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•There was no evidence of pregnancy or cumulative exposures associating with any DMP.•Surrounding greenness exposure was inversely associated with four DMRs.•Two of these DMRs were ...annotated to genes previously associated with green space.
Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the association between green space exposure and cord and child blood DNA methylation.
Data from eight European birth cohorts with a total of 2,988 newborns and 1,849 children were used. Two indicators of residential green space exposure were assessed: (i) surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m and 300 m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300 m). For these indicators we assessed two exposure windows: (i) pregnancy, and (ii) the period from pregnancy to child blood DNA methylation assessment, named as cumulative exposure. DNA methylation was measured with the Illumina 450K or EPIC arrays. To identify differentially methylated positions (DMPs) we fitted robust linear regression models between pregnancy green space exposure and cord blood DNA methylation and between cumulative green space exposure and child blood DNA methylation. Two sensitivity analyses were conducted: (i) without adjusting for cellular composition, and (ii) adjusting for air pollution. Cohort results were combined through fixed-effect inverse variance weighted meta-analyses. Differentially methylated regions (DMRs) were identified from meta-analysed results using the Enmix-combp and DMRcate methods.
There was no statistical evidence of pregnancy or cumulative exposures associating with any DMP (False Discovery Rate, FDR, p-value < 0.05). However, surrounding greenness exposure was inversely associated with four DMRs (three in cord blood and one in child blood) annotated to ADAMTS2, KCNQ1DN, SLC6A12 and SDK1 genes. Results did not change substantially in the sensitivity analyses.
Overall, we found little evidence of the association between green space exposure and blood DNA methylation. Although we identified associations between surrounding greenness exposure with four DMRs, these findings require replication.
•Employing absorption system in lieu of precooling stage of C3MR and DMR cycles.•Sensitivity analysis of economic parameters with respect to the price of products.•Applying thermal integration for ...reducing equipment and specific power.
In this paper, the potential of absorption refrigeration cycle to be replaced by C3MR and DMR cycles and to reduce energy consumption in the integrated structure of NGL, LNG and NRU is investigated. Having simulated and optimized, the absorption refrigeration cycle is replaced by one of the compression cycles in the two presented integrated structures, and the new integrated process with AR-MR1 refrigeration cycle (pre-cooling by absorption refrigeration system and liquefaction by mixed refrigerant) is presented. The new structures are investigated through exergy and economic analyses. The integrated structure of AR-MR1 in comparison with C3MR and DMR processes has reduced the power consumption by about 18.4% and 12.6%, respectively. Sensitivity analysis of economic parameters has been carried out with respect to the utility price as well as effect of product price on the market with respect to the presented structures.
DMR is a promising technique to utilize the rising greenhouse gases and produce an alternative energy source. The main hurdle in the commercialization of DMR is the catalyst deactivation. Presently, ...the effect of Tungsten (W) addition on Ni-based catalysts supported on mixed oxide (Al2O3–MgO) support is tested for DMR. The Ni–W bimetallic catalysts are synthesized via co-precipitation followed by the impregnation technique. An equimolar stream of feed (CH4:CO2) is used for DMR at 800 °C. The Ni–W catalyst with 4 wt% of W showed steady performance with elevated conversions of CH4 and CO2, even after 24 h of DMR. The freshly and spent catalysts are characterized by BET, XRD, FESEM, EDX, elemental mapping, TPR-H2, TPD-CO2, and XPS to confirm the elemental composition and the type of carbon formed on the catalysts. The activity of Ni catalyst declined due to formation of amorphous carbon-nanosheets, whereas Ni–W catalyst remained active due to formation of MWCNT.
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•Ni–W/Al2O3–MgO proved out to be superior then Ni/Al2O3–MgO catalyst.•Diminished carbon formation and optimum performance is seen with 4 wt% W loading.•Ni/Al2O3–MgO catalyst deactivates due to formation of amorphous carbon nanosheets.•Ni–W/Al2O3–MgO catalyst remained activated due to formation of MWCNT.•Ni–W bimetallic catalyst delivered above 90% conversion even after 12 h of DMR.
