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We evaluate total‐column ozone trends using a piecewise linear regression approach and maximizing usage of five gridded total‐column ozone data sets. The new approach yields more consistent estimates of observed ozone loss during 1979–2000, when halocarbon concentrations were increasing, and consequently, using CMIP6 simulations, an increased effective radiative forcing estimate of ozone‐depleting substances with a substantially reduced uncertainty range versus an earlier evaluation. At more than 84% confidence, it is now larger than zero and compares more favorably with three previous evaluations. We furthermore find significant positive post‐1997 global‐ and Southern‐Hemisphere‐mean trends, respectively, in these five data sets. For the extrapolar region (60°S–60°N) and for the Northern Hemisphere, the assessment whether there is a positive trend is inconclusive and depends on which observational data set is included in the calculation. Plain Language Summary: Changes in overhead ozone amounts reflect the impact of the Montreal Protocol, designed to protect the ozone layer, and several other influences. Here, we assess five different ozone data sets using satellite and ground‐based observations as well as fields generated by present‐generation climate models. For the period 1979–2000, during which stratospheric ozone depletion got established, we find good agreement for the whole globe and for selected subregions across the observational data sets. For 1997–2020, in the global and Southern Hemisphere means, we find significant, positive ozone trends. For a region excluding both poles and for the Northern Hemisphere, the uncertainty ranges still include zero. Using observational and modeled ozone trends for 1979–2000, we recalculate the impact of ozone‐depleting substances, accounting for ozone depletion, on the Earth' radiation balance. We find a slightly larger net impact than a previous evaluation, which within the uncertainty bounds is much more likely to be positive and is more consistent with three other literature references. Key Points: We evaluate total‐column ozone trends for 1979–2000 and 1997–2020For 1997–2020, we find significant global‐ and Southern‐Hemisphere‐mean positive trendsThe effective radiative forcing of ozone‐depleting substances is now more consistent with three previous evaluations [ABSTRACT FROM AUTHOR]

We assess the effective radiative forcing due to ozone‐depleting substances using models participating in the Aerosols and Chemistry and Radiative Forcing Model Intercomparison Projects (AerChemMIP, RFMIP). A large intermodel spread in this globally averaged quantity necessitates an "emergent constraint" approach whereby we link the radiative forcing to ozone declines measured and simulated during 1979–2000, excluding two volcanically perturbed periods. During this period, ozone‐depleting substances were increasing, and several merged satellite‐based climatologies document the ensuing decline of total‐column ozone. Using these analyses, we find an effective radiative forcing of −0.05 to 0.13 W m−2. Our best estimate (0.04 W m−2) is on the edge of the "likely" range given by the Fifth Assessment Report of IPCC of 0.03 to 0.33 W m−2 but is in better agreement with two other literature results. Plain Language Summary: Chloroflourocarbons and other compounds involved in ozone depletion are also powerful greenhouse gases, but their contribution to global warming is reduced due to the cooling effect of the ozone loss which they induce. Models informing an upcoming climate report disagree on the ozone loss and thus on the climate influence of these gases. Here we use observed ozone loss to reduce the resultant uncertainty in their overall climate influence and infer a smaller warming influence of these substances than was considered likely in a 2013 climate report. The result implies a smaller benefit to climate due to their phase‐out, mandated under the Montreal Protocol, than would have been the case under previous understanding. Key Points: Effective radiative forcing of ozone‐depleting substances, as discerned from CMIP6 simulations, spans a large rangeUsing an emergent constraint approach, our new estimate is consistent with observational climatologies of total‐column ozoneThis range implies a smaller forcing than the estimate provided by the Fifth Assessment Report of the Intergovernmental Panel on Climate Change [ABSTRACT FROM AUTHOR]

In this work we analyse the impact of including a regional, high-resolution ocean model on simulated atmospheric climate in a coupled earth system model. The resolution of the regional, nested ocean model is approximately 0.2° compared to the ~1° resolution of the global ocean model within which it is embedded and this work complements previously published work on ocean circulation and marine heatwaves using this setup, referred to as the New Zealand Earth System Model, NZESM. After a brief discussion of the wider model setup, the persistent Southern Ocean warm bias in climate models and the validation data sets used, we show the effects of the altered ocean physics on air temperature, precipitation and evaporation, latent and sensible surface heat balances, westerly winds, the storm track and the effect on total cloud amount. Overall we find that the NZESM provides a better representation of regional atmospheric climate compared to its parent model - UKESM1 - although this improvement is not universal. For example, although the NZESM shows better agreement in surface air temperature within the nested ocean region, there is also some deterioration in the agreement at higher southern latitudes where the seasonal sea ice edge coincides with a transition from negative to positive correlation between air temperature and cloud amount. The lack of additional model tuning in the NZESM after the nested ocean model's inclusion largely accounts for the presence of these improvement-deterioration pairs with respect to observations. The reader is encouraged to read the paper of Behrens et al. (Behrens et al, 2020) before this one since it provides much additional information which will aid understanding. This study aims to provide a high-level reference ontology for how changing one aspect of the ocean physics in a coupled model can impact simulated atmospheric climate. [ABSTRACT FROM AUTHOR]

We present an overview of state-of-the-art chemistry-climate and chemistry transport models that are used within phase 1 of the Chemistry-Climate Model Initiative (CCMI-1). The CCMI aims to conduct a detailed evaluation of participating models using process-oriented diagnostics derived from observations in order to gain confidence in the models' projections of the stratospheric ozone layer, tropospheric composition, air quality, where applicable global climate change, and the interactions between them. Interpretation of these diagnostics requires detailed knowledge of the radiative, chemical, dynamical, and physical processes incorporated in the models. Also an understanding of the degree to which CCMI-1 recommendations for simulations have been followed is necessary to understand model responses to anthropogenic and natural forcing and also to explain intermodel differences. This becomes even more important given the ongoing development and the ever-growing complexity of these models. This paper also provides an overview of the available CCMI-1 simulations with the aim of informing CCMI data users. [ABSTRACT FROM AUTHOR]

We present an overview of state-of-the-art chemistry-climate and -transport models that are used within the Chemistry-Climate Model Initiative (CCMI). CCMI aims to conduct a detailed evaluation of participating models using process-oriented diagnostics derived from observations in order to gain confidence in the models' projections of the stratospheric ozone layer, air quality, where applicable global climate change, and the interactions between them. Interpretation of these diagnostics requires detailed knowledge of the radiative, chemical, dynamical, and physical processes incorporated in the models. Also an understanding of the degree to which CCMI recommendations for simulations have been followed is necessary to understand model response to anthropogenic and natural forcing and also to explain inter-model differences. This becomes even more important given the ongoing development and the ever-growing complexity of these models. This paper also provides an overview of the available CCMI simulations with the aim to inform CCMI data users. [ABSTRACT FROM AUTHOR]

Local excess of nitric oxide (NO) has been implicated in β-cell damage, thus, a possible approach to the treatment of autoimmune IDDM is the selective inhibition of inducible nitric oxide synthase (iNOS). A series of variously substituted hexahydropyridazine-1-carbothioamides, -carbothioimidic acid esters and -carboximidamides was synthesized and dose-dependently evaluated as potential inhibitors of iNOS. The screening of the title compounds was performed with insulin-producing RIN-5AH cells and a combination of IL1-1β and IFN-γ as inducers of cellular NO production. The structure–activity analysis revealed that the variation of substituents in the position 1 of the hexahydropyridazine strongly influences the inhibitory activity to iNOS as well as being critical for RIN cell survival. Among the compounds tested, the hexahydropyridazine-1-carbothioamides showed particularly significant inhibitory effects. However, for an efficient iNOS inhibition substitution at the nitrogen of the 1-carbothioamide group is important. Thus, the introduction of aliphatic chains such as propyl or butyl and of cyclic moieties such as cyclohexyl, 3-methoxyphenyl, and 4-methoxyphenyl (IC50: 0.5–2.1 mM), respectively, provided compounds with similar inhibitory activity to aminoguanidine (IC50: 0.3 mM), a common standard substance used for the selective inhibition of iNOS. However, the 1-carboximidamides, which represent more structurally related semicyclic derivatives of aminoguanidine, caused only incomplete iNOS inhibition. The hexahydropyridazine-1-carbothioimidic acid esters caused dose- and substituent-dependent damage of RIN-5AH cells. The toxicity of the synthesized compounds increased markedly if aliphatic substituents at the exocyclic N atom(s) were replaced by variously substituted aromatic rings. [Copyright &y& Elsevier]

