443 research outputs found

    Correlating in situ RHEED and XRD to study growth dynamics of polytypism in nanowires

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    Design of novel nanowire (NW) based semiconductor devices requires deep understanding and technological control of NW growth. Therefore, quantitative feedback over the structure evolution of the NW ensemble during growth is highly desirable. We analyse and compare the methodical potential of reflection high-energy electron diffraction (RHEED) and X-ray diffraction reciprocal space imaging (XRD) for in situ growth characterization during molecular-beam epitaxy (MBE). Simultaneously recorded in situ RHEED and in situ XRD intensities show strongly differing temporal behaviour and provide evidence of the highly complementary information value of both diffraction techniques. Exploiting the complementarity by a correlative data analysis presently offers the most comprehensive experimental access to the growth dynamics of statistical NW ensembles under standard MBE growth conditions. In particular, the combination of RHEED and XRD allows for translating quantitatively the time-resolved information into a height-resolved information on the crystalline structure without a priori assumptions on the growth model. Furthermore, we demonstrate, how careful analysis of in situ RHEED if supported by ex situ XRD and scanning electron microscopy (SEM), all usually available at conventional MBE laboratories, can also provide highly quantitative feedback on polytypism during growth allowing validation of current vapour–liquid–solid (VLS) growth models

    Robust Association Tests Under Different Genetic Models, Allowing for Binary or Quantitative Traits and Covariates

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    The association of genetic variants with outcomes is usually assessed under an additive model, for example by the trend test. However, misspecification of the genetic model will lead to a reduction in power. More robust tests for association might therefore be preferred. A useful approach is to consider the maximum of the three test statistics under additive, dominant and recessive models (MAX3). The p-value however has to be adjusted to maintain the type I error rate. Previous studies and software on robust association tests have focused on binary traits without covariates. In this study we developed an analytic approach to robust association tests using MAX3, allowing for quantitative or binary traits as well as covariates. The p-values from our theoretical calculations match very well with those from a bootstrap resampling procedure. The methodology is implemented in the R package RobustSNP which is able to handle both small-scale studies and GWAS. The package and documentation are available at http://sites.google.com/site/honcheongso/software/robustsnp

    Solving a Coupled Set of Truncated QCD Dyson-Schwinger Equations

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    Truncated Dyson-Schwinger equations represent finite subsets of the equations of motion for Green's functions. Solutions to these non-linear integral equations can account for non-perturbative correlations. A closed set of coupled Dyson-Schwinger equations for the propagators of gluons and ghosts in Landau gauge QCD is obtained by neglecting all contributions from irreducible 4-point correlations and by implementing the Slavnov-Taylor identities for the 3-point vertex functions. We solve this coupled set in an one-dimensional approximation which allows for an analytic infrared expansion necessary to obtain numerically stable results. This technique, which was also used in our previous solution of the gluon Dyson-Schwinger equation in the Mandelstam approximation, is here extended to solve the coupled set of integral equations for the propagators of gluons and ghosts simultaneously. In particular, the gluon propagator is shown to vanish for small spacelike momenta whereas the previoulsy neglected ghost propagator is found to be enhanced in the infrared. The running coupling of the non-perturbative subtraction scheme approaches an infrared stable fixed point at a critical value of the coupling, alpha_c approximately 9.5.Comment: 23 pages, 6 figures, LaTeX2

    Anatomy of terminal moraine segments and implied lake stability on Ngozumpa Glacier, Nepal, from electrical resistivity tomography (ERT)

