The quality of the retrieved temperature-versus-pressure (or T(p)) profiles is described for the middle atmosphere for the publicly available Sounding of the Atmosphere using Broadband Emission ...Radiometry (SABER) Version 1.07 (V1.07) data set. The primary sources of systematic error for the SABER results below about 70 km are (1) errors in the measured radiances, (2) biases in the forward model, and (3) uncertainties in the corrections for ozone and in the determination of the reference pressure for the retrieved profiles. Comparisons with other correlative data sets indicate that SABER T(p) is too high by 1-3 K in the lower stratosphere but then too low by 1 K near the stratopause and by 2 K in the middle mesosphere. There is little difference between the local thermodynamic equilibrium (LTE) algorithm results below about 70 km from V1.07 and V1.06, but there are substantial improvements/differences for the non-LTE results of V1.07 for the upper mesosphere and lower thermosphere (UMLT) region. In particular, the V1.07 algorithm uses monthly, diurnally averaged CO2 profiles versus latitude from the Whole Atmosphere Community Climate Model. This change has improved the consistency of the character of the tides in its kinetic temperature (T(sub k)). The T(sub k) profiles agree with UMLT values obtained from ground-based measurements of column-averaged OH and O2 emissions and of the Na lidar returns, at least within their mutual uncertainties. SABER T(sub k) values obtained near the mesopause with its daytime algorithm also agree well with the falling sphere climatology at high northern latitudes in summer. It is concluded that the SABER data set can be the basis for improved, diurnal-to-interannual-scale temperatures for the middle atmosphere and especially for its UMLT region.
U.K. HiGEM Shaffrey, L. C.; Stevens, I.; Norton, W. A. ...
Journal of climate,
04/2009, Letnik:
22, Številka:
8
Journal Article
Recenzirano
Odprti dostop
This article describes the development and evaluation of the U.K.’s new High-Resolution Global Environmental Model (HiGEM), which is based on the latest climate configuration of the Met Office ...Unified Model, known as the Hadley Centre Global Environmental Model, version 1 (HadGEM1). In HiGEM, the horizontal resolution has been increased to 0.83° latitude × 1.25° longitude for the atmosphere, and 1/3° × 1/3° globally for the ocean. Multidecadal integrations of HiGEM, and the lower-resolution HadGEM, are used to explore the impact of resolution on the fidelity of climate simulations.
Generally, SST errors are reduced in HiGEM. Cold SST errors associated with the path of the North Atlantic drift improve, and warm SST errors are reduced in upwelling stratocumulus regions where the simulation of low-level cloud is better at higher resolution. The ocean model in HiGEM allows ocean eddies to be partially resolved, which dramatically improves the representation of sea surface height variability. In the Southern Ocean, most of the heat transports in HiGEM is achieved by resolved eddy motions, which replaces the parameterized eddy heat transport in the lower-resolution model. HiGEM is also able to more realistically simulate small-scale features in the wind stress curl around islands and oceanic SST fronts, which may have implications for oceanic upwelling and ocean biology.
Higher resolution in both the atmosphere and the ocean allows coupling to occur on small spatial scales. In particular, the small-scale interaction recently seen in satellite imagery between the atmosphere and tropical instability waves in the tropical Pacific Ocean is realistically captured in HiGEM. Tropical instability waves play a role in improving the simulation of the mean state of the tropical Pacific, which has important implications for climate variability. In particular, all aspects of the simulation of ENSO (spatial patterns, the time scales at which ENSO occurs, and global teleconnections) are much improved in HiGEM.
Introduction
Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain ...cases genotype–phenotype correlations are important for predicting the clinical course of the disease and to allow tailor‐made follow‐up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next‐generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost.
Aim
The aim of this study was to design and to analyse the applicability of a 23‐gene NGS panel in the molecular diagnosis of patients with IBCDs.
Methods
A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology.
Results
In all patients, our NGS approach detected causative mutations. Twenty‐one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant.
Conclusion
Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs.
Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is ...generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Anthropogenic increases in atmospheric greenhouse gas
concentrations are the main driver of current and future climate change. The
integrated assessment community has quantified anthropogenic ...emissions for
the shared socio-economic pathway (SSP) scenarios, each of which represents
a different future socio-economic projection and political environment.