Dynamical downscaling provides physics-based high-resolution climate change projections across regional and local scales. This is particularly important for island nations characterized by complex terrain, where the coarse resolution of global climate model (GCM) output often prohibits direct use. One of the main motivations for dynamical downscaling is to reduce biases relative to the host GCM at the local scale, which can be quantified through assessing 'added value'. However, added value from downscaling is not guaranteed; quantifying this can help users make informed decisions about how best to use available climate projection data. Here we describe the experiment design of the updated national climate projections for New Zealand based on dynamical downscaling. The global non-hydrostatic Conformal Cubic Atmospheric Model (CCAM) is primarily used for downscaling, with a global stretched grid targeting high resolution over New Zealand (12-km) and the wider South Pacific region (12–35-km). Focusing on the historical simulations, we assess added value for a range of metrics, climatological fields, extreme indices, and tropical cyclones. The main strengths of the downscaling include generally large improvements relative to the host GCM for temperature and orographic precipitation. Inter-annual variability in temperature is well captured across New Zealand, and several temperature and precipitation-based extreme indices show large improvements. The representation of tropical cyclones reaching at least category 2 intensity is generally improved relative to the large consistent under-representation in the host GCMs. The remaining biases are explored and discussed forming the basis for ongoing bias-correction work. [ABSTRACT FROM AUTHOR]

Automatic lidars and ceilometers (ALCs) provide valuable information on cloud and aerosols but have not been systematically used in the evaluation of general circulation models (GCMs) and numerical weather prediction (NWP) models. Obstacles associated with the diversity of instruments, a lack of standardisation of data products and open processing tools mean that the value of large ALC networks worldwide is not being realised. We discuss a tool, called the Automatic Lidar and Ceilometer Framework (ALCF), that overcomes these problems and also includes a ground-based lidar simulator, which calculates the radiative transfer of laser radiation and allows one-to-one comparison with models. Our ground-based lidar simulator is based on the Cloud Feedback Model Intercomparison Project (CFMIP) Observation Simulator Package (COSP), which has been extensively used for spaceborne lidar intercomparisons. The ALCF implements all steps needed to transform and calibrate raw ALC data and create simulated attenuated volume backscattering coefficient profiles for one-to-one comparison and complete statistical analysis of clouds. The framework supports multiple common commercial ALCs (Vaisala CL31, CL51, Lufft CHM 15k and Droplet Measurement Technologies MiniMPL), reanalyses (JRA-55, ERA5 and MERRA-2) and models (the Unified Model and AMPS – the Antarctic Mesoscale Prediction System). To demonstrate its capabilities, we present case studies evaluating cloud in the supported reanalyses and models using CL31, CL51, CHM 15k and MiniMPL observations at three sites in New Zealand. We show that the reanalyses and models generally underestimate cloud fraction. If sufficiently high-temporal-resolution model output is available (better than 6-hourly), a direct comparison of individual clouds is also possible. We demonstrate that the ALCF can be used as a generic evaluation tool to examine cloud occurrence and cloud properties in reanalyses, NWP models, and GCMs, potentially utilising the large amounts of ALC data already available. This tool is likely to be particularly useful for the analysis and improvement of low-level cloud simulations which are not well monitored from space. This has previously been identified as a critical deficiency in contemporary models, limiting the accuracy of weather forecasts and future climate projections. While the current focus of the framework is on clouds, support for aerosol in the lidar simulator is planned in the future. [ABSTRACT FROM AUTHOR]

