Establishment and characterization of single and triple‐agent resistant osteosarcoma cell lines

Two human osteosarcoma cell lines (MG-63 and HOS-143B) are developed into drug-resistant models using a short-term drug exposure and recovery in drug-free media. Cisplatin, doxorubicin, and methotrexate are used as single agents and in triple combination. The highest level of resistance to cisplatin is observed in MG-63/CISR8, doxorubicin in HOS-143B/DOXR8, and methotrexate in HOS-143B/MTXR8. The MG-63/TRIR8 and HOS-143B/TRIR8 tripleresistance models show lower levels of resistance to combination treatment and are not resistant to the drugs individually. Apoptosis assays suggest that the resistance in MG-63/TRIR8 isfrom cisplatin and methotrexate and not doxorubicin. In contrast, the resistance in HOS-143B/TRIR8 is from doxorubicin and methotrexate instead of cisplatin. Upregulation of P-glycoprotein is seen in all resistant models except those developed with single-agent methotrexate. However, P-glycoprotein is not causing resistance in all cell lines as the inhibitor elacridar only reverses the resistance of doxorubicin on MG-63/ DOXR8 and HOS-143B/TRIR8. The migration of the MG-63 resistant models is significantly increased, their invasion rate tends to increase, and RT-PCR shows a switch from epithelial to mesenchymal gene signaling. In contrast, a significant decrease in migration is seen in HOS-143B resistant models with their invasion rate tending to decrease and a switch from mesenchymal to epithelial gene signaling

Is there a trend in cirrus cloud cover due to aircraft traffic?

Trends in cirrus cloud cover have been estimated based on 16 years of data from ISCCP (International Satellite Cloud Climatology Project). The results have been spatially correlated with aircraft density data to determine the changes in cirrus cloud cover due to aircraft traffic. The correlations are only moderate, as many other factors have also contributed to changes in cirrus. Still we regard the results to be indicative of an impact of aircraft on cirrus amount. The main emphasis of our study is on the area covered by the METEOSAT satellite to avoid trends in the ISCCP data resulting from changing satellite viewing geometry. In Europe, which is within the METEOSAT region, we find indications of a trend of about 1-2% cloud cover per decade due to aircraft, in reasonable agreement with previous studies. The positive trend in cirrus in areas of high aircraft traffic contrasts with a general negative trend in cirrus. Extrapolation in time to cover the entire period of aircraft operations and in space to cover the global scale yields a mean estimate of 0.03 Wm^-2 (lower limit 0.01, upper limit 0.08 Wm^-2) for the radiative forcing due to aircraft induced cirrus. The mean is close to the value given by IPCC (1999) as an upper limit

Modeling Studies of the Effects of the Heterogeneous Reaction ClOOCl + HCl → Cl2 + HOOCl on Stratospheric Chlorine Activation and Ozone Depletion

The heterogeneous reaction ClOOCl + HCl → Cl2 + HOOCl was introduced into a chemical trajectory model of the stratosphere. Ten-day trajectories ending at ozonesonde stations at various northern latitudes were run to simulate the period January–March 1994. The reaction on sulfuric acid aerosol surfaces has a negligible effect on ozone chemistry if a sticking coefficient similar to that of ClONO2 + HCl is assumed. On polar stratospheric cloud (PSC) surfaces the chemical effects of the addition of this reaction depend on the fate of proposed product HOOCl: if this species photolyzes to produce either ClO + OH or Cl + HO2, then HCl is activated by the reaction with chlorine peroxide. This heterogeneous activation of chlorine by active chlorine can have a significant effect on Arctic ozone depletion rates in the days following an air parcel\u27s encounter with PSC surfaces. The ozone depletion rate usually increased but in some cases decreased, depending on the extent of PSC processing and on the initial [HCl]/[ClONO2] ratio. Averaged over 3 months, the column ozone loss rates between 350 and 675 K were accelerated by as much as 35% for a set of 10-day trajectories ending at an Arctic station. If, on the other hand, HOOCl decomposes at the surface into HCl and O2, the net effect of these reactions is to convert ClOOCl into Cl2. These species are functionally equivalent, and such a conversion does not perturb the model chemistry

Is there a trend in cirrus cloud cover due to aircraft traffic?

