPASM cells measured. Additionally, I incubated RGS2 KD HPASM cells in hypoxia and measured RGS2 expression along with Ca2+ mobilization and contraction.|5. To determine whether RGS2 KO mice develop right ventricular hypertrophy. I measured the heart wt /body wt (HW/BW) and Fulton Index of RGS2 KO and WT mice.|U46619- and ET-1-mediated Ca2+ mobilization and contraction were significantly increased in RGS2 KD HPASM cells compared to scrambled control cells. Pulmonary arteries from RGS2 KO lung slices also exhibited enhanced constriction induced by 5-HT and U46619 compared to WT mice. Hypoxia enhanced the Ca2+ mobilization and contraction induced by U46619 and ET-1 in HPASM cells. Hypoxia did not significantly down-regulate RGS2 expression in RGS2 KD HPASM cells but did increase the Ca2+ mobilization and contraction of RGS2 KD HPASM cells. Hypoxia enhanced the pulmonary arterial constriction of WT mouse lung slices; however, it did not increase constriction of RGS2 KO lung slices. HW/BW and Fulton Index were significantly increased in RGS2 KO mice in comparison to WT mice.|In conclusion, RGS2 plays a role in GPCR-mediated contraction and Ca2+ mobilization of HPASM cells and mouse pulmonary arteries. Hypoxia downregulates RGS2, which is associated with augmented Ca2+ signaling and constriction that may contribute to the development of PH.ProQuest Traditional Publishing Option185 page
A Unified, Modular and Multimodal Approach to Search and Hyperlinking Video
No full textThis paper describes a modular architecture for searching and hyperlinking clips of TV programmes. The architecture aimed to unify the combination of features from different modalities through a common representation based on a set of probability density functions over the timeline of a programme. The core component of the system consisted of analysis of sections of transcripts based on a textual query. Results show that search is made worse by the addition of other components, whereas in hyperlinking precision is increased by the addition of visual features
Identifying the Geographic Location of an Image with a Multimodal Probability Density Function
No full textThere is a wide array of online photographic content that is not geotagged. Algorithms for efficient and accurate geographical estimation of an image are needed to geolocate these photos. This paper presents a general model for using both textual metadata and visual features of photos to automatically place them on a world map
Experiments in Diversifying Flickr Result Sets
No full textThe 2013 MediaEval Retrieving Diverse Social Images Task looked to tackling the problem of search result diversification of Flickr results sets formed from queries about geographic places and landmarks. In this paper we describe our approach of using a min-max similarity diversifier coupled with pre-filters and a reranker. We also demonstrate a number of novel features for measuring similarity to use in the diversification step
Justice in a geopolitical world
No full textThis contribution was delivered on 5 May 2022 on the occasion of the hybrid 2022 edition of EUI State of the Union on ‘A Europe fit for the next generation?'Institutions can never meet the longing which inspires them. But how are the world’s global institutions doing in the pursuit of (wo)men’s longing for justice? Which understandings of justice have found protection through institutions? Which are (still) missing out? How do global justice institutions navigate the tensions between local and universal conceptions of justice? Whose interests do these institutions serve and what impact do they have on the ground? Are there circumstances in which global justice institutions may end up exacerbating rather than ameliorating existing inequalities
EU sanctions : what’s their place in the world?
No full textThis contribution was delivered online on 6 May 2021 on the occasion of the hybrid 2021 edition of EUI State of the Union on ‘Europe in a Changing World'.One instrument used by the EU to promote human rights and peace is sanctions. How significant a player is the EU in the international sanctions regime? Does it set the standard or follow others, such as the US and the UN? What’s the added value of autonomous EU sanctions? Do they have a “Brussels effect”? Who feels threatened, who feels the pain? How effective are the EU’s sanctions in promoting human rights and peace? Are they “smart” enough
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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