Mechanisms Of Genesis Research Articles

Bisphenol F-induced precocious genesis of aggressive neurobehavioral response is associated with heightened monoamine oxidase activity and neurodegeneration in zebrafish brain

The production and use of plastics and plastics products has increased dramatically in recent decades. Moreover, their unprotected disposal into ambient life sustaining environment poses a significant health risk. Bisphenol F (BPF) an alternative to bisphenol A (BPA) has been extensively employed for making of plastics. Recent reports have documented the neurotoxic potential of BPF through induction of altered neurochemical profile, microglia-astrocyte-mediated neuroinflammation, oxidative stress, transformed neurobehavioral response, cognitive dysfunction, etc. In the present study, our approach was to understand the underlying mechanism of BPF-persuaded genesis of aggressive neurobehavioral response in zebrafish. The basic findings advocated a temporal transformation in native explorative behaviour and progressive induction of aggressive behavioural response in zebrafish following exposure to BPF. Our neurobehavioral findings supported the argument of oxidative stress-mediated neuromorphological transformation in the periventricular grey zone (PGZ) of the zebrafish brain. In line with earlier reports, our findings also showed that heightened monoamine oxidase (MAO) activity and downregulation in tyrosine hydroxylase expression in the zebrafish brain is associated with the precocious genesis of aggressive neurobehavioral response in zebrafish brain. Our findings also shed light on BPF-instigated apoptotic neuronal death as revealed by augmented chromatin condensation and cleaved caspase-3 expression. Further observation showed that the downregulation of NeuN (a marker of post-mitotic mature neuron) expression provided substantial neurotoxicity, leading to neurodegeneration in the PGZ region of the zebrafish brain. These basic findings grossly advocate that BPF acts as a potent neurotoxicant in transmuting native neurobehavioral response through the induction of oxidative stress, heightened MAO activity and neuromorphological transformation in the zebrafish brain.

Catalog of focal mechanism solutions for the Sichuan and Yunnan region from 2012 to 2022 using the community velocity model of Southwest China

The focal mechanism solution is one of the important focal parameters for exploring fault activity and studying regional stress distribution and it has a wide range of applications. The geological structure of the Sichuan-Yunnan region in China is complex, with frequent earthquakes and abundant historical observation data, making it one of the popular areas of concern for scholars. This study utilizes the high-precision community velocity model v2.0 of southwest China, obtained through joint inversion based on multiple data methods. The Cut-And-Paste (CAP) method was employed to fit and invert the observed waveforms of 1475 events with ML ​≥ ​3.5 in the Sichuan-Yunnan region from January 2012 to December 2022, thereby constructing a catalog of double-couple focal mechanisms. By comparing the focal mechanism inversion results of small earthquakes with those from multiple one-dimensional velocity models and conducting comparative statistical analysis on events below magnitude 4, it has been demonstrated that the model used in this study provides a better fit than one-dimensional models. This contributes to establishing the lower magnitude limit for producing deeper focal mechanism solutions. This study compares the results of larger magnitude earthquakes in the catalog with those published by the Global Centroid-Moment Tensor (GCMT) project and smaller magnitude earthquakes with the catalog released by the Institute of Earthquake Forecasting, China Earthquake Administration. These comparisons serve to validate the accuracy of the catalog results. Leveraging the high-resolution velocity model, this catalog has re-examined the historical earthquake focal mechanism catalog of the Sichuan-Yunnan region. The inversion has yielded reliable results for smaller magnitudes and a greater number of events, providing additional data and support for understanding the regional stress field, active faults, the mechanisms of large earthquake genesis, and earthquake prediction efforts. Consequently, this enhances the depth of scientific research in the Sichuan-Yunnan region.

Study on the changes and transformation characteristics of intermediate liquid products in hydrogen sulfide production from lignite degraded by sulfate-reducing bacteria.

The changes and transformation laws of intermediate liquid-phase products during the anaerobic degradation of lignite by sulfate-reducing bacteria in the formation of hydrogen sulfide play an important role in supplementing and improving the existing theories on the genesis of hydrogen sulfide gas in coal mines. In this paper, H2S gas and key intermediate liquid-phase products produced during the anaerobic degradation of lignite by sulfate-reducing bacteria were detected and analyzed by gas chromatography and gas chromatography-mass spectrometry. The results showed that the process of hydrogen sulfide production from lignite degradation by sulfate-reducing bacteria can be roughly divided into four stages: slow production phase, rapid growth phase, steady production phase, and slight decline phase. In this reaction system, the SO42- concentration showed a decreasing trend, the pH value showed an increasing trend, and the ORP value decreased and then slightly increased with time. Ten volatile component types were detected during the experiment: straight-chain alkanes, branched-chain alkanes, alcohols, aldehydes, ketones, olefins, amines, lipids, acids and phenols. The key components in the intermediate liquid phase products were straight chain alkanes, straight chain alkanes, acids, alcohols, phenols and amines. PAHs, alkanes, and phenols are closely related to H2S production, while amides stimulate nitrogen production. The process is divided into three stages: hydrolysis stage, H2S gas production stage, and decay stage. Liquid-phase intermediates play an important role in the formation process of coal mine BSR hydrogen sulfide and the mechanism of coal mine H2S genesis.

Abstract Mo065: An Anti-arrhythmic Action and Novel Molecular Mechanisms of Alda-1 in Holiday Heart Syndrome

Introduction: Holiday Heart Syndrome (HHS) is caused by excessive binge alcohol intake. Atrial fibrillation (AF) is the most common arrhythmia in HHS patients. With a worldwide rising trend in heavy alcohol consumption despite significant prevention efforts, effective drugs against alcohol-evoked AF are in urgent need. Methods: We assessed the effect of Alda-1, a cardiac protective agent, on mitigating binge alcohol-evoked AF and alcohol-activated stress kinase JNK2 in 50mM alcohol-exposed (24hr) H9c2 differentiated myocytes and in a well-characterized HHS mouse model (2g/kg ethanol i.p., 4 injections, every other day). Alda-1’s effect on alcohol-evoked RyR2 channel-mediated Ca 2+ waves/sparks & tachycardia/fibrillation (AT/AF) incidence were measured in intact mouse atria. RyR2 channel open probability was assessed in human RyR2 single-channel recordings. Results: We found that Alda-1 significantly reduced atrial arrhythmia inducibility in HHS mouse atria, as evidenced by a decreased incidence of alcohol-evoked AT/AF (0 vs. 0.21 incidences/pacing attempts/animal; n=6, 8). Alda-1 is an agonist of aldehyde dehydrogenase 2 (ALDH2; a key enzyme in alcohol detoxification), which inhibits cellular apoptosis. We found that ALDH2 was increased by 42%±6 in HHS mice compared to controls, and which remained elevated upon Alda-1 treatment (n=6,7,7; p<0.05). HHS hearts showed unchanged apoptotic signaling pathways, suggesting alternative mechanisms in AF genesis. Our lab recently revealed a critical role of activated cardiac stress kinase JNK2 in AF risk. Intriguingly, Alda-1 suppressed alcohol-activated JNK2 by 70%±13 (immunoprecipitated JNK2-specific activity; n=9,9, p<0.001) (but not JNK1, the other cardiac JNK isoform) in cells, while JNK2 inhibition alleviated alcohol-evoked RyR2 channel dysfunction in human RyR2 channels as well as Ca 2+ -triggered atrial arrhythmic activities and AT/AF (0 out of 8; p<0.05) in intact mouse hearts. Conclusion: Alda-1 effectively mitigates binge alcohol-evoked atrial arrhythmogenesis by suppressing JNK2 activity independently of an ALDH2-mediated anti-apoptosis effect. Our findings highlight the potential of Alda-1 as a therapeutic agent for the increasing incidence of alcohol-evoked AF.

A mechanism for coastal fog genesis at evening transition

AbstractTransitional changes in the atmospheric boundary layer (ABL) are known to facilitate the onset of terrestrial fog, which is defined as a condition with near‐surface visibility <1 km due to airborne water droplets. In particular, the evening transition from a daytime convective ABL to a night‐time stable ABL provides favorable conditions for fog. This article describes a local fog event observed during the evening transition at a Canadian islet in the north Atlantic known as Sable Island during the “Fog and Turbulence Interactions in the Marine Atmosphere (Fatima)” field campaign. The comprehensive set of data collected using a myriad of instruments covering a wide range of scales allowed identification of a novel mechanism underlying this fog event. Therein an ocean–land discontinuity created a flow regime consisting of several stacked boundary layers, interplay of which produced a thin low‐level cloud that then diffused downward to the surface, causing visibility reduction. This mechanism offers useful insights on the role of boundary layers, stratification, and turbulence in fog genesis over oceanic islands.