The Agricultural Payments Agency (supervisory and registry authority) of the Slovak Republic has announced an erosion hazard layer to meet the requirements of GAEC5 (Minimising soil erosion. Limit ...soil erosion by putting in place suitable practical measures). If a farmer fails to observe the layer data, they will be fined and might lose access to direct subsidies (also known as direct payments). The layer that has been announced raises a number of questions and concerns amongst beneficiaries of direct subsidies and users of land parcels. For instance, with the Pastuchov land parcel, the uncertainties associated with the application of GAEC5 were raised. A comparison of the water erosion layer commitment for 2023 with the erosion calculated by the Universal Soil Loss Equation (USLE) method based on the Digital Relief Model (DRM) generated from airborne laser scanning has confirmed the uniformity in all classified categories of water erosion over a 65% land parcel area. The situation of the land user has been diminished (i.e. they have to comply with GAEC5 even when there is no reason to) over 11% of the area. The situation of the land user has improved over 24% of the area (i.e. they do not have to comply with the conditions even when there is reason to). This paper describes the problems and outlines the possibilities for the necessary adjustment of compliance with the GAEC5 conditions in Slovakia.
IGF2 is essential in breast differentiation, lactation, tumor growth, and in breast cancer (BC) development and progression. This growth factor also inhibits apoptosis and promotes metastasis and ...chemoresistance, contributing to more aggressive tumors. We previously demonstrated that IGF2 protein levels are higher in BC tissues from African American women than in Caucasian women. We also showed that high IGF2 protein levels are expressed in normal breast tissues of African American women while little or no IGF2 was detected in tissues from Caucasian women. Others showed that decreased DNA methylation of the IGF2 gene leads to different BC clinical features. Thus, we designed this study to determine if differentially methylated regions of the IGF2 gene correspond to IGF2 protein expression in paired (Normal/Tumor) breast tissues and in BC cell lines. Methylation analysis was performed using Sodium Bisulphite Analysis and Methylation Sensitive Restriction Enzyme digestion methods. Our results show that a unique site in the INS-IGF2 region is hypermethylated in normal breast and hypomethylated in breast cancer. We designated this region the DVDMR. Furthermore, the methylation levels in the DVDMR significantly correlated with IGF2 protein levels. This novel DMR consists of 257bp localized in the INS-IGF2 gene. We propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer. Since IGF2 promotes metastasis and chemoresistance, we propose that IGF2 levels contribute to BC aggressiveness. Validation of IGF2 as a biomarker will improve diagnosis and treatment of BC patients.
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•Dual mixed refrigerant LNG process is improved successfully.•Joule-Thomson expansion device is replaced with hydraulic turbine.•Teaching-learning self-study optimization algorithm is ...adopted.•The DMR process gives LNG at the expense of 0.255 kWh/kg-LNG.•Exergy efficiency of the LNG process is increased by 13.37% exergy.
This study unfolds the advanced process configuration modification in the evolution of a dual mixed refrigerant (DMR) process for natural gas liquefaction, followed by its optimization through a unique approach i.e., teaching–learning self-study optimization (TLSO). The DMR process is improved by replacing Joule Thomson valves with the isentropic cryogenic turbines. To ensure the maximum possible thermodynamic performance of the retrofitted DMR process, the TLSO paradigm is used and evaluated. The energy, exergy, coefficient of performance, and figure of merit are determined and compared with conventional bench-scale DMR process to find the performance improvement opportunities in the proposed cryogenic turbine-retrofitted DMR process. The performance analysis revealed that the proposed optimal retrofitted DMR process could produce LNG using 28.57% less energy than the base case. The detailed thermodynamic evaluation revealed that the proposed DMR process has 64.68% exergy efficiency, 2.42 coefficient of performance, and 41.6% figure of merit, which are 13.37%, 19%, and 11.9%, higher than the conventional DMR process, respectively. This study would significantly help process engineers overcome the challenges of relating energy efficiency of the LNG plants for both onshore and offshore applications.
