Advanced microsamples: Current applications and considerations for mass spectrometry-based metabolic phenotyping pipelines

Microsamples are collections usually less than 50 µL, although all devices that we have captured as part of this review do not fit within this definition (as some can perform collections of up to 600 µL); however, they are considered microsamples that can be self-administered. These microsamples have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venepuncture. However, venepuncture remains the sampling gold standard for the metabolic phenotyping of blood. This presents several challenges in metabolic phenotyping workflows: accessibility for individuals in rural and remote areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample collection difficulty in the young and elderly. Furthermore, venous sample stability may be compromised when the temperate conditions necessary for cold-chain transport are beyond control. Alternatively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into the metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for microsampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for the employment of microsamples in metabolic phenotyping research. This review supports the translation of research from the ‘bench to the community’

The potential of small unmanned aircraft systems and structure-from-motion for topographic surveys: a test of emerging integrated approaches at Cwm Idwal, North Wales

This paper was accepted for publication in the journal Geomorphology and the definitive published version is available at http://dx.doi.org/10.1016/j.geomorph.2014.07.021Novel topographic survey methods that integrate both structure-from-motion (SfM) photogrammetry and small unmanned aircraft systems (sUAS) are a rapidly evolving investigative technique. Due to the diverse range of survey configurations available and the infancy of these new methods, further research is required. Here, the accuracy, precision and potential applications of this approach are investigated. A total of 543 images of the Cwm Idwal moraine–mound complex were captured from a light (b5 kg) semi-autonomous multi-rotor unmanned aircraft system using a consumer-grade 18 MP compact digital camera. The imageswere used to produce a DSM(digital surfacemodel) of themoraines. The DSMis in good agreement with 7761 total station survey points providing a total verticalRMSE value of 0.517mand verticalRMSE values as lowas 0.200mfor less densely vegetated areas of the DSM. High-precision topographic data can be acquired rapidly using this technique with the resulting DSMs and orthorectified aerial imagery at sub-decimetre resolutions. Positional errors on the total station dataset, vegetation and steep terrain are identified as the causes of vertical disagreement. Whilst this aerial survey approach is advocated for use in a range of geomorphological settings, care must be taken to ensure that adequate ground control is applied to give a high degree of accuracy

Dynamical mean-field theory of spiking neuron ensembles: response to a single spike with independent noises

Dynamics of an ensemble of $N$-unit FitzHugh-Nagumo (FN) neurons subject to white noises has been studied by using a semi-analytical dynamical mean-field (DMF) theory in which the original $2 N$-dimensional {\it stochastic} differential equations are replaced by 8-dimensional {\it deterministic} differential equations expressed in terms of moments of local and global variables. Our DMF theory, which assumes weak noises and the Gaussian distribution of state variables, goes beyond weak couplings among constituent neurons. By using the expression for the firing probability due to an applied single spike, we have discussed effects of noises, synaptic couplings and the size of the ensemble on the spike timing precision, which is shown to be improved by increasing the size of the neuron ensemble, even when there are no couplings among neurons. When the coupling is introduced, neurons in ensembles respond to an input spike with a partial synchronization. DMF theory is extended to a large cluster which can be divided into multiple sub-clusters according to their functions. A model calculation has shown that when the noise intensity is moderate, the spike propagation with a fairly precise timing is possible among noisy sub-clusters with feed-forward couplings, as in the synfire chain. Results calculated by our DMF theory are nicely compared to those obtained by direct simulations. A comparison of DMF theory with the conventional moment method is also discussed.Comment: 29 pages, 2 figures; augmented the text and added Appendice

CVD diamond coated silicon nitride self-mated systems : tribological behaviour under high loads

Friction and wear behaviour of self-mated chemical vapour deposited (CVD) diamond films coating silicon nitride ceramics (Si3N4) were investigated in ambient atmosphere. The tribological tests were conducted in a reciprocal motion ball-on-flat type tribometer under applied normal loads up to 80 N (~10 GPa). Several characterisation techniques - including scanning electron microscopy (SEM), atomic force microscopy (AFM) and micro-Raman studies - were used in order to assess the quality, stress state and wear resistance of the coatings. In addition, a novel method is presented to estimate the wear coefficient of the diamond coated flat specimens from AFM and optical microscopy (OM) observations of the wear tracks

Investigations of the Mars Upper Atmosphere with ExoMars Trace Gas Orbiter

The Martian mesosphere and thermosphere, the region above about 60 km, is not the primary target of the ExoMars 2016 mission but its Trace Gas Orbiter (TGO) can explore it and address many interesting issues, either in-situ during the aerobraking period or remotely during the regular mission. In the aerobraking phase TGO peeks into thermospheric densities and temperatures, in a broad range of latitudes and during a long continuous period. TGO carries two instruments designed for the detection of trace species, NOMAD and ACS, which will use the solar occultation technique. Their regular sounding at the terminator up to very high altitudes in many different molecular bands will represent the first time that an extensive and precise dataset of densities and hopefully temperatures are obtained at those altitudes and local times on Mars. But there are additional capabilities in TGO for studying the upper atmosphere of Mars, and we review them briefly. Our simulations suggest that airglow emissions from the UV to the IR might be observed outside the terminator. If eventually confirmed from orbit, they would supply new information about atmospheric dynamics and variability. However, their optimal exploitation requires a special spacecraft pointing, currently not considered in the regular operations but feasible in our opinion. We discuss the synergy between the TGO instruments, specially the wide spectral range achieved by combining them. We also encourage coordinated operations with other Mars-observing missions capable of supplying simultaneous measurements of its upper atmosphere

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements