Scalable Inference for Markov Processes with Intractable Likelihoods

Bayesian inference for Markov processes has become increasingly relevant in recent years. Problems of this type often have intractable likelihoods and prior knowledge about model rate parameters is often poor. Markov Chain Monte Carlo (MCMC) techniques can lead to exact inference in such models but in practice can suffer performance issues including long burn-in periods and poor mixing. On the other hand approximate Bayesian computation techniques can allow rapid exploration of a large parameter space but yield only approximate posterior distributions. Here we consider the combined use of approximate Bayesian computation (ABC) and MCMC techniques for improved computational efficiency while retaining exact inference on parallel hardware

Micromanipulation of InP lasers with optoelectronic tweezers for integration on a photonic platform

The integration of light sources on a photonic platform is a key aspect of the fabrication of self-contained photonic circuits with a small footprint that does not have a definitive solution yet. Several approaches are being actively researched for this purpose. In this work we propose optoelectronic tweezers for the manipulation and integration of light sources on a photonic platform and report the positional and angular accuracy of the micromanipulation of standard Fabry-Pérot InP semiconductor laser die. These lasers are over three orders of magnitude bigger in volume than any previously assembled with optofluidic techniques and the fact that they are industry standard lasers makes them significantly more useful than previously assembled microdisk lasers. We measure the accuracy to be 2.5 ± 1.4 µm and 1.4 ± 0.4° and conclude that optoelectronic tweezers are a promising technique for the micromanipulation and integration of optoelectronic components in general and semiconductor lasers in particular

Topological properties of quantum periodic Hamiltonians

We consider periodic quantum Hamiltonians on the torus phase space (Harper-like Hamiltonians). We calculate the topological Chern index which characterizes each spectral band in the generic case. This calculation is made by a semi-classical approach with use of quasi-modes. As a result, the Chern index is equal to the homotopy of the path of these quasi-modes on phase space as the Floquet parameter (\theta) of the band is varied. It is quite interesting that the Chern indices, defined as topological quantum numbers, can be expressed from simple properties of the classical trajectories.Comment: 27 pages, 14 figure

Progressing the care, husbandry and management of ageing mice used in scientific studies

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with ageing research have developed their own systems to determine intervention points for potential refinements and to identify humane end points. Several good systems are in use, but variations between them could contribute to poor reproducibility of the science achieved. Working with scientific and regulatory communities in the UK, we have reviewed the clinical signs observed in ageing mice and developed recommendations for enhanced monitoring, behaviour assessment, husbandry and veterinary interventions. We advocate that the default time point for enhanced monitoring should be 15 months of age, unless prior information is available. Importantly, the enhanced monitoring should cause no additional harms to the animals. Where a mouse strain is well characterised, the onset of age-related enhanced monitoring may be modified based on knowledge of the onset of an expected age-related clinical sign. In progeroid models where ageing is accelerated, enhanced monitoring may need to be brought forward. Information on the background strain must be considered, as it influences the onset of age-related clinical signs. The range of ageing models currently used means that there will be no ‘one-size fits all’ solution. Increased awareness of the issues will lead to more refined and consistent husbandry of ageing mice, and application of humane end points will help to reduce the numbers of animals maintained for longer than is scientifically justified

The Challenge of Urban Heat Exposure under Climate Change: An Analysis of Cities in the Sustainable Healthy Urban Environments (SHUE) Database

The so far largely unabated emissions of greenhouse gases (GHGs) are expected to increase global temperatures substantially over this century. We quantify the patterns of increases for 246 globally-representative cities in the Sustainable Healthy Urban Environments (SHUE) database. We used an ensemble of 18 global climate models (GCMs) run under a low (RCP2.6) and high (RCP8.5) emissions scenario to estimate the increase in monthly mean temperatures by 2050 and 2100 based on 30-year averages. Model simulations were from the Coupled Model Inter-comparison Project Phase 5 (CMIP5). Annual mean temperature increases were 0.93 degrees Celsius by 2050 and 1.10 degrees Celsius by 2100 under RCP2.6, and 1.27 and 4.15 degrees Celsius under RCP8.5, but with substantial city-to-city variation. By 2100, under RCP2.6 no city exceeds an increase in Tmean > 2 degrees Celsius (relative to a 2017 baseline), while all do under RCP8.5, some with increases in Tmean close to, or even greater than, 7 degrees Celsius. The increases were greatest in cities of mid to high latitude, in humid temperate and dry climate regions, and with large seasonal variation in temperature. Cities are likely to experience large increases in hottest month mean temperatures under high GHG emissions trajectories, which will often present substantial challenges to adaptation and health protection

Effect of dialysate composition on intercompartmental fluid shift

Effect of dialysate composition on intercompartmental fluid shift. Effect of dialysate composition on intercompartmental fluid shift and hemodynamics was studied in 12 patients during 1.5 or 2 hours of hemodialysis without net ultrafiltration, using high (H;Na 154 mmol/liter), normal (N;Na 140 mmol/liter) or low (L:Na 126 mmol/liter) concentration dialysate. H dialysate was associated with a small (0.9%) increase in blood volume, a larger increase in plasma volume and a decrease in erythrocyte volume. L dialysate resulted in a 2.3% decrease in blood volume, a larger decrease in plasma volume and an increase in erythrocyte volume. N dialysate gave results which were intermediately between the other two dialysis conditions. There was no difference in the post-dialysis mean arterial pressure between the groups, although heart rate increased more during H dialysis than during the other two conditions. Change in blood and erythrocyte volume correlated significantly with change in plasma Na concentration and osmolality, but not with change in plasma urea concentration. We conclude that dialysate composition affects the movement of water into and out of the plasma and erythrocytes in a manner that can be accounted for by altered plasma concentrations of osmotically active substances

Environmental Risks of Cities in the European Region:Analyses of the Sustainable Healthy Urban Environments (SHUE) Database

Introduction: In an increasingly urbanized world, cities are a key focus for action on health and sustainability. The Sustainable Healthy Urban Environments (SHUE) project aims to provide a shared information resource to support such action. Its aim is to test the feasibility and methods of assembling data about the characteristics of a globally distributed sample of cities and the populations within them for comparative analyses, and to use such data to assess how policies may contribute to sustainable urban development and human health. Methods: As a first illustration of the database, we present analyses of selected parameters on climate change, air pollution and flood risk for 64 cities in the WHO European Region. Results: Under a high greenhouse gas emissions trajectory (RCP8.5), the analyses suggest damaging temperature rises in European cities that are among the highest of any cities in the global database, while air pollution (PM2.5) levels are appreciably above the WHO guideline level for all but a handful of cities. In several areas, these environmental hazards are compounded by flood risk. Discussion: Such evidence, though preliminary and based on limited data, underpins the need for urgent action on climate change (adaptation and mitigation) and risks relating to air pollution and other environmental hazards

Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes