Click beetle luciferase mutant and near infrared naphthyl-luciferins for improved bioluminescence imaging

The sensitivity of bioluminescence imaging in animals is primarily dependent on the amount of photons emitted by the luciferase enzyme at wavelengths greater than 620 nm where tissue penetration is high. This area of work has been dominated by firefly luciferase and its substrate, D-luciferin, due to the system's peak emission (~ 600 nm), high signal to noise ratio, and generally favorable biodistribution of D-luciferin in mice. Here we report on the development of a codon optimized mutant of click beetle red luciferase that produces substantially more light output than firefly luciferase when the two enzymes are compared in transplanted cells within the skin of black fur mice or in deep brain. The mutant enzyme utilizes two new naphthyl-luciferin substrates to produce near infrared emission (730 nm and 743 nm). The stable luminescence signal and near infrared emission enable unprecedented sensitivity and accuracy for performing deep tissue multispectral tomography in mice

Liberal market economies, business, and political finance: Britain under New Labour

The extent and nature of business financing of parties is an important feature of political finance. Britain’s transparent and permissive regulatory system provides an excellent opportunity to study business financing of parties. Business donations have been very important to the Conservative party over the last decade, and of only marginal importance to Labour. Unlike other Conservative contributors, business donors are more likely to contribute when the party is popular. In contrast to the previous period of Conservative government, the biggest British businesses tended to abstain from political finance under New Labour. However, their bias towards the Conservatives is affected by the party’s popularity and the closeness of an election. Britain shares the political importance of business financing of parties and its mixture of ideological and pragmatic motivations with other liberal market economies. However, in Britain the bias towards the right is much stronger and the role of big business more marginal

Increasing Diversion of Methadone in Vancouver, Canada, 2005-2015

Background and Aim: Although methadone, an opioid agonist, has been an effective medication used to treat opioid use disorder for over 40 years, recent studies have found that methadone was identified in more than a quarter of prescription opioid-related deaths among people who use illicit drugs in Vancouver, Canada. Thus, we sought to longitudinally examine the availability of diverted methadone among people who inject drugs (PWID). Design and Methods: Data were collected from three prospective cohorts of PWID in Vancouver, Canada between December 2005 and May 2015. Multivariable generalized estimating equation logistic regression was used to identify temporal trends in the immediate availability of diverted methadone (defined as the ability to acquire illicit methadone in <10 minutes). Results: A total of 2092 participants, including 727 (34.8%) women, were included in the present study. In the multivariable analyses after adjusting for a range of potential confounders, later calendar year (adjusted odds ratio [AOR] = 1.21 per year; 95% confidence interval [CI]: 1.19–1.23) was independently and positively associated with reporting immediate availability of diverted methadone. Conclusions: We observed a significant increase in the reported availability of diverted methadone among PWID over a ten-year follow-up period. Further research is needed to identify strategies to limit methadone diversion and assess the impact of alternative medications that are equally effective but safer, such as buprenorphine/naloxone

Relationship Between Quorum Sensing and Secretion Systems

Quorum sensing (QS) is a communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation, virulence factor expression, production of secondary metabolites and stress adaptation mechanisms such as bacterial competition systems including secretion systems (SS). These SS have an important role in bacterial communication. SS are ubiquitous; they are present in both Gram-negative and Gram-positive bacteria and in Mycobacterium sp. To date, 8 types of SS have been described (T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, T7SS, and T9SS). They have global functions such as the transport of proteases, lipases, adhesins, heme-binding proteins, and amidases, and specific functions such as the synthesis of proteins in host cells, adaptation to the environment, the secretion of effectors to establish an infectious niche, transfer, absorption and release of DNA, translocation of effector proteins or DNA and autotransporter secretion. All of these functions can contribute to virulence and pathogenesis. In this review, we describe the known types of SS and discuss the ones that have been shown to be regulated by QS. Due to the large amount of information about this topic in some pathogens, we focus mainly on Pseudomonas aeruginosa and Vibrio spp

Quantification of titanium dioxide (TiO2) anatase and rutile polymorphs in binary mixtures by Raman spectroscopy: an interlaboratory comparison

This article presents an interlaboratory comparison (ILC) on Raman spectroscopy as a technique for relative quantification of the two most common polymorphs of titanium dioxide (TiO2)-anatase and rutile-in binary mixtures. Some standard methods are currently employed internationally for the determination of TiO2 content in samples (ISO 591-1, ASTM D3720-90), but require extensive sample preparation, do not distinguish between the two polymorphs or are accurate only for small fractions of either polymorph. Raman spectroscopy is a well-suited characterization technique for measuring and differentiating TiO2 in a fast, non-invasive way, while requiring no particular reagent or sample preparation. Eleven international participants conducted the study under the framework of Versailles Project on Advanced Materials and Standards. The collected data was analyzed by means of partial least squares regression after spectral preprocessing. The resulting models all show discrepancies of lower than 2% from the nominal values in the quantitative analysis over the concentration range of 5%-95% mixture fractions, with many datasets showing substantial improvement margins on this figure. The results of this ILC provide validation of Raman spectroscopy as a reliable method for quantification of TiO2 phases