International audienceTrends in cirrus cloud cover have been estimated based on 16 years of data from ISCCP (International Satellite Cloud Climatology Project). The results have been spatially correlated with aircraft density data to determine the changes in cirrus could cover due to aircraft traffic. Main emphasis has been on the area covered by the METEOSAT satellite, to avoid trends in the ISCCP data resulting from changing satellite positions. An alternative retrieval of high clouds in this region has been used to complement the analysis based on ISCCP data. In Europe, which is within the METEOSAT region, we find indications of a trend of about 2%/decade due to aircraft, in reasonable agreement with previous studies. The positive trend in cirrus in areas of high aircraft traffic seems to have contrasted a general negative trend in cirrus. Extrapolation in time to cover the entire period of aircraft operations and in space to cover the global scale yields a best estimate of 0.05 Wm?2 for the radiative forcing due to aircraft. This is close to the value given by IPCC (1999) as an upper limit

Combined observational and modeling based study of the aerosol indirect effect

International audienceThe indirect effect of aerosols via liquid clouds is investigated by comparing aerosol and cloud characteristics from the Global Climate Model CAM-Oslo to those observed by the MODIS instrument onboard the TERRA and AQUA satellites http://modis.gsfc.nasa.gov). The comparison is carried out for 15 selected regions ranging from remote and clean to densely populated and polluted. For each region, the regression coefficient and correlation coefficient for the following parameters are calculated: Aerosol Optical Depth vs. Liquid Cloud Optical Thickness, Aerosol Optical Depth vs. Liquid Cloud Droplet Effective Radius and Aerosol Optical Depth vs. Cloud Liquid Water Path. Modeled and observed correlation coefficients and regression coefficients are then compared for a 3-year period starting in January 2001. Additionally, global maps for a number of aerosol and cloud parameters crucial for the understanding of the aerosol indirect effect are compared for the same period of time. Significant differences are found between MODIS and CAM-Oslo both in the regional and global comparison. However, both the model and the observations show a positive correlation between Aerosol Optical Depth and Cloud Optical Depth in practically all regions and for all seasons, in agreement with the current understanding of aerosol-cloud interactions. The correlation between Aerosol Optical Depth and Liquid Cloud Droplet Effective Radius is variable both in the model and the observations. However, the model reports the expected negative correlation more often than the MODIS data. Aerosol Optical Depth is overall positively correlated to Cloud Liquid Water Path both in the model and the observations, with a few regional exceptions

TRADEOFFs in climate effects through aircraft routing: forcing due to radiatively active gases

We have estimated impacts of alternative aviation routings on the radiative forcing. Changes in ozone and OH have been estimated in four Chemistry Transport Models (CTMs) participating in the TRADEOFF project. Radiative forcings due to ozone and methane have been calculated accordingly. In addition radiative forcing due to CO2 is estimated based on fuel consumption. Three alternative routing cases are investigated; one scenario assuming additional polar routes and two scenarios assuming aircraft cruising at higher (+2000 ft) and lower (−6000 ft) altitudes. Results from the base case in year 2000 are included as a reference. Taking first a steady state backward looking approach, adding the changes in the forcing from ozone, CO2 and CH4, the ranges of the models used in this work are −0.8 to −1.8 and 0.3 to 0.6 m Wm−2 in the lower (−6000 ft) and higher (+2000 ft) cruise levels, respectively. In relative terms, flying 6000ft lower reduces the forcing by 5–10% compared to the current flight pattern, whereas flying higher, while saving fuel and presumably flying time, increases the forcing by about 2–3%. Taking next a forward looking approach we have estimated the integrated forcing (m Wm−2 yr) over 20 and 100 years time horizons. The relative contributions from each of the three climate gases are somewhat different from the backward looking approach. The differences are moderate adopting 100 year time horizon, whereas under the 20 year horizon CO2 naturally becomes less important relatively. Thus the forcing agents impact climate differently on various time scales. Also, we have found significant differences between the models for ozone and methane. We conclude that we are not yet at a point where we can include non-CO2 effects of aviation in emission trading schemes. Nevertheless, the rerouting cases that have been studied here yield relatively small changes in the radiative forcing due to the radiatively active gases

