71 research outputs found
Gut microbiota and its influence on the Gut-Brain axis in comparison with chemotherapy patients and cancer-free control data in Breast cancer—A computational perspective
No full textComputational molecular insights into ibrutinib as a potent inhibitor of HER2-L755S mutant in breast cancer: gene expression studies, virtual screening, docking, and molecular dynamics analysis
No full textBackgroundThe proposed study integrates several advanced computational techniques to unravel the molecular mechanisms underlying breast cancer progression and drug resistance.MethodsWe investigated HER2-L755S mutation through a multi-step approach, including gene expression analysis, molecular docking, and molecular dynamics simulations.Results and DiscussionBy conducting a network-based analysis of gene expression data from breast cancer samples, key hub genes such as MYC, EGFR, CDKN2A, ERBB2, CDK1, E2F1, TOP2A, MDM2, TGFB1, and FOXM1 were identified, all of which are critical in tumor growth and metastasis. The study mainly focuses on the ERBB2 gene, which encodes the HER2 protein, and its common mutation HER2-L755S, associated with breast cancer and resistance to the drug lapatinib. The HER2-L755S mutation contributes to both tumorigenesis and therapeutic failure. To address this, alternative therapeutic strategies were investigated using combinatorial computational approaches. The stability and flexibility of the HER2-L755S mutation were evaluated through comparative molecular dynamics simulations over 1000 ns using Gromacs in the unbound (Apo) state. Virtual screening with Schrodinger Glide identified ibrutinib as a promising alternative to lapatinib for targeting the HER2-L755S mutant. Detailed docking and molecular dynamics simulations in the bound (Holo) state demonstrated that the HER2-L755S-ibrutinib complex exhibited higher binding affinity and lower binding energy, indicating more stable interactions compared to other complexes. MM-PBSA analysis revealed that the HER2-L755S-ibrutinib complex had more negative binding energy than the HER2-L755S-afatinib, HER2-L755S-lapatinib, and HER2-L755S-neratinib complexes, suggesting that ibrutinib forms the most stable complex with favorable binding interactions.ConclusionThese results provide in-depth atomic-level insights into the binding mechanisms of these inhibitors, highlighting ibrutinib as a potentially effective inhibitor for the clinical treatment of breast cancer
Multi-omics insights into biomarkers of breast cancer associated diabetes: a computational approach
No full textIntroductionBreast cancer (BC) and diabetes are multifaceted diseases with interconnected molecular mechanisms that are not yet fully elucidated. These diseases share common risk factors, biological pathways, and treatment outcomes.MethodsThis study utilizes an integrative computational approach to investigate the interplay between BC and diabetes in African American (AA) and European American (EA) cohorts. It employs transcriptomic and exomic analyses to identify shared pathways and potential therapeutic targets.ResultsThe pooled cohort of differential expression analysis identified 2,815 genes differentially expressed in BC patients with diabetes compared to those without diabetes, including 1824 upregulated and 990 downregulated genes. We reanalyzed transcriptomic data by stratifying BC patients with and without diabetes into two cohorts, identifying 3,245 DEGs in AA and 3,208 DEGs in EA, with 786 genes commonly altered between both groups. Whole-exome sequencing (WES) of 23 BC patients with diabetes revealed 899 variants across 208 unique genes, predominantly missense mutations. Among these, nine key genes were prioritized, with TNFRSF1B (L264P) and PDPN (A105G) identified as the most deleterious variants. Functional enrichment analyses highlighted the significant involvement of pathways related to extracellular matrix organization, angiogenesis, immune regulation, and signaling processes critical to cancer progression and metabolic dysfunction. The TNF pathway emerged as a central link connecting chronic inflammation, insulin resistance, and tumor growth. TNF-mediated mechanisms, including NF-κB activation, oxidative stress, and epithelial-to-mesenchymal transition (EMT), were found to drive both diseases, promoting tumorigenesis, immune evasion, and metabolic dysregulation.ConclusionThis study provides critical molecular insights into the shared mechanisms of BC and diabetes, identifying the TNF pathway as a key therapeutic target to improve outcomes for patients with these interconnected conditions
A Study on the Impact of Corporate Digital Transformation on Environmental, Social, and Governance (ESG) Performance: Mechanism Analysis Based on Resource Allocation Efficiency and Technological Gap
No full textFor a country like China, which places equal emphasis on economic development and environmental governance, the exploration of the potential of digital transformation to enhance corporate Environmental, Social, and Governance (ESG) performance is of paramount importance in achieving the carbon peak target by 2030. Accordingly, this paper employs a two-way fixed-effects model to analyze the impact of digital transformation on corporate ESG performance, based on annual data from Chinese listed companies from 2014 to 2023. On this basis, we established a theoretical framework and implemented a dual fixed-effects model. The findings argue that digital transformation materially enhances corporate ESG performance, primarily by enhancing resource allocation efficiency and narrowing the technological gap. The research results are confirmed to be valid through rigorous robustness testing and endogeneity analysis, with evident effects observed in large-scale, technology-intensive, asset-intensive, central–eastern regions, and high-tech enterprises. This research offers both theoretical foundations and practical insights for companies pursuing ESG performance enhancement through digital transformation while also providing a valuable point of reference for policymakers working toward green transformation and the carbon peaking target