This paper describes the development of New Zealand's Earth System Model (NZESM) and evaluates its performance against its parent model (United Kingdom Earth System Model, UKESM) and observations. The main difference between the two earth system models is an embedded high‐resolution (1/5°) nested region over the oceans around New Zealand in the NZESM. Due to this finer ocean model mesh, currents such as the East Australian Current, East Australian Current Extension, Tasman Front, and Tasman Leakage, and their volume and heat transports are better simulated in the NZESM. The improved oceanic transports have led to a reduction in upper ocean temperature and salinity biases over the nested region. In addition, net transports through the Tasman Sea of volume, heat and salt in the NZESM agree better with previously reported estimates. A consequence of the increased cross‐Tasman Sea transports in the NZESM is increased temperatures and salinity west of Australia and in the Southern Ocean reducing the meridional sea surface temperature gradient between the subtropics and sub‐Antarctic. This also leads to a weakening of the westerly winds between 60°S and 45°S over large parts of the Southern Ocean, which reduces the northward Ekman transport, reduces the formation of Antarctic Intermediate Water, and allows for a southward expansion of the Super‐Gyre in all ocean basins. Connecting an improved oceanic circulation around New Zealand to a basin‐wide Super‐Gyre response is an important step forward in our current understanding of how local scales can influence global scales in a fully coupled earth system model. Plain Language Summary: We describe the model development of the New Zealand Earth System Model and assess its performance against the model on which it is based (United Kingdom Earth System Model) and observations. The New Zealand Earth System Model is a fully coupled earth system model, which aims to model all relevant bio‐physical processes in and between the atmosphere, land, ocean, and sea‐ice. The main difference between both models is that the oceans around New Zealand in the New Zealand Earth System Model are more precisely modeled, due to a refined ocean model mesh in this region. That results in a more accurate oceanic circulation around New Zealand in the New Zealand Earth System Model compared to the United Kingdom Earth System Model and reduced model biases of temperature and salinity. These oceanic changes have implications beyond the oceans around New Zealand, causing a warming in the Southern Ocean and a related weakening of the westerly winds over the Southern Ocean. This weakening of the winds allows subtropical waters to reach further south into the Southern Ocean. It is notable that regional changes in the ocean circulation can have implications on the global scale. Key Points: NZESM is a nested fully coupled ESM based on UKESM with a high‐resolution ocean grid of 1/5° around New ZealandThe oceanic circulation is improved in NZESM over the nested domain and model biases of temperature and salinity are reducedThe Super‐Gyre intensifies and expands southward due to wind changes triggered by changes in the large‐scale heat transport [ABSTRACT FROM AUTHOR]

Automatic lidars and ceilometers provide valuable information on cloud and aerosols, but have not been used systematically in the evaluation of GCMs and NWP models. Obstacles associated with the diversity of instruments, a lack of standardisation of data products and open processing tools mean that the value of the large ALC networks worldwide is not being realised. We discuss a tool, called the Automatic Lidar and Ceilometer Framework (ALCF), that overcomes these problems and also includes a ground-based lidar simulator, which calculates the radiative transfer of laser radiation, and allows one-to-one comparison with models. Our ground-based lidar simulator is based on the Cloud Feedback Model Intercomparison Project (CFMIP) Observation Simulator Package (COSP) which has been used extensively for spaceborne lidar intercomparisons. The ALCF implements all steps needed to transform and calibrate raw ALC data and create simulated backscatter profiles for one-to-one comparison and complete statistical analysis of cloud. The framework supports multiple common commercial ALCs (Vaisala CL31, CL51, Lufft CHM 15k and Sigma Space MiniMPL), reanalyses (JRA-55, ERA5 and MERRA-2) and models (AMPS and the Unified Model). To demonstrate its capabilities, we present case studies evaluating cloud in the supported reanalyses and models using CL31, CL51, CHM 15k and MiniMPL observations at three sites in New Zealand. We show that the reanalyses and models generally underestimate cloud fraction and overestimate cloud albedo, the common too few too bright problem. If sufficiently high temporal resolution model output is available (better than 6 hourly), a direct comparison of individual clouds is also possible. We demonstrate that the ALCF can be used as a generic evaluation tool to examine cloud occurrence and cloud properties in reanalyses, NWP models and GCMs, potentially utilising the large amounts of ALC data already available. This tool is likely to be particularly useful for the analysis and improvement of low-level cloud simulations which are not well monitored from space. This has previously been identified as a critical deficiency in contemporary models, limiting the accuracy of weather forecasts and future climate projections. [ABSTRACT FROM AUTHOR]

Improvements are made to two areas of the United Kingdom Chemistry and Aerosol (UKCA) module, which forms part of the Met Office Unified Model (UM) used for weather and climate applications. Firstly, a solar cycle is added to the photolysis scheme. The effect on total column ozone of this addition was found to be around 1 %–2 % in midlatitude and equatorial regions, in phase with the solar cycle. Secondly, reactions occurring on the surfaces of polar stratospheric clouds and sulfate aerosol are updated and extended by modification of the uptake coefficients of five existing reactions and the addition of a further eight reactions involving bromine species. These modifications are shown to reduce the overabundance of modelled total column ozone in the Arctic during October to February, southern midlatitudes during August and the Antarctic during September. Antarctic springtime ozone depletion is shown to be enhanced by 25 DU on average, which now causes the ozone hole to be somewhat too deep compared to observations. We show that this is in part due to a cold bias of the Antarctic polar vortex in the model. [ABSTRACT FROM AUTHOR]