Abstract
Epigenome-wide association studies (EWASs) have become increasingly popular for studying DNA methylation (DNAm) variations in complex diseases. The Illumina methylation arrays provide an ...economical, high-throughput and comprehensive platform for measuring methylation status in EWASs. A number of software tools have been developed for identifying disease-associated differentially methylated regions (DMRs) in the epigenome. However, in practice, we found these tools typically had multiple parameter settings that needed to be specified and the performance of the software tools under different parameters was often unclear. To help users better understand and choose optimal parameter settings when using DNAm analysis tools, we conducted a comprehensive evaluation of 4 popular DMR analysis tools under 60 different parameter settings. In addition to evaluating power, precision, area under precision-recall curve, Matthews correlation coefficient, F1 score and type I error rate, we also compared several additional characteristics of the analysis results, including the size of the DMRs, overlap between the methods and execution time. The results showed that none of the software tools performed best under their default parameter settings, and power varied widely when parameters were changed. Overall, the precision of these software tools were good. In contrast, all methods lacked power when effect size was consistent but small. Across all simulation scenarios, comb-p consistently had the best sensitivity as well as good control of false-positive rate.
Natural gas liquefaction plants have adopted mixed refrigerant (MR) cascade configurations to improve energy efficiency and process irreversibility. The MR cascade processes consist of multi-stream ...heat exchangers (MSHEs) and compression systems for each MR cycle. In this study, MR cascade cycles were modeled and optimized to compare and analyze the MR cascade processes. Compared to a single MR process with one MSHE, considered as the base case herein (995.0 kJ/kg LNG), a triple MR process showed 19.0% energy reduction (805.6 kJ/kg LNG). Because triple MR processes require at least three MSHEs, a single MR process with three MSHEs was also compared, which obtained only 3.9% energy reduction (956.1 kJ/kg LNG) compared to the base case. Additional process configurations, such as MR cascades with two MSHEs per MR cycle and dual MR processes, were also considered in this study. An exergy analysis of the optimized energy results revealed that the decreased exergy loss in the heat exchangers was the main factor for the energy reductions. For example, a specific work reduction of 129.5 kJ/kg LNG among 189.4 kJ/kg LNG for the triple MR process was attributed to the exergy improvement at the MSHEs and coolers.
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•Mixed refrigerant cycles to liquefy natural gas optimized.•Single, dual, and triple mixed refrigerant cycles compared.•Single cycle with 1, 2, and 3 multistream heat exchangers investigated.•Energy requirement of 995 kJ/kg LNG in base case.•Energy savings of 19% (806 kJ/kg LNG) for triple cycles from base case.
MT-45 is a synthetic opioid that was developed in the 1970s as an analgesic compound. However, in recent years MT-45 has been associated with multiple deaths in Europe and has been included in the ...class of novel psychoactive substances known as novel synthetic opioids (NSOs). Little is known about the pharmaco-toxicological effects of MT-45. Therefore, we used a dynamic mass redistribution (DMR) assay to investigate the pharmacodynamic profile of this NSO in vitro compared with morphine. We then used in vivo studies to investigate the effect of the acute systemic administration of MT-45 (0.01–15 mg/kg i.p.) on motor and sensorimotor (visual, acoustic and tactile) responses, mechanical and thermal analgesia, muscle strength and body temperature in CD-1 male mice. Higher doses of MT-45 (6–30 mg/kg i.p.) were used to investigate cardiorespiratory changes (heart rate, respiratory rate, SpO2 saturation and pulse distention). All effects of MT-45 were compared with those of morphine. In vitro DMR assay results demonstrated that at human recombinant opioid receptors MT-45 behaves as a potent selective mu agonist with a slightly higher efficacy than morphine. In vivo results showed that MT-45 progressively induces tail elevation at the lowest dose tested (0.01 mg/kg), increased mechanical and thermal antinociception (starting from 1 to 6 mg/kg), decreased visual sensorimotor responses (starting from 3 to 6 mg/kg) and reduced tactile responses, modulated motor performance and induced muscle rigidity at higher doses (15 mg/kg). In addition, at higher doses (15–30 mg/kg) MT-45 impaired the cardiorespiratory functions. All effects were prevented by the administration of the opioid receptor antagonist naloxone. These findings reveal the risks associated with the ingestion of opioids and the importance of studying these drugs and undertaking more clinical studies of the current molecules to better understand possible therapeutic interventions in the case of toxicity.
•MT-45 behaves as a potent selective mu agonist in DMR assay.•MT-45 and morphine dose-dependently increased mechanical and thermal analgesia.•MT-45 progressively impaired the motor-sensorimotor responses in mice as morphine.•MT-45 altered cardiorespiratory responses in mice at higher doses.
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