Realising transition pathways for a more electric, low-carbon energy system in the United Kingdom: challenges, insights and opportunities

The United Kingdom has placed itself on a transition towards a low-carbon economy and society, through the imposition of a legally-binding goal aimed at reducing its ‘greenhouse gas’ emissions by 80% by 2050 against a 1990 baseline. A set of three low-carbon, socio-technical transition pathways were developed and analysed via an innovative collaboration between engineers, social scientists and policy analysts. The pathways focus on the power sector, including the potential for increasing use of low-carbon electricity for heating and transport, within the context of critical European Union developments and policies. Their development started from narrative storylines regarding different governance framings, drawing on interviews and workshops with stakeholders and analysis of historical analogies. The quantified UK pathways were named Market Rules, Central Co-ordination and Thousand Flowers; each reflecting a dominant logic of governance arrangements. The aim of the present contribution was to use these pathways to explore what is needed to realise a transition that successfully addresses the so-called energy policy ‘trilemma,’ i.e. the simultaneous delivery of low carbon, secure and affordable energy services. Analytical tools were developed and applied to assess the technical feasibility,social acceptability, and environmental and economic impacts of the pathways. Technological and behavioural developments were examined, alongside appropriate governance structures and regulations for these low-carbon transition pathways, as well as the roles of key energy system ‘actors’ (both large and small). An assessment of the part that could possibly be played by future demand side response was also undertaken in order to understand the factors that drive energy demand and energy-using behaviour, and reflecting growing interest in demand side response for balancing a system with high proportions of renewable generation. A set of interacting and complementary engineering and technoeconomic models or tools were then employed to analyse electricity network infrastructure investment and operational decisions to assist market design and option evaluation. This provided a basis for integrating the analysis within a whole systems framework of electricity system development, together with the evaluation of future economic benefits, costs and uncertainties. Finally, the energy and environmental performance of the different energy mixes were appraised on a‘life-cycle’ basis to determine the greenhouse gas emissions and other ecological or health burdens associated with each of the three transition pathways. Here, the challenges, insights and opportunities that have been identified over the transition towards a low-carbon future in the United Kingdom are described with the purpose of providing a valuable evidence base for developers, policy makers and other stakeholders

Partition function of N = 2* SYM on a large four-sphere

We examine the partition function of N=2* supersymmetric SU(N) Yang-Mills theory on the four-sphere in the large radius limit. We point out that the large radius partition function, at fixed N, is computed by saddle points lying on particular walls of marginal stability on the Coulomb branch of the theory on R^4. For N an even (odd) integer and \theta_YM=0, (\pi), these include a point of maximal degeneration of the Donagi-Witten curve to a torus where BPS dyons with electric charge [N/2] become massless. We argue that the dyon singularity is the lone saddle point in the SU(2) theory, while for SU(N) with N>2, we characterize potentially competing saddle points by obtaining the relations between the Seiberg-Witten periods at such points. Using Nekrasov's instanton partition function, we solve for the maximally degenerate saddle point and obtain its free energy as a function of g_YM and N, and show that the results are "large-N exact". In the large-N theory our results provide analytical expressions for the periods/eigenvalues at the maximally degenerate saddle point, precisely matching previously known formulae following from the correspondence between N=2* theory and the elliptic Calogero-Moser integrable model. The maximally singular point ceases to be a saddle point of the partition function above a critical value of the coupling, in agreement with the recent findings of Russo and Zarembo

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

An IL28B Genotype-Based Clinical Prediction Model for Treatment of Chronic Hepatitis C

BACKGROUND:Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. METHODS:HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC). RESULTS:Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. CONCLUSION:A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC

Synthesis of freestanding HfO2 nanostructures

Two new methods for synthesizing nanostructured HfO2 have been developed. The first method entails exposing HfTe2 powders to air. This simple process resulted in the formation of nanometer scale crystallites of HfO2. The second method involved a two-step heating process by which macroscopic, freestanding nanosheets of HfO2 were formed as a byproduct during the synthesis of HfTe2. These highly two-dimensional sheets had side lengths measuring up to several millimeters and were stable enough to be manipulated with tweezers and other instruments. The thickness of the sheets ranged from a few to a few hundred nanometers. The thinnest sheets appeared transparent when viewed in a scanning electron microscope. It was found that the presence of Mn enhanced the formation of HfO2 by exposure to ambient conditions and was necessary for the formation of the large scale nanosheets. These results present new routes to create freestanding nanostructured hafnium dioxide

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

Idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis: a case report

BACKGROUND: Pulmonary vein thrombosis represents a potentially fatal disease. This syndrome may clinically mimic pulmonary embolism but has a different investigation strategy and prognosis. Pulmonary vein thrombosis is difficult to diagnose clinically and usually requires a combination of conventionally used diagnostic modalities. CASE PRESENTATION: The authors report a case of a 78-year-old previously healthy female presenting with collapse and shortness of breath. Serum biochemistry revealed acute kidney injury, positive D-dimmer's and increased C reactive protein. Chest radiography demonstrated volume loss in the right lung. The patient was started on antibiotics and also therapeutic doses of low molecular weight heparin. The working diagnosis included community acquired pneumonia & pulmonary embolism. A computed tomography pulmonary angiogram was performed to confirm the clinical suspicions of pulmonary embolism. This demonstrated a thrombus in the pulmonary vein, with associated fibrosis and volume loss of the right lower lobe. A subsequent thrombophilia screen revealed a positive lupus anticoagulant antibody and rheumatoid factor and also decreased anti thrombin III and protein C levels. The urine protein/creatinine ratio was found to be 553 mg/mmol. CONCLUSION: The diagnosis of this patient was therefore of idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis. Whether or not the pulmonary vein thrombosis was a primary cause of the fibrosis or a consequence of it was unclear. There are few data on the management of pulmonary vein thrombosis, but anticoagulation, antibiotics, and, in cases of large pulmonary vein thrombosis, thrombectomy or pulmonary resection have been used

The SpikerBox: A Low Cost, Open-Source BioAmplifier for Increasing Public Participation in Neuroscience Inquiry

Although people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed) the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience