656 research outputs found
Combustion and Society: A Fire-Centred History of Energy Use
No full textFire is a force that links everyday human activities to some of the most powerful energetic movements of the Earth. Drawing together the energy-centred social theory of Georges Bataille, the fire-centred environmental history of Stephen Pyne, and the work of a number of ‘pyrotechnology’ scholars, the paper proposes that the generalized study of combustion is a key to contextualizing human energetic practices within a broader ‘economy’ of terrestrial and cosmic energy flows. We examine the relatively recent turn towards fossil-fuelled ‘internal combustion’ in the light of a much longer human history of ‘broadcast’ burning of vegetation and of artisanal pyrotechnologies – the use of heat to transform diverse materials. A combustion-centred analysis, it is argued, brings human collective life into closer contact with the geochemical and geologic conditions of earthly existence, while also pointing to the significance of explorative, experimental and even playful dispositions towards energy and matter. © 2014, SAGE Publications. All rights reserved
Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
Regulation of cell survival by lipid phosphate phosphatases involves the modulation of intracellular phosphatidic acid and sphingosine 1-phosphate pools
No full textWe have shown previously that LPPs (lipid phosphate phosphatases) reduce the stimulation of the p42/p44 MAPK (p42/p44 mitogen-activated protein kinase) pathway by the GPCR (G-protein-coupled receptor) agonists S1P (sphingosine 1-phosphate) and LPA (lysophosphatidic acid) in serum-deprived HEK-293 cells [Alderton, Darroch, Sambi, McKie, Ahmed, N. J. Pyne and S. Pyne (2001) J. Biol. Chem. 276, 13452-13460]. In the present study, we now show that this can be blocked by pretreating HEK-293 cells with the caspase 3/7 inhibitor, Ac-DEVD-CHO [N-acetyl-Asp-Glu-Val-Asp-CHO (aldehyde)]. Therefore LPP2 and LPP3 appear to regulate the apoptotic status of serum-deprived HEK-293 cells. This was supported further by: (i) caspase 3/7-catalysed cleavage of PARP [poly(ADP-ribose) polymerase] was increased in serum-deprived LPP2-overexpressing compared with vector-transfected HEK-293 cells; and (ii) serum-deprived LPP2- and LPP3-overexpressing cells exhibited limited intranucleosomal DNA laddering, which was absent in vector-transfected cells. Moreover, LPP2 reduced basal intracellular phosphatidic acid levels, whereas LPP3 decreased intracellular S1P in serum-deprived HEK-293 cells. LPP2 and LPP3 are constitutively co-localized with SK1 (sphingosine kinase 1) in cytoplasmic vesicles in HEK-293 cells. Moreover, LPP2 but not LPP3 prevents SK1 from being recruited to a perinuclear compartment upon induction of PLD1 (phospholipase D1) in CHO (Chinese-hamster ovary) cells. Taken together, these data are consistent with an important role for LPP2 and LPP3 in regulating an intracellular pool of PA and S1P respectively, that may govern the apoptotic status of the cell upon serum deprivation
Hydrogen from Radiolysis of Aqueous Fluid Inclusions during Diagenesis
No full textAcknowledgments We are grateful to J. Bowie and J. Still for skilled technical support and the staff at ICL-UK’s Boulby mine (especially Thomas Edwards), STFC’s Boulby underground Laboratory and the UK Centre for Astrobiology MINAR programme team (especially Sean Paling) for their support and supervised access to the site. The critical comments of two reviewers helped to improve the manuscript. Author Contributions John Parnell undertook the sampling. Nigel Blamey performed all analytical work. John Parnell wrote the manuscript.Peer reviewe
L’assurance-vie face aux nouveaux instruments financiers et à la déréglementation
No full textDeregulation is the outcome of the unification of the industry throughout Europe. Insurance companies have been slow to react to
the sweeping change we are witnessing. This is partly owing to the
legislation in force in each of the member countries. But, with the
emergence of a single European market, the situation is beginning to
change.