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    This research was supported financially by the European Commission FP7-MC-IEF (PIEF-GA-2012-330805), the University Centre in Svalbard (UNIS), National Geographic Society GRANT #W135-10.Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common and pose significant outburst flood hazards if the dam is breached. While moraine subsurface structure and internal processes are likely to influence dam stability, only few sites have so far been investigated. We conducted electrical resistivity tomography (ERT) surveys at two sites on the terminal moraine complex of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability. The resistivity signature of glacier ice at the site (100-15 kΩ m) is more consistent with values measured from cold glacier ice and while this may be feasible, uncertainties in the data inversion introduce ambiguity to this thermal interpretation. However, the ERT data does provide a significant improvement to our knowledge of the subsurface characteristics at these sites, clearly showing the presence (or absence) of glacier ice. Our interpretation is that of a highly complex latero-terminal moraine, resulting from interaction between previous glacier advance, recession and outburst flooding. If the base-level Spillway Lake continues to expand to a fully formed moraine-dammed glacial lake, the degradation of the ice core could have implications for glacial lake outburst risk.Publisher PDFPeer reviewe

    LevothyroxÂź new and old formulations: are they switchable for millions of patients?

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    International audienceIn France, more than 2.5 million patients are currently treated with levothyroxine, mainly as the marketed product Levothyrox Âź. In March 2017, at the request of French authorities, a new formulation of Levothyrox Âź was licensed, with the objective of avoiding stability deficiencies of the old formulation. Before launching this new formulation, an average bioequivalence trial, based on European Union recommended guidelines, was performed. The implicit rationale was the assumption that the two products, being bioequivalent, would also be switchable, allowing substitution of the new for the old formulation, thus avoiding the need for individual calibration of the dosage regimen of thyroxine, using the thyroid-stimulating hormone level as the endpoint, as required for a new patient on initiating treatment. Despite the fact that both formulations were shown to be bioequivalent, adverse drug reactions were reported in several thousands of patients after taking the new formulation. In this opinion paper, we report that more than 50% of healthy volunteers enrolled in a successful regulatory average bioequivalence trial were actually outside the a priori bioequivalence range. Therefore, we question the ability of an average bioequivalence trial to guarantee the switchability within patients of the new and old levothyroxine formulations. We further propose an analysis of this problem using the conceptual framework of individual bioequivalence. This involves investigating the bioavailability of the two formulations within a subject, by comparing not only the population means (as established by average bioequivalence) but also by assessing two variance terms, namely the within-subject variance and the variance estimating subject-by-formulation interaction. A higher within individual variability for the new formulation would lead to reconsideration of the appropriateness of the new formulation. Alternatively, a possible subject-by-formulation interaction would allow a judgement on the ability, or not, of doctors to manage patients effectively during transition from the old to the new formulation

    αB Crystallin Is Apically Secreted within Exosomes by Polarized Human Retinal Pigment Epithelium and Provides Neuroprotection to Adjacent Cells

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    αB Crystallin is a chaperone protein with anti-apoptotic and anti-inflammatory functions and has been identified as a biomarker in age-related macular degeneration. The purpose of this study was to determine whether αB crystallin is secreted from retinal pigment epithelial (RPE) cells, the mechanism of this secretory pathway and to determine whether extracellular αB crystallin can be taken up by adjacent retinal cells and provide protection from oxidant stress. We used human RPE cells to establish that αB crystallin is secreted by a non-classical pathway that involves exosomes. Evidence for the release of exosomes by RPE and localization of αB crystallin within the exosomes was achieved by immunoblot, immunofluorescence, and electron microscopic analyses. Inhibition of lipid rafts or exosomes significantly reduced αB crystallin secretion, while inhibitors of classic secretory pathways had no effect. In highly polarized RPE monolayers, αB crystallin was selectively secreted towards the apical, photoreceptor-facing side. In support, confocal microscopy established that αB crystallin was localized predominantly in the apical compartment of RPE monolayers, where it co-localized in part with exosomal marker CD63. Severe oxidative stress resulted in barrier breakdown and release of αB crystallin to the basolateral side. In normal mouse retinal sections, αB crystallin was identified in the interphotoreceptor matrix. An increased uptake of exogenous αB crystallin and protection from apoptosis by inhibition of caspase 3 and PARP activation were observed in stressed RPE cultures. αB Crystallin was taken up by photoreceptors in mouse retinal explants exposed to oxidative stress. These results demonstrate an important role for αB crystallin in maintaining and facilitating a neuroprotective outer retinal environment and may also explain the accumulation of αB crystallin in extracellular sub-RPE deposits in the stressed microenvironment in age-related macular degeneration. Thus evidence from our studies supports a neuroprotective role for αB crystallin in ocular diseases

