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The calculation of the radiative transfer is a key component of global circulation models. In this article, we describe the most recent updates of the radiation infrastructure in the Modular Earth Submodel System (MESSy). These updates include the implementation of the PSrad radiation scheme within the RAD submodel. Furthermore, the radiation-related submodels CLOUDOPT (for the calculation of cloud optical properties) and AEROPT (for the calculation of aerosol optical properties) have been updated and are now more flexible in order to deal with different sets of shortwave and longwave bands of radiation schemes. In the wake of these updates, a new submodel (ALBEDO), which features solar-zenith-angle-dependent albedos and a new satellite-based background (white sky) albedo, was created. All of these developments are backward compatible, and previous features of the MESSy radiation infrastructure remain available. Moreover, these developments mark an important step in the use of the ECHAM/MESSy Atmospheric Chemistry (EMAC) model, as the update of the radiation scheme was a key aspect in the development of the sixth generation of the European Centre for Medium-Range Weather Forecasts – HAMburg (ECHAM6) model from ECHAM5. The developments presented here are also aimed towards using the MESSy infrastructure with the ICOsahedral Non-hydrostatic (ICON) model as a base model. The improved infrastructure will also aid in the implementation of additional radiation schemes once this should be needed. We have optimized the set of free parameters for two general circulation model-type (GCM-type) setups for pre-industrial and present-day conditions: one with the radiation scheme that was used to date (i.e. the radiation scheme of ECHAM5) and one with the newly implemented PSrad radiation scheme. After this parameter optimization, we performed four model simulations and evaluated the corresponding model results using reanalysis and observational data. The most apparent improvements related to the updated radiation scheme are the reduced cold biases in the tropical upper troposphere and lower stratosphere and the extratropical lower stratosphere and a strengthened polar vortex. The former is also related to improved stratospheric humidity and its variability if the new radiation scheme is employed. Using the multiple radiation call capability of MESSy, we have applied the two model configurations to calculate instantaneous and stratospheric-adjusted radiative forcings related to changes in greenhouse gases. Overall, we find that for many forcing experiments the simulations with the new radiation scheme show improved radiative forcing values. This is in particular the case for methane radiative forcings, which are considerably higher when assessed with the new radiation scheme and thus in better agreement with reference values.

Abstract Spaceflight and simulated spaceflight microgravity induced osteoarthritic-like alterations at the transcriptomic and proteomic levels in the articular and meniscal cartilages of rodents. But little is known about the effect of spaceflight or simulated spaceflight microgravity on the transcriptome of tissue-engineered cartilage developed from human cells. In this study, we investigate the effect of simulated spaceflight microgravity facilitated by parabolic flights on tissue-engineered cartilage developed from in vitro chondrogenesis of human bone marrow mesenchymal stem cells obtained from age-matched female and male donors. The successful induction of cartilage-like tissue was confirmed by the expression of well-demonstrated chondrogenic markers. Our bulk transcriptome data via RNA sequencing demonstrated that parabolic flight altered mostly fundamental biological processes, and the modulation of the transcriptome profile showed sex-dependent differences. The secretome profile analysis revealed that two genes (WNT7B and WNT9A) from the Wnt-signaling pathway, which is implicated in osteoarthritis development, were only up-regulated for female donors. The results of this study showed that the engineered cartilage tissues responded to microgravity in a sex-dependent manner, and the reported data offers a strong foundation to further explore the underlying mechanisms.

