Real-Time analysis and visualization for single-molecule based super-resolution microscopy

Accurate multidimensional localization of isolated fluorescent emitters is a time consuming process in single-molecule based super-resolution microscopy. We demonstrate a functional method for real-time reconstruction with automatic feedback control, without compromising the localization accuracy. Compatible with high frame rates of EM-CCD cameras, it relies on a wavelet segmentation algorithm, together with a mix of CPU/GPU implementation. A combination with Gaussian fitting allows direct access to 3D localization. Automatic feedback control ensures optimal molecule density throughout the acquisition process. With this method, we significantly improve the efficiency and feasibility of localization-based super-resolution microscopy

Adam Smith’s Green Thumb and Malthus’ Three Horsemen: Cautionary tales from classical political economy

This essay identifies a contradiction between the flourishing interest in the environmental economics of the classical period and a lack of critical parsing of the works of its leading representatives. Its focus is the work of Adam Smith and Thomas Malthus. It offers a critical analysis of their contribution to environmental thought and surveys the work of their contemporary devotees. It scrutinizes Smith's contribution to what Karl Polanyi termed the "economistic fallacy," as well as his defenses of class hierarchy, the "growth imperative" and consumerism. It subjects to critical appraisal Malthus's enthusiasm for private property and the market system, and his opposition to market regulation. While Malthus's principal attraction to ecological economists lies in his having allegedly broadened the scope of economics, and in his narrative of scarcity, this article shows that he, in fact, narrowed the scope of the discipline and conceptualized scarcity in a reified and pseudo-scientific way

Trial Forge Guidance 1 : what is a Study Within A Trial (SWAT)?

Randomised trials are a central component of all evidence-informed health care systems and the evidence coming from them helps to support health care users, health professionals and others to make more informed decisions about treatment. The evidence available to trialists to support decisions on design, conduct and reporting of randomised trials is, however, sparse. Trial Forge is an initiative that aims to increase the evidence base for trial decision-making and in doing so, to improve trial efficiency.One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. This guidance document provides a brief definition of SWATs, an explanation of why they are important and some practical 'top tips' that come from existing experience of doing SWATs. We hope the guidance will be useful to trialists, methodologists, funders, approvals agencies and others in making clear what a SWAT is, as well as what is involved in doing one

NOx Control Options and Integration for US Coal Fired Boilers: Final Report

This is the Final Report for DOE Cooperative Agreement No: DE-FC26-00NT40753. The goal of the project was to develop cost-effective analysis tools and techniques for demonstrating and evaluating low-NOx control strategies and their possible impact on boiler performance for boilers firing US coals. The Electric Power Research Institute (EPRI) provided co-funding for this program. This project included research on: (1) In furnace NOx control; (2) Impacts of combustion modifications on boiler operation; (3) Selective Catalytic Reduction (SCR) catalyst testing and (4) Ammonia adsorption/removal on fly ash. Important accomplishments were achieved in all aspects of the project. Rich Reagent Injection (RRI), an in-furnace NOx reduction strategy based on injecting urea or anhydrous ammonia into fuel rich regions in the lower furnace, was evaluated for cyclone-barrel and PC fired utility boilers. Field tests successfully demonstrated the ability of the RRI process to significantly reduce NOx emissions from a staged cyclone-fired furnace operating with overfire air. The field tests also verified the accuracy of the Computational Fluid Dynamic (CFD) modeling used to develop the RRI design and highlighted the importance of using CFD modeling to properly locate and configure the reagent injectors within the furnace. Low NOx firing conditions can adversely impact boiler operation due to increased waterwall wastage (corrosion) and increased soot production. A corrosion monitoring system that uses electrochemical noise (ECN) corrosion probes to monitor, on a real-time basis, high temperature corrosion events within the boiler was evaluated. Field tests were successfully conducted at two plants. The Ohio Coal Development Office provided financial assistance to perform the field tests. To investigate soot behavior, an advanced model to predict soot production and destruction was implemented into an existing reacting CFD modeling tool. Comparisons between experimental data collected in a pilot scale furnace and soot behavior predicted by the CFD model showed good agreement. Field and laboratory tests were performed for SCR catalysts used for coal and biomass co-firing applications. Fundamental laboratory studies were performed to better understand mechanisms involved with catalyst deactivation. Field tests with a slip stream reactor were used to create catalyst exposed to boiler flue gas for firing coal and for co-firing coal and biomass. The field data suggests the mechanisms leading to catalyst deactivation are, in order of importance, channel plugging, surface fouling, pore plugging and poisoning. Investigations were performed to better understand the mechanisms involved with catalyst regeneration through mechanical or chemical methods. A computer model was developed to predict NOx reduction across the catalyst in a SCR. Experiments were performed to investigate the fundamentals of ammonia/fly ash interactions with relevance to the operation of advanced NOx control technologies such as selective catalytic reduction. Measurements were performed for ammonia adsorption isotherms on commercial fly ash samples subjected to a variety of treatments and on the chemistry of dry and semi-dry ammonia removal processes. This work resulted in the first fundamental ammonia isotherms on carbon-containing fly ash samples. This work confirms industrial reports that aqueous solution chemistry takes place upon the introduction of even very small amounts of water, while the ash remains in a semi-dry state

Trial Forge Guidance 2: how to decide if a further Study Within A Trial (SWAT) is needed

The evidence base available to trialists to support trial process decisions—e.g. how best to recruit and retain participants, how to collect data or how to share the results with participants—is thin. One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. These are self-contained research studies embedded within a host trial that aim to evaluate or explore alternative ways of delivering or organising a particular trial process. SWATs are increasingly being supported by funders and considered by trialists, especially in the UK and Ireland. At some point, increasing SWAT evidence will lead funders and trialists to ask: given the current body of evidence for a SWAT, do we need a further evaluation in another host trial? A framework for answering such a question is needed to avoid SWATs themselves contributing to research waste. This paper presents criteria on when enough evidence is available for SWATs that use randomised allocation to compare different interventions

Entrapment of Viral Capsids in Nuclear PML Cages Is an Intrinsic Antiviral Host Defense against Varicella-Zoster Virus

The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Congestion avoidance in multiagent-based egress simulation

Abstract We focus on multi-agent-based egress simulation from large sports stadiums. We present the efficient Portal Clearinghouse algorithm for locating bottlenecks that are temporarily congested by agents. The purpose of this step is to allow agents who intend to use the congested portals to re-rout and avoid adding to existing congestions. We present simple heuristic techniques for other sub-problems in congestion avoidance, and demonstrate our approach on a small hand-crafted domain. Interestingly, we observe that a sophisticated vision based avoidance behavior can be emulated with our simple and efficient technique, on some maps