A modified seasonal cycle during MIS31 super-interglacial favors stronger interannual ENSO and monsoon variability

It has long been recognized that the amplitude of the seasonal cycle can substantially modify climate features in distinct timescales. This study evaluates the impact of the enhanced seasonality characteristic of the Marine Isotope Stage 31 (MIS31) on the El Niño–Southern Oscillation (ENSO). Based upon coupled climate simulations driven by present-day (CTR) and MIS31 boundary conditions, we demonstrate that the CTR simulation shows a significant concentration of power in the 3–7-year band and on the multidecadal timescale between 15 and 30 years. However, the MIS31 simulation shows drastically modified temporal variability of the ENSO, with stronger power spectrum at interannual timescales but the absence of decadal periodicity. Increased meridional gradient of sea surface temperature (SST) and wind stress in the Northern Hemisphere subtropics are revealed to be the primary candidates responsible for changes in the equatorial variability. The oceanic response to the MIS31 ENSO extends to the extratropics, and fits nicely with SST anomalies delivered by paleoreconstructions. The implementation of the MIS31 conditions results in a distinct global monsoon system and its link to the ENSO in respect to current conditions. In particular, the Indian monsoon intensified but no correlation with ENSO is found in the MIS31 climate, diverging from conditions delivered by our current climate in which this monsoon is significantly correlated with the NIÑO34 index. This indicates that monsoonal precipitation for this interglacial is more closely connected to hemispherical features than to the tropical–extratropical climate interaction.</p

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1

Celiac Disease and Anorexia Nervosa: A Nationwide Study

BACKGROUND AND OBJECTIVE: Previous research suggests an association of celiac disease (CD) with anorexia nervosa (AN), but data are mostly limited to case reports. We aimed to determine whether CD is associated with the diagnosis of AN. METHODS: Register-based cohort and case-control study including women with CD (n = 17 959) and sex- and age-matched population-based controls (n = 89 379). CD (villous atrophy) was identified through the histopathology records of Sweden's 28 pathology departments. Inpatient and hospital-based outpatient records were used to identify AN. Hazard ratios for incident AN diagnosis were estimated by using stratified Cox regression with CD diagnosis as a time-dependent exposure variable. In the secondary analyses, we used conditional logistic regression to estimate odds ratios for being diagnosed with AN before CD. RESULTS: Median age of CD diagnosis was 28 years. During 1 174 401 person-years of follow-up, 54 patients with CD were diagnosed with AN (27/100 000 person-years) compared with 180 matched controls (18/100 000 person-years). The hazard ratio for later AN was 1.46 (95% confidence interval [CI], 1.08-1.98) and 1.31 beyond the first year after CD diagnosis (95% CI, 0.95-1.81). A previous AN diagnosis was also associated with CD (odds ratio, 2.18; 95% CI, 1.45-3.29). Estimates remained largely unchanged when adjusted for socioeconomic characteristics and type 1 diabetes. CONCLUSIONS: The bidirectional association between AN diagnosis and CD warrants attention in the initial assessment and follow-up of these conditions because underdiagnosis and misdiagnosis of these disorders likely cause protracted and unnecessary morbidity