Water vapor (H2O) is the source of reactive hydrogen radicals in the middle atmosphere, whereas carbon monoxide (CO), being formed by CO2 photolysis, is suitable as a dynamical tracer. In the mesosphere, both H2O and CO are sensitive to solar irradiance (SI) variability because of their destruction/production by solar radiation. This enables us to analyze the solar signal in both models and observed data. Here, we evaluate the mesospheric H2O and CO response to solar irradiance variability using the Chemistry-Climate Model Initiative (CCMI-1) simulations and satellite observations. We analyzed the results of four CCMI models (CMAM, EMAC-L90MA, SOCOLv3, and CESM1-WACCM 3.5) operated in CCMI reference simulation REF-C1SD in specified dynamics mode, covering the period from 1984–2017. Multiple linear regression analyses show a pronounced and statistically robust response of H2O and CO to solar irradiance variability and to the annual and semiannual cycles. For periods with available satellite data, we compared the simulated solar signal against satellite observations, namely the GOZCARDS composite for 1992–2017 for H2O and Aura/MLS measurements for 2005–2017 for CO. The model results generally agree with observations and reproduce an expected negative and positive correlation for H2O and CO, respectively, with solar irradiance. However, the magnitude of the response and patterns of the solar signal varies among the considered models, indicating differences in the applied chemical reaction and dynamical schemes, including the representation of photolyzes. We suggest that there is no dominating thermospheric influence of solar irradiance in CO, as reported in previous studies, because the response to solar variability is comparable with observations in both low-top and high-top models. We stress the importance of this work for improving our understanding of the current ability and limitations of state-of-the-art models to simulate a solar signal in the chemistry and dynamics of the middle atmosphere.

In a previous study the quasi-instantaneous chemical impacts (rapid adjustments) of strongly enhanced methane (CH4) mixing ratios have been analysed. However, to quantify the influence of the respective slow climate feedbacks on the chemical composition it is necessary to include the radiation-driven temperature feedback. Therefore, we perform sensitivity simulations with doubled and quintupled present-day (year 2010) CH4 mixing ratios with the chemistry–climate model EMAC (European Centre for Medium-Range Weather Forecasts, Hamburg version – Modular Earth Submodel System (ECHAM/MESSy) Atmospheric Chemistry) and include in a novel set-up a mixed-layer ocean model to account for tropospheric warming. Strong increases in CH4 lead to a reduction in the hydroxyl radical in the troposphere, thereby extending the CH4 lifetime. Slow climate feedbacks counteract this reduction in the hydroxyl radical through increases in tropospheric water vapour and ozone, thereby dampening the extension of CH4 lifetime in comparison with the quasi-instantaneous response. Changes in the stratospheric circulation evolve clearly with the warming of the troposphere. The Brewer–Dobson circulation strengthens, affecting the response of trace gases, such as ozone, water vapour and CH4 in the stratosphere, and also causing stratospheric temperature changes. In the middle and upper stratosphere, the increase in stratospheric water vapour is reduced with respect to the quasi-instantaneous response. We find that this difference cannot be explained by the response of the cold point and the associated water vapour entry values but by a weaker strengthening of the in situ source of water vapour through CH4 oxidation. However, in the lower stratosphere water vapour increases more strongly when tropospheric warming is accounted for, enlarging its overall radiative impact. The response of the stratosphere adjusted temperatures driven by slow climate feedbacks is dominated by these increases in stratospheric water vapour as well as strongly decreased ozone mixing ratios above the tropical tropopause, which result from enhanced tropical upwelling. While rapid radiative adjustments from ozone and stratospheric water vapour make an essential contribution to the effective CH4 radiative forcing, the radiative impact of the respective slow feedbacks is rather moderate. In line with this, the climate sensitivity from CH4 changes in this chemistry–climate model set-up is not significantly different from the climate sensitivity in carbon-dioxide-driven simulations, provided that the CH4 effective radiative forcing includes the rapid adjustments from ozone and stratospheric water vapour changes.

Calculating a multi-model mean, a commonly used method for ensemble averaging, assumes model independence and equal model skill. Sharing of model components amongst families of models and research centres, conflated by growing ensemble size, means model independence cannot be assumed and is hard to quantify. We present a methodology to produce a weighted-model ensemble projection, accounting for model performance and model independence. Model weights are calculated by comparing model hindcasts to a selection of metrics chosen for their physical relevance to the process or phenomena of interest. This weighting methodology is applied to the Chemistry–Climate Model Initiative (CCMI) ensemble to investigate Antarctic ozone depletion and subsequent recovery. The weighted mean projects an ozone recovery to 1980 levels, by 2056 with a 95 % confidence interval (2052–2060), 4 years earlier than the most recent study. Perfect-model testing and out-of-sample testing validate the results and show a greater projective skill than a standard multi-model mean. Interestingly, the construction of a weighted mean also provides insight into model performance and dependence between the models. This weighting methodology is robust to both model and metric choices and therefore has potential applications throughout the climate and chemistry–climate modelling communities.

