Controlling Engineered P2X Receptors with Light

This chapter details methods to express and modify ATP-gated P2X receptor channels so that they can be controlled using light. Following expression in cells, a photoswitchable tool compound can be used to covalently modify mutant P2X receptors, as previously demonstrated for homomeric P2X2 and P2X3 receptors, and heteromeric P2X2/3 receptors. Engineered P2X receptors can be rapidly and reversibly opened and closed by different wavelengths of light. Light-activated P2X receptors can be mutated further to impart ATP-insensitivity if required. This method offers control of specific P2X receptor channels with high spatiotemporal precision to study their roles in physiology and pathophysiology

The assessment of the implementation of fuel related legislations and their impact on air quality and public health

The main focus of Work Package 6 of the Aphekom project was: to develop innovative methods to analyse the decrease in air pollution levels following implementation of an European regulation to reduce the sulphur content in liquid fuels; to follow the evolution of health risks over time; to track related effect modifiers; and to quantify the monetary costs of health impacts of the implemented regulation

Profiling SO2 air pollution patterns in 9 EU Aphekom cities: The Aphekom Project

A detailed analysis of hourly pollutant concentrations mainly focusing on SO2 data obtained from 9 centres involved in the Aphekom project was conducted. This involved the generation of individual diurnal SO2 profiles in order to: (i) identify city specific patterns including source apportionment and quantification, (ii) track changes over time, (iii) analyse the changes in SO2 concentrations from different emission sources, i.e. traffic, heating, shipping and industrial sources, overtime

Mortality impacts of sulphur concetrations in 20 European cities in the APHEKOM Project

The implementation of three EU directives to reduce sulphur content in fuel was assessed for mortality impacts in 20 European cities, between 1990 and 2007 in the APHEKOM project. This specific study aimed to examine whether different lag structures apply to the relationships between cardiovascular and respiratory events and SO2 concentrations, which will therefore result in differences in mortality impacts from regulation implementation. Prior evidence has shown that cardiovascular mortality is more likely to be affected by SO2 concentrations on the same or the previous day of the event, while respiratory mortality more likely to show a delayed effect of exposure to the same pollutant

Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

Introduction The precise trigger of podoconiosis — endemic non-filarial elephantiasis of the lower legs — is unknown. Epidemiological and ecological studies have linked the disease with barefoot exposure to red clay soils of volcanic origin. Histopathology investigations have demonstrated that silicon, aluminium, magnesium and iron are present in the lower limb lymph node macrophages of both patients and non-patients living barefoot on these clays. We studied the spatial variation (variations across an area) in podoconiosis prevalence and the associated environmental factors with a goal to better understanding the pathogenesis of podoconiosis. Methods Fieldwork was conducted from June 2011 to February 2013 in 12 kebeles (administrative units) in northern Ethiopia. Geo-located prevalence data and soil samples were collected and analysed along with secondary geological, topographic, meteorological and elevation data. Soil data were analysed for chemical composition, mineralogy and particle size, and were interpolated to provide spatially continuous information. Exploratory, spatial, univariate and multivariate regression analyses of podoconiosis prevalence were conducted in relation to primary (soil) and secondary (elevation, precipitation, and geology) covariates. Results Podoconiosis distribution showed spatial correlation with variation in elevation and precipitation. Exploratory analysis identified that phyllosilicate minerals, particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline silica), iron oxide, and zirconium were associated with podoconiosis prevalence. The final multivariate model showed that the quantities of smectite (RR = 2.76, 95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001) and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive associations with podoconiosis prevalence. Conclusions More quantities of smectite, mica and quartz within the soil were associated with podoconiosis prevalence. Together with previous work indicating that these minerals may influence water absorption, potentiate infection and be toxic to human cells, the present findings suggest that these particles may play a role in the pathogenesis of podoconiosis and acute adenolymphangitis, a common cause of morbidity in podoconiosis patients

Color Confinement, Quark Pair Creation and Dynamical Chiral-Symmetry Breaking in the Dual Ginzburg-Landau Theory

We study the color confinement, the $q$-$\bar q$ pair creation and the dynamical chiral-symmetry breaking of nonperturbative QCD by using the dual Ginzburg-Landau theory, where QCD-monopole condensation plays an essential role on the nonperturbative dynamics in the infrared region. As a result of the dual Meissner effect, the linear static quark potential, which characterizes the quark confinement, is obtained in the long distance within the quenched approximation. We obtain a simple expression for the string tension similar to the energy per unit length of a vortex in the superconductivity physics. The dynamical effect of light quarks on the quark confining potential is investigated in terms of the infrared screening effect due to the $q$-$\bar q$ pair creation or the cut of the hadronic string. The screening length of the potential is estimated by using the Schwinger formula for the $q$-$\bar q$ pair creation. We introduce the corresponding infrared cutoff to the strong long-range correlation factor in the gluon propagator as a dynamical effect of light quarks, and obtain a compact formula of the quark potential including the screening effect in the infrared region. We investigate the dynamical chiral-symmetry breaking by using the Schwinger-Dyson equation, where the gluon propagator includes the nonperturbative effect related toComment: 37 pages, plain TeX (using `phyzzx' macro), (( 8 figures - available on request from [email protected] )

Effects of deceptive running speed on physiology, perceptual responses, and performance during sprint-distance triathlon

