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1.
Accid Anal Prev ; 207: 107763, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39232396

RESUMO

This paper evaluates the performance of two different types of long combination vehicles (A-double and DuoCAT) using naturalistic driving data across four scenarios: lane changes, manoeuvring through roundabouts, turning in intersections, and negotiating tight curves. Four different performance-based standards measures are used to assess the stability and tracking performance of the vehicles: rearward amplification, high-speed transient offtracking, low-speed swept path, and high-speed steady-state offtracking. Also, the steering reversal rate metric is employed to estimate the cognitive workload of the drivers in low-speed scenarios. In the majority of the identified cases of the four scenarios, both combination types have a good performance. The A-double shows slightly better stability in high-speed lane changes, while the DuoCAT has slightly better manoeuvrability at low-speed scenarios like roundabouts and intersections.


Assuntos
Condução de Veículo , Humanos , Automóveis , Acidentes de Trânsito/prevenção & controle , Veículos Automotores
2.
Biochem Pharmacol ; 183: 114351, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33253644

RESUMO

Cancer is one of the leading causes of mortality worldwide, ranked second after heart disease. Despite recent advancements in diagnosis and treatment, there are still numerous problems associated with cancer progression, disease recurrence, and therapeutic resistance that are partially explored. Several studies have recently revealed that Krüppel-like factor 8 (KLF8) regulates transcription of genes linked with diverse biological processes, including proliferation, epithelial to mesenchymal transition (EMT), migration, invasion, and inflammation. KLF8 is expressed ubiquitously in mammalian cells, and its aberrant expression has been manifested with several cancer types. Earlier studies demonstrated the crucial role of KLF8 in DNA repair and resistance to apoptosis in numerous cancer types. Hence, studying the function of KLF8 from the perspective of cancer progression and therapy resistance would help develop a new therapeutic avenue. In this review, we summarize the clinical relevance of KLF8 expression in various malignancies, focusing on recent updates in EMT, cellular signaling, and cancer stem cells. We also address the contribution of KLF8 in development, DNA repair, chemoresistance, and its clinical utility as a predictive biomarker.


Assuntos
Pesquisa Biomédica/tendências , Fatores de Transcrição Kruppel-Like/biossíntese , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Reparo do DNA/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Fatores de Transcrição Kruppel-Like/química , Fatores de Transcrição Kruppel-Like/genética , Neoplasias/genética , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Estrutura Secundária de Proteína
3.
Heliyon ; 6(9): e04820, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32984578

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is a lethal and aggressive gynecological malignancy. Despite recent advances, existing therapies are challenged by a high relapse rate, eventually resulting in disease recurrence and chemoresistance. Emerging evidence indicates that a subpopulation of cells known as cancer stem-like cells (CSLCs) exists with non-tumorigenic cancer cells (non-CSCs) within a bulk tumor and is thought to be responsible for tumor recurrence and drug-resistance. Therefore, identifying the molecular drivers for cancer stem cells (CSCs) is critical for the development of novel therapeutic strategies for the treatment of EOC. METHODS: Two gene datasets were downloaded from the Gene Expression Omnibus (GEO) database based on our search criteria. Differentially expressed genes (DEGs) in both datasets were obtained by the GEO2R web tool. Based on log2 (fold change) >2, the top thirteen up-regulated genes and log2 (fold change) < -1.5 top thirteen down-regulated genes were selected, and the association between their expressions and overall survival was analyzed by OncoLnc web tool. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways analysis, and protein-protein interaction (PPI) networks were performed for all the common DEGs found in both datasets. SK-OV-3 cells were cultured in an adherent culture medium and spheroids were generated in suspension culture with CSCs specific medium. RNA from both cell population was extracted to validate the selected DEGs expression by q-PCR. Growth inhibition assay was performed in SK-OV-3 cells after carboplatin treatment. RESULTS: A total of 200 DEGs, 117 up-regulated and 83 down-regulated genes were commonly identified in both datasets. Analysis of pathways and enrichment tests indicated that the extracellular matrix part, cell proliferation, tissue development, and molecular function regulation were enriched in CSCs. Biological pathways such as interferon-alpha/beta signaling, molecules associated with elastic fibers, and synthesis of bile acids and bile salts were significantly enriched in CSCs. Among the top 13 up-regulated and down-regulated genes, MMP1 and PPFIBP1 expression were associated with overall survival. Higher expression of ADM, CXCR4, LGR5, and PTGS2 in carboplatin treated SK-OV-3 cells indicate a potential role in drug resistance. CONCLUSIONS: The molecular signature and signaling pathways enriched in ovarian CSCs were identified by bioinformatics analysis. This analysis could provide further research ideas to find the new mechanism and novel potential therapeutic targets for ovarian CSCs.

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