Variations in the solar spectral irradiance (SSI) with the 11-year sunspot cycle have been shown to have a significant impact on temperatures and the mixing ratios of atmospheric constituents in the stratosphere and mesosphere. Uncertainties in modelling the effects of SSI variations arise from uncertainties in the empirical models reconstructing the prescribed SSI data set as well as from uncertainties in the chemistry–climate model (CCM) formulation. In this study CCM simulations with the ECHAM/MESSy Atmospheric Chemistry (EMAC) model and the Community Earth System Model 1 (CESM1)–Whole Atmosphere Chemistry Climate Model (WACCM) have been performed to quantify the uncertainties of the solar responses in chemistry and dynamics that are due to the usage of five different SSI data sets or the two CCMs. We apply a two-way analysis of variance (ANOVA) to separate the influence of the SSI data sets and the CCMs on the variability of the solar response in shortwave heating rates, temperature, and ozone. The solar response is derived from climatological differences of time slice simulations prescribing SSI for the solar maximum in 1989 and near the solar minimum in 1994. The SSI values for the solar maximum of each SSI data set are created by adding the SSI differences between November 1994 and November 1989 to a common SSI reference spectrum for near-solar-minimum conditions based on ATLAS-3 (Atmospheric Laboratory of Applications and Science-3). The ANOVA identifies the SSI data set with the strongest influence on the variability of the solar response in shortwave heating rates in the upper mesosphere and in the upper stratosphere–lower mesosphere. The strongest influence on the variability of the solar response in ozone and temperature is identified in the upper stratosphere–lower mesosphere. However, in the region of the largest ozone mixing ratio, in the stratosphere from 50 to 10 hPa, the SSI data sets do not contribute much to the variability of the solar response when the Spectral And Total Irradiance REconstructions-T (SATIRE-T) SSI data set is omitted. The largest influence of the CCMs on variability of the solar responses can be identified in the upper mesosphere. The solar response in the lower stratosphere also depends on the CCM used, especially in the tropics and northern hemispheric subtropics and mid-latitudes, where the model dynamics modulate the solar responses. Apart from the upper mesosphere, there are also regions where the largest fraction of the variability of the solar response is explained by randomness, especially for the solar response in temperature.

The top-of-atmosphere (TOA) outgoing longwave flux over the 9.6 µm ozone band is a fundamental quantity for understanding chemistry–climate coupling. However, observed TOA fluxes are hard to estimate as they exhibit considerable variability in space and time that depend on the distributions of clouds, ozone (O3), water vapor (H2O), air temperature (Ta), and surface temperature (Ts). Benchmarking present-day fluxes and quantifying the relative influence of their drivers is the first step for estimating climate feedbacks from ozone radiative forcing and predicting radiative forcing evolution. To that end, we constructed observational instantaneous radiative kernels (IRKs) under clear-sky conditions, representing the sensitivities of the TOA flux in the 9.6 µm ozone band to the vertical distribution of geophysical variables, including O3, H2O, Ta, and Ts based upon the Aura Tropospheric Emission Spectrometer (TES) measurements. Applying these kernels to present-day simulations from the Chemistry-Climate Model Initiative (CCMI) project as compared to a 2006 reanalysis assimilating satellite observations, we show that the models have large differences in TOA flux, attributable to different geophysical variables. In particular, model simulations continue to diverge from observations in the tropics, as reported in previous studies of the Atmospheric Chemistry Climate Model Intercomparison Project (ACCMIP) simulations. The principal culprits are tropical middle and upper tropospheric ozone followed by tropical lower tropospheric H2O. Five models out of the eight studied here have TOA flux biases exceeding 100 mW m−2 attributable to tropospheric ozone bias. Another set of five models have flux biases over 50 mW m−2 due to H2O. On the other hand, Ta radiative bias is negligible in all models (no more than 30 mW m−2). We found that the atmospheric component (AM3) of the Geophysical Fluid Dynamics Laboratory (GFDL) general circulation model and Canadian Middle Atmosphere Model (CMAM) have the lowest TOA flux biases globally but are a result of cancellation of opposite biases due to different processes. Overall, the multi-model ensemble mean bias is -133±98 mW m−2, indicating that they are too atmospherically opaque due to trapping too much radiation in the atmosphere by overestimated tropical tropospheric O3 and H2O. Having too much O3 and H2O in the troposphere would have different impacts on the sensitivity of TOA flux to O3 and these competing effects add more uncertainties on the ozone radiative forcing. We find that the inter-model TOA outgoing longwave radiation (OLR) difference is well anti-correlated with their ozone band flux bias. This suggests that there is significant radiative compensation in the calculation of model outgoing longwave radiation.

