From LIMS to OMPS-LP: Limb Ozone Observations for Future Reanalyses

High vertical resolution and accuracy of ozone data from satellite-borne limb sounders has made them an invaluable tool in scientific studies of the middle and upper atmosphere. However, it was not until recently that these measurements were successfully incorporated in atmospheric reanalyses: of the major multidecadal reanalyses only ECMWF's (European Centre for Medium-Range Weather Forecasts') ERA (ECMWF Re-Analysis)-Interim/ERA5 and NASA's MERRA-2 (Modern-Era Retrospective Analysis for Research and Applications-2) use limb ozone data. Validation and comparison studies have demonstrated that the addition of observations from the Microwave Limb Sounder (MLS) on EOS (Earth Observing System) Aura greatly improved the quality of ozone fields in MERRA-2 making these assimilated data sets useful for scientific research. In this presentation, we will show the results of test experiments assimilating retrieved ozone from the Limb Infrared Monitor of the Stratosphere (LIMS, 1978/1979) and Ozone Mapping Profiler Suite Limb Profiler (OMPS-LP, 2012 to present). Our approach builds on the established assimilation methodology used for MLS in MERRA-2 and, in the case of OMPS-LP, extends the excellent record of MLS ozone assimilation into the post-EOS era in Earth observations. We will show case studies, discuss comparisons of the new experiments with MERRA-2, strategies for bias correction and the potential for combined assimilation of multiple limb ozone data types in future reanalyses for studies of multidecadal stratospheric ozone changes including trends

<i>N,N</i>-bis-(dimethylfluorosilylmethyl)amides of <i>N</i>-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and <i>in silico</i> studies

(O→Si)-Chelate difluorides R3R2NCH(R1)C(O)N(CH2SiMe2F)2 (9a–c, R1R2 = (CH2)3, R3 = Ms (a), Ts (b); R1 = H, R2 = Me, R3 = Ms (c)), containing one penta- and one tetracoordinate silicon atoms were synthesized by silylmethylation of amides R3R2NCH(R1)C(O)NH2, subsequent hydrolysis of unstable intermediates R3R2NCH(R1)C(O)N(CH2SiMe2Cl)2 (7a–c) into 4-acyl-2,6-disilamorpholines R3R2NCH(R1)C(O)N(CH2SiMe2O)2 (8a–c) and the reaction of the latter compounds with BF3·Et2O. The structures of disilamorpholines 8a,c and difluoride 9a were confirmed by an X-ray diffraction study. According to the IR and NMR data, the O→Si coordination in solutions of these compounds was weaker than that in the solid state due to effective solvation of the Si–F bond. A permutational isomerisation involving an exchange of equatorial Me groups at the pentacoordinate Si atom in complexes 9a–c was detected, and its activational parameters were determined by 1H DNMR. In silico estimation of possible pharmacological effects and acute rat toxicity by PASS Online and GUSAR Online services showed a potential for their further pharmacological study

Solar Backscatter UV (SBUV) total ozone and profile algorithm

We describe the algorithm that has been applied to develop a 42 yr record of total ozone and ozone profiles from eight Solar Backscatter UV (SBUV) instruments launched on NASA and NOAA satellites since April 1970. The Version 8 (V8) algorithm was released more than a decade ago and has been in use since then at NOAA to produce their operational ozone products. The current algorithm (V8.6) is basically the same as V8, except for updates to instrument calibration, incorporation of new ozone absorption cross-sections, and new ozone and cloud height climatologies. Since the V8 algorithm has been optimized for deriving monthly zonal mean (MZM) anomalies for ozone assessment and model comparisons, our emphasis in this paper is primarily on characterizing the sources of errors that are relevant for such studies. When data are analyzed this way the effect of some errors, such as vertical smoothing of short-term variability, and noise due to clouds and aerosols diminish in importance, while the importance of others, such as errors due to vertical smoothing of the quasi-biennial oscillation (QBO) and other periodic and aperiodic variations, become more important. With V8.6 zonal mean data we now provide smoothing kernels that can be used to compare anomalies in SBUV profile and partial ozone columns with models. In this paper we show how to use these kernels to compare SBUV data with Microwave Limb Sounder (MLS) ozone profiles. These kernels are particularly useful for comparisons in the lower stratosphere where SBUV profiles have poor vertical resolution but partial column ozone values have high accuracy. We also provide our best estimate of the smoothing errors associated with SBUV MZM profiles. Since smoothing errors are the largest source of uncertainty in these profiles, they can be treated as error bars in deriving interannual variability and trends using SBUV data and for comparing with other measurements. In the V8 and V8.6 algorithms we derive total column ozone by integrating the SBUV profiles, rather than from a separate set of wavelengths, as was done in previous algorithm versions. This allows us to extend the total ozone retrieval to 88° solar zenith angle (SZA). Since the quality of total column data is affected by reduced sensitivity to ozone in the lower atmosphere by cloud and Rayleigh attenuation, which gets worse with increasing SZA, we provide our best estimate of these errors, as well as the kernels that can be used to test the sensitivity of the derived columns to long-term changes in ozone in the lower atmosphere

