533 research outputs found

    Overcoming data scarcity of Twitter: using tweets as bootstrap with application to autism-related topic content analysis

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    Notwithstanding recent work which has demonstrated the potential of using Twitter messages for content-specific data mining and analysis, the depth of such analysis is inherently limited by the scarcity of data imposed by the 140 character tweet limit. In this paper we describe a novel approach for targeted knowledge exploration which uses tweet content analysis as a preliminary step. This step is used to bootstrap more sophisticated data collection from directly related but much richer content sources. In particular we demonstrate that valuable information can be collected by following URLs included in tweets. We automatically extract content from the corresponding web pages and treating each web page as a document linked to the original tweet show how a temporal topic model based on a hierarchical Dirichlet process can be used to track the evolution of a complex topic structure of a Twitter community. Using autism-related tweets we demonstrate that our method is capable of capturing a much more meaningful picture of information exchange than user-chosen hashtags.Comment: IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining, 201

    The evolving landscape of sea-level rise science from 1990 to 2021

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    As sea-level rise (SLR) accelerates due to climate change, its multidisciplinary field of science has similarly expanded, from 41 articles published in 1990 to 1475 articles published in 2021, and nearly 15,000 articles published in the Web of Science over this 32-year period. Here, big-data bibliometric techniques are adopted to systematically analyse this large literature set. Four main research clusters (themes) emerge: (I) geological dimensions and sea-level indicators, (II) impacts, risks, and adaptation, (III) physical components of sea-level change, and (IV) coastal ecosystems and habitats, with 16 associated sub-themes. This analysis provides insights into the evolution of research agendas, the challenges and opportunities for future assessments (e.g. next IPCC reports), and growing focus on adaptation. For example, the relative importance of sub-themes evolves consistently with a relative decline in pure science analysis towards solution-focused topics associated with SLR risks such as high-end rises, declining ecosystem services, flood hazards, and coastal erosion/squeeze

    Ordering ambiguity revisited via position dependent mass pseudo-momentum operators

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    Ordering ambiguity associated with the von Roos position dependent mass (PDM) Hamiltonian is considered. An affine locally scaled first order differential introduced, in Eq.(9), as a PDM-pseudo-momentum operator. Upon intertwining our Hamiltonian, which is the sum of the square of this operator and the potential function, with the von Roos d-dimensional PDM-Hamiltonian, we observed that the so-called von Roos ambiguity parameters are strictly determined, but not necessarily unique. Our new ambiguity parameters' setting is subjected to Dutra's and Almeida's [11] reliability test and classified as good ordering.Comment: 10 pages, no figures, revised/expanded, mathematical presentations in section 2 (Especially, the typological Errors in Eqs.(9)-(12))are now corrected. To appear in the Int. J. Theor. Phy

    Aharonov Bohm Effect in Graphene Fabry P\'erot Quantum Hall Interferometers

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    Quantum interferometers are powerful tools for probing the wave-nature and exchange statistics of indistinguishable particles. Of particular interest are interferometers formed by the chiral, one-dimensional (1D) edge channels of the quantum Hall effect (QHE) that guide electrons without dissipation. Using quantum point contacts (QPCs) as beamsplitters, these 1D channels can be split and recombined, enabling interference of charged particles. Such quantum Hall interferometers (QHIs) can be used for studying exchange statistics of anyonic quasiparticles. In this study we develop a robust QHI fabrication technique in van der Waals (vdW) materials and realize a graphene-based Fabry-P\'erot (FP) QHI. By careful heterostructure design, we are able to measure pure Aharonov-Bohm (AB) interference effect in the integer QHE, a major technical challenge in finite size FP interferometers. We find that integer edge modes exhibit high visibility interference due to relatively large velocities and long phase coherence lengths. Our QHI with tunable QPCs presents a versatile platform for interferometer studies in vdW materials and enables future experiments in the fractional QHE

    Bistability in Apoptosis by Receptor Clustering

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    Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

    ITS-NANO - Prioritising nanosafety research to develop a stakeholder driven intelligent testing strategy