Here, we provide the greenhouse gas concentrations for these SSP scenarios
– using the reduced-complexity climate–carbon-cycle model MAGICC7.0. We
extend historical, observationally based concentration data with SSP
concentration projections from 2015 to 2500 for 43 greenhouse gases with monthly and latitudinal resolution. CO2 concentrations by 2100 range
from 393 to 1135 ppm for the lowest (SSP1-1.9) and highest (SSP5-8.5)
emission scenarios, respectively. We also provide the concentration
extensions beyond 2100 based on assumptions regarding the trajectories of fossil
fuels and land use change emissions, net negative emissions, and the
fraction of non-CO2 emissions. By 2150, CO2 concentrations in the
lowest emission scenario are approximately 350 ppm and approximately plateau
at that level until 2500, whereas the highest fossil-fuel-driven scenario
projects CO2 concentrations of 1737 ppm and reaches concentrations
beyond 2000 ppm by 2250. We estimate that the share of CO2 in the total
radiative forcing contribution of all considered 43 long-lived greenhouse
gases increases from 66 % for the present day to roughly 68 % to 85 % by
the time of maximum forcing in the 21st century. For this estimation,
we updated simple radiative forcing parameterizations that reflect the Oslo
Line-By-Line model results. In comparison to the representative concentration pathways (RCPs), the five main SSPs
(SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) are more evenly spaced
and extend to lower 2100 radiative forcing and temperatures. Performing two
pairs of six-member historical ensembles with CESM1.2.2, we estimate the
effect on surface air temperatures of applying latitudinally and seasonally
resolved GHG concentrations. We find that the ensemble differences in the
March–April–May (MAM) season provide a regional warming in higher northern
latitudes of up to 0.4 K over the historical period, latitudinally averaged
of about 0.1 K, which we estimate to be comparable to the upper bound
(∼5 % level) of natural variability. In comparison to the
comparatively straight line of the last 2000 years, the greenhouse gas
concentrations since the onset of the industrial period and this studies'
projections over the next 100 to 500 years unequivocally depict a
“hockey-stick” upwards shape. The SSP concentration time series derived in
this study provide a harmonized set of input assumptions for long-term
climate science analysis; they also provide an indication of the wide set of
futures that societal developments and policy implementations can lead to –
ranging from multiple degrees of future warming on the one side to
approximately 1.5 ∘C warming on the other.
The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited ...statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results ...from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
We describe Global Atmosphere 4.0 (GA4.0) and Global Land 4.0 (GL4.0): configurations of the Met Office Unified Model and JULES (Joint UK Land Environment Simulator) community land surface model ...developed for use in global and regional climate research and weather prediction activities. GA4.0 and GL4.0 are based on the previous GA3.0 and GL3.0 configurations, with the inclusion of developments made by the Met Office and its collaborators during its annual development cycle. This paper provides a comprehensive technical and scientific description of GA4.0 and GL4.0 as well as details of how these differ from their predecessors. We also present the results of some initial evaluations of their performance. Overall, performance is comparable with that of GA3.0/GL3.0; the updated configurations include improvements to the science of several parametrisation schemes, however, and will form a baseline for further ongoing development.
Highlights • Faecalibacterium prausnitzii is an ubiquitary bacterium of intestinal microbiota of all animals. • F. prausnitzii is a dominant member of human intestinal microbiota of healthy adults. • ...F. prausnitzii is a sensor of health especially for active Crohn's disease patients. • Beneficial mechanisms and roles of F. prausnitzii in microbiota are still unclear. • F. prausnitzii is a potential novel probiotic bacterium for human diseases as IBD and IBS.
The EU-supported EuroFlow Consortium aimed at innovation and standardization of immunophenotyping for diagnosis and classification of hematological malignancies by introducing 8-color flow cytometry ...with fully standardized laboratory procedures and antibody panels in order to achieve maximally comparable results among different laboratories. This required the selection of optimal combinations of compatible fluorochromes and the design and evaluation of adequate standard operating procedures (SOPs) for instrument setup, fluorescence compensation and sample preparation. Additionally, we developed software tools for the evaluation of individual antibody reagents and antibody panels. Each section describes what has been evaluated experimentally versus adopted based on existing data and experience. Multicentric evaluation demonstrated high levels of reproducibility based on strict implementation of the EuroFlow SOPs and antibody panels. Overall, the 6 years of extensive collaborative experiments and the analysis of hundreds of cell samples of patients and healthy controls in the EuroFlow centers have provided for the first time laboratory protocols and software tools for fully standardized 8-color flow cytometric immunophenotyping of normal and malignant leukocytes in bone marrow and blood; this has yielded highly comparable data sets, which can be integrated in a single database.
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