Carnobacterium divergens is frequently isolated from natural environments and is a predominant species found in refrigerated foods, particularly meat, seafood, and dairy. While there is substantial... Show moreCarnobacterium divergens is frequently isolated from natural environments and is a predominant species found in refrigerated foods, particularly meat, seafood, and dairy. While there is substantial interest in using C. divergens as biopreservatives and/or probiotics, some strains are known to be fish pathogens, and the uncontrolled growth of C. divergens has been associated with food spoilage. Bacteriophages offer a selective approach to identify and control the growth of bacteria; however, to date, few phages targeting C. divergens have been reported. In this study, we characterize bacteriophage cd2, which we recently isolated from minced beef. A detailed host range study reveals that phage cd2 infects certain phylogenetic groups of C. divergens. This phage has a latent period of 60 min and a burst size of ~28 PFU/infected cell. The phage was found to be acid and heat sensitive, with a complete loss of phage activity when stored at pH 2 or heated to 60°C. Electron microscopy shows that phage cd2 is a siphophage, and while it shares the B3 morphotype with a unique cluster of Listeria and Enterococcus phages, a comparison of genomes reveals that phage cd2 comprises a new genus of phage, which we have termed as Carnodivirus. Show less
Decarbonizing the building stock is critical for realizing the climate-neutral target for the Netherlands. This thesis uses multi-source data, mainly including GIS data of building footprints and... Show moreDecarbonizing the building stock is critical for realizing the climate-neutral target for the Netherlands. This thesis uses multi-source data, mainly including GIS data of building footprints and the archetypes representative of Dutch residential buildings, to develop a series of bottom-up building stock models to track future material stock and flows, energy demand, electricity generation, and GHG emissions. Results demonstrate the great potential for decarbonizing the Dutch residential building sector, while decarbonization strategies should be effectively and extensively implemented. Saving space heating energy consumption is the most direct way to reduce annual GHG emissions. Considering that most existing residential buildings will still be in use in 2050, renovating them with high energy performance standards is required. Despite the great potential of renovation, it alone is not enough to realize the climate-neutral target in the residential building stock because the upstream fossil fuel-based energy systems still emit large amounts of GHG. Replacing fossil fuels with renewable energy sources is a critical path, mainly involving onsite natural gas combustion for space heating and offsite natural gas and coal combustion for electricity and heat (in heat networks) generation. Urban mining cannot contribute to as much GHG emission reduction as energy transition strategies, though, should still be implemented as it can reduce the primary material consumption and CDW landfill. In addition to the technical aspects considered in this thesis, it is also necessary to develop feasible policies in terms of socioeconomic aspects to guarantee the effective and quick deployment of these technical strategies. Show less
The building sector plays a key role in energy transition and carbon reduction while capturing the dynamic characteristics (e.g. materials, energy performance, and environmental impact) of building... Show moreThe building sector plays a key role in energy transition and carbon reduction while capturing the dynamic characteristics (e.g. materials, energy performance, and environmental impact) of building stock is a great challenge during the gradual process. This study presents a bottom-up dynamic building stock model that links dynamic material flow analysis with building energy modeling. The environmental impact of material and energy requirements is assessed by considering future electricity mix. The model is applied to evaluate the pathways to the climate-neutral energy supply of residential building stock in the Netherlands by 2050. Results show that space heating demand decreases by about 2/3 by 2050, while the energy for hot water increases to 92% of space heating demand. 80% of public grid electricity for appliances and lighting can be potentially substituted if rooftop photovoltaic (PV) systems are installed on 50% of renovated buildings and all the new buildings. Greenhouse gas (GHG) emissions of operational energy are reduced by approximately 60-90%, depending on the electricity mix. Annual GHG emissions from material production are not as important as those related to operational energy. Insulation materials account for a large proportion of the carbon footprint of material production. The model has a high spatial and temporal resolution and can be linked with local energy source availability (e.g. buildings or neighborhoods) to provide more accurate support for policymaking. Show less