The impact of changes in incoming solar irradiance on stratospheric ozone abundances should be included in climate simulations to aid in capturing the atmospheric response to solar cycle variability. This study presents the first systematic comparison of the representation of the 11-year solar cycle ozone response (SOR) in chemistry–climate models (CCMs) and in pre-calculated ozone databases specified in climate models that do not include chemistry, with a special focus on comparing the recommended protocols for the Coupled Model Intercomparison Project Phase 5 and Phase 6 (CMIP5 and CMIP6). We analyse the SOR in eight CCMs from the Chemistry–Climate Model Initiative (CCMI-1) and compare these with results from three ozone databases for climate models: the Bodeker Scientific ozone database, the SPARC/Atmospheric Chemistry and Climate (AC&C) ozone database for CMIP5 and the SPARC/CCMI ozone database for CMIP6. The peak amplitude of the annual mean SOR in the tropical upper stratosphere (1–5 hPa) decreases by more than a factor of 2, from around 5 to 2 %, between the CMIP5 and CMIP6 ozone databases. This substantial decrease can be traced to the CMIP5 ozone database being constructed from a regression model fit to satellite and ozonesonde measurements, while the CMIP6 database is constructed from CCM simulations. The SOR in the CMIP6 ozone database therefore implicitly resembles the SOR in the CCMI-1 models. The structure in latitude of the SOR in the CMIP6 ozone database and CCMI-1 models is considerably smoother than in the CMIP5 database, which shows unrealistic sharp gradients in the SOR across the middle latitudes owing to the paucity of long-term ozone measurements in polar regions. The SORs in the CMIP6 ozone database and the CCMI-1 models show a seasonal dependence with enhanced meridional gradients at mid- to high latitudes in the winter hemisphere. The CMIP5 ozone database does not account for seasonal variations in the SOR, which is unrealistic. Sensitivity experiments with a global atmospheric model without chemistry (ECHAM6.3) are performed to assess the atmospheric impacts of changes in the representation of the SOR and solar spectral irradiance (SSI) forcing between CMIP5 and CMIP6. The larger amplitude of the SOR in the CMIP5 ozone database compared to CMIP6 causes a likely overestimation of the modelled tropical stratospheric temperature response between 11-year solar cycle minimum and maximum by up to 0.55 K, or around 80 % of the total amplitude. This effect is substantially larger than the change in temperature response due to differences in SSI forcing between CMIP5 and CMIP6. The results emphasize the importance of adequately representing the SOR in global models to capture the impact of the 11-year solar cycle on the atmosphere. Since a number of limitations in the representation of the SOR in the CMIP5 ozone database have been identified, we recommend that CMIP6 models without chemistry use the CMIP6 ozone database and the CMIP6 SSI dataset to better capture the climate impacts of solar variability. The SOR coefficients from the CMIP6 ozone database are published with this paper.

