Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress

An early and precise diagnosis of disease is a crucial requirement for fast and targeted therapy in the era of precision medicine. Most diseases possess molecular alterations in their early stages, which precede noticeable morphological changes. One important molecular change that contributes to dysfunction in a wide range of pathologies, including cancer and neurological disorders, is an increase in levels of reactive oxygen species (ROS) and associated oxidative damage. Our understanding of how ROS influence disease biology is currently limited by our inability to perform sensitive and specific assessment of ROS levels with high spatial and temporal resolution in living systems. The goal of the research described in this thesis was to overcome the challenge of assessing ROS during disease development in cancer and neurodegenerative disease through the design, synthesis and validation of two classes of novel bifunctional, ROS-sensitive contrast agents. To shed light on the complex redox biology in cancer, the new method of photoacoustic imaging was exploited. A novel activatable, targeted near infrared cyanine dye is reported that enables specific detection of pathological levels of hydrogen peroxide, a major and abundant ROS in living organisms. This approach uses photoacoustic and fluorescence imaging in cancerous tissue to evaluate the performance of the new probe under in vitro and in vivo conditions. In neurodegeneration, there exists a bidirectional interaction between oxidative stress and protein aggregates. To scrutinise this relationship, both bulk and single-molecule fluorescence imaging methods were used to assess the capability of novel bifunctional fluorescence dyes to localise the presence of the two putative disease-causing species, ROS and protein aggregates, simultaneously under in vitro conditions. The data shown here provides a promising foundation for the systematic design of contrast agents based on small molecule dyes, that possess ideal optical and biological characteristics to study oxidative stress in a broad range of pathological applications with high temporal and spatial resolution.Cancer Research U

Imaging studies of peripheral nerve regeneration induced by porous collagen biomaterials

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references.There is urgent need to develop treatments for inducing regeneration in injured organs. Porous collagen-based scaffolds have been utilized clinically to induce regeneration in skin and peripheral nerves, however still there is no complete explanation about the underlying mechanism. This thesis utilizes advanced microscopy to study the expression of contractile cell phenotypes during wound healing, a phenotype believed to affect significantly the final outcome. The first part develops an efficient pipeline for processing challenging spectral fluorescence microscopy images. Images are segmented into regions of objects by refining the outcome of a pixel-wide model selection classifier by an efficient Markov Random Field model. The methods of this part are utilized by the following parts. The second part extends the image informatics methodology in studying signal transduction networks in cells interacting with 3D matrices. The methodology is applied in a pilot study of TGFP signal transduction by the SMAD pathway in fibroblasts seeded in porous collagen scaffolds. Preliminary analysis suggests that the differential effect of TGFP1 and TGFP3 to cells could be attributed to the "non-canonical" SMADI and SMAD5. The third part is an ex vivo imaging study of peripheral nerve regeneration, which focuses on the formation of a capsule of contractile cells around transected rat sciatic nerves grafted with collagen scaffolds, 1 or 2 weeks post-injury. It follows a recent study that highlights an inverse relationship between the quality of the newly formed nerve tissue and the size of the contractile cell capsule 9 weeks post-injury. Results suggest that "active" biomaterials result in significantly thinner capsule already 1 week post-injury. The fourth part describes a novel method for quantifying the surface chemistry of 3D matrices. The method is an in situ binding assay that utilizes fluorescently labeled recombinant proteins that emulate the receptor of , and is applied to quantify the density of ligands for integrins a113, a2p1 on the surface of porous collagen scaffolds. Results provide estimates for the density of ligands on "active" and "inactive" scaffolds and demonstrate that chemical crosslinking can affect the surface chemistry of biomaterials, therefore can affect the way cells sense and respond to the material.by Dimitrios S. Tzeranis.Ph. D