According to the author, Nigel J. Sedgewick, insurers, while
remaining competitive, should adopt a more offensive stance by not
only gaining more control over general expenses, but also by
broadening their range of products to include caps, floors, swaps
and others
Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics
No full textSphingosine 1-phosphate (S1P) is a bioactive lipid that is formed by the phosphorylation of sphingosine and catalysed by sphingosine kinase 1 (SK1) or sphingosine kinase 2 (SK2). Sphingosine kinases play a fundamental role in many signaling pathways associated with cancer, suggesting that proteins belonging to this signaling network represent potential therapeutic targets. Over the last years, many improvements have been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL); however, novel and less toxic therapies are still needed, especially for relapsing and chemo-resistant patients. Here, we analyzed the therapeutic potential of SKi and ROMe, a sphingosine kinase 1 and 2 inhibitor and SK2-selective inhibitor, respectively. While SKi induced apoptosis, ROMe initiated an autophagic cell death in our in vitro cell models. SKi treatment induced an increase in SK1 protein levels in Molt-4 cells, whereas it activated the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) pathway in Jurkat and CEM-R cells as protective mechanisms in a sub-population of T-ALL cells. Interestingly, we observed a synergistic effect of SKi with the classical chemotherapeutic drug vincristine. In addition, we reported that SKi affected signaling cascades implicated in survival, proliferation and stress response of cells. These findings indicate that SK1 or SK2 represent potential targets for treating T-ALL
A standing ovation for Nigel: An informal study
No full textThis article analyses a series of emails thanking Nigel for his stewardship of JASSS and the characteristics of their authors. It identifies a correlation between two measures of author activity in social simulation research, but no pattern between these activity measures and the email timing. Instead, the sequence suggests a classic standing ovation effect.</p
Role of sphingosine 1-phosphate receptors, sphingosine kinases and sphingosine in cancer and inflammation
No full textSphingosine kinase (there are two isoforms, SK1 and SK2) catalyses the formation of sphingosine 1-phosphate (S1P), a bioactive lipid that can be released from cells to activate a family of G protein-coupled receptors, termed S1P1-5. In addition, S1P can bind to intracellular target proteins, such as HDAC1/2, to induce cell responses. There is increasing evidence of a role for S1P receptors (e.g. S1P4) and SK1 in cancer, where high expression of these proteins in ER negative breast cancer patient tumours is linked with poor prognosis. Indeed, evidence will be presented here to demonstrate that S1P4 is functionally linked with SK1 and the oncogene HER2 (ErbB2) to regulate mitogen-activated protein kinase pathways and growth of breast cancer cells. Although much emphasis is placed on SK1 in terms of involvement in oncogenesis, evidence will also be presented for a role of SK2 in both T-cell and B-cell acute lymphoblastic leukemia. In patient T-ALL lymphoblasts and T-ALL cell lines, we have demonstrated that SK2 inhibitors promote T-ALL cell death via autophagy and induce suppression of c-myc and PI3K/AKT pathways. We will also present evidence demonstrating that certain SK inhibitors promote oxidative stress and protein turnover via proteasomal degradative pathways linked with induction of p53-and p21-induced growth arrest. In addition, the SK1 inhibitor, PF-543 exacerbates disease progression in an experimental autoimmune encephalomyelitis mouse model indicating that SK1 functions in an anti-inflammatory manner. Indeed, sphingosine, which accumulates upon inhibition of SK1 activity, and sphingosine-like compounds promote activation of the inflammasome, which is linked with multiple sclerosis, to stimulate formation of the pro-inflammatory mediator, IL-1β. Such compounds could be exploited to produce antagonists that diminish exaggerated inflammation in disease. The therapeutic potential of modifying the SK-S1P receptor pathway in cancer and inflammation will therefore, be reviewed
Distributed human computation framework for linked data co-reference resolution
No full textDistributed Human Computation (DHC) is a technique used to solve computational problems by incorporating the collaborative effort of a large number of humans. It is also a solution to AI-complete problems such as natural language processing. The Semantic Web with its root in AI is envisioned to be a decentralised world-wide information space for sharing machine-readable data with minimal integration costs. There are many research problems in the Semantic Web that are considered as AI-complete problems. An example is co-reference resolution, which involves determining whether different URIs refer to the same entity. This is considered to be a significant hurdle to overcome in the realisation of large-scale Semantic Web applications. In this paper, we propose a framework for building a DHC system on top of the Linked Data Cloud to solve various computational problems. To demonstrate the concept, we are focusing on handling the co-reference resolution in the Semantic Web when integrating distributed datasets. The traditional way to solve this problem is to design machine-learning algorithms. However, they are often computationally expensive, error-prone and do not scale. We designed a DHC system named iamResearcher, which solves the scientific publication author identity co-reference problem when integrating distributed bibliographic datasets. In our system, we aggregated 6 million bibliographic data from various publication repositories. Users can sign up to the system to audit and align their own publications, thus solving the co-reference problem in a distributed manner. The aggregated results are published to the Linked Data Cloud
Sphingosine 1-phosphate is a missing link between chronic inflammation and colon cancer
No full textIn this issue of Cancer Cell, Liang and colleagues demonstrated that sphingosine kinase 1, the enzyme that catalyzes formation of the biologically active lipid sphingosine 1-phosphate, drives a malicious amplification loop involving sphingosine 1-phosphate receptor 1 and the NF-kappaB/IL-6/STAT3 pathway. This appears critical for progression from chronic inflammation to colon cancer
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