5,407 research outputs found

    Unreal property: Anarchism, anthropology and alchemy

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    © 2018 selection and editorial matter, James Arvanitakis and Martin Fredriksson; individual chapters, the contributors. ‘Property’ is complicated. We shall argue that property is constituted within a paradoxical field of vague boundaries, personal relations, poetry and violence. It is not constituted by a set of universal rules (although rules may grow around it), but by ongoing culturally negotiated, psychologically based and enforced categorisations, disorders and persuasions. Consequently, there are many different types of ‘property’ and relations we can define as ‘ownership’ across different cultures. We use anarchism because it notices the violence of property, anthropology because it notices the strangeness and variety of property, and alchemy as a way of thinking about transformations, that make or undermine property

    New high-pressure phases of ammonia dihydrate

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    A Social Exploration of the West Australian Gorgon Gas, Carbon Capture and Storage Project

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    Carbon capture and storage (CCS) appears to be essential for lowering emissions during the necessary energy transition. However, in Australia, it has not delivered this result, at any useful scale, and this needs explanation. To investigate the reasons for this failure, the paper undertakes a historical and social case study of the Gorgon gas project in Western Australia, which is often declared to be one of the biggest CCS projects in the world. The Gorgon project could be expected to succeed, as it has the backing of government, a practical and economic reason for removing CO2, a history of previous exploration, nearby storage sites, experienced operators and managers, and long-term taxpayer liability for problems. However, it has run late, failed to meet its targets, and not lowered net emissions. The paper explores the social factors which seem to be disrupting the process. These factors include the commercial imperatives of the operation, the lack of incentives, the complexity of the process, the presence of ignored routine problems, geological issues (even in a well-explored area), technical failures, regulatory threats even if minor, tax issues, and the project increasing emissions and consuming carbon budgets despite claims otherwise. The results of this case study suggest that CCS may work in theory, but not well enough under some contemporary forms of social organisation, and the possibilities of CCS cannot be separated from its social background. Social dynamics should be included in CCS projections to enhance the accuracy of expectations.</jats:p

    Thermodynamics of an ideal generalized gas:II Means of order α\alpha

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    The property that power means are monotonically increasing functions of their order is shown to be the basis of the second laws not only for processes involving heat conduction but also for processes involving deformations. In an LL-potentail equilibration the final state will be one of maximum entropy, while in an entropy equilibrium the final state will be one of minimum LL. A metric space is connected with the power means, and the distance between means of different order is related to the Carnot efficiency. In the ideal classical gas limit, the average change in the entropy is shown to be proportional to the difference between the Shannon and R\'enyi entropies for nonextensive systems that are multifractal in nature. The LL-potential, like the internal energy, is a Schur convex function of the empirical temperature, which satisfies Jensen's inequality, and serves as a measure of the tendency to uniformity in processes involving pure thermal conduction.Comment: 8 page

    RNA Sequencing Reveals Candidate Genes and Pathways Associated with Resistance to MDM2 Antagonist Idasanutlin in <em>TP53</em> Wild-Type Chronic Lymphocytic Leukemia

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    \ua9 2024 by the authors. Chronic lymphocytic leukemia (CLL) is a genetically and clinically diverse hematological cancer affecting middle-aged and elderly individuals. Novel targeted therapy options are needed for patients who relapse following initial responses or who are intrinsically resistant to current treatments. There is a growing body of investigation currently underway on MDM2 inhibitors in clinical trials, reflecting the increasing interest in including these drugs in cancer treatment regimens. One of the developed compounds, idasanutlin (RG7388), has shown promise in early-stage clinical trials. It is a second-generation MDM2–p53-binding antagonist with enhanced potency, selectivity, and bioavailability. In addition to the TP53 status, which is an important determinant of the response, we have shown in our previous studies that the SF3B1 mutational status is also an independent predictive biomarker of the ex vivo CLL patient sample treatment response to RG7388. The objective of this study was to identify novel biomarkers associated with resistance to RG7388. Gene set enrichment analysis of differentially expressed genes (DEGs) between RG7388-sensitive and -resistant CLL samples showed that the increased p53 activity led to upregulation of pro-apoptosis pathway genes while DNA damage response pathway genes were additionally upregulated in resistant samples. Furthermore, differential expression of certain genes was detected, which could serve as the backbone for novel combination treatment approaches. This research provides preclinical data to guide the exploration of drug combination strategies with MDM2 inhibitors, leading to future clinical trials and associated biomarkers that may improve outcomes for CLL patients

    Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition

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    Several molecular subtypes of cancer are highly dependent on splicing for cell survival. There is a general interest in the therapeutic targeting of splicing by small molecules. E7107, a first-in-class spliceosome inhibitor, showed strong growth inhibitory activities against a large variety of human cancer xenografts. Chronic lymphocytic leukaemia (CLL) is a clinically heterogeneous hematologic malignancy, with approximately 90% of cases being TP53 wild-type at diagnosis. An increasing number of studies are evaluating alternative targeted agents in CLL, including MDM2–p53 binding antagonists. In this study, we report the effect of splicing modulation on key proteins in the p53 signalling pathway, an important cell death pathway in B cells. Splicing modulation by E7107 treatment reduced full-length MDM2 production due to exon skipping, generating a consequent reciprocal p53 increase in TP53WT cells. It was especially noteworthy that a novel p21WAF1 isoform with compromised cyclin-dependent kinase inhibitory activity was produced due to intron retention. E7107 synergized with the MDM2 inhibitor RG7388, via dual MDM2 inhibition; by E7107 at the transcript level and by RG7388 at the protein level, producing greater p53 stabilisation and apoptosis. This study provides evidence for a synergistic MDM2 and spliceosome inhibitor combination as a novel approach to treat CLL and potentially other haematological malignancies

    Are lay people good at recognising the symptoms of schizophrenia?

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    ©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis
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