GEOTECHNICAL ASSET MANAGEMENT FOR UK RAILWAY EMBANKMENTS

The British railway system is one of the oldest in the world. Most railway embankments are aged around 150 years old and, the percentage of track disruption due to embankment failure is frequently higher than other types of railway infrastructure. Remarkable works have been done to understand embankment deterioration and develop asset modelling. Nevertheless, they do not represent a sufficient way of managing assets in detail. One of the biggest challenges that geotechnical asset managers and railway operator face is the detection of embankment failure at an early stage. Unplanned disruptions compromise safety for passengers, reliability of railway operators and require emergency budget deployment. To guarantee good system performance and meet costumer’s expectations, industries would benefit efficient and pro-active management activities and adoption of Geotechnical Asset Management (GAM) programs. To support the challenge, this research improves the understanding of the interaction between causes of embankment instability and visible signs of embankment instability. In this thesis, the signs of embankment instability are identified thanks to the use of a new metric called Embankment Instability Metric EIM developed by AECOM in 2018. The EIM measures the worsening of track geometry that is likely due to embankment instability. This research work presents the results of the analysis aiming to evaluate whether a link existed between track deterioration, due to embankment instability, and the geotechnical parameters known from literature as playing a role in the embankment disruption. Results of this analysis proved that, based on the specific analysis undertaken, different levels of correlation between causes and symptoms can be assessed and that some parameters show a better link with the EIM than others. The final outcome of this research work was the development of a decision-making tool based on a Multi-Criteria Decision-Making MCDM approach. The novel tool supports the decision-makers in the process of selecting the most appropriate intervention to be undertaken for a specific embankment asset given its current geotechnical conditions

GEOTECHNICAL ASSET MANAGEMENT FOR UK RAILWAY EMBANKMENTS

The British railway system is one of the oldest in the world. Most railway embankments are aged around 150 years old and, the percentage of track disruption due to embankment failure is frequently higher than other types of railway infrastructure. Remarkable works have been done to understand embankment deterioration and develop asset modelling. Nevertheless, they do not represent a sufficient way of managing assets in detail. One of the biggest challenges that geotechnical asset managers and railway operator face is the detection of embankment failure at an early stage. Unplanned disruptions compromise safety for passengers, reliability of railway operators and require emergency budget deployment. To guarantee good system performance and meet costumer’s expectations, industries would benefit efficient and pro-active management activities and adoption of Geotechnical Asset Management (GAM) programs. To support the challenge, this research improves the understanding of the interaction between causes of embankment instability and visible signs of embankment instability. In this thesis, the signs of embankment instability are identified thanks to the use of a new metric called Embankment Instability Metric EIM developed by AECOM in 2018. The EIM measures the worsening of track geometry that is likely due to embankment instability. This research work presents the results of the analysis aiming to evaluate whether a link existed between track deterioration, due to embankment instability, and the geotechnical parameters known from literature as playing a role in the embankment disruption. Results of this analysis proved that, based on the specific analysis undertaken, different levels of correlation between causes and symptoms can be assessed and that some parameters show a better link with the EIM than others. The final outcome of this research work was the development of a decision-making tool based on a Multi-Criteria Decision-Making MCDM approach. The novel tool supports the decision-makers in the process of selecting the most appropriate intervention to be undertaken for a specific embankment asset given its current geotechnical conditions

Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains

Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer's disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3 beta compared to healthy controls suggesting an impairment of metabolism in the AD patient's brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment

Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains

Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptorand an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study wasto identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment

Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains

Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment

Plasma proteome profiling of healthy individuals across the life span in a Sicilian cohort with long-lived individuals

The study of healthy human aging is important for shedding light on the molecular mechanisms behind aging to promote well-being and to possibly predict and/or avoid the development of age-related disorders such as atherosclerosis and diabetes. Herein, we have employed an untargeted mass spectrometry-based approach to study age-related protein changes in a healthy Sicilian plasma cohort including long-lived individuals. This approach confirmed some of the previously known proteins correlated with age including fibulin-1, dystroglycan, and gamma-glutamyl hydrolase. Furthermore, our findings include novel proteins that correlate with age and/or with location and uric acid, which could represent a unique signature for healthy aging

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity : Focus on Sicilian Long-Living Individuals (LLIs)

Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: The first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers

Révolutions arabes : un événement pour les sciences sociales ?

Les soulèvements aussi inattendus que spectaculaires qui se sont produits à partir de la fin de l’année 2010 au sud et à l’est de la Méditerranée ont bouleversé des sociétés entières, bien au-delà du champ politique. Leurs prolongements tout aussi divers, imprévisibles et parfois dramatiques, continuent d’affecter l’ensemble de la région, au-delà des pays directement concernés. Face à l’accélération de l’histoire, la demande sociale s’intensifie pour mieux comprendre. Dans le concert d’expertise mobilisée, l'ensemble des sciences sociales et humaines est mis à contribution. Ce dossier propose d’examiner comment les chercheurs de diverses disciplines (histoire, science politique, sociologie, anthropologie, linguistique…) ont pu répondre à l’épreuve de cette interpellation à partir d’expériences concrètes et comparées fort diverses. Investissement professionnel et personnel à la fois, la recherche en sciences sociales ne peut faire l’économie d’une réflexion sur les conditions de production du savoir, sur la façon d’écrire et de décrire une histoire dans laquelle les observateurs sont eux-mêmes engagés. Les révolutions arabes invitent à une démarche réflexive qui interroge la position du chercheur, la spécificité de son métier et sa capacité à rendre intelligibles les événements majeurs de l’histoire récente. Les auteurs rassemblés dans ce volume s’interrogent donc sur l’évolution des grilles de lecture, l’émergence d’objets originaux ou de pistes de recherche inédites, l’activation de nouveaux débats à l’intérieur des disciplines ou entre elles. Mais ils se penchent aussi sur les conditions pratiques de la recherche à un moment où certains terrains d’enquêtes se ferment et d’autres s’ouvrent, où de nouveaux espaces et objets d’investigation se créent, où l’apparition de sources, l’ouverture d’archives ne peut faire oublier que des pans entiers de sociétés sont menacés de destruction