This paper describes the recommended solar forcing dataset for CMIP6 and highlights changes with respect to CMIP5. The solar forcing is provided for radiative properties, namely total solar irradiance (TSI), solar spectral irradiance (SSI), and the F10.7 index as well as particle forcing, including geomagnetic indices Ap and Kp, and ionization rates to account for effects of solar protons, electrons, and galactic cosmic rays. This is the first time that a recommendation for solar-driven particle forcing has been provided for a CMIP exercise. The solar forcing datasets are provided at daily and monthly resolution separately for the CMIP6 preindustrial control, historical (1850–2014), and future (2015–2300) simulations. For the preindustrial control simulation, both constant and time-varying solar forcing components are provided, with the latter including variability on 11-year and shorter timescales but no long-term changes. For the future, we provide a realistic scenario of what solar behavior could be, as well as an additional extreme Maunder-minimum-like sensitivity scenario. This paper describes the forcing datasets and also provides detailed recommendations as to their implementation in current climate models.For the historical simulations, the TSI and SSI time series are defined as the average of two solar irradiance models that are adapted to CMIP6 needs: an empirical one (NRLTSI2–NRLSSI2) and a semi-empirical one (SATIRE). A new and lower TSI value is recommended: the contemporary solar-cycle average is now 1361.0 W m−2. The slight negative trend in TSI over the three most recent solar cycles in the CMIP6 dataset leads to only a small global radiative forcing of −0.04 W m−2. In the 200–400 nm wavelength range, which is important for ozone photochemistry, the CMIP6 solar forcing dataset shows a larger solar-cycle variability contribution to TSI than in CMIP5 (50 % compared to 35 %).We compare the climatic effects of the CMIP6 solar forcing dataset to its CMIP5 predecessor by using time-slice experiments of two chemistry–climate models and a reference radiative transfer model. The differences in the long-term mean SSI in the CMIP6 dataset, compared to CMIP5, impact on climatological stratospheric conditions (lower shortwave heating rates of −0.35 K day−1 at the stratopause), cooler stratospheric temperatures (−1.5 K in the upper stratosphere), lower ozone abundances in the lower stratosphere (−3 %), and higher ozone abundances (+1.5 % in the upper stratosphere and lower mesosphere). Between the maximum and minimum phases of the 11-year solar cycle, there is an increase in shortwave heating rates (+0.2 K day−1 at the stratopause), temperatures ( ∼ 1 K at the stratopause), and ozone (+2.5 % in the upper stratosphere) in the tropical upper stratosphere using the CMIP6 forcing dataset. This solar-cycle response is slightly larger, but not statistically significantly different from that for the CMIP5 forcing dataset.CMIP6 models with a well-resolved shortwave radiation scheme are encouraged to prescribe SSI changes and include solar-induced stratospheric ozone variations, in order to better represent solar climate variability compared to models that only prescribe TSI and/or exclude the solar-ozone response. We show that monthly-mean solar-induced ozone variations are implicitly included in the SPARC/CCMI CMIP6 Ozone Database for historical simulations, which is derived from transient chemistry–climate model simulations and has been developed for climate models that do not calculate ozone interactively. CMIP6 models without chemistry that perform a preindustrial control simulation with time-varying solar forcing will need to use a modified version of the SPARC/CCMI Ozone Database that includes solar variability. CMIP6 models with interactive chemistry are also encouraged to use the particle forcing datasets, which will allow the potential long-term effects of particles to be addressed for the first time. The consideration of particle forcing has been shown to significantly improve the representation of reactive nitrogen and ozone variability in the polar middle atmosphere, eventually resulting in further improvements in the representation of solar climate variability in global models.

The year 1980 has often been used as a benchmark for the return of Antarctic ozone to conditions assumed to be unaffected by emissions of ozone-depleting substances (ODSs), implying that anthropogenic ozone depletion in Antarctica started around 1980. Here, the extent of anthropogenically driven Antarctic ozone depletion prior to 1980 is examined using output from transient chemistry–climate model (CCM) simulations from 1960 to 2000 with prescribed changes of ozone-depleting substance concentrations in conjunction with observations. A regression model is used to attribute CCM modelled and observed changes in Antarctic total column ozone to halogen-driven chemistry prior to 1980. Wintertime Antarctic ozone is strongly affected by dynamical processes that vary in amplitude from year to year and from model to model. However, when the dynamical and chemical impacts on ozone are separated, all models consistently show a long-term, halogen-induced negative trend in Antarctic ozone from 1960 to 1980. The anthropogenically driven ozone loss from 1960 to 1980 ranges between 26.4 ± 3.4 and 49.8 ± 6.2 % of the total anthropogenic ozone depletion from 1960 to 2000. An even stronger ozone decline of 56.4 ± 6.8 % was estimated from ozone observations. This analysis of the observations and simulations from 17 CCMs clarifies that while the return of Antarctic ozone to 1980 values remains a valid milestone, achieving that milestone is not indicative of full recovery of the Antarctic ozone layer from the effects of ODSs.