Causal relationship between inflammatory proteins and glioblastoma: a two-sample bi‑directional mendelian randomization study.

Background: Observational studies have indicated a potential correlation between glioblastoma and circulating inflammatory proteins. Further investigation is required to establish a causal relationship between these two factors. Methods: We performed a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on glioblastoma. The GWAS summary data for glioblastoma included 243 cases and 287,137 controls. The inverse variance weighted (IVW) method was used as the primary analytical method to assess causality. Four additional MR methods [simple mode, MR-Egger, weighted median, and weighted mode] were used to supplement the IVW results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Reverse MR analysis was also performed. glioblastoma transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed to validate the findings obtained through MR, while pathway and functional enrichment analyses were conducted to predict the potential underlying mechanisms. Results: Our findings from employing the inverse variance weighted method in our forward MR analysis provide robust evidence supporting a potential association between glioblastoma and elevated levels of Cystatin D, as well as decreased levels of fibroblast growth factor 21 (FGF21) in the circulation. Moreover, our reverse MR analysis revealed that glioblastoma may contribute to increased concentrations of C-X-C motif chemokine 9 (CXCL9) and Interleukin-33 (IL-33) in the bloodstream. Transcriptomic analysis showed that FGF21 expression was inversely associated with the risk of developing glioblastoma, whereas an increased risk was linked to elevated levels of CXCL9 and IL-33. Pathway and functional enrichment analyses suggested that Cystatin D might exert its effects on glioblastoma through intracellular protein transport, whereas FGF21 might affect glioblastoma via glucose response mechanisms. Conclusion: These results indicate that FGF21 is a significant factor in glioblastoma susceptibility. Glioblastoma also affects the expression of inflammatory proteins such as C-X-C motif chemokine 9 and Interleukin-33, providing new insights into the mechanisms of glioblastoma genesis and clinical research.

A functional 3D full-thickness model for comprehending the interaction between airway epithelium and connective tissue in cystic fibrosis

Patients with cystic fibrosis (CF) experience severe lung disease, including persistent infections, inflammation, and irreversible fibrotic remodeling of the airways. Although therapy with transmembrane conductance regulator (CFTR) protein modulators reached optimal results in terms of CFTR rescue, lung transplant remains the best line of care for patients in an advanced stage of CF. Indeed, chronic inflammation and tissue remodeling still represent stumbling blocks during treatment, and underlying mechanisms are still unclear. Nowadays, animal models are not able to fully replicate clinical features of the human disease and the conventional in vitro models lack a stromal compartment undergoing fibrotic remodeling. To address this gap, we show the development of a 3D full-thickness model of CF with a human bronchial epithelium differentiated on a connective airway tissue. We demonstrated that the epithelial cells not only underwent mucociliary differentiation but also migrated in the connective tissue and formed gland-like structures. The presence of the connective tissue stimulated the pro-inflammatory behaviour of the epithelium, which activated the fibroblasts embedded into their own extracellular matrix (ECM). By varying the composition of the model with CF epithelial cells and a CF or healthy connective tissue, it was possible to replicate different moments of CF disease, as demonstrated by the differences in the transcriptome of the CF epithelium in the different conditions. The possibility to faithfully represent the crosstalk between epithelial and connective in CF through the full thickness model, along with inflammation and stromal activation, makes the model suitable to better understand mechanisms of disease genesis, progression, and response to therapy.

Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma.

Hydrochemical characteristics and genetic mechanism of porous sandstone geothermal water in northern Jinan, Shandong, China.

Porous sandstone geothermal water is an important geothermal resource, which is a low-carbon and clean resource, but lacks systematic research on a regional scale. The northern part of Jinan City is rich in geothermal resources, specifically porous sandstone thermal reservoirs. However, there is still incomplete research on the mechanism of geothermal genesis and the hydrochemical characteristics of geothermal water in porous sandstone. This study aims to address this gap by collecting 21 groundwater samples from northern Jinan and comparing their conventional ion and isotope characteristics to investigate the hydrochemical characteristics during the formation of geothermal water and uncover the genesis mechanism of porous sandstone geothermal water. The results indicate that the geothermal water is classified as Na-Cl type and Na-SO4-Cl type. The hydrochemical characteristics of geothermal water are primarily influenced by water-rock interaction and groundwater mixing. The water source primarily comes from the atmospheric precipitation in the Taiyi mountains, with an altitude of 910.75-1542.2m.s.a.l.. The estimated temperature of the thermal reservoir ranges from 51 to 78 °C, and the depth of geothermal water circulation is estimated to be between 1316 and 2216m. Based on the characteristics of the geothermal field, including the "cap rock, water source, heat source, reservoir, and channel," a conceptual model of the porous sandstone geothermal water flow system is proposed. This model offers novel insights into the genesis mechanism of geothermal water under similar geological conditions.

