Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio

A Performance Comparison Between the SystemC-AMS Models of Computation

International audienceThe refinement of a design is optimum when it reaches the best trade-off between simulation speed and simulation accuracy. This trade-off can be obtained only if the most relevant modeling style is selected at each abstraction level. SystemC-AMS is a high versatile language made for analog descriptions at high abstraction levels. This language offers several modeling styles and models of computation. It is not always obvious to choose the most appropriate ones for each abstraction level. The aim of this paper is to help the designer in this task, especially by comparing the simulation speeds between the different SystemC-AMS modeling styles

Explosive formulation by experimental design

In order to increase the safety of ammunitions over their full life cycle (from the conception to the disposal), we are developping new explosive compositions called EIDS (Extremely Insensitive Detonating Substances). This work requires substantial investments because some raw materials, the development of the formulations, the preparation of samples and the achievement of the characterization tests are very expensive. To be able to carry out this task at the lowest cost, we focussed on two tools, the experimental designs and the performance predicting codes. By using together several experimental matrixes, we could define a very small number of samples which were assessed mainly by the mean of our predicting codes. Then, from the mathematical modelling of observed characteristics we could establish a narrow domain of formulations meeting the expected compromise between the explosive performances and the safety characteristics. The experimental validation test we carried out then, has confirmed the forecast results

Logiciel

HORUS est un outil de vérification semi-formelle de systèmes embarqués matériels et logiciels en cours de conception et/ou de fonctionnement, basé sur des propriétés logiques et temporelles exprimées dans des langages standards (PSL, SVA) : d'une part au niveau transfert de registres, comportemental ou structurel, d'autre part au niveau transactionnel (TLM) SystemC

Synthesis, biological activity and quantitative structure-activity relationships of N-substituted-3,4-dihydro-2H-1-benzopyran derivatives

International audienc