Etude du démélange en imagerie hyperspectrale infrarouge

Thermal hyperspectral remote sensing provides information about materials from the measured radiance image. It is achieved using temperature and emissivity separation (TES) methods, estimating the emissivity and the temperature of the materials, and using unmixing methods, estimating their abundances. TES methods have been well investigated while too few studies have been working on unmixing in thermal infrared domain : this is the objective of this PhD. Therefore, three strategies have been studied. First, the unmixing is applied on radiance. It achieves good results but depends on the spatial variation of temperature. Applying the unmixing on the emissivities, estimated using the TES methods, gets rid of the spatial variation of temperature but provides a noisy abundance estimation. Eventually, a new method called Thermal Remote sensing Unmixing for Subpixel Temperature (TRUST) is designed to jointly estimate the abundance and the temperature of materials within the pixels. It gives better results than the first strategy and is more robust to spatial variation of temperature.La télédétection en imagerie hyperspectrale infrarouge thermique est l'étude d'images en luminance, acquises depuis un avion ou un satellite dans le domaine spectral de l'infrarouge thermique. Ces images sont liées à l'émissivité et à la température, estimées par les méthodes de découplage température/émissivité (T/E), ainsi qu'à l'abondance, estimée par les méthodes de démélange, des matériaux présents dans la scène. Si les méthodes de découplage T/E ont été largement étudiées, les méthodes de démélange dans ce domaine spectral restent peu explorées : c'est l'objectif de cette thèse. Pour cela, nous avons mis en place trois stratégies de démélange. Dans un premier temps, le démélange est effectué sur les luminances. Cette stratégie donne globalement de bons résultats mais est relativement sensible aux variations spatiales de la température. La deuxième stratégie, démélangeant à partir des estimations d'émissivité des méthodes de découplage T/E, s'affranchit de cette variation spatiale mais donne des résultats plus bruités. Enfin, une méthode de démélange basée sur l'estimation conjointe de la température et des abondances a été élaborée. Cette méthode s'appelle Thermal Remote sensing Unmixing for Subpixel Temperature (TRUST) et donne de meilleurs résultats que la première stratégie tout en étant robuste aux variations spatiales de la température

New Methods for ferrous raw materials characterization in electric steelmaking

425 p.In the siderurgical sector, the steel scrap is the most important raw material in electric steelmaking,contributing between 70% of the total production costs. It is well-known how the degree of which thescrap mix can be optimized, and also the degree of which the melting operation can be controlled andautomated, is limited by the knowledge of the properties of the scrap and other raw-materials in thecharge mix.Therefore, it is of strategic importance having accurate information about the scrap composition of thedifferent steel scrap types. In other words, knowing scrap characteristics is a key point in order to managethe steel-shop resources, optimize the scrap charge mix/composition at the electric arc furnace (EAF),increase the plant productivity, minimize the environmental footprint of steelmaking activities and tohave the lowest total cost of ownership of the plant.As a main objective of present doctoral thesis, the doctorate will provide new tools and methods of scrapcharacterization to increase the current recycling ration, through better knowledge of the quality of thescrap, and thus go in the direction of a 100% recycling ratio. In order to achieve it, two main workinglines were developed in present research. Firstly, it was analysed not only the different existingmethodologies for scrap characterization and EAF process optimization, but also to develop new methodsor combination of existing, Secondly, it was defined a general recommendations guide for implementingthese methods based on the specifics of each plant

The brushstroke and materials of Amadeo de Souza-Cardoso combined in an authentication tool

