Influence of dissolved oxygen on the nitrification kinetics in a circulating bed biofilm reactor

The influence of dissolved oxygen concentration on the nitrification kinetics was studied in the circulating bed reactor (CBR). The study was partly performed at laboratory scale with synthetic water, and partly at pilot scale with secondary effluent as feed water. The nitrifi- cation kinetics of the laboratory CBR as a function of the oxygen concentration can be described according to the half order and zero order rate equations of the diffusion-reaction model applied to porous catalysts. When oxygen was the rate limiting substrate, the nitrification rate was close to a half order function of the oxygen concentration. The average oxygen diffusion coefficient estimated by fitting the diffusion-reaction model to the experimental results was around 66% of the respective value in water. The experimental results showed that either the ammonia or the oxygen concentration could be limiting for the nitri fication kinetics. The latter occurred for an oxygen to ammonia concentration ratio below 1.5-2 gO2/gN-NH4+ for both laboratory and pilot scale reactors. The volumetric oxygen mass transfer coefficient (kLa) determined in the laboratory scale reactor was 0.017 sˉ¹ for a superficial air velocity of 0.02 m sˉ¹, and the one determined in the pilot scale reactor was 0.040 sˉ¹ for a superficial air velocity of 0.031 m sˉ¹. The kLa for the pilot scale reactor did not change significantly after biofilm development, compared to the value measured without biofilm.Fundação para a Ciência e a Tecnologia (FCT) - PRAXIS XXI, project 2/2.1/Bio/37/94.INTERREG

Transcriptome-wide association study reveals candidate causal genes for lung cancer.

We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E-99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E-6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E-5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Transcriptome‐wide association study reveals candidate causal genes for lung cancer

We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of this study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n=1,038) to identify candidate causal genes for lung cancer. We performed transcriptome‐wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma, small cell lung cancer) and smoking subgroups (never‐ and ever‐smokers). We performed replication analysis using lung data from the Genotype‐Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever‐smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (PTWAS=1.09E‐99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (PTWAS=3.72E‐6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3‐adenocarcinoma on 9p13.3 was replicated using GTEx (PTWAS=6.55E‐5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influence lung cancer risk

Control of nitrification efficiency in a new biofilm reactor

The study of the nitrification capacity of a new gas-lift circulating bed reactor (CBR) carried out with laboratory and industrial scale prototypes, showed a high nitrification rate (1.2-2 kgN mˉ³ dˉ¹) without any nitrite accumulation. A good nitrification performance 0.5-0.6 kgN mˉ³dˉ¹ was maintained even when the CODs/N-NH4 ratio was increased up to 1.8-3.4 (laboratory CBR) and 4-10 (industrial prototype). The comparison of the apparent and intrinsic kinetics indicates that the CBR ensures high specific nitrification rates close to the maximum value. These results indicates an effective control of the attached biomass growth and activity in this type of bioreactor. The intinsic kinetics and diffusion limitations were studied by respirometric tests. It was demonstrated that apparent kinetics are zero-order for bulk concentrations of ammonia above 2 mgN lˉ¹ and half-order for lower substrate concentrations. The diffusivity values calculated using the half-order diffusion-reaction model are in the range of 1.09x10ˉ9 to 1.58x10ˉ9 m² sˉ¹ for ammonia nitrogen and of 1.1x10ˉ9 to 1.37x10ˉ9 m² sˉ¹ for nitrite within the range of tempperature studied (16-28ºC). The application of the diffusion-reaction model requires a very precise determination of the biofilm thickness or density. In the case of biofilms developed in heterogeneous granular surfaces, new methods have to be developed for the best estimation of the biofilm density and active cells distribution. In conclusion it can be stated that this new three-phase bioreactor ensures a high nitrification rate and enhanced process stability through an effective biofilm control. The CBR is a good tool for more fundamental studies of biofilm kinetics and activity thanks to the homogeneous distribution of the fixed biomass in the reactor

Influence of dissolved oxygen on nitrification kinetics in a circulating bed reactor

The influence of dissolved oxygen concentration in nitrification kinetics was studied in a new biofilm reactor, the circulating bed reactor (CBR). The study was carried out partly at laboratory scale with synthetic water containing inorganic carbon and nitrogen compounds, and partly at pilot scale for secondary and tertiary nitrification of municipal wastewater. The experimental results showed that either the ammonia or the oxygen concentration could be limiting for the nitrification rate. The transition from the ammonia to oxygen limiting conditions occurred for an oxygen to ammonia concentration ratio of about 1.5-2 gO2/gN-NH4+ for both laboratory- and pilot-scale reactors. The nitrification kinetics of the laboratory-scale reactor was close to a half-order function of the oxygen concentration, when oxygen was the rate limiting substrate

Influence of dissolved oxygen in nitrification kinetics in a circulating bed reactor

The influence of dissolved oxygen concentration in nitrification kinetics was studied in a new biofilm reactor, the circulating bed reactor (CBR). The study was carried out partly at laboratory scale with synthetic water containing inorganic carbon and nitrogen compounds, and partly at pilot scale for secondary and tertiary nitrification of municipal wastewater. The experimental results showed that, either the ammonia or the oxygen concentration could be limiting for the nitrification rate. The transition from ammonia to oxygen limiting conditions occurred for an oxygen to ammonia concentration ratio of about 1,5 - 2 gO2/gN-NH4+ for both laboratory and pilot-scale reactors. The nitrification kinetics of the laboratory scale reactor was close to half order function of the oxygen concentration, when oxygen was the rate limiting substrate