Long-Term Ozone Variability and Trends from Reanalyses

Stratospheric ozone has a profound impact on radiation and chemistry over various spatial and temporal scales. The evolution of stratospheric ozone over the 21st century, however, is not well understood, especially in the lower stratosphere. Highly vertically resolved ozone data from satellite-borne limb sounders have proved to be invaluable for studying ozone in the middle and upper stratosphere but it was not until recently that these measurements were successfully incorporated in atmospheric reanalyses. Validation and comparison studies have demonstrated that the addition of observations from the Microwave Limb Sounder (MLS) on EOS (Earth Observing System) Aura greatly improved the quality of ozone fields in MERRA-2 (Modern-Era Retrospective analysis for Research and Applications, Version 2) making these assimilated data sets more useful for scientific research. In this presentation we demonstrate that multidecadal lower-stratospheric ozone variability and trends can be derived from NASA's MERRA-2 reanalysis ozone. In particular, the reanalysis ozone bias-corrected using a chemistry model simulation as a transfer function agrees very well with recently reprocessed long ozonesonde records. Ozone trends in the lower stratosphere will be discussed in the context of recent findings (Ball et al., 2018) and interpreted in connection with long-term circulation changes in the lower stratosphere. Next, we show that the use of ozone data retrieved from the next generation OMPS (Ozone Mapping Profiler Suite) instruments, including the OMPS Limb Profiler, can successfully extend the reanalyses into the future allowing comprehensive monitoring of global ozone and interpretation of its evolution during the critical period of expected ozone recovery and climate change from increasing concentration of greenhouse gases

Merged SAGE II, Ozone_cci and OMPS ozone profile dataset and evaluation of ozone trends in the stratosphere

In this paper, we present a merged dataset of ozone profiles from several satellite instruments: SAGE II on ERBS, GOMOS, SCIAMACHY and MIPAS on Envisat, OSIRIS on Odin, ACE-FTS on SCISAT, and OMPS on Suomi-NPP. The merged dataset is created in the framework of the European Space Agency Climate Change Initiative (Ozone_cci) with the aim of analyzing stratospheric ozone trends. For the merged dataset, we used the latest versions of the original ozone datasets. The datasets from the individual instruments have been extensively validated and intercompared; only those datasets which are in good agreement, and do not exhibit significant drifts with respect to collocated ground-based observations and with respect to each other, are used for merging. The long-term SAGE–CCI–OMPS dataset is created by computation and merging of deseasonalized anomalies from individual instruments. The merged SAGE–CCI–OMPS dataset consists of deseasonalized anomalies of ozone in 10° latitude bands from 90° S to 90° N and from 10 to 50 km in steps of 1 km covering the period from October 1984 to July 2016. This newly created dataset is used for evaluating ozone trends in the stratosphere through multiple linear regression. Negative ozone trends in the upper stratosphere are observed before 1997 and positive trends are found after 1997. The upper stratospheric trends are statistically significant at midlatitudes and indicate ozone recovery, as expected from the decrease of stratospheric halogens that started in the middle of the 1990s and stratospheric cooling

Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis

BACKGROUND: Due to limited access to brain tissue, the precise mechanisms underlying neuro-axonal dysfunction in neurological disorders such as multiple sclerosis (MS) are largely unknown. In that context, profiling DNA methylation, which is a stable and cell type-specific regulatory epigenetic mark of genome activity, offers a unique opportunity to characterize the molecular mechanisms underpinning brain pathology in situ. We examined DNA methylation patterns of neuronal nuclei isolated from post-mortem brain tissue to infer processes that occur in neurons of MS patients. RESULTS: We isolated subcortical neuronal nuclei from post-mortem white matter tissue of MS patients and non-neurological controls using flow cytometry. We examined bulk DNA methylation changes (total n = 29) and further disentangled true DNA methylation (5mC) from neuron-specific DNA hydroxymethylation (5hmC) (n = 17), using Illumina Infinium 450K arrays. We performed neuronal sub-type deconvolution using glutamate and GABA methylation profiles to further reduce neuronal sample heterogeneity. In total, we identified 2811 and 1534 significant (genome-wide adjusted P value < 0.05) differentially methylated and hydroxymethylated positions between MS patients and controls. We found striking hypo-5mC and hyper-5hmC changes occurring mainly within gene bodies, which correlated with reduced transcriptional activity, assessed using published RNAseq data from bulk brain tissue of MS patients and controls. Pathway analyses of the two cohorts implicated dysregulation of genes involved in axonal guidance and synaptic plasticity, with meta-analysis confirming CREB signalling as the most highly enriched pathway underlying these processes. We functionally investigated DNA methylation changes of CREB signalling-related genes by immunohistofluoresence of phosphorylated CREB in neurons from brain sections of a subcohort of MS patients and controls (n = 15). Notably, DNA methylation changes associated with a reduction of CREB activity in white matter neurons of MS patients compared to controls. CONCLUSIONS: Our data demonstrate that investigating 5mC and 5hmC modifications separately allows the discovery of a substantial fraction of changes occurring in neurons, which can escape traditional bisulfite-based DNA methylation analysis. Collectively, our findings indicate that neurons of MS patients acquire sustained hypo-5mC and hyper-5hmC, which may impair CREB-mediated neuro-axonal integrity, in turn relating to clinical symptoms

