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Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins., SCOPUS: ar.j, info:eu-repo/semantics/published

Breast cancer is the most common cancer in women. It is a highly heterogeneous disease in terms of histology, therapeutic response and patient outcomes. Early and accurate detection of breast cancer is crucial as the patient prognosis varies greatly depending on the diagnosis of the disease. Nonetheless current breast cancer classification methods fail to precisely sub-classify the disease, resulting in potential inadequate therapeutic management of patients and subsequent poor clinical outcomes. Substantial effort is therefore put in cancer research to develop methods and find new biomarkers efficiently identifying and characterizing breast tumor cells. Moreover it is now well-recognized that the intensive cross-talk between cancer cells and their microenvironment (including non-tumor cells) highly influences cancer progression. Recently, a growing body of clinical evidence reported the prognostic and predictive value associated with the presence of tumor infiltrating lymphocytes (TILs) in the microenvironment of breast tumors. Although the evaluation of TILs would be of great value for the management of patients and the development of new immunotherapies, it is currently not assessed in routine practice. Furthermore Fourier transform infrared (FTIR) imaging has shown its usefulness to study a panel of human cancers. Infrared (IR) spectroscopy coupled to microscopy provides images composed of multiple spectra reflecting the biochemical composition and subtle modifications within biological samples. IR imaging therefore provides useful information to improve breast cancer identification and characterization. The ultimate aim of this thesis is to improve breast cancer diagnosis using FTIR imaging to better identify and characterize cancer cells and the tumor microenvironment of breast cancers. In a first step we carried out a feasibility study aiming at evaluating the impact of the sample fixation process on IR spectra. While spectra were undeniably influenced by thi, Doctorat en Sciences agronomiques et ingénierie biologique, info:eu-repo/semantics/nonPublished

It is now widely accepted that the immune microenvironment of tumors and more precisely Tumor Infiltrating Lymphocytes (TIL) play an important role in cancer development and outcome. TILs are considered to be important prognostic and predictive factors based on a growing body of clinical evidence; however, their presence at the tumor site is not currently assessed routinely. FTIR (Fourier transform infrared) imaging has proven it has value in studying a range of tumors, particularly for characterizing tumor cells. Currently, very little is known about the potential for FTIR imaging to characterize TIL. The present proof of concept study investigates the ability of FTIR imaging to identify the principal lymphocyte subpopulations present in human peripheral blood (PB). A negative cell isolation method was employed to select pure, label-free, helper T cells (CD4(+)), cytotoxic T cells (CD8(+)) and B cells (CD19(+)) from six healthy donors PB by Fluorescence Activated Cell Sorting (FACS). Cells were centrifuged onto Barium Fluoride windows and ten infrared images were recorded for each lymphocyte subpopulation from all six donors. After spectral pre-treatment, statistical analyses were performed. Unsupervised Principal Component Analyses (PCA) revealed that in the absence of donor variability, CD4(+) T cells, CD8(+) T cells and B cells each display distinct IR spectral features. Supervised Partial Least Square Discriminant Analyses (PLS-DA) demonstrated that the differences between the three lymphocyte subpopulations are reflected in their IR spectra, permitting their individual identification even when significant donor variability is present. Our results also show that a distinct spectral signature is associated with antibody binding. To our knowledge this is the first study reporting that FTIR imaging can effectively identify T and B lymphocytes and differentiate helper T cells from cytotoxic T cells. This proof of concept study demonstrates that FTIR imaging is a re, SCOPUS: ar.j, info:eu-repo/semantics/published

57P, info:eu-repo/semantics/published

Current evaluation of histological sections of breast cancer samples remains unsatisfactory. The search for new predictive and prognostic factors is ongoing. Infrared spectroscopy and its potential to probe tissues and cells at the molecular level without requirement for contrast agents could be an attractive tool for clinical and diagnostic analysis of breast cancer. In this study, we report the successful application of FTIR (Fourier transform infrared) imaging for breast tissue component characterization. We show that specific FTIR spectral signatures can be assigned to the major tissue components of breast tumor samples. We demonstrate that a tissue component classifier can be built based on a spectral database of well-annotated tissues and successfully validated on independent breast samples. We also demonstrate that spectral features can reveal subtle differences within a tissue component, capturing for instance lymphocytic and stromal activation. By investigating in parallel lymph nodes, tonsils and wound healing tissues, we prove the uniqueness of the signature of both lymphocytