Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores

Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca2+ signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca2+ signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca2+ signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca2+ stores, thereby leaving less Ca2+ available for release upon IP3- and ryanodine-receptor activation. The Ca2+-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca2+ release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression

The European COST Action EUBrewNet: towards consistency in quality control, quality assurance and coordinated operations of the Brewer Instrument

Presentación realizada en: 10th meeting of the Ozone Research Managers (ORM) como parte de "Vienna Convention for the Protection of the Ozone Layer", celebrado en Ginebra (Suiza) del 28 al 30 de marzo de 2017

Characterisation of light-absorbing atmospheric particles in the Brussels sub-urban atmosphere

The particle composition is important for air quality studies in the urban atmosphere. In particular, particles smaller than 1 μm are increasingly in the focus with respect to human health because of they are inhalable deeply into the human lung. A relevant part of such (ultra-)fine particles are light-absorbing particles. Important sources for such particles in the cities and residential areas are emissions from traffic (mainly soot), but also emissions from wood-burning stoves in private households. The relative contributions of these sources to the atmospheric particle load are important to know in order to be able to reduce hazardous emissions by specific measures. The Royal Meteorological Institute of Belgium (RMI) gathers ambient aerosol data in Brussels with a 7-wavelengths aethalometer (mass concentration and absorption coefficient of light-absorbing aerosol). The measurement site is located in the sub-urban, rather residential southern part of Brussels and measurements are representative for the urban background. At the same site, the boundary layer height and atmospheric stability parameter are derived from a co-located ceilometer and eddy-covariance system. Further, RMI uses the multi-scale chemical transport model CHIMERE, coupled to the high resolution regional numerical weather prediction limited area model ALARO. In this context, CHIMERE will be used to evaluate emission scenarios. The wavelength dependency of the measured aerosol parameters revealed distinct variations of aerosol composition, both on a daily, weekly, and seasonal scale. The Absorption Angstrom Exponent (AAE; spectral dependency of the absorption coefficient) revealed values around 1.3 during winter and around 1.0 during summer months. As fresh soot has a flat spectrum, (i.e., AAE around 1.0), higher AAE values during winter meant that other light-absorbing compounds, which absorb stronger in the UV, increased in importance (e.g., wood burning aerosol). The multi-wavelengths data is exploited to derive the relative contribution of fresh soot (thus traffic emissions) and other sources to the amount of light-absorbing aerosol. The influence of boundary layer height and atmospheric stability on the aerosol data will be presented

Detecting volcanic sulfur dioxide plumes in the Northern Hemisphere using the Brewer spectrophotometer, other networks, and satellite observations

This paper demonstrates that SO 2 columnar amounts have significantly increased following the five largest volcanic eruptions of the past decade in the Northern Hemisphere. A strong positive signal was detected by all the existing networks either ground based (Brewer, EARLINET, AirBase) or from satellites (OMI, GOME-2). The study particularly examines the adequacy of the existing Brewer network to detect SO 2 plumes of volcanic origin in comparison to other networks and satellite platforms. The comparison with OMI and 45 GOME-2 SO 2 space-borne retrievals shows statistically significant agreement between the Brewer network data and the collocated satellite overpasses. It is shown that the Brewer instrument is capable of detecting significant columnar SO 2 increases following large volcanic eruptions, when SO 2 levels rise well above the instrumental noise of daily observations, estimated to be of the order of 2 DU. A model exercise from the MACC project shows that the large increases of SO 2 over Europe following the Bárðarbunga eruption in Iceland were not caused by local sources or ship emissions but are clearly linked to the eruption. We propose that by combining Brewer data with that from other networks and satellites, a useful tool aided by trajectory analyses and modeling could be created which can be used to forecast high SO 2 values both at ground level and in air flight corridors following future eruptions

Advanced exploitation of Ground-Based measurements for Atmospheric Chemistry and Climate Applications "AGACC"

We live in an era in which human activities are causing significant changes to the atmospheric environment which result in local to global consequences on the ecosystems. Changes in the atmospheric composition impact our climate via chemical and dynamical feedback mechanisms; in many instances they also affect air quality, and the health of the biosphere. Monitoring and understanding those changes and their consequences is fundamental to establish adequate actions for adaptation to and mitigation of the environmental changes. Furthermore, after implementation of regulatory measures like the Montreal Protocol, it is necessary to verify whether the measures are effective. This can only be achieved if we have adequate detection methods and a reliable long record of a series of key geophysical parameters. Thus the AGACC project contributes to the provision of basic new knowledge regarding the atmospheric composition and its changes, based on advanced groundbased monitoring, in combination with satellite and numerical modelling data. Its results are integrated in ongoing international research programmes. The general objective of AGACC has been to improve and extend the groundbased detection capabilities for a number of climate-related target species and, based hereupon, analyse past and present observations to derive new information about the atmospheric composition, its variability and long-term changes. Despite the advent of a growing and more performant fleet of Earth Observation satellites, ground-based observations are still indispensable to (1) guarantee long-term continuity, homogeneity and high quality of the data, and (2) to underpin the satellite data for calibration and (long-term) validation. A first target gas is atmospheric water vapour. It is the key trace gas controlling weather and climate. It is also the most important greenhouse gas in the Earth’s atmosphere. Its amount and vertical distribution are changing, but how and why? Especially in the upper troposphere - lower stratosphere, the radiative effects of changes in the water vapour are significant and should be quantified. The measurement of water vapour is a hot topic since several years. It is a challenge, because water vapour exhibits a large gradient in its concentration when going from the ground to the stratosphere, and because it is highly variable in time and space. For example, we have found that the time scale of the variations of the total water vapour amount at Jungfraujoch is in the order of minutes. In AGACC, we have therefore investigated various experimental techniques to measure the concentration of water vapour in the atmosphere, focusing on the total column as well as on the vertical distribution in the troposphere up to the lower stratosphere. The retrieval of water vapour vertical profiles and total columns from ground-based FTIR data has been initiated at three very different stations where correlative data for verification are available, namely Ukkel (± sea level, mid-latitude), Ile de La Réunion (± sea level, tropical) and Jungfraujoch (high altitude, mid-latitude), with promising results. In particular, at Jungfraujoch, it has been demonstrated that the precision of the FTIR integrated water vapour (IWV) measurements is of order 2%. The capability to retrieve individual isotopologues of water vapour, and to monitor their daily and diurnal variations, has also been demonstrated. This could open new ways to study in the future the role of water vapour in the radiative balance, the global circulation, precipitation etc. We also started joint exploitation of ground-based FTIR and satellite IASI data for water vapour and its isotopologues, in order to exploit fully the potential of the existing instrumentation. A correction method for the radiosoundings at Ukkel has been successfully implemented, resulting in a homogeneous and reliable time series from 1990 to 2008 from which trends in upper troposphere humidity (UTH) and tropopause characteristics have been derived. One observes a rising UTH until September 2001, followed by a decline, accompanied by a descent and heating of the tropopause up to the turning point and an ascent and cooling afterwards. The changes after September 2001 in the upper troposphere can be explained by surface heating and convective uplift. At Jungfraujoch, one does not observe any significant trend in the total water vapour abundance above the station over the 1988-2010 time period, although significant positive summer and negative winter trends have been detected. We have made