Study on the Formation Mechanism of The Strike-slip Fracture Zone in the Gulongnan Area of the Songliao Basin

The Gulongnan strike-slip fracture zone consists of multi-phase active faults, which play a crucial role in the transportation of hydrocarbons generated from depressions to the slope area, and is of high research value. However, the main controlling factors of reservoir formation in the context of the development of strike- slip fracture are still unclear, and the success rate of drilling wells is low, so there is an urgent need to carry out the research work on the formation process of strike-slip fracture zones and the mechanism of genesis. Based on the principle of similarity, this paper investigates the tectonic style and evolution law of extension and extrusion under the control of strike-slip faults in the study area through tectonophysical simulation experiments, in order to reproduce the dynamical evolution process, and achieves a high degree of agreement with the actual geological situation. The experimental results show that at the end of the depositional stage of the Qingshankou Formation in the study area, a weak east-west extrusion formed the dorsal tectonics, and then a strong east-west stretching formed the strike-slip fault zone, and the tectonic pattern of the study area was controlled by the two main faults formed in the early stage of the extrusion.

Mechanism of genesis of long 7 authigenic Illite colluvium in the Xiasiwan area and its effect on physical properties

Mechanism of genesis of long 7 authigenic Illite colluvium in the Xiasiwan area and its effect on physical properties

Telomerase and hallmarks of cancer: An intricate interplay governing cancer cell evolution

Transformed cells must acquire specific characteristics to be malignant. Weinberg and Hanahan characterize these characteristics as cancer hallmarks. Though these features are independently driven, substantial signaling crosstalk in transformed cells efficiently promotes these feature acquisitions. Telomerase is an enzyme complex that maintains telomere length. However, its main component, Telomere reverse transcriptase (TERT), has been found to interact with various signaling molecules like cMYC, NF-kB, BRG1 and cooperate in transcription and metabolic reprogramming, acting as a strong proponent of malignant features such as cell death resistance, sustained proliferation, angiogenesis activation, and metastasis, among others. It allows cells to avoid replicative senescence and achieve endless replicative potential. This review summarizes both the canonical and noncanonical functions of TERT and discusses how they promote cancer hallmarks. Understanding the role of Telomerase in promoting cancer hallmarks provides vital insight into the underlying mechanism of cancer genesis and progression and telomerase intervention as a possible therapeutic target for cancer treatment. More investigation into the precise molecular mechanisms of telomerase-mediated impacts on cancer hallmarks will contribute to developing more focused and customized cancer treatment methods.

An information model concept for a thermomechanical process in grinding

The purpose of the work is to present the concept of an information modelof the thermomechanical process in grinding of products from materials prone to defect formation due to the fact that their surface layer has hereditary defects of structural or technological origin.The products' strength and functionality depend on the inhomogeneity and defectiveness of the structure of the materials from which they are made. Such materials have many different micro defects formed in the surface layer of parts during the technological operations of their production. Reducing number of defectsin the finishing operations of these materials and increasing the operational properties of products made of these materials is an essential national and economical task, the solution of which leads to a significant saving of material resources, labour intensity and cost of manufacturing parts. The currently available information on the thermal processes of diamond abrasive processing is obtained on the assumption of the homogeneity of the materials being polished and needs to consider the presence of defects in the technological heredity of the products. The phenomenological approach in studying the causes of cracking of materials prone to this type of defect does not allow to revealthe mechanism of genesis and development of grinding cracks. The choice of the method of investigation of the mechanism of crack formation is based on micro-research related to inhomogeneities, which are formed in the surface layer of parts during previous technological operations. A mathematical model has been developed that describes thermomechanical processes in the surface layer during grinding of parts made of materials and alloys, taking into account their inhomogeneities, which affect the intensity of the formation of grinding cracks. Calculated dependences between the crack resistance criterion and the main controlling technological parameters were obtained. According to the known characteristics of hereditary defects, the limit values of thermomechanical criteria, which ensure the necessary quality of the surfaces of the processed products, are determined. Based on the obtained criterion ratios, an algorithm for selecting technological possibilities for defect-free processing of products from materials prone to loss of quality of the surface layer of parts was built. A decision support system has been developed to increase the efficiency of the finishing process management.