Improvements are made to two areas of the United Kingdom Chemistry and Aerosol (UKCA) module, which forms part of the Met Office Unified Model (UM) used for weather and climate applications. Firstly, a solar cycle is added to the photolysis scheme. The effect on total column ozone of this addition was found to be around 1-2% in mid-latitude and equatorial regions in phase with the solar cycle. Secondly, reactions occurring on the surfaces of polar stratospheric clouds and sulfate aerosol are updated and extended by modification of the uptake coefficients of five existing reactions and the addition of a further eight reactions involving bromine species. These modifications are shown to reduce the overabundance of modeled total-column ozone in the Arctic during October to February, southern mid-latitudes during August, and the Antarctic during September. Antarctic springtime ozone depletion is shown to be enhanced by 25 DU on average, which now causes the ozone hole to be somewhat too deep compared to observations. We show that this is in part due to a cold bias of the Antarctic polar vortex in the model. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning the climate monitoring of Lauder research station operated by the National Institute of Water and Atmospheric Research (NIWA) in New Zealand.

Here we present a description of the UKCA StratTrop chemical mechanism, which is used in the UKESM1 Earth system model for CMIP6. The StratTrop chemical mechanism is a merger of previously well-evaluated tropospheric and stratospheric mechanisms, and we provide results from a series of bespoke integrations to assess the overall performance of the model. We find that the StratTrop scheme performs well when compared to a wide array of observations. The analysis we present here focuses on key components of atmospheric composition, namely the performance of the model to simulate ozone in the stratosphere and troposphere and constituents that are important for ozone in these regions. We find that the results obtained for tropospheric ozone and its budget terms from the use of the StratTrop mechanism are sensitive to the host model; simulations with the same chemical mechanism run in an earlier version of the MetUM host model show a range of sensitivity to emissions that the current model does not fall within. Whilst the general model performance is suitable for use in the UKESM1 CMIP6 integrations, we note some shortcomings in the scheme that future targeted studies will address. [ABSTRACT FROM AUTHOR]

Here we present a description of the UKCA StratTrop chemical mechanism which is used in the UKESM1 Earth System Model for CMIP6. The StratTrop chemical mechanism is a merger of previously well evaluated tropospheric and stratospheric mechanisms and we provide results from a series of bespoke integrations to assess the overall performance of the model. We find that the StratTrop scheme performs well when compared to a wide array of observations. The analysis we present here focuses on key components of atmospheric composition, namely the performance of the model to simulate ozone in the stratosphere and troposphere and constituents that are important for ozone in these regions. We find that the results obtained from the use of the StratTrop mechanism are sensitive to the host model; simulations with the same chemical mechanism run in an earlier version of the MetUM host model show a range of sensitivity to emissions that the current model does not fall within. Whilst the general model performance is suitable for use in the UKESM1 CMIP6 integrations, we note some shortcomings in the scheme that future targeted studies will address. [ABSTRACT FROM AUTHOR]

Studies have recently reported statistically significant relationships between observed year-to-year spring Antarctic ozone variability and the Southern Hemisphere annular mode and surface temperatures in spring–summer. This study investigates whether current chemistry–climate models (CCMs) can capture these relationships, in particular, the connection between November total column ozone (TCO) and Australian summer surface temperatures, where years with anomalously high TCO over the Antarctic polar cap tend to be followed by warmer summers. The interannual ozone–temperature teleconnection is examined over the historical period in the observations and simulations from the Whole Atmosphere Community Climate Model (WACCM) and nine other models participating in the Chemistry–Climate Model Initiative (CCMI). There is a systematic difference between the WACCM experiments forced with prescribed observed sea surface temperatures (SSTs) and those with an interactive ocean. Strong correlations between TCO and Australian temperatures are only obtained for the uncoupled experiment, suggesting that the SSTs could be important for driving both variations in Australian temperatures and the ozone hole, with no causal link between the two. Other CCMI models also tend to capture this relationship with more fidelity when driven by observed SSTs, although additional research and targeted modeling experiments are required to determine causality and further explore the role of model biases and observational uncertainty. The results indicate that CCMs can reproduce the relationship between spring ozone and summer Australian climate reported in observational studies, suggesting that incorporating ozone variability could improve seasonal predictions; however, more work is required to understand the difference between the coupled and uncoupled simulations. [ABSTRACT FROM AUTHOR]

