199 research outputs found

    Narrative and Interpretation on Twitter: Reading tweets by telling stories

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    Existing research on communication on Twitter has largely ignored the question of how users make sense of the fragmentary tweets with which they are presented. Focusing on the use of Twitter for political reporting in post-revolutionary Egypt, this article argues that the production of mental stories provides readers with a mechanism for interpreting the meaning of individual tweets in terms of their relationships to other material. Drawing on contemporary narratology, it argues that Twitter exhibits key elements of narrativity, but that a creative reading process is nonetheless required to transform this incipient narrativity into coherent, sense-making mental narratives. This foregrounding of the reader’s creative role makes stories on Twitter highly fluid and dynamic. Through reference to classic critical theory, I propose that this nonetheless represents an evolution rather than a radical break from earlier forms of narrative reception, which in many cases demanded similarly creative reading practices

    Associations between preschool attendance and developmental impairments in pre-school children in a six-year retrospective survey

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    BACKGROUND: Many school-aged children suffer physical and mental impairments which can adversely affect their development and result in significant morbidity. A high proportion of children in western countries attend pre-school, and it is likely that the preschool environment influences the prevalence and severity of these impairments. Currently there is insufficient data available on the prevalence of these impairments and their causal associations. The influence that location of a pre-school and the duration of preschool attendance have on the prevalence of these impairments is not known. METHODS: In a retrospective survey spanning six years (1997–2002) we reviewed the records of 6,230 preschool children who had undergone routine school entry assessments. These children had been assessed utilising a modified manual of the "Bavarian Model" for school entry examinations. This model outlines specific criteria for impairments of motor, cognitive, behavioural and psychosocial functioning. Prevalence rates for physical and behavioural impairments were based on the results of these assessments. The relationship between the prevalence of impairments and the duration of preschool attendance and the location of the preschool attended was estimated utilizing logistic regression models. RESULTS: We found that 20.7% of children met the criteria for at least one type of impairment. Highest prevalence rates (11.5%) were seen for speech impairments and lowest (3.5%) for arithmetic impairments. Boys were disproportionately over represented, with 25.5% meeting the criteria for impairment, compared to 13.0% for girls. Children who had attended preschool for less than one year demonstrated higher rates of impairment (up to 19.1% for difficulties with memory, concentration or perseverance) compared to those who had attended for a longer duration (up to 11.6% for difficulties with pronouncation). Children attending preschool in an urban location had slightly elevated rates of impairment (up to 12.7%), compared to their rural counterparts (up to 11.1%). CONCLUSION: Our results demonstrate that there are high prevalence rates for physical and mental impairments among preschool children. Furthermore, children without preschool experience are a risk group for struggling with educational successes. The associations between the duration of preschool attendance and location of preschool attended and rates of impairment need replication and further exploration. Larger prospective studies are needed to examine if these relationships are causal and may therefore lend themselves to specific intervention strategies

    VEGF-A isoforms differentially regulate ATF-2-dependent VCAM-1 gene expression and endothelial-leukocyte interactions

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    Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology. VEGF-A stimulates signal transduction pathways that modulate endothelial outputs such as cell migration, proliferation, tubulogenesis, and cell-cell interactions. Multiple VEGF-A isoforms exist, but the biological significance of this is unclear. Here we analyzed VEGF-A isoform-specific stimulation of VCAM-1 gene expression, which controls endothelial-leukocyte interactions, and show that this is dependent on both ERK1/2 and activating transcription factor-2 (ATF-2). VEGF-A isoforms showed differential ERK1/2 and p38 MAPK phosphorylation kinetics. A key feature of VEGF-A isoform-specific ERK1/2 activation and nuclear translocation was increased phosphorylation of ATF-2 on threonine residue 71 (T71). Using reverse genetics, we showed ATF-2 to be functionally required for VEGF-A-stimulated endothelial VCAM-1 gene expression. ATF-2 knockdown blocked VEGF-A-stimulated VCAM-1 expression and endothelial-leukocyte interactions. ATF-2 was also required for other endothelial cell outputs, such as cell migration and tubulogenesis. In contrast, VCAM-1 was essential only for promoting endothelial-leukocyte interactions. This work presents a new paradigm for understanding how soluble growth factor isoforms program complex cellular outputs and responses by modulating signal transduction pathways

    Community indicators: a framework for observing and supporting community activity on Cloudworks

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    Cloudworks (Cloudworks.ac.uk) is a social networking site designed for sharing, finding and discussing learning and teaching ideas and experiences. Design and development of the site has been based on an iterative analysis, development and implementation approach, underpinned by ongoing research and evaluation. To this end, we have been seeking to establish strategies to enable us to systematically position transactions and emerging patterns of activity on the site so that we can more reliably use the empirical evidence we have gathered (Galley, 2009a, Galley 2009b, Alevizou et al., 2010a, Conole et al, 2010). In this paper we will introduce a framework we have developed for observing and supporting community development on the site. In building our framework we have used empirical evidence gathered from the site, then related it to the literature from a range of disciplines concerned with professional and learning communities. We link research relating to distance learning communities with studies into Computer Mediated Communication (CMC), self-organising communities on the web, and wider research about the nature of learning organisations and continuous professional development. We argue that this framework can be used to capture the development of productive communities in the space (i.e. how far cohesive, productive groups can be said to be emerging or not) and also help focus futur

    Piezo1 integration of vascular architecture with physiological force

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    The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic¹⁻⁵. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca²⁺-permeable non-selective cationic channels for detection of noxious mechanical impact⁶⁻⁸. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology

    Treatment of osteochondral lesions of the talus: a systematic review

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    The aim of this study was to summarize all eligible studies to compare the effectiveness of treatment strategies for osteochondral defects (OCD) of the talus. Electronic databases from January 1966 to December 2006 were systematically screened. The proportion of the patient population treated successfully was noted, and percentages were calculated. For each treatment strategy, study size weighted success rates were calculated. Fifty-two studies described the results of 65 treatment groups of treatment strategies for OCD of the talus. One randomized clinical trial was identified. Seven studies described the results of non-operative treatment, 4 of excision, 13 of excision and curettage, 18 of excision, curettage and bone marrow stimulation (BMS), 4 of an autogenous bone graft, 2 of transmalleolar drilling (TMD), 9 of osteochondral transplantation (OATS), 4 of autologous chondrocyte implantation (ACI), 3 of retrograde drilling and 1 of fixation. OATS, BMS and ACI scored success rates of 87, 85 and 76%, respectively. Retrograde drilling and fixation scored 88 and 89%, respectively. Together with the newer techniques OATS and ACI, BMS was identified as an effective treatment strategy for OCD of the talus. Because of the relatively high cost of ACI and the knee morbidity seen in OATS, we conclude that BMS is the treatment of choice for primary osteochondral talar lesions. However, due to great diversity in the articles and variability in treatment results, no definitive conclusions can be drawn. Further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCD of the talus

    Comparison of the ligand‐binding properties of fluorescent VEGF‐A isoforms to VEGF receptor 2 in living cells and membrane preparations using NanoBRET

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    Background and Purpose: Vascular Endothelial Growth Factor A (VEGF-A) is a key mediator of angiogenesis. A striking feature of the binding of a fluorescent analogue of VEGF165a to NanoLuciferase-tagged VEGF Receptor 2 (VEGFR2) in living cells is that the bioluminescence resonance energy transfer (BRET) signal is not sustained and declines over time. This may be secondary to receptor internalisation. Here we have compared the binding of three fluorescent VEGF-A isoforms to VEGFR2 in cells and isolated membrane preparations.Experimental Approach: Ligand binding kinetics were monitored in both intact HEK293T cells and membranes (expressing NanoLuciferase tagged VEGFR2) using BRET between the tagged receptor and fluorescent analogues of VEGF165a, VEGF165b and VEGF121a. VEGFR2 endocytosis in intact cells expressing VEGFR2 was monitored by following the appearance of fluorescent ligand-associated receptors in intracellular endosomes using automated quantitative imaging.Key Results: Quantitiative analysis of the effect of fluorescent VEGF-A isoforms onVEGFR2 endocytosis in cells demonstrated that they produced a rapid and potent translocation of ligand-bound VEGFR2 into intracellular endosomes. NanoBRET can be used to monitor the kinetics of the binding of fluorescent VEGF-A isoforms to VEGFR2. In isolated membrane preparations, ligand binding association curves were maintained for the duration of the 90 minute experiment. Measurement of koff at pH 6.0 in membrane preparations indicated shorter ligand residence times than those obtained at pH 7.4.Conclusions and Implications: These studies suggest that rapid VEGF-A isoform-induced receptor endocytosis shortens agonist residence times on the receptor (1/koff) as VEGFR2 moves from the plasma membrane to intracellular endosomes

    Mechanical Bonds and Topological Effects in Radical Dimer Stabilization

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    While mechanical bonding stabilizes tetrathiafulvalene (TTF) radical dimers, the question arises: what role does topology play in catenanes containing TTF units? Here, we report how topology, together with mechanical bonding, in isomeric [3]- and doubly interlocked [2]catenanes controls the formation of TTF radical dimers within their structural frameworks, including a ring-in-ring complex (formed between an organoplatinum square and a {2+2} macrocyclic polyether containing two 1,5-dioxynaphthalene (DNP) and two TTF units) that is topologically isomeric with the doubly interlocked [2]catenane. The separate TTF units in the two {1+1} macrocycles (each containing also one DNP unit) of the isomeric [3]catenane exhibit slightly different redox properties compared with those in the {2+2} macrocycle present in the [2]catenane, while comparison with its topological isomer reveals substantially different redox behavior. Although the stabilities of the mixed-valence (TTF2)^(•+) dimers are similar in the two catenanes, the radical cationic (TTF^(•+))_2 dimer in the [2]catenane occurs only fleetingly compared with its prominent existence in the [3]catenane, while both dimers are absent altogether in the ring-in-ring complex. The electrochemical behavior of these three radically configurable isomers demonstrates that a fundamental relationship exists between topology and redox properties

    Next-generation in vivo optical imaging with short-wave infrared quantum dots

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    The short-wavelength infrared region (SWIR; 1000—2000 nm) provides several advantages over the visible and near-infrared regions for in vivo imaging. The general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering can render a mouse translucent when imaged in the SWIR region. Despite these advantages, the lack of a versatile emitter platform has prevented its general adoption by the biomedical research community. Here we introduce high-quality SWIR-emitting core/shell quantum dots (QDs) for the next generation of in vivo SWIR imaging. Our QDs exhibit a dramatically higher emission quantum yield (QY) than previously described SWIR probes, as well as a narrow and size-tunable emission that allows for multiplexing in the SWIR region. To demonstrate some of its capabilities, we used this imaging platform to measure the heartbeat and breathing rates in awake and unrestrained mice, as well as to quantify the metabolic turnover rates of lipoproteins in several organs simultaneously in real time in mice. Finally, we generate detailed three-dimensional quantitative flow maps of brain vasculature by intravital microscopy and visualize the differences between healthy tissue and a tumor in the brain. In conclusion, SWIR QDs enable biological optical imaging with an unprecedented combination of deep penetration, high spatial resolution, and fast acquisition speed
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