Identifying effective approaches for monitoring national natural capital for policy use

In order to effectively manage natural resources at national scales national decision makers require data on the natural capital which supports the delivery of ecosystem services (ES). Key data sources used for the provision of national natural capital metrics include Satellite Remote Sensing (SRS), which provides information on land cover at an increasing range of resolutions, and field survey, which can provide very high resolution data on ecosystem components, but is constrained in its potential coverage by resource requirements. Here we combine spatially representative field data from a historic national survey of Great Britain (Countryside Survey (CS)) with concurrent low resolution SRS data land cover map within modelling frameworks to produce national natural capital metrics. We present three examples of natural capital metrics; top soil carbon, headwater stream quality and nectar species plant richness which show how highly resolved, but spatially representative field data can be used to significantly enhance the potential of low resolution SRS land cover data for providing national spatial data on natural capital metrics which have been linked to ecosystem services (ES). We discuss the role of such metrics in evaluations of ecosystem service provision and areas of further development to improve their utility for stakeholders

The Met Office Unified Model Global Atmosphere 6.0/6.1 and JULES Global Land 6.0/6.1 configurations

We describe Global Atmosphere 6.0 and Global Land 6.0: the latest science configurations of the Met Office Unified Model and JULES land surface model developed for use across all timescales. Global Atmosphere 6.0 includes the ENDGame dynamical core, which significantly increases mid-latitude variability improving a known model bias. Alongside developments of the model’s physical parametrisations, ENDGame also increases variability in the tropics, which leads to an improved representation of tropical cyclones and other tropical phenomena. Further developments of the atmospheric and land surface parametrisations improve other aspects of model performance, including the forecasting of surface weather phenomena. We also describe Global Atmosphere 6.1 and Global Land 6.1, which include a small number of long-standing differences from our main trunk configurations that we continue to require for operational global weather prediction. Since July 2014, GA6.1/GL6.1 has been used by the Met Office for operational global NWP, whilst GA6.0/GL6.0 was implemented in its remaining global prediction systems over the following year

Don't Stop Thinking About Leptoquarks: Constructing New Models

We discuss the general framework for the construction of new models containing a single, fermion number zero scalar leptoquark of mass $\simeq 200-220$ GeV which can both satisfy the D0/CDF search constraints as well as low energy data, and can lead to both neutral and charged current-like final states at HERA. The class of models of this kind necessarily contain new vector-like fermions with masses at the TeV scale which mix with those of the Standard Model after symmetry breaking. In this paper we classify all models of this type and examine their phenomenological implications as well as their potential embedding into SUSY and non-SUSY GUT scenarios. The general coupling parameter space allowed by low energy as well as collider data for these models is described and requires no fine-tuning of the parameters.Comment: Modified text, added table, and updated reference

Mechanical chest compression devices at in-hospital cardiac arrest: A systematic review and meta-analysis

AIM: To summarise the evidence in relation to the routine use of mechanical chest compression devices during resuscitation from in-hospital cardiac arrest. METHODS: We conducted a systematic review of studies which compared the effect of the use of a mechanical chest compression device with manual chest compressions in adults that sustained an in-hospital cardiac arrest. Critical outcomes were survival with good neurological outcome, survival at hospital discharge or 30-days, and short-term survival (ROSC/1-h survival). Important outcomes included physiological outcomes. We synthesised results in a random-effects meta-analysis or narrative synthesis, as appropriate. Evidence quality in relation to each outcome was assessed using the GRADE system. DATA SOURCES: Studies were identified using electronic databases searches (Cochrane Central, MEDLINE, EMBASE, CINAHL), forward and backward citation searching, and review of reference lists of manufacturer documentation. RESULTS: Eight papers, containing nine studies [689 participants], were included. Three studies were randomised controlled trials. Meta-analyses showed an association between use of mechanical chest compression device and improved hospital or 30-day survival (odds ratio 2.34, 95% CI 1.42-3.85) and short-term survival (odds ratio 2.14, 95% CI 1.11-4.13). There was also evidence of improvements in physiological outcomes. Overall evidence quality in relation to all outcomes was very low. CONCLUSIONS: Mechanical chest compression devices may improve patient outcome, when used at in-hospital cardiac arrest. However, the quality of current evidence is very low. There is a need for randomised trials to evaluate the effect of mechanical chest compression devices on survival for in-hospital cardiac arrest