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    Background To assess the risk of all nanomaterials (NMs) on a case-by-case basis is challenging in terms of financial, ethical and time resources. Instead a more intelligent approach to knowledge gain and risk assessment is required. Methods A framework of future research priorities was developed from the accorded opinion of experts covering all major stake holder groups (government, industry, academia, funders and NGOs). It recognises and stresses the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling approaches as key components of the current and future risk assessment of NMs. Results The framework for future research has been developed from the opinions of over 80 stakeholders, that describes the research priorities for effective development of an intelligent testing strategy (ITS) to allow risk evaluation of NMs. In this context, an ITS is a process that allows the risks of NMs to be assessed accurately, effectively and efficiently, thereby reducing the need to test NMs on a case-by-case basis. For each of the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling, key-priority research areas are described via a series of stepping stones, or hexagon diagrams structured into a time perspective. Importantly, this framework is flexible, allowing individual stakeholders to identify where their own activities and expertise are positioned within the prioritisation pathway and furthermore to identify how they can effectively contribute and structure their work accordingly. In other words, the prioritisation hexagon diagrams provide a tool that individual stakeholders can adapt to meet their own particular needs and to deliver an ITS for NMs risk assessment. Such an approach would, over time, reduce the need for testing by increasing the reliability and sophistication of in silico approaches. The manuscript includes an appraisal of how this framework relates to the current risk assessment approaches and how future risk assessment could adapt to accommodate these new approaches. A full report is available in electronic format (pdf) at http://www.nano.hw.ac.uk/research-projects/itsnano.html webcite. Conclusion ITS-NANO has delivered a detailed, stakeholder driven and flexible research prioritisation (or strategy) tool, which identifies specific research needs, suggests connections between areas, and frames this in a time-perspective

    Phosphorylation of Puma modulates its apoptotic function by regulating protein stability

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    Puma is a potent BH3-only protein that antagonises anti-apoptotic Bcl-2 proteins, promotes Bax/Bak activation and has an essential role in multiple apoptotic models. Puma expression is normally kept very low, but can be induced by several transcription factors including p53, p73, E2F1 and FOXO3a, whereby it can induce an apoptotic response. As Puma can to bind and inactivate all anti-apoptotic members of the Bcl-2 family, its activity must be tightly controlled. We report here, for the first time, evidence that Puma is subject to post-translational control through phosphorylation. We show that Puma is phosphorylated at multiple sites, with the major site of phosphorylation being serine 10. Replacing serine 10 with alanine causes reduced Puma turnover and enhanced cell death. Interestingly, Puma turnover occurs through the proteasome, and substitution of serine 10 causes elevated Puma levels independently of macroautophagy, Bcl-2 family member binding, caspase activity and apoptotic death. We conclude, therefore, that phosphorylation of Puma at serine 10 promotes Puma turnover, represses Puma's cell death potential and promotes cell survival. Owing to the highly pro-apoptotic nature of Puma, these studies highlight an important additional regulatory step in the determination of cellular life or death

    Bronchial artery revascularization in lung transplantation: a systematic review and meta-analysis.

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    Background: Bronchial artery revascularization (BAR) during lung transplantation has been hypothesized to improve early tracheal healing and delay the onset of bronchiolitis obliterans syndrome (BOS). We aimed to assess the outcomes of BAR after lung transplantation. Methods: Electronic search in Ovid Medline, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and Cochrane Controlled Trials Register (CCTR) databases was performed to identify all relevant studies published about lung transplantation with BAR. Studies discussing lung transplantation utilizing BAR were included while those without outcome data such as BOS and survival were excluded. Cohort-level data were extracted and pooled for analysis. A binary outcome meta-analysis of proportions with logit transformation was conducted. Newcastle-Ottawa scale was used for risk of bias assessment. Results: Seven studies were selected for the analysis comprising 143 patients. Mean patient age was 47 (95% CI: 40-55) years. Sixty-one percent (48-72%) were male. Seventy-three percent (65-79%) of patients underwent double lung transplant while 27% (21-25%) underwent single lung transplant. In patients with postoperative angiography, successful BAR was demonstrated in 93% (82-97%) of all assessed conduits. The 30-day/in-hospital mortality was 6% (3-11%). Seventy-nine percent (63-89%) of patients were free from rejection at three months. Eighty-three percent (29-98%) of patients were free from signs of airway ischemia at three and six months. Pooled survival at one year and five years was 87% (78-92%) and 71% (46-87%), respectively, with a mean follow-up time of 21 (3-38) months. Pooled freedom from bronchiolitis obliterans was 86% (77-91%) at two years. Conclusions: While this systematic review and meta-analysis is limited by the available surgeons, institutions, and papers discussing a highly specialized technique, it does show that BAR is a viable technique to minimize BOS and early anastomotic intervention following lung transplantation

    Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

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    Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

    The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

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    available in PMC 2011 February 3.MCL-1 has emerged as a major oncogenic and chemoresistance factor. A screen of stapled peptide helices identified the MCL-1 BH3 domain as selectively inhibiting MCL-1 among the related anti-apoptotic Bcl-2 family members, providing insights into the molecular determinants of binding specificity and a new approach for sensitizing cancer cells to apoptosis.National Institutes of Health (U.S.) (NIH award 5RO1GM084181)National Institutes of Health (U.S.) (NIH grant 5P01CA92625)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F31CA144566)Burroughs Wellcome Fund (Career Award
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