What can we learn from geographical comparisons of childhood cancer survival?

With improvements in treatment for childhood cancer, comparisons of survival rates between countries have become important to inform future health policies and treatment strategies. Population-based cancer registry data are viewed as the gold standard for such comparisons, but even these have potential confounding factors. Here, we review the interpretation of recent geographical comparisons of childhood cancer survival from the viewpoint of the British Isles, a region with a 45-year record of national population-based cancer registration and a national childhood cancer clinical trials organisation in place for nearly 30 years. Using national data on referral patterns to tertiary paediatric oncology centres, we explore some of the reasons for lower survival rates in the past for some tumour groups and anticipate continued improvement in the next decade. Participation in international clinical trials coincided with rapid gains in survival for hepatoblastoma. This exemplifies the potential benefits of international collaborative clinical research, particularly for rare subgroups

Interaction between Thymidylate Synthase and Its Cognate mRNA in Zebrafish Embryos

Thymidylate synthase (TS), which catalyzes the de novo synthesis of dUMP, is an important target for cancer therapy. In this report, the effects of 5-fluorouracil (5-FU) and ZD1694 on the regulation of TS gene expression were evaluated in zebrafish embryos. Our results revealed that the expression of TS was increased by about six-fold when embryos were treated with 1.0 µM 5-FU and there was a greater than 10-fold increase in the TS protein level after treatment with 0.4 µM ZD1694. Northern blot analysis confirmed that expression of TS mRNA was identical in treated or untreated embryos. Gel shift and immunoprecipitation assays revealed that zebrafish TS was specifically bound with its cognate mRNA in vitro and in vivo. We identified a 20 nt RNA sequence, TS:N20, localized to the 5′-UTR of TS mRNA, which corresponded to nt 13–32; TS:N20 bound to the TS protein with an affinity similar to that of the full-length TS mRNA. The MFold program predicted that TS:N20 formed a stable stem-loop structure similar to that of the cis-acting element found in human TS mRNA. Variant RNAs with either a deletion or mutation in the core motif of TS:N20 were unable to bind to the TS protein. In vitro translation experiments, using the rabbit lysate system, confirmed that zebrafish TS mRNA translation was significantly repressed when an excess amount of TS protein was included in the system. Additionally, a TS stability experiment confirmed that treatment of zebrafish embryos with 5-FU could increase the TS stability significantly, and the half life of TS protein was about 2.7 times longer than in untreated embryos. Our study revealed a structural requirement for the interaction of TS RNA with TS protein. These findings also demonstrated that the increase in TS protein induced by 5-FU occurs at the post-transcriptional level and that increased stability and translation efficiency both contributed to the increase in TS protein levels induced by TS inhibitors

Childhood solid tumours in relation to population mixing around the time of birth

In a retrospective cohort study of 673 787 live births in the Northern Region of England, 1975 - 1994, we investigated whether a higher level of population mixing around birth was a risk factor for solid tumours, by diagnostic group (Hodgkin's disease, brain and spinal tumours, neuroblastoma, other solid tumours), diagnosed during 1975-2001 under age 15 years. Logistic regression was used to relate risk to population mixing, based on (i) all movers and (ii) incomers from outside the region. Both ward and county district level analyses were performed. There was a decreased risk of brain and spinal tumours with increasing population mixing based on incomers from outside the region (OR for trend across three categories = 0.79, 95% CI: 0.66-0.95, P = 0.01 in the ward level analysis). Although this may be because of chance, it is consistent with a role of exposure to infection and immunological response in the aetiology of these tumours. For other tumour groups, there was no consistent evidence of an association between risk and population mixing