During boreal summer the upper troposphere/lower stratosphere (UTLS) in the Northern Hemisphere shows a distinct maximum in water vapour (H2O) mixing ratios and a coincident minimum in ozone (O3) mixing ratios, both confined within the Asian monsoon anticyclone (AMA). This well-known feature has been related to transport processes emerging above the convective systems during the Asian summer monsoon (ASM), further modified by the dynamics of the AMA. We compare the ability of chemistry–climate models (CCMs) to reproduce the climatological characteristics and variability of H2O, O3, and temperature in the UTLS during the boreal summer with MIPAS satellite observations and ERA-Interim reanalyses. By using a multiple linear regression model the main driving factors, the strength of the ASM, the quasi-biennial oscillation (QBO), and the El Niño–Southern Oscillation (ENSO), are separated. The regression patterns related to ENSO show a coherent, zonally asymmetric signal for temperatures and H2O mixing ratios for ERA-Interim and the CCMs and suggest a weakening of the ASM during ENSO warm events. The QBO modulation of the lower-stratospheric temperature near the Equator is well represented as a zonally symmetric pattern in the CCMs. Changes in H2O and O3 mixing ratios are consistent with the QBO-induced temperature and circulation anomalies but less zonally symmetric than the temperature pattern. Regarding the ASM, the results of the regression analysis show for ERA-Interim and the CCMs enhanced H2O and reduced O3 mixing ratios within the AMA for stronger ASM seasons. The CCM results can further confirm earlier studies which emphasize the importance of the Tibetan Plateau/southern slope of the Himalayas as the main source region for H2O in the AMA. The results suggest that H2O is transported towards higher latitudes at the north-eastern edge of the AMA rather than towards low equatorial latitudes to be fed into the tropical pipe.

The Modular Earth Submodel System (MESSy) provides an interface to couple submodels to a base model via a highly flexible data management facility (Jöckel et al., 2010). In the present paper we present the four new radiation related submodels RAD, AEROPT, CLOUDOPT, and ORBIT. The submodel RAD (including the shortwave radiation scheme RAD_FUBRAD) simulates the radiative transfer, the submodel AEROPT calculates the aerosol optical properties, the submodel CLOUDOPT calculates the cloud optical properties, and the submodel ORBIT is responsible for Earth orbit calculations. These submodels are coupled via the standard MESSy infrastructure and are largely based on the original radiation scheme of the general circulation model ECHAM5, however, expanded with additional features. These features comprise, among others, user-friendly and flexibly controllable (by namelists) online radiative forcing calculations by multiple diagnostic calls of the radiation routines. With this, it is now possible to calculate radiative forcing (instantaneous as well as stratosphere adjusted) of various greenhouse gases simultaneously in only one simulation, as well as the radiative forcing of cloud perturbations. Examples of online radiative forcing calculations in the ECHAM/MESSy Atmospheric Chemistry (EMAC) model are presented.

Three types of reference simulations, as recommended by the Chemistry–Climate Model Initiative (CCMI), have been performed with version 2.51 of the European Centre for Medium-Range Weather Forecasts – Hamburg (ECHAM)/Modular Earth Submodel System (MESSy) Atmospheric Chemistry (EMAC) model: hindcast simulations (1950–2011), hindcast simulations with specified dynamics (1979–2013), i.e. nudged towards ERA-Interim reanalysis data, and combined hindcast and projection simulations (1950–2100). The manuscript summarizes the updates of the model system and details the different model set-ups used, including the on-line calculated diagnostics. Simulations have been performed with two different nudging set-ups, with and without interactive tropospheric aerosol, and with and without a coupled ocean model. Two different vertical resolutions have been applied. The on-line calculated sources and sinks of reactive species are quantified and a first evaluation of the simulation results from a global perspective is provided as a quality check of the data. The focus is on the intercomparison of the different model set-ups. The simulation data will become publicly available via CCMI and the Climate and Environmental Retrieval and Archive (CERA) database of the German Climate Computing Centre (DKRZ). This manuscript is intended to serve as an extensive reference for further analyses of the Earth System Chemistry integrated Modelling (ESCiMo) simulations.