a quantitative statistical comparison between ground-based FTIR, CIMEL, GPS and integrated (corrected) radio sounding measurements of the IWV at Ukkel. This work is important to better characterize the different sensors in order to exploit together different observations made by different instruments. A second target species is atmospheric aerosol. There is a very large variety of aerosol both from natural or anthropogenic origin. One of the reasons why they are so important is that they affect the optical properties of the atmosphere. In particular, it has been demonstrated in previous studies that the aerosols have a large impact on the quantity of harmful UV-B radiation received at the Earth’s surface. The latest IPCC Report also stressed that the radiative forcing caused by atmospheric aerosols is one of the largest uncertainties in determining the total radiative forcing in the atmosphere. Better monitoring capabilities of aerosol properties can therefore improve our understanding and forecasting of the atmospheric processes and evolution, and in particular of UV-B and climate changes. Several measurement techniques are now operational in the AGACC consortium for the ground-based monitoring of aerosol properties. These are the Brewer spectrometer and CIMEL observations at Ukkel, the latter contributing also to the AERONET network since July 2006, and the newly developed MAXDOAS observations. Unlike CIMEL and Brewer measurements, that provide the total Aerosol Optical Depth, it has been demonstrated that the MAXDOAS measurements also provide additional information about the vertical distribution of the aerosol extinction in the lowest kilometres of the troposphere. A better understanding of the ultimate capabilities of MAXDOAS aerosol remote sensing has been gained through participation to the international CINDI campaign (Cabauw Intercomparison Campaign of Nitrogen Dioxide measuring Instruments ) in summer 2009. The combination of Brewer, CIMEL and MAXDOAS instruments gives us a remote-sensing dataset that will enable a more comprehensive characterization of the tropospheric aerosol optical properties. The usefulness of these aerosol observations has already been demonstrated in the improvement of the UVindex predictions for the general public. Another application is their use as input data in the retrieval of vertical profiles of tropospheric pollutants from MAXDOAS measurements, like tropospheric NO2 and formaldehyde. Third we have focused on a few climate-related trace gases. Changing greenhouse gas and aerosol concentrations directly affect the radiative budget of the atmosphere, and therefore climate. But many species known as pollutants like carbon monoxide (CO), nitrogen oxides (NOx) and hydrocarbons, - often related to fossil fuel or biomass burning -, also affect climate through their role in chemical reactions that produce tropospheric ozone, which is a well-known greenhouse gas, or that modify the lifetime of gases like methane, or the oxidation capacity of the atmosphere. Therefore in AGACC, we have focused on the measurement of a number of trace gases that are subject to changing concentrations, that directly or indirectly affect climate, and that are either difficult to monitor or that have not yet been measured from the ground. We have included attempts to observe distinctly some isotopologues, because the isotopic ratios observed in an airmass provide information on its history, and because the FTIR solar absorption measurements provide a rather unique capability hereto. The investigated species are the isotopologues of CH4 and CO, and hydrogen cyanide (HCN), as examples of biomass burning tracers, some hydrocarbons like formaldehyde (HCHO), ethylene (C2H4) and acetylene (C2H2), and HCFC-142b, a replacement product for CFCs and a greenhouse gas. In many cases, retrieval strategies had to be adapted when going from one site to another with different atmospheric conditions, especially when the local humidity and abundances are very different as is the case between Jungfraujoch (dry, high altitude, mid-latitude) and Ile de La Réunion (humid, low altitude, low latitude). Still we have been able to show the feasibility of retrieving particular trace gas information even under difficult conditions. Many of our results have been compared to correlative data, to validate the approach and to gain complementary information. It is also important to note that the retrieval strategies developed in AGACC have regularly been presented to the global Network for the Detection of Atmospheric