Extracellular Matrix Dynamics in Biology, Bioengineering, and Pathology
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
The Impact of micro-tunnelling on adjacent pile foundations: Numerical modelling of micro-tunnel excavation in PLAXIS
No full textA series of finite element simulations via PLAXIS were carried out to investigate the effects of micro- tunnelling on nearby pile foundations. A numerical model concerning the large diameter tunnel boring machine was first established based on identical properties of the centrifuge experiment executed by Loganathan et al. (2000). Results from numerical simulation were validated by measured data from the centrifuge test. After the validation of the numerical modelling method, the model was adjusted to match the case of micro-tunnel and a new model regarding the micro-tunnelling procedure was generated based on geotechnical conditions of the North/South Metro Line Amsterdam. The Hardening Soil constitutive model was chosen for all soil layers. In the model, the condition of single bored pile with working load was activated in the greenfield condition before the simulation of micro- tunnel. Advancement procedure of the micro-tunnel was simulated, and pile responses were collected under the plane strain condition. Based on the study of the model, two load transfer mechanisms of piles during tunnel-pile interaction process were identified. Impact of tunnel advancement on adjacent piles was also interpreted. A set of parametric studies were implemented to study changes of pile settlement and bearing capacity with increasing volume loss. An influence zone around the micro- tunnel respecting the potential of pile critical movements was established. Although the lack of field data makes the validation of results hard, comparison with analytical prediction and measured data from the centrifuge test shows good agreements for soil movements and pile responses. The results of this research remain to be validated by field data but it can provide insights into the problem of the impact of micro-tunnelling on piles.Geo-Engineerin
Soft magnetic materials for aerospace applications
No full textThis author collated and reviewed existing literature regarding soft magnetic materials, to better
understand the materials suited for aerospace applications and compare the functionality and
characteristics of these given materials. It is quickly clear that Fe-Co alloys are the most
attractive candidates for usage in an electric engine, and review was narrowed to a focus on the
aforementioned material. The consensus that followed was the observation that the Fe-Co-V
ternary alloy would exhibit the most suitable attributes for the given application. This report then
follows the different routes taken to improve the Fe-Co-V alloy and comparatively analyse the
effectiveness of the different alloying elements and processing methods suggested in the relevant
literature.Bachelor of Engineering (Materials Engineering
The implementation of a risk based maintenance policy to a power plant
No full textThe unexpected failures, the down time (outage) associated with such failures, the loss of production of power and, the higher maintenance costs are major problems in operation of thermal power plants. The unexpected failure of an equipments and systems causes economic risk and can be minimized using an effective maintenance strategy. The risk based approach ensures a strategy, which is cost effective. Such an approach uses the information obtained from the study of failure modes and their consequences. -- The purpose of the thesis is to develop and show how to implement a risk based maintenance (RBM) policy to a power plant. This quantitative approach will provide a basis for selection of the best alternative strategy to minimize the risk resulting from breakdowns or failures. -- The proposed methodology is comprised of three modules: risk assessment, risk evaluation, and maintenance planning. This work presents a mechanism for the study of the occurrence of failures and functional failures in equipment and the severity of their consequences, known as risk. Maintenance of equipment is prioritized based on the risk, and the reduction in overall risk of the plant is accomplished by focusing on the maintenance of high-risk items first. To the author's knowledge this quantitative approach has not been developed before. -- The study is conducted for Newfoundland and Labrador Hydro, Holyrood thermal power generation plant. Failure data is collected from the existing power station (Unit 3-150 MW) over a period of twelve years. The data is modeled using Weibull and Exponential distributions to estimate the parameters. A probabilistic risk analysis is performed to quantify the risk at the plant. An acceptable risk criterion is determined and the major systems and subsystems that are found to have a risk higher than acceptable risk are identified. The maintenance interval is calculated by reverse or target probability analysis for reducing the level or risk resulting from the failure of a system. -- To conclude, the risk based maintenance strategy can be employed to prioritize the systems for maintenance planning, and to improve the existing maintenance policies. In addition, this strategy provides cost-effective means for maintenance as well it minimizes the consequences (safety, economic and environment) related to a system failure.Bibliography: leaves 88-91
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