Hypoxia is known to be a major factor in the induction of angiogenesis during tumor development but its role in lymphangiogenesis remains unclear. Blood and lymphatic vasculatures are stimulated by the vascular endothelial family of growth factors – the VEGFs. In this review, we investigate the role of hypoxia in the molecular regulation of synthesis of the lymphangiogenic growth factors VEGF-A, VEGF-C, and VEGF-D. Gene expression can be regulated by hypoxia at either transcriptional or translational levels. In contrast to strong induction of DNA transcription by hypoxia-inducible factors (HIFs), the majority of cellular stresses such as hypoxia lead to inhibition of cap-dependent translation of mRNA and downregulation of protein synthesis. Here, we describe how initiation of translation of VEGF mRNA is induced by hypoxia through an internal ribosome entry site (IRES)-dependent mechanism. Considering the implications of the lymphatic vasculature for metastatic dissemination, it is crucial to understand the molecular regulation of lymphangiogenic growth factors by hypoxia to obtain new insights into cancer therapy.
Break prediction models can help water utility decision-makers to build pipe rehabilitation programs. For many years, using them has been a specialist matter. After more than 15 years of research into the ageing of water pipes, Irstea (formerly Cemagref) has developed the Linear Extension of the Yule Process (LEYP) model based on counting process theory, which relies not only on a pipe's characteristics and environment but also on its age and previous breaks. It was then decided to develop a break prediction tool usable by water utilities: the ‘Casses’ freeware. To make this possible, it was necessary to deal with several constraints. To cope with the diversity of available data for various water utilities, flexible input data formats were designed as well as an importation module which checks the conformity and coherence of data. Tools for data management and an advice module dedicated to model calibration were conceived for non-statistician users. The break prediction results can be used directly to compare break evolution with different rehabilitation strategies and they can also feed multicriteria decision tools. In this case, the ‘Casses’ freeware can work as a ‘slave’ of the integrated application.
Stakeholders involved in the renewal of drinking water pipes almost always use mean ‘lifetime’ values, which are set by an expert based on material type. A common approach to estimating replacement requirements is to assume that all pipes of the same class of material are renewed when they reach an age equal to their average ‘lifetime’. However, experience shows that for the same type of pipes, very different average ‘lifetime’ values are used, leading to inaccurate estimations of renewal requirements. Furthermore, the notion of ‘lifetime’ can lead to confusion between ‘financial requirements’ and ‘practical rehab requirements’. This study highlights the advantage of considering that pipes of the same class of material can have different lifetimes, the values of which can then be represented in a statistical ‘survival curve’. Replacement needs generated through this curve are then smoothed, allowing realistic annual renewal budgets to be calculated. Given the risk of incorrect evaluation that the term ‘lifetime’ may entail, the term should be avoided when discussing pipe renewal. It would appear preferable to use the term ‘service life’, which clearly expresses the choice to be made by decision makers between repair and renewal.
An objective of infrastructure asset management of drinking water network is to minimize risks (service outage, or disruption of vehicular traffic...). However there are several methods to assess their frequency. This paper first discusses the different models used in predicting the structural deterioration, because it is a compulsory preliminary step to calculate risk. Risk models for service outage are then discussed.
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