On thermodynamic and quantum fluctuations of cosmological constant

We discuss from the condensed-matter point of view the recent idea that the Poisson fluctuations of cosmological constant about zero could be a source of the observed dark energy. We argue that the thermodynamic fluctuations of Lambda are much bigger. Since the amplitude of fluctuations is proportional to V^{-1/2}, where V is the volume of the Universe, the present constraint on the cosmological constant provides the lower limit for V, which is much bigger than the volume within the cosmological horizon.Comment: 4 pages, version submitted to JETP Letter

From ‘civil’ to ‘civic’ conflict? Violence and the city in ‘fragile states’

By past International development, LSE staff members: Tom Goodfellow, Dennis Rodgers & Jo Beal

Selective inhibition of the p53–MDM2 interaction by nutlin drugs: a new therapeutic perspective for neuroblastoma

Neuroblastoma is one of the most common and most deadly childhood tumors. There is an unmet need to develop new therapeutic modalities for this malignancy that preferentially should be guided by our increasing knowledge of the biology of neuroblastoma. Proliferation and survival of neuroblastoma cells is critically dependent on suppression of the activity of the tumor suppressor protein p53, which is often mediated by increased activity of the MDM2 oncoprotein. Accordingly, small-molecule inhibitors of the interaction between MDM2 and p53 may provide a useful therapeutic option for the treatment of neuroblastoma by restoring the potent antitumor activity of wild-type p53. One of the most promising classes of selective inhibitors of the p53–MDM2 interaction are the nutlins, which have been extensively studied over the last years in several tumor types, including neuroblastoma. We discuss here preclinical data that support the notion that nutlin drugs may offer therapeutic benefit for children with neuroblastoma, on condition that wild-type p53 is present

Thermodynamic framework to assess low abundance DNA mutation detection by hybridization

The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine

A cost-effectiveness analysis of temperate silvoarable systems: what contribution do ecosystem services make?

Silvoarable systems have the potential to be an effective and productive form of sustainable agriculture, in part due to the enhancement of biodiversity and associated ecosystem services. However, currently there is limited understanding of how higher biodiversity in silvoarable systems promotes ecosystem services, such as pest regulation, pollination and nutrient cycling (for example, see Peng et al. 1993; Thevathasan and Gordon 2004; Varah et al. 2013), versus ecosystem disservices, such as encouraging certain pests and weeds (Griffiths et al. 1998; Burgess et al. 2003), and, furthermore, how this cost-benefit ratio might change with how the system is designed, managed and matures over time (but see Burgess et al 2003; Stamps et al. 2009). This paper reports on preliminary results of a cost effectiveness analysis based on the FarmSAFE model (Graves et al. 2011; 2016), as part of a PhD investigating how management of silvoarable influences biodiversity-derived ecosystem services, and their economic implications. Our study is focussed on silvoarable systems in the UK that combine top-fruit production with arable alley-cropping, which are emerging as a promising design with limited shade effects (Smith et al. 2016). We compare our findings to a monocropped arable system, with and without purported associated biodiversity benefits (Varah et al. 2013, 2015)