Impacts of climate and farming management on maize yield in southern Tanzania

Climate is one of the major factors controlling agricultural productivity in Africa. Changes in meteorological variables such as rising temperatures, changes in precipitation and increase in atmospheric carbon dioxide levels affect crop production. The objective of this study was to evaluate the impacts of climate change and variability, and crop management on yield of maize ( Zea mays L. ) grown in the southern part of Tanzania. Using the Decision Support System for Agrotechnology Transfer Cropping System Model (DSSAT-CSM), a series of sensitivity experiments were conducted to evaluate the response of maize yields to a range of principal changes in rainfall and temperatures. The sensitivities were estimated under two management practices, one with traditional farming practices, and the other with application of external farm inputs. Dry-spells during the growing season caused yield losses of all cultivars of up to 43% for the prolonged dry-spells of 20 days. Increased rainfall intensity, during vegetative and reproductive stages, caused the decrease in yield of 5 and 2%, respectively. A 50-100% decrease in rainfall intensity during the growing season caused a loss of yields between 40-100%. Increased or decreased temperatures from the baseline values reduced or increased days to flowering and to physiological maturity, respectively. In addition, a decrease in temperature from the baseline values to 2 \ub0C had an overall impact of yields loss for all cultivars. However, yields increased with an increase of temperature by up to 2.5 \ub0C (UH6303 and H628) and 4.5 \ub0C (PAN691). Growing seasons with lower total rainfall (&lt;50 mm) and temperature (&lt;1\ub0C) from their climatological values, caused yield loss as much as 71 and 15%, respectively for PAN691 cultivar. Generally, the impacts depended on the management, cultivar, soil characteristics, magnitude, timing and duration of the stress.Le Climat est l\u2019un des facteurs majeurs contr\uf4lant la productivit\ue9 agricole en Afrique. Les changements de donn\ue9es m\ue9t\ue9orologiques tels que l\u2019\ue9l\ue9vation des temp\ue9ratures, variabilit\ue9 dans les pr\ue9cipitations et l\u2019augmentation du CO2 atmosph\ue9rique affecte la production agricole. L\u2019objectif de cette \ue9tude \ue9tait d\u2019\ue9valuer les impacts du changement climatique, de variabilit\ue9, et des pratiques agronomiques sur le rendement du ma\uefs ( Zea mays L. ) cultiv\ue9 dans la partie Sud de la Tanzanie. Une s\ue9rie d\u2019exp\ue9rimentations sur la sensibilit\ue9 a \ue9t\ue9 conduite au moyen du Syst\ue8me d\u2019appui \ue0 la prise de d\ue9cisions pour les transferts agro technologiques (DSSAT) afin d\u2019\ue9valuer la r\ue9ponse en terme de rendement de ma\uefs \ue0 une range de variabilit\ue9s majeures dans les pr\ue9cipitations et les temp\ue9ratures. Les sensibilit\ue9s ont \ue9t\ue9 estim\ue9es sous deux pratiques culturales, l\u2019une avec les pratiques de culture traditionnelle et l\u2019autre avec apport ext\ue9rieur d\u2019intrants agricoles. Des p\ue9riodes durant la saison culturales a caus\ue9 des pertes de rendement au niveau de tous les cultivars et ceci allant jusqu\u2019\ue0 43% pour des p\ue9riodes s\ue8ches prolong\ue9es de 20 jours. Les augmentations de l\u2019intensit\ue9 de pr\ue9cipitations durant les p\ue9riodes v\ue9g\ue9tative et reproductive ont caus\ue9 respectivement une diminution de 5 \ue0 2% du rendement. Une r\ue9duction de l\u2019intensit\ue9 des pr\ue9cipitations de 50-100% durant la saison culturale a caus\ue9 une perte de rendement entre 40-100%. L\u2019augmentation ou la diminution des temp\ue9ratures r\ue9duit ou augmente la date de floraison et de maturit\ue9. De plus, une diminution de temp\ue9rature de 2 \ub0C par rapport \ue0 la valeur moyenne a un impact significatif sur le rendement au niveau de tous les cultivars. N\ue9anmoins, le rendement augmente lorsque la temp\ue9rature augmente de 2.5 \ub0C (UH6303 and H628) et 4.5 \ub0C (PAN691). Les saisons culturales avec des pr\ue9cipitations globales (&lt;50 mm) et (&lt;1\ub0C) par rapport \ue0 leur valeurs climatologiques, ont caus\ue9 respectivement une perte de rendement aussi \ue9lev\ue9e que 71 et 15% pour le cultivar PAN691. De fa\ue7on g\ue9n\ue9rale, les impacts d\ue9pendent des pratiques culturales, du cultivar, des caract\ue9ristiques de sol, de la magnitude, du moment et de la dur\ue9e du stress