Model evaluation is difficult and generally relies on analysis that can mask compensating errors. This paper defines new metrics, using clusters generated from a machine learning algorithm, to estimate mean and compensating errors in different model runs. As a test case, we investigate the Southern Ocean shortwave radiative bias using clusters derived by applying self‐organizing maps to satellite data. In particular, the effects of changing cloud phase parameterizations in the MetOffice Unified Model are examined. Differences in cluster properties show that the regional radiative biases are substantially different than the global bias, with two distinct regions identified within the Southern Ocean, each with a different signed bias. Changing cloud phase parameterizations can reduce errors at higher latitudes but increase errors at lower latitudes of the Southern Ocean. Ranking the parameterizations often shows a contrast in mean and compensating errors, notably in all cases large compensating errors remain. Key Points: A novel method for climate model evaluation is used to identify both mean errors and potential compensating errorsAs an example, we apply this methodology to investigate the quality of different cloud parameterizations over the Southern OceanChanges to the cloud phase parameterizations can reduce shortwave radiative bias regionally, but large compensating errors remain [ABSTRACT FROM AUTHOR]

Simulated stratospheric temperatures over the period 1979–2016 in models from the Chemistry‐Climate Model Initiative are compared with recently updated and extended satellite data sets. The multimodel mean global temperature trends over 1979–2005 are −0.88 ± 0.23, −0.70 ± 0.16, and −0.50 ± 0.12 K/decade for the Stratospheric Sounding Unit (SSU) channels 3 (~40–50 km), 2 (~35–45 km), and 1 (~25–35 km), respectively (with 95% confidence intervals). These are within the uncertainty bounds of the observed temperature trends from two reprocessed SSU data sets. In the lower stratosphere, the multimodel mean trend in global temperature for the Microwave Sounding Unit channel 4 (~13–22 km) is −0.25 ± 0.12 K/decade over 1979–2005, consistent with observed estimates from three versions of this satellite record. The models and an extended satellite data set comprised of SSU with the Advanced Microwave Sounding Unit‐A show weaker global stratospheric cooling over 1998–2016 compared to the period of intensive ozone depletion (1979–1997). This is due to the reduction in ozone‐induced cooling from the slowdown of ozone trends and the onset of ozone recovery since the late 1990s. In summary, the results show much better consistency between simulated and satellite‐observed stratospheric temperature trends than was reported by Thompson et al. (2012, https://doi.org/10.1038/nature11579) for the previous versions of the SSU record and chemistry‐climate models. The improved agreement mainly comes from updates to the satellite records; the range of stratospheric temperature trends over 1979–2005 simulated in Chemistry‐Climate Model Initiative models is comparable to the previous generation of chemistry‐climate models. Plain Language Summary: A previous analysis by Thompson et al. (2012, https://doi.org/10.1038/nature11579) showed substantial differences between satellite‐observed and model‐simulated stratospheric cooling trends since the late 1970s. Here we compare recently revised and extended satellite temperature records with new simulations from 14 chemistry‐climate models. The results show much better agreement in the magnitude of stratospheric cooling over 1979–2005 between models and observations. This cooling was predominantly driven by increasing greenhouse gases and declining stratospheric ozone levels. An extended satellite temperature record and the chemistry‐climate models show weaker global stratospheric cooling over 1998–2016 compared to 1979–1997. This is due to the reduction in ozone‐induced cooling from the slowdown of ozone trends and the onset of ozone recovery since the late 1990s. There are larger differences in the latitudinal structure of past stratospheric temperature trends due to the effects of unforced atmospheric variability. In summary, the results show much better consistency between simulated and satellite‐observed stratospheric temperature trends than was reported by Thompson et al. (2012, https://doi.org/10.1038/nature11579) for the previous versions of the satellite record and last generation of chemistry‐climate models. The improved agreement mainly comes from updates to the satellite records, while the range of simulated trends is comparable to the previous generation of models. Key Points: There is substantial improvement in the comparison between modeled and observed stratospheric temperature trends over the satellite eraObservations and models show weaker stratospheric cooling since ~1998 when ozone‐depleting substances have been declining in the atmosphereLarger differences exist between modeled and observed stratospheric temperature trends at high latitudes partly due to internal variability [ABSTRACT FROM AUTHOR]