Nicole M Kunze1, Jessica E Goetz2, Daniel R Thedens3, Thomas E Baer2, Ericka A Lawler2, Thomas D Brown21Department of Biomedical Engineering, 2Department of Orthopaedics and Rehabilitation, 3Department of Radiology, University of Iowa, Iowa City, IA, USAAbstract: Carpal tunnel syndrome is commonly viewed as resulting from chronic mechanical insult of the median nerve by adjacent anatomical structures. Both the median nerve and its surrounding soft tissue structures are well visualized on magnetic resonance (MR) images of the wrist and hand. Addressing nerve damage from impingement of flexor digitorum tendons co-occupying the tunnel is attractive, but to date has been restricted by a lack of means for making individual identifications of the respective tendons. In this image analysis work, we have developed a region-growing method to positively identify each individual digital flexor tendon within the carpal tunnel by tracking it from a more distal MR section where the respective tendon identities are unambiguous. Illustratively, the new method was applied to MRI scans from four different subjects in a variety of hand poses. Conventional shape measures yielded less discriminatory information than did evaluations of individual tendon location and arrangement. This new method of rapid identification of individual tendons will facilitate analysis of tendon/nerve interactions within the tunnel, thereby providing better information about mechanical insult of the median nerve.Keywords: carpal tunnel syndrome, magnetic resonance imaging, region growing, digital flexor tendons

We report the sensitivity of the Berlin Climate Middle Atmosphere Model (CMAM) to different gravity-wave (GW) parameterisations. We perform five perpetual January experiments: 1) Rayleigh friction (RF) (control), 2) non-orographic GWs, 3) orographic GWs, 4) orographic and non-orographic GWs with no background stress, and 5) as for 4) but with background stress. We also repeat experiment 4) but for July conditions. Our main aim is to improve the model climatology by introducing orographic and non-orographic parameterisations and to investigate the individual effect of these schemes in the Berlin CMAM. We compare with an RF control to determine the improvement upon a previously-published model version employing RF. Results are broadly similar to previously-published works. The runs having both orographic and non-orographic GWs produce a statistically-significant warming of 4-8K in the wintertime polar lower stratosphere. These runs also feature a cooling of the warm summer pole in the mesosphere by 10-15K, more in line with observations. This is associated with the non-orographic GW scheme. This scheme is also associated with a heating feature in the winter polar upper stratosphere directly below the peak GW-breaking region. The runs with both orographic and non-orographic GWs feature a statistically-significant deceleration in the polar night jet (PNJ) of 10-20ms-1 in the lower stratosphere. Both orographic and non-orographic GWs individually produce some latitudinal tilting of the polar jet with height, although the main effect comes from the non-orographic waves. The resulting degree of tilt, although improved, is nevertheless still weaker than that observed. Accordingly, wintertime variability in the zonal mean wind, which peaks at the edge of the vortex, tends to maximise too far polewards in the model compared with observations. Gravity-planetary wave interaction leads to a decrease in the amplitudes of stationary planetary waves 1 and 2 by up to 50% in the upper stratosphere and mesosphere, more in line with observations. Comparing modelled and observed Eliassen-Palm fluxes suggests that planetary wave (PW) breaking occurs too far polewards in the model. The wind and temperature changes are consistent with changes in the Brewer-Dobson (BD) circulation. Results suggest that the effect of enforcing a minimum background wave stress in the McFarlane scheme could be potentially important. In the Southern Hemisphere (SH) in July, the GW schemes had only a small impact on the high-latitude lower stratosphere but there featured strong warming near 0.1hPa.

Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR)-kinase, alternative modes of translation, such as internal ribosome entry site (IRES)-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase) to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM). Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR) of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K) inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.