Current photochemical models developed to simulate the atmospheric degradation of aromatic hydrocarbons tend to underestimate OH radical concentrations. In order to analyse OH budgets, we performed ...experiments with benzene, toluene, p-xylene and 1,3,5-trimethylbenzene in the atmosphere simulation chamber SAPHIR. Experiments were conducted under low-NO conditions (typically 0.1–0.2 ppb) and high-NO conditions (typically 7–8 ppb), and starting concentrations of 6–250 ppb of aromatics, dependent on OH rate constants. For the OH budget analysis a steady-state approach was applied in which OH production and destruction rates (POH and DOH) have to be equal. The POH were determined from measurements of HO2, NO, HONO, and O3 concentrations, considering OH formation by photolysis and recycling from HO2. The DOH were calculated from measurements of the OH concentrations and total OH reactivities. The OH budgets were determined from DOH/POH ratios. The accuracy and reproducibility of the approach were assessed in several experiments using CO as a reference compound where an average ratio DOH/POH = 1.13 ± 0.19 was obtained. In experiments with aromatics, these ratios ranged within 1.1–1.6 under low-NO conditions and 0.9–1.2 under high-NO conditions. The results indicate that OH budgets during photo-oxidation experiments with aromatics are balanced within experimental accuracies. Inclusion of a further, recently proposed OH production via HO2 + RO2 reactions led to improvements under low-NO conditions but the differences were small and insignificant within the experimental errors.
Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of ...vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC.
Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan® genotyping assays or polymerase chain reaction. Chi-square test, Kaplan–Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms.
VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001).
VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.
The aim of this study was to investigate oxidation of SOA formed from ozonolysis of α-pinene and limonene by hydroxyl radicals. This paper focuses on changes of particle volatility, using a ...Volatility Tandem DMA (VTDMA) set-up, in order to explain and elucidate the mechanism behind atmospheric ageing of the organic aerosol. The experiments were conducted at the AIDA chamber facility of Karlsruhe Institute of Technology (KIT) in Karlsruhe and at the SAPHIR chamber of Forchungzentrum Jülich (FZJ) in Jülich. A fresh SOA was produced from ozonolysis of α-pinene or limonene and then aged by enhanced OH exposure. As an OH radical source in the AIDA-chamber the ozonolysis of tetramethylethylene (TME) was used while in the SAPHIR-chamber the OH was produced by natural light photochemistry. A general feature is that SOA produced from ozonolysis of α-pinene and limonene initially was rather volatile and becomes less volatile with time in the ozonolysis part of the experiment. Inducing OH chemistry or adding a new portion of precursors made the SOA more volatile due to addition of new semi-volatile material to the aged aerosol. The effect of OH chemistry was less pronounced in high concentration and low temperature experiments when lower relative amounts of semi-volatile material were available in the gas phase. Conclusions drawn from the changes in volatility were confirmed by comparison with the measured and modelled chemical composition of the aerosol phase. Three quantified products from the α-pinene oxidation; pinonic acid, pinic acid and methylbutanetricarboxylic acid (MBTCA) were used to probe the processes influencing aerosol volatility. A major conclusion from the work is that the OH induced ageing can be attributed to gas phase oxidation of products produced in the primary SOA formation process and that there was no indication on significant bulk or surface reactions. The presented results, thus, strongly emphasise the importance of gas phase oxidation of semi- or intermediate-volatile organic compounds (SVOC and IVOC) for atmospheric aerosol ageing.
Recent studies have shown that measured OH under NOx‐limited, high‐isoprene conditions are many times higher than modeled OH. In this study, a detailed analysis of the HOx radical budgets under ...low‐NOx, rural conditions was performed employing a box model based on the Master Chemical Mechanism (MCMv3.2). The model results were compared with HOx radical measurements performed during the international HOxComp campaign carried out in Jülich, Germany, during summer 2005. Two different air masses influenced the measurement site denoted as high‐NOx (NO, 1–3 ppbv) and low‐NOx (NO, < 1 ppbv) periods. Both modeled OH and HO2 diurnal profiles lay within the measurement range of all HOx measurement techniques, with correlation slopes between measured and modeled OH and HO2 around unity. Recently discovered interference in HO2 measurements caused by RO2 cross sensitivity was found to cause a 30% increase in measured HO2 during daytime on average. After correction of the measured HO2 data, the model HO2 is still in good agreement with the observations at high NOx but overpredicts HO2 by a factor of 1.3 to 1.8 at low NOx. In addition, for two different set of measurements, a missing OH source of 3.6 ± 1.6 and 4.9 ± 2.2 ppb h−1 was estimated from the experimental OH budget during the low‐NOx period using the corrected HO2 data. The measured diurnal profile of the HO2/OH ratio, calculated using the corrected HO2, is well reproduced by the MCM at high NOx but is significantly overestimated at low NOx. Thus, the cycling between OH and HO2 is better described by the model at high NOx than at low NOx. Therefore, similar comprehensive field measurements accompanied by model studies are urgently needed to investigate HOx recycling under low‐NOx conditions.