Combined Transcriptome and Proteome Analysis of the Protein Composition of the Brochosomes of the Leafhopper Nephotettix cincticeps.

Brochosomes, unique coatings on the integuments of Cicadellidae, are synthesized in specialized glandular sections of Malpighian tubules. However, limited knowledge exists regarding the protein composition of brochosomes. In this study, we conducted transcriptomic and proteomic profiling to characterize the brochosome protein composition in the rice green leafhopper Nephotettix cincticeps. Brochosomes were collected from the forewings of leafhoppers using ultrasonic treatment, allowing for more effective brochosome collection and shaking treatment, resulting in purer brochosomes. Transcriptome sequencing analysis identified 106 genes specifically expressed in the Malpighian tubules; combined with proteomic data, we identified 22 candidate brochosome proteins. These proteins were classified into 12 brochosomins (BSM) and 10 brochosome-associated proteins (BSAP) based on previous research. Conserved motif analysis and functional predictions unveiled unique motifs in each BSM, while BSAP appeared to play a crucial role in BSM folding and pathogen resistance. Comparative analysis of other Hemiptera species demonstrated that all BSM and some BSAP are specific to the Cicadellidae family. Our findings could contribute to understanding the mechanism of brochosome synthesis, its function, and evolutionary genesis.

Estimation of reservoir temperature and analysis of the mechanism of origin of a granite dome-controlled geothermal system in the western Wugongshan area, southeast China

The escalating issues of worldwide energy scarcity and environmental contamination have brought geothermal resources into the spotlight as a sustainable and eco-friendly energy alternative. The circum-Wugongshan geothermal belt has abundant geothermal resources at a medium-low temperature, offering significant potential for development and utilization. In this study, samples of geothermal groundwater, cold spring water, and surface water were collected from the western Wugongshan area. Hydrochemical and thermodynamic methods were used to estimate the reservoir temperature and analyze its mechanism of origin. The results of these analyses indicated that, in terms of hydrochemical characteristics, most geothermal groundwater samples were Na-HCO3 and Na-SO4, while cold spring and surface water samples were Na-HCO3 and Ca-HCO3, respectively. Quartz and multicomponent geothermometers provided the most reliable estimations of reservoir temperatures, ranging from 64.8°C to 93.4°C. The circulation depth of geothermal water was found to range from 1729.3 m to 2,292.5 m. A mixing model indicated that shallow cold water was blended at a rate of 62.1%–78.8%. The δD and δ18O values validated the conclusion that the geothermal water originates from atmospheric precipitation, with recharge elevations varying between 503.1 m and 1,375.6 m. Based on the above analysis, a conceptual model is proposed to illustrate the mechanism of geothermal groundwater genesis.

The investigation of a likely scenario for natural tornado genesis and evolution from an initial instability profile

A likely mechanism for the little-understood tornado genesis is proposed and its numerical implementation is presented. The Burgers-Rott vortex with its axis in the vertical direction is introduced as an instability mechanism, and the flow field then evolves under the influence of the atmospheric pressure, temperature and density variations with altitude. Buoyancy effects are implemented using the Boussinesq model. Results are presented and discussed for a set of conditions including mesh type and size, different turbulence models, and a few different boundary conditions. Post-processed results of the transient simulations including animations contain a wealth of information to help analyze tornado behavior. Velocity contours, pressure contours, vorticity contours, streamlines, and iso-surfaces show the evolution of a complex flow field possessing many characteristics of a tornado. At longer times from the start, the flow field becomes more asymmetric with the vortex core becoming more twisted, and the eye of the vortex drifting away from the axis of the computational domain. The single initial vortex then transitions into multiple vortices of varying size and orientation. These high Reynolds number (ReΓ ∼109) simulation results show flow fields that resemble highly unsteady, turbulent flows with large regions of flow separation, and large eddy size range.

Multifocal and multicentric glioblastoma: Imaging signature, molecular characterization, patterns of spread, and treatment.