Composition Change (NDACC) UV-Vis and Infrared communities and have often been adopted by others or even proposed for adoption as a standard in the community (e.g., for hydrogen cyanide (HCN)). In particular: We have been able to study the seasonal variations of HCN at the Jungfraujoch and at Ile de La Réunion, and to show the dominant impact of biomass burning. Formaldehyde was studied in much detail at Ukkel, Jungfraujoch and Ile de la Réunion. The challenge for detection at Jungfraujoch is the small abundance (about 10 times smaller than at Ukkel and Ile de La Réunion); a particular observation strategy was developed successfully, resulting in a time series that already shows the day-to-day and seasonal variations. At Ile de La Réunion, comparisons of FTIR, MAXDOAS, satellite and model data have (1) shown the good agreement between the various data sets, but also, (2), the variability of HCHO (diurnal, seasonal, day-to-day), and (3), thanks to the complementarities of the various data sets, they have enabled us to learn more about the long-range transport of Non-methane Volatile Organic Compounds (NMVOCS, precursors of HCHO) and deficiencies in the models. It was shown that fast, direct transport of NMVOCS from Madagascar has a significant impact on the HCHO abundance and its variability at Ile de La Réunion, and that this is underestimated in the model. Significant progress was made as to the detection of 13CH4 and CH3D from ground-based FTIR observations, both at Jungfraujoch and Ile de La Réunion. To our knowledge, it is the first time that a d13C data set is derived from ground-based FTIR observations. More work is needed to improve the CH3D retrieval at Ile de La Réunion, and to interpret the results, in combination with models. Also for the first time, 12CO and 13CO have been retrieved individually at Jungfraujoch. The d13C time series shows significant seasonal and interannual changes. As to the hydrocarbon ethylene, it is shown that it can be detected at Jungfraujoch only in spectra at low solar elevation, given its small atmospheric abundance. Regarding acetylene, the observed time series at Jungfraujoch and Ile de La Réunion show clear seasonal variations and enhancements due to the impact of biomass burning events, correlated with enhancements in CO, C2H6 and HCN. It is not clear yet whether we can reliably retrieve the concentration of HCFC- 142b, a replacement product that is increasing strongly in the troposphere. New line parameters for the interfering species HFC-134a are required to confirm/infirm the preliminary results. This highlights again the importance of the laboratory work for providing such parameters. Improved line parameters have been obtained for water vapour and its isotopologues, ethylene and formic acid. These AGACC results have been integrated in the international spectroscopic databases. We also showed that line intensities available around 2096 cm–1 for the 13C16O isotopologue of carbon monoxide in the HITRAN database seem to be accurate to 2%. We failed to improve line intensities for the 13.6 μm region of acetylene. The new data sets that have been derived in AGACC from FTIR and MAXDOAS observations have been archived in the NDACC data centre, where they are available for users (generally modelers and satellite teams). In addition, they are stored locally and are available to users upon request. AGACC results have been reported to the international scientific community, via the literature, via integration in geophysical or spectroscopic databases, and via participation to international research initiatives like the Atmospheric Water Vapour in the Climate System (WAVACS) Cost Action, the International Space Science Institute (ISSI) Working Group on Atmospheric Water Vapour, the International Union of Pure and Applied Chemistry (IUPAC) project, the International CINDI campaign, etc. The results have already found important scientific applications. A few examples are worth mentioning: the re-evaluation of methane emissions in the tropics from SCIAMACHY based on the new H2O spectroscopy, and the improved retrievals of HCOOH from the satellite experiments ACE-FTS and IASI, and from the ground. In the longer-term, the AGACC results will no doubt benefit the research in atmospheric sciences –in particular in the monitoring of its composition changes–, which is the fundamental basis of environmental assessment reports for supporting policy makers.Advanced exploitation of ground-based measurements for atmospheric chemistry and climate applications "AGACC

Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures

PurposeA relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD.Patients and MethodsThe cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data.ResultsThe median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91).ConclusionA significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC. (C) 2017 by American Society of Clinical Oncology.</p

Validation of TROPOMI Surface UV Radiation Product

The TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor (S5P) satellite was launched on 13 October 2017 to provide the atmospheric composition for atmosphere and climate research. The S5P is a sun-synchronous polar-orbiting satellite providing global daily coverage. The TROPOMI swath is 2600 km wide, and the ground resolution for most data products is 7.2x3.5 km2 (5.6x3.5 km2 since 6 August 2019) at nadir. The Finnish Meteorological Institute (FMI) is responsible for the development and processing of the TROPOMI Surface Ultraviolet (UV) Radiation Product which includes 36 UV parameters in total. Ground-based data from 25 sites located in arctic, subarctic, temperate, equatorial and antarctic areas were used for validation of TROPOMI overpass irradiance at 305, 310, 324 and 380 nm, overpass erythemally weighted dose rate / UV index and erythemally weighted daily dose for the period from 1 January 2018 to 31 August 2019. The validation results showed that for most sites 60–80% of TROPOMI data was within ±20% from ground-based data for snow free surface conditions. The median relative differences to ground-based measurements of TROPOMI snow free surface daily doses were within ±10% and ±5% at two thirds and at half of the sites, respectively. At several sites more than 90% of clear sky TROPOMI data were within ±20% from ground-based measurements. Generally median relative differences between TROPOMI data and ground-based measurements were a little biased towards negative values, but at high latitudes where nonhomogeneous topography and albedo/snow conditions occurred, the negative bias was exceptionally high, from -30% to -65%. Positive biases of 10–15% were also found for mountainous sites due to challenging topography. The TROPOMI Surface UV Radiation Product includes quality flags to detect increased uncertainties in the data due to heterogeneous surface albedo and rough terrain which can be used to filter the data retrieved under challenging conditions

Analysis and interpretation of Aerosol Optical Depth values retrieved from a Brewer spectrophotometer at Uccle, Belgium

Aerosols are particles in the solid or liquid phase that are suspended in the atmosphere. They have an important influence on the atmospheric chemistry and physics, affect the tropospheric chemical composition, can reduce visibility and have important impacts on human health. Aerosols also influence the Earth’s radiation budget. Although a lot of research has been done to investigate the influence of aerosols on the climate, they remain key contributors to the uncertainties in current climate studies due to the lack of information concerning their temporal and spatial distribution. One of the parameters that is of importance to understand the influence of aerosols is the aerosol optical depth (AOD), an integral measurement of the combined aerosol scattering and absorption in the atmospheric column. The first part of this PhD describes an adapted and improved method for the retrieval of AOD values using sun scan measurements from a Brewer spectrophotometer at 340 nm at Uccle. The retrieved AOD values are subjected to a cloud screening technique and are compared to quasi simultaneous, collocated CIMEL AOD values. The good agreement between both instruments highlights that the Brewer is largely sensitive to AOD at 340 nm and it justifies its use in sun scan mode to expand the AOD retrieval network of instruments. The monthly and seasonal behavior of the retrieved AOD values is also studied in this work and our results agree with results found in literature.Another point of concern in scientific communities is the known adverse effect of UV radiation on human health, the biosphere and atmospheric chemistry. Apart from its obvious relation with global solar radiation and ozone, the amount of UV radiation that reaches the surface of the Earth also depends on the characteristics and quantity of aerosols in the atmosphere and accuracy in UV prediction can be improved if the influence of aerosols on surface UV radiation is clarified. For this reason, the second part of this work focuses on the relation between the erythemal UV dose, global solar radiation, total ozone column and AOD (at 320 nm) at Uccle. Simultaneous measurements of these variables are available for a time period of 25 years (1991–2015) and this time series is long enough to allow for reliable determination of significant changes. Different analysis techniques (linear trend analysis, change point analysis and multiple linear regression) are combined to allow for an extensive study of the relations between the variables.Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Characterisation of light-absorbing particles in the Brussels sub-urban atmosphere and implications for the emission scheme of a regional chemical transport model

The Royal Meteorological Institute of Belgium (RMI) gathered ambient aerosol data in Brussels with a 7-wavelengths aethalometer and a 3 wavelengths integrating nephelometer. The amount of light-absorbing particles showed a clear daily and weekly cycle, with a sharp peak in the morning rush hour time and a broader peak in the evening. During weekends, the rush hour peak diminished. The spectral dependency of the absorption coefficient revealed peak contributions of traffic emissions to the amount of light-absorbing particles of up to 90%. Other sources (like wood burning from households) showed peak contributions of up to 35%. These percentages showed in addition a clear daily, weekly and seasonal cycle, with higher contributions of these other sources during night time, weekends and summer