Nowadays, authentication studies for paintings require a multidisciplinary approach, based on the contribution of visual features analysis but also on characterizations of materials and techniques. Moreover, it is important that the assessment of the authorship of a painting is supported by technical studies of a selected number of original artworks that cover the entire career of an artist. This dissertation is concerned about the work of modernist painter Amadeo de Souza-Cardoso. It is divided in three parts. In the first part, we propose a tool based on image processing that combines information obtained by brushstroke and materials analysis. The resulting tool provides qualitative and quantitative evaluation of the authorship of the paintings; the quantitative element is particularly relevant, as it could be crucial in solving authorship controversies, such as judicial disputes. The brushstroke analysis was performed by combining two algorithms for feature detection, namely Gabor filter and Scale Invariant Feature Transform. Thanks to this combination (and to the use of the Bag-of-Features model), the proposed method shows an accuracy higher than 90% in distinguishing between images of Amadeo’s paintings and images of artworks by other contemporary artists. For the molecular analysis, we implemented a semi-automatic system that uses hyperspectral imaging and elemental analysis. The system provides as output an image that depicts the mapping of the pigments present, together with the areas made using materials not coherent with Amadeo’s palette, if any. This visual output is a simple and effective way of assessing the results of the system. The tool proposed based on the combination of brushstroke and molecular information was tested in twelve paintings obtaining promising results. The second part of the thesis presents a systematic study of four selected paintings made by Amadeo in 1917. Although untitled, three of these paintings are commonly known as BRUT, Entrada and Coty; they are considered as his most successful and genuine works. The materials and techniques of these artworks have never been studied before. The paintings were studied with a multi-analytical approach using micro-Energy Dispersive X-ray Fluorescence spectroscopy, micro-Infrared and Raman Spectroscopy, micro-Spectrofluorimetry and Scanning Electron Microscopy. The characterization of Amadeo’s materials and techniques used on his last paintings, as well as the investigation of some of the conservation problems that affect these paintings, is essential to enrich the knowledge on this artist. Moreover, the study of the materials in the four paintings reveals commonalities between the paintings BRUT and Entrada. This observation is supported also by the analysis of the elements present in a photograph of a collage (conserved at the Art Library of the Calouste Gulbenkian Foundation), the only remaining evidence of a supposed maquete of these paintings. The final part of the thesis describes the application of the image processing tools developed in the first part of the thesis on a set of case studies; this experience demonstrates the potential of the tool to support painting analysis and authentication studies. The brushstroke analysis was used as additional analysis on the evaluation process of four paintings attributed to Amadeo, and the system based on hyperspectral analysis was applied on the painting dated 1917. The case studies therefore serve as a bridge between the first two parts of the dissertation

Desertification in Europe: mitigation strategies, land use planning: Proceedings of the advanced study course held in Alghero, Sardinia, Italy from 31 May to 10 June 1999

The present volume is based on lectures given at the course held in Alghero, Sardinia, Italy, from 31 May to 10 June 1999 on ‘Desertification in Europe: Mitigation Strategies, Land Use Planning’. It also contains presentations, given by the participating students, on their own research activities and interests. With the adoption of the International Convention to Combat Desertification, which represents a follow up of the Rio recommendations, this publication is timely. It highlights the specific situation of the Southern European regions and provides a comprehensive and state-of-the-art review of this complex issue

The WWRP Polar Prediction Project (PPP)

Mission statement: “Promote cooperative international research enabling development of improved weather and environmental prediction services for the polar regions, on time scales from hours to seasonal”. Increased economic, transportation and research activities in polar regions are leading to more demands for sustained and improved availability of predictive weather and climate information to support decision-making. However, partly as a result of a strong emphasis of previous international efforts on lower and middle latitudes, many gaps in weather, sub-seasonal and seasonal forecasting in polar regions hamper reliable decision making in the Arctic, Antarctic and possibly the middle latitudes as well. In order to advance polar prediction capabilities, the WWRP Polar Prediction Project (PPP) has been established as one of three THORPEX (THe Observing System Research and Predictability EXperiment) legacy activities. The aim of PPP, a ten year endeavour (2013-2022), is to promote cooperative international research enabling development of improved weather and environmental prediction services for the polar regions, on hourly to seasonal time scales. In order to achieve its goals, PPP will enhance international and interdisciplinary collaboration through the development of strong linkages with related initiatives; strengthen linkages between academia, research institutions and operational forecasting centres; promote interactions and communication between research and stakeholders; and foster education and outreach. Flagship research activities of PPP include sea ice prediction, polar-lower latitude linkages and the Year of Polar Prediction (YOPP) - an intensive observational, coupled modelling, service-oriented research and educational effort in the period mid-2017 to mid-2019