Multifocal and multicentric glioblastoma (GBM) or collectively, m-GBM, is an imaging diagnosis present in up to 34% of patients with GBM. Compared to unifocal disease, patients with m-GBM have worse outcomes owing to the enhanced aggressive nature of the disease and its resistance to currently available treatments. To improve the understanding of its complex behavior, many associations have been established between the radiologic findings of m-GBM and its gross histology, genetic composition, and patterns of spread. Additionally, the holistic knowledge of the exact mechanisms of m-GBM genesis and progression is crucial for identifying potential targets permitting enhanced diagnosis and treatment. In this review, we aim to provide a comprehensive summary of the cumulative knowledge of the unique molecular biology and behavior of m-GBM and the association of these features with neuroimaging.

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Monitoring of methane in groundwater from the Vale of Pickering, UK: Temporal variability and source discrimination

Groundwater abstracted from aquifers in the Vale of Pickering, North Yorkshire, UK and monitored over the period 2015–2022, shows evidence of variable but commonly high concentrations of dissolved CH4. Sampled groundwater from the Jurassic organic-rich Kimmeridge Clay Formation (boreholes up to 180 m depth) has concentrations up to 57 mg/L, and concentrations up to 59 mg/L are found in groundwater from underlying confined Corallian Group limestone (borehole depths 50–227 m). The high concentrations are mainly from boreholes in the central parts of the vale. Small concentrations of ethane (C2H6, up to 800 μg/L) have been found in the Kimmeridge Clay and confined Corallian groundwaters, and of propane (C3H8, up to 160 μg/L) in deeper boreholes (110–180 m) from these formations. The concentrations are typically higher in groundwater from the deeper boreholes and vary with hydrostatic pressure, reflecting the pressure control on CH4 solubility. The occurrences contrast with groundwater from shallow Quaternary superficial deposits which have low CH4 concentrations (up to 0.39 mg/L), and with the unconfined and semi-confined sections of the Corallian aquifer (up to 0.7 mg/L) around the margins of the vale. Groundwater from the Quaternary, Kimmeridge Clay formations and to a small extent the confined Corallian aquifer, supports local private-water supplies, that from the peripheral unconfined sections of Corallian also supports public supply for towns and villages across the region.Dissolved methane/ethane (C1/C2) ratios and stable-isotopic compositions (δ13C-CH4, δ2H-CH4 and δ13C-CO2) suggest that the high-CH4 groundwater from both the Kimmeridge Clay and confined Corallian formations derives overwhelmingly from biogenic reactions, the methanogenesis pathway by CO2 reduction. A small minority of groundwater samples shows a more enriched δ13C-CH4 composition (−50 to −44 ‰) which has been interpreted as due to anaerobic or aerobic methylotrophic oxidation in situ or post-sampling oxidation, rather than derivation by a thermogenic route.Few of the existing groundwater sites are proximal to abandoned or disused conventional hydrocarbon wells that exist in the region, and little evidence has been found for an influence on groundwater dissolved gases from these sites. The Vale of Pickering has also been under recent consideration for development of an unconventional hydrocarbon (shale-gas) resource. In this context, the monitoring of dissolved gases has been an important step in establishing the high-CH4 baseline of groundwaters from Jurassic deposits in the region and in apportioning their sources and mechanisms of genesis.

Phase-field modelling of electromigration-induced intergranular slit propagation in metal interconnects

We use a phase-field method to elucidate grain-boundary grooving as a mechanism of genesis and subsequent propagation of intergranular slit in metal interconnects under concurrent surface and grain boundary diffusion. Surface diffusion is assumed to be the rate limiting transport mechanism. Accelerated grain-boundary grooving induced by electromigration is shown to ensue a narrow channel-like slit which advances at a steady state along the grain-boundary preserving its shape near the tip region. The slit characteristics namely the width and velocity dependence on electric field derived are shown to be in excellent agreement with the sharp interface calculations which treat the tip region of the slit independently. Furthermore, the simulations reveal that for the same magnitude of electric field, a slit conceived from a smaller grain exhibits a slower kinetics and delay damage dissemination. The apparent discrepancy from the sharp interface description is resolved on the basis of curvature gradient and electromigration-induced surface flux which heal the root during groove to slit transition and is predominant in smaller grains. Finally, drawing analogy from the nucleation and growth models of electromigration voids, failure due to intergranular slit is divided into serial process of initial grooving followed by slit propagation stage. The lifetime analysis suggests the grooving stage to be the rate determining step in the failure process, yielding an exponent of 1.33 in Black’s law.