Key Points
Hox budget and radical recycling at low NOx conditions
Comparison of measured to modeled HOx budgets
The influence of HO2 inteferences due to RO2 cross sensitivity on HOx Budgets
Metastasis is the main cause of cancer-related death and therapies specifically targeting metastasis are highly needed. Cortical cell polarity (CCP) is a prometastatic property of circulating tumor ...cells affecting their ability to exit blood vessels and form new metastases that constitute a promising point of attack to prevent metastasis. However, conventional fluorescence microscopy on single cells and manual quantification of CCP are time-consuming and unsuitable for screening regulators. In this study, we developed an imaging flow cytometry-based method for high-throughput screening of factors affecting CCP in melanoma cells. The artificial intelligence-supported analysis method we developed is highly reproducible, accurate, and orders of magnitude faster than manual quantification. Additionally, this method is flexible and can be adapted to include additional cellular parameters. In a small-scale pilot experiment using polarity-, cytoskeleton-, or membrane-affecting drugs, we demonstrate that our workflow provides a straightforward and efficient approach for screening factors affecting CCP in cells in suspension and provide insights into the specific function of these drugs in this cellular system. The method and workflow presented here will facilitate large-scale studies to reveal novel cell-intrinsic as well as systemic factors controlling CCP during metastasis.
Summary Colorectal cancer is the third most common malignancy worldwide. Anti–epidermal growth factor receptor (EGFR)–targeted therapy shows clinical evidence in this malignancy and improves outcome. ...The tumor suppressor gene phosphatase and tensin homologue ( PTEN ) is considered a potential predictor of nonresponse to anti-EGFR agents. The purpose of this study was to assess whether associations between PTEN alterations ( PTEN gene deletion or PTEN gene disruption) and clinical outcome could be caused by a prognostic (and not predictive) effect of PTEN inactivation. Therefore, we analyzed 404 colorectal cancers not previously treated with anti-EGFR drugs in a tissue microarray format. PTEN deletion and PTEN gene rearrangements were analyzed by fluorescence in situ hybridization. Heterogeneity analysis of all available large tissue sections was performed in 6 cases with genomic PTEN alteration. Twenty-seven (8.8%) of 307 analyzable colorectal cancer spots showed genomic PTEN alterations including 24 hemizygous and 1 homozygous deletion as well as 2 PTEN gene disruptions. Genomic PTEN alterations were associated with reduced patient survival in rectal cancer in univariate and multivariate analyses ( P = .012; hazard ratio, 2.675; 95% confidence interval, 1.242-5.759) but not in colon cancer. Large-section evaluation revealed a homogeneous distribution pattern in all 4 analyzed cases with PTEN deletion and in both cases with a PTEN gene disruption. In conclusion, genomic PTEN gene alterations caused by deletion or gene disruption characterize a fraction of rectal cancers with particularly poor outcome.
Within the Emission and Chemical Transformation of Biogenic Volatile Organic Compounds (ECHO) project the photochemistry of biogenic organic compounds in a forest was investigated. In this context, ...two spectroradiometers were used to determine solar spectral actinic flux and photolysis frequencies within and above a deciduous forest at Jülich, Germany. Locations in the forest and in a small clearing were examined 2 m above ground. Under overcast conditions, photolysis frequencies were within 1–3% and 6–8% of above canopy values at forest and clearing locations, respectively. In a spectral range below 500 nm the canopy was found to act as a gray filter that diminished spectral actinic flux independent of daytime and wavelength. Under clear‐sky conditions, diurnal variations within the forest also followed that of diffuse sky radiation above the forest except for sharp peaks from direct sunlight that was incident sporadically at the selected locations. The results under all conditions were in accord with the foliage being opaque toward UV and gaps in the canopy being responsible for the remaining actinic flux. Sky photographs showed that the distribution and size of gaps in the foliage were extremely heterogeneous with patterns changing rapidly upon changing location. Regarding daytime chemical reactions of biogenic compounds within the forest, it was estimated that degradation by OH was reduced by a factor similar to the photolysis frequencies, while potential degradation by NO3 was increased by a factor of ∼3 compared with above forest conditions. As a result, it was estimated that minor fractions of 0.8% of isoprene and 3.4% of monoterpenes were degraded by reactions with OH, NO3, and O3 prior to transport into the layer above the forest.
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