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could... Show morePolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs. Show less
Li, H.Y.; Engel, C.; Hoya, M. de la; Peterlongo, P.; Yannoukakos, D.; Livraghi, L.; ... ; CIMBA Consortium 2022
Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense... Show morePurpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants.Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2. We analyzed 324 pedigrees with PTC variants in BRCA1 and 214 pedigrees with PTC variants in BRCA2. Cancer risks were estimated using modified segregation analysis.Results: Estimated breast cancer risks were markedly lower for women aged >50 years carrying BRCA1 missense PVs than for the women carrying BRCA1 PTC variants (hazard ratio [HR] = 3.9 [2.4-6.2] for PVs vs 12.8 [5.7-28.7] for PTC variants; P =.01), particularly for missense PVs in the BRCA1 C-terminal domain (HR = 2.8 [1.4-5.6]; P =.005). In case of BRCA2, for women aged >50 years, the HR was 3.9 (2.0-7.2) for those heterozygous for missense PVs compared with 7.0 (3.3-14.7) for those harboring PTC variants. BRCA1 p.[Cys64Arg] and BRCA2 p.[Trp2626Cys] were associated with particularly low risks of breast cancer compared with other PVs.Conclusion: These results have important implications for the counseling of at-risk women who harbor missense PVs in the BRCA1/2 genes. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved. Show less
Yang, X.; Hu, M.; Zhang, C.; Steubing, B.R.P. 2022
The construction sector is the biggest driver of resource consumption and waste generation in Europe. The European Union (EU) is making efforts to move from its traditional linear resource and... Show moreThe construction sector is the biggest driver of resource consumption and waste generation in Europe. The European Union (EU) is making efforts to move from its traditional linear resource and waste management system in the construction sector to a level of high circularity. Based on the theory of circular economy, a new paradigm called waste hierarchy was introduced in the EU Waste Framework Directive. This work uses the framework of the waste hierarchy to analyze the practice of construction and demolition waste (CDW) management in Europe. We explore the evolution of the waste hierarchy in Europe and how it compares with the circular economy. Then, based on the framework, we analyze the performance of CDW management in each EU member state. Innovative treatment methods of CDW, focusing on waste concrete, is investigated. This brings insight into optimizing and upgrading the CDW management in light of advanced technologies and steering the pathway for transitioning the EU towards a circular society. Show less
Lin, J.; Yang, X.; Kosters, W.A.; Xu, T.; Jia, Y.; Wang, S.; ... ; Ye, K. 2022
Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate... Show moreBackground: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management. Show less
Zhang, C.; Hu, M.; Laclau, B.; Garnesson, T.; Yang, X.; Tukker, A. 2021
Buildings have become a major concern because of their high energy use and carbon emissions. Thus, a material-efficient prefabricated concrete element (PCE) system was developed to incorporate... Show moreBuildings have become a major concern because of their high energy use and carbon emissions. Thus, a material-efficient prefabricated concrete element (PCE) system was developed to incorporate construction and demolition waste as feedstock for residential building energy renovation by over-cladding the walls of old buildings. By conducting life cycle assessment and life cycle costing using the payback approach, this study aims to explore the life cycle performance of energy conservation, carbon mitigation, and cost reduction of the PCE system in three European member states: Spain, the Netherlands, and Sweden. The results show that the energy payback periods for Spain, the Netherlands, and Sweden were 20.45 years, 17.60 years, 19.95 years, respectively, and the carbon payback periods were 23.33 years, 16.78 years, and 8.58 years, respectively. However, the financial payback periods were less likely to be achieved within the building lifetime, revealing that only the Swedish case achieved a payback period within 100 years (83.59 years). Thus, circularity solutions were considered to shorten the PCE payback periods. Using secondary materials in PCE fabrication only slightly reduced the payback period. However, reusing the PCE considerably reduced the energy and carbon payback periods to less than 6 years and 11 years, respectively in all three cases. Regarding cost, reusing the PCE shortened the Swedish payback period to 29.30 years, while the Dutch and Spanish cases achieved investment payback at 42.97 years and 85.68 years, respectively. The results can be extrapolated to support the design of sustainable building elements for energy renovation in Europe. Show less
Zhang, C.; Hu, M.; Sprecher, B.; Yang, X.; Zhong, X.; Li, C.; Tukker, A. 2021
DOM* can not only be regarded as a "controller" of other reactive intermediates, but also effectively promote the photodegradation of bezafibrate, which is classified as a persistent organic... Show moreDOM* can not only be regarded as a "controller" of other reactive intermediates, but also effectively promote the photodegradation of bezafibrate, which is classified as a persistent organic contaminant. This study gives deep insights into effects of UV/chlorine on the photophysical and photochemical properties of DOM, and is helpful for understanding the dynamic roles of DOM in the photodegradation of micropollutants. Show less
Segmentation of medical images, particularly late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) used for visualizing diseased atrial structures, is a crucial first step for ablation... Show moreSegmentation of medical images, particularly late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) used for visualizing diseased atrial structures, is a crucial first step for ablation treatment of atrial fibrillation. However, direct segmentation of LGE-MRIs is challenging due to the varying intensities caused by contrast agents. Since most clinical studies have relied on manual, labor-intensive approaches, automatic methods are of high interest, particularly optimized machine learning approaches. To address this, we organized the 2018 Left Atrium Segmentation Challenge using 154 3D LGE-MRIs, currently the world's largest atrial LGE-MRI dataset, and associated labels of the left atrium segmented by three medical experts, ultimately attracting the participation of 27 international teams. In this paper, extensive analysis of the submitted algorithms using technical and biological metrics was performed by undergoing subgroup analysis and conducting hyper-parameter analysis, offering an overall picture of the major design choices of convolutional neural networks (CNNs) and practical considerations for achieving state-of-the-art left atrium segmentation. Results show that the top method achieved a Dice score of 93.2% and a mean surface to surface distance of 0.7 mm, significantly outperforming prior state-of-the-art. Particularly, our analysis demonstrated that double sequentially used CNNs, in which a first CNN is used for automatic region-of-interest localization and a subsequent CNN is used for refined regional segmentation, achieved superior results than traditional methods and machine learning approaches containing single CNNs. This large-scale benchmarking study makes a significant step towards much-improved segmentation methods for atrial LGE-MRIs, and will serve as an important benchmark for evaluating and comparing the future works in the field. Furthermore, the findings from this study can potentially be extended to other imaging datasets and modalities, having an impact on the wider medical imaging community. (C) 2020 Elsevier B.V. All rights reserved. Show less
Adenosine receptors, G protein-coupled receptors (GPCRs) that are activated by the endogenous ligand adenosine, have been considered potential therapeutic targets in several disorders. To date... Show moreAdenosine receptors, G protein-coupled receptors (GPCRs) that are activated by the endogenous ligand adenosine, have been considered potential therapeutic targets in several disorders. To date however, only very few adenosine receptor modulators have made it to the market. Increased understanding of these receptors is required to improve the success rate of adenosine receptor drug discovery. To improve our understanding of receptor structure and function, over the past decades, a diverse array of molecular probes has been developed and applied. These probes, including radioactive or fluorescent moieties, have proven invaluable in GPCR research in general. Specifically for adenosine receptors, the development and application of covalent or reversible probes, whether radiolabeled or fluorescent, have been instrumental in the discovery of new chemical entities, the characterization and interrogation of adenosine receptor subtypes, and the study of adenosine receptor behavior in physiological and pathophysiological conditions. This review summarizes these applications, and also serves as an invitation to walk another mile to further improve probe characteristics and develop additional tags that allow the investigation of adenosine receptors and other GPCRs in even finer detail. Show less