Abstract: The inducible nitric oxide synthase (iNOS) is a target of great research interest due to its importance in a number of diseases, for example, septic shock and inflammatory lung diseases. A variety of 3-substituted [1,2,4]triazolo[1,2-a]pyridazine derivatives was synthesized by ring closure with hexahydropyridazine-1-carbothioamide by using aliphatic and aromatic aldehydes. The activity of the new substances was tested on the insulin-secreting rat insulinoma cell line RINm5F. iNOS was expressed through exposure to interleukin-1β (IL-1β) and interferon-γ (IFN-γ). A number of the investigated compounds were more active than the reference inhibitor aminoguanidine (AG). Structure–activity relationships showed that a phenyl substituent in position 3 is apparently essential for inhibition. [Copyright &y& Elsevier]

The assessment model for ultraviolet radiation and risk ' AMOUR' is applied to output from two chemistry-climate models ( CCMs). Results from the UK Chemistry and Aerosols CCM are used to quantify the worldwide skin cancer risk avoided by the Montreal Protocol and its amendments: by the year 2030, two million cases of skin cancer have been prevented yearly, which is 14% fewer skin cancer cases per year. In the 'World Avoided,' excess skin cancer incidence will continue to grow dramatically after 2030. Results from the CCM E39C-A are used to estimate skin cancer risk that had already been inevitably committed once ozone depletion was recognized: excess incidence will peak mid 21st century and then recover or even super-recover at the end of the century. When compared with a 'No Depletion' scenario, with ozone undepleted and cloud characteristics as in the 1960s throughout, excess incidence (extra yearly cases skin cancer per million people) of the 'Full Compliance with Montreal Protocol' scenario is in the ranges: New Zealand: 100-150, Congo: −10-0, Patagonia: 20-50, Western Europe: 30-40, China: 90-120, South-West USA: 80-110, Mediterranean: 90-100 and North-East Australia: 170-200. This is up to 4% of total local incidence in the Full Compliance scenario in the peak year. [ABSTRACT FROM AUTHOR]

Abstract: Benzodiazepines are psychoactive drugs with anxiolytic, sedative, skeletal muscle relaxant and amnestic properties. Recently triazolo-benzodiazepines have been also described as potent and highly selective protein interaction inhibitors of bromodomain and extra-terminal (BET) proteins, a family of transcriptional co-regulators that play a key role in cancer cell survival and proliferation, but the requirements for high affinity interaction of this compound class with bromodomains has not been described. Here we provide insight into the structure–activity relationship (SAR) and selectivity of this versatile scaffold. In addition, using high resolution crystal structures we compared the binding mode of a series of benzodiazepine (BzD) and related triazolo-benzotriazepines (BzT) derivatives including clinically approved drugs such as alprazolam and midazolam. Our analysis revealed the importance of the 1-methyl triazolo ring system for BET binding and suggests modifications for the development of further high affinity bromodomain inhibitors. [Copyright &y& Elsevier]

Autoimmune β-cell destruction occurs directly by cell-mediated cytotoxicity or indirectly by cytokines released from infiltrating lymphocytes. Cytokines (IL-1β/IFN-γ) modify or induce expression of MHC antigens and ICAM-1 on β-cells which can lead to an improved binding of T-lymphocytes to β-cells and finally to an enhanced cell-mediated cytotoxicity. Cytokines also induce Fas-expression and inducible nitric oxide synthase (iNOS) causing generation of nitric oxide (NO) which is toxic for β-cells. The iNOS inhibitor aminoguanidine (AG) delays diabetes onset, but does not reduce diabetes incidence. We wanted to know whether AG inhibits cytokine-induced expression of Fas, MHC antigens and ICAM-1 on β-cells of LEW.1W and BB/OK rat islets after culture with IL-1β/IFN-γ. NO was completely inhibited by 5.0 mmol/L AG while 0.5 mmol/L had no inhibitory effect. AG downregulated Fas-expression on the surface of β-cells. Cytokine-induced/enhanced expression of MHC class-II and ICAM-1 was not affected by any AG concentration. AG syngergistically increased cytokine-induced enhancement of MHC class-I antigen density. AG possibly blocks the indirect pathway of β-cell damage in vivo due to inhibition of Fas and iNOS and improves direct cell-mediated cytotoxicity due to drastic increased MHC class-I expression. Inhibition of only one pathway of β-cell destruction is not sufficient to prevent diabetes. [Copyright &y& Elsevier]