Objective This study examined the effects of speed deception on performance, physiological and perceptual responses, and pacing during sprint-distance triathlon running. Methods Eight competitive triathletes completed three simulated sprint-distance triathlons (0.75 km swim, 20 km bike, 5 km run) in a randomised order, with swimming and cycling sections replicating baseline triathlon performance. During the first 1.66 km of the run participants maintained an imposed speed, completing the remaining 3.33 km as quickly as possible. Although participants were informed that initially prescribed running speed would reflect baseline performance, this was true during only one trial (Tri-Run100%). As such, other trials were either 3% faster (Tri-Run103%), or 3% slower (Tri-Run97%) than baseline during this initial period. Results Performance during Tri-Run103% (1346 ± 108 s) was likely faster than Tri-Run97% (1371 ± 108 s), and possibly faster than Tri-Run100% (1360 ± 125 s), with these differences likely to be competitively meaningful. The first 1.66 km of Tri-Run103% induced greater physiological strain compared to other conditions, whilst perceptual responses were not significantly different between trials. Conclusions It appears that even during ‘all-out’ triathlon running, athletes maintain some form of ‘reserve’ capacity which can be accessed by deception. This suggests that expectations and beliefs have a practically meaningful effect on pacing and performance during triathlon, although it is apparent that an individual’s conscious intentions are secondary to the brains sensitivity to potentially harmful levels of physiological and perceptual strain

Gas-phase and particulate products from the atmospheric degradation of an isoxazole fungicide

[EN] The isoxazole structure is present in several pesticides. However, there is a lack of information about its degradation products after the release to the atmosphere. The main atmospheric reactions of hymexazol (5-methylisoxazol-3-ol), selected as representative model, were investigated at a large outdoor simulation chamber. The predominant products of atmospheric degradations were gaseous nitrogen derivates (nitric acid, nitrogen dioxide, nitrogen oxide, nitrous acid, and peroxyacetylnitrate), ozone, and small oxygenated compounds (formic acid, formaldehyde, and methylglyoxal). The aerosol yields were lower than 5%, and an OH rate-dependence was observed in the nucleation, particle growth, and size distribution. Also, the chemical composition of minor multi-oxygenated products was studied for OH-photooxidations. More than 20 products were detected in the gas or particulate phase. The most abundant were heterocyclic cleavage products with C4-chain and oxygenated moieties at positions 1 and 3, such as 3,4-dioxobutanoic acid, 3-oxobutanoic acid, and 3-oxobutanal. The suggested reaction pathway is the opening of heterocycle ring by the cleavage of N O bond and C N bond, releasing nitrogen oxides.The authors wish to thank the EUPHORE staff and J.T.B. The authors wish to acknowledge Ministerio de Ciencia y Tecnologia for IMPESTAT (CGL2010-18474/CLI) and the European Community's Seventh Framework Program under the Grant agreement no. 228335 (Eurochamp2). The Fundacion CEAM is partly supported by Generalitat Valenciana, and the projects GRACCIE (Consolider-Ingenio 2010) and FEEDBACKS (Prometeo - Generalitat Valenciana). EUPHORE instrumentation is partly funded by the Spanish Ministry of Science and Innovation, through INNPLANTA Project: PCT-440000-2010-003.Tortajada-Genaro, LA.; Borrás García, EM.; Muñoz, A. (2013). Gas-phase and particulate products from the atmospheric degradation of an isoxazole fungicide. Chemosphere. 92(8):1035-1041. https://doi.org/10.1016/j.chemosphere.2013.03.041S1035104192

Spatial and spectral features utilization on a hyperspectral imaging system for rice seed varietal purity inspection

A conventional method to inspect the varietal purity of rice seeds is based on evaluating human visual inspection where a random sample is drawn from a batch. This is a tedious, laborious, time consuming and extremely inefficient task. This paper presents an automatic rice seed inspection method using Hyperspectral imaging and machine learning, to automatically detect unwanted seeds from other varieties which may be contained in a batch. Hyperspectral image data from Near-infrared (NIR) and Visible cameras are acquired for six common rice seed varieties. The results of applying two classifiers are presented, a Support Vector Machine (SVM) and a Random Forest (RF), where each consists of six one-versus-rest binary classifiers. The results show that combining spectral and shape- based features derived from the rice seeds, increase precision of the multi-label classification to 84% compared 74% when only visual features are used

A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD

Background: Individuals with post-traumatic stress disorder (PTSD) have a heightened sensitivity to subsequent stressors, addictive drugs, and symptom recurrence, a form of behavioral sensitization. N-methyl-D-aspartate receptors (NMDARs) are involved in the establishment and activation of sensitized behavior. Objective: We describe a protocol of a randomized placebo-controlled Phase 1b proof-of-mechanism trial to examine target engagement, safety, tolerability, and possible efficacy of the NMDAR antagonist lanicemine in individuals with symptoms of PTSD (Clinician Administered PTSD Scale [CAPS-5] score ≥ 25) and evidence of behavioral sensitization measured as enhanced anxiety-potentiated startle (APS; T-score ≥ 2.8). Methods: Subjects (n = 24; age range 21–65) receive three 60-min intravenous infusions of placebo or 100 mg lanicemine over 5 non-consecutive days. Primary endpoint is change in APS from pre-treatment baseline to after the third infusion. NMDAR engagement is probed with resting state EEG gamma band power, 40 Hz auditory steady state response, the mismatch negativity amplitude, and P50 sensory gating. Change in CAPS-5 scores is an exploratory clinical endpoint. Bayesian statistical methods will evaluate endpoints to determine suitability of this agent for further study. Conclusion: In contrast to traditional early-phase trials that use symptom severity to track treatment efficacy, this study tracks engagement of the study drug on expression of behavioral sensitization, a functional mechanism likely to cut across disorders. This experimental therapeutics design is consistent with recent NIMH-industry collaborative studies, and could serve as a template for testing novel pharmacological agents in psychiatry