117 research outputs found
Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer
Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to firstâline chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer
Observation of Andreev Reflection Enhanced Shot Noise
We have experimentally investigated the quasiparticle shot noise in
NbN/MgO/NbN superconductor - insulator - superconductor tunnel junctions. The
observed shot noise is significantly larger than theoretically expected. We
attribute this to the occurrence of multiple Andreev reflection processes in
pinholes present in the MgO barrier. This mechanism causes the current to flow
in large charge quanta (Andreev clusters), with a voltage dependent average
value of m = 1+ 2 Delta/eV times the electron charge. Because of this charge
enhancement effect, the shot noise is increased by the factor m.Comment: 4 pages, 5 figures include
A chemical biology screen reveals a role for Rab21-mediated control of actomyosin contractility in fibroblast-driven cancer invasion
Global energy governance : a review and research agenda
Over the past few years, global energy governance (GEG) has emerged as a major new field of enquiry in international studies. Scholars engaged in this field seek to understand how the energy sector is governed at the global level, by whom and with what consequences. By focusing on governance, they broaden and enrich the geopolitical and hard-nosed security perspectives that have long been, and still are, the dominant perspectives through which energy is analysed. Though still a nascent field, the literature on GEG is thriving and continues to attract the attention of a growing number of researchers. This article reviews the GEG literature as it has developed over the past 10 years. Our aim is to highlight both the progress and limitations of the field, and to identify some opportunities for future research. The article proceeds as follows. First, it traces the origins of the GEG literature (section âOrigins and roots of GEG researchâ). The subsequent sections deal with the two topics that have received the most attention in the GEG literature: Why does energy need global governance (section âThe goals and rationale of global energy governanceâ)? And, who governs energy (section âMapping the global energy architectureâ)? We then address a third question that has received far less attention: How well or poor is energy governed (section âEvaluating global energy governanceâ)? In our conclusions (section âConclusions and outlookâ), we reflect on the current state of GEG, review recent trends and innovations, and identify some questions that warrant future consideration by scholars. This article is published as part of a thematic collection on global governance
Coal and Climate Change
This overview adopts a critical social science perspective to examine the state of play and potential futures for coal in the context of climate change. It introduces key trends in coal consumption, production and trade, before appraising the relevant literature. Finding surprisingly little literature directly focussed on coal and climate change compared with related fields, it appraises existing work and highlights key areas for future work. In addition to established bodies of work on the situated politics of coal and the political economy of coal, new work calling for demand side policies to be supplemented with supply side policies highlights the increasing importance of how normative contestations drive debates over coal, suggesting that future work needs to engage not only much more directly with climate change as an issue, but particularly with the place of coal in a just transition. Because of coalâs mammoth contribution to climate change and the complex political economy which drives its production and consumption, it is likely that coal will remain at the centre of difficult questions about the relationship between climate action and development for some time
- âŠ