    Global Carbon Budget 2015

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    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (E-FF) are based on energy statistics and cement production data, while emissions from land-use change (E-LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (G(ATM)) is computed from the annual changes in concentration. The mean ocean CO2 sink (S-OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S-OCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (S-LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen-carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as +/- 1 sigma, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (20052014), E-FF was 9.0 +/- 0.5 GtC yr(-1) E-LUC was 0.9 +/- 0.5 GtC yr(-1), GATM was 4.4 +/- 0.1 GtC yr(-1), S-OCEAN was 2.6 +/- 0.5 GtC yr(-1), and S LAND was 3.0 +/- 0.8 GtC yr(-1). For the year 2014 alone, E FF grew to 9.8 +/- 0.5 GtC yr(-1), 0.6% above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2% yr(-1) that took place during 2005-2014. Also, for 2014, E-LUC was 1.1 +/- 0.5 GtC yr(-1), G(ATM) was 3.9 +/- 0.2 GtC yr(-1), S-OCEAN was 2.9 +/- 0.5 GtC yr(-1), and S-LAND was 4.1 +/- 0.9 GtC yr(-1). G(ATM) was lower in 2014 compared to the past decade (2005-2014), reflecting a larger S-LAND for that year. The global atmospheric CO2 concentration reached 397.15 +/- 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in E-FF will be near or slightly below zero, with a projection of 0.6 [ range of 1.6 to C 0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of E-FF and assumed constant E LUC for 2015, cumulative emissions of CO2 will reach about 555 +/- 55 GtC (2035 +/- 205 GtCO(2)) for 1870-2015, about 75% from E FF and 25% from E LUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quere et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi: 10.3334/CDIAC/GCP_2015)

    Treatment of cerebral cavernous malformations:a systematic review and meta-regression analysis

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    Item does not contain fulltextOBJECTIVE: The reported effects of treating cerebral cavernous malformations (CCMs) by neurosurgical excision or stereotactic radiosurgery are imprecise and vary between studies. METHODS: We searched Ovid Medline, EMBASE and The Cochrane Library for peer-reviewed publications of cohort studies describing outcomes of treating 20 or more patients with CCM with at least 80% completeness of follow-up. Two reviewers extracted data to quantify the incidence of a composite outcome (death, non-fatal intracranial haemorrhage, or new/worse persistent focal neurological deficit) after CCM treatment. We explored associations between summary measures of study characteristics and outcome using Poisson meta-regression analyses. RESULTS: We included 63 cohorts, involving 3424 patients. The incidence of the composite outcome was 6.6 (95% CI 5.7 to 7.5) per 100 person-years after neurosurgical excision (median follow-up 3.3 years) and 5.4 (95% CI 4.5 to 6.4) after stereotactic radiosurgery (median follow-up 4.1 years). After neurosurgical excision the incidence of the composite outcome increased with every per cent point increase in patients with brainstem CCM (rate ratio (RR) 1.03, 95% CI 1.01 to 1.05), and decreased with each more recent study midyear (RR 0.91, 95% CI 0.85 to 0.98) and each per cent point increase in patients presenting with haemorrhage (RR 0.98, 95% CI 0.96 to 1.00). We did not find significant associations in studies of stereotactic radiosurgery. CONCLUSIONS: The reported risks of CCM treatment (and the lower risks of neurosurgical excision over time, from recently bled CCMs, and for CCMs outside the brainstem) compare favourably with the risks of recurrent haemorrhage from CCM. Long-term effects, especially important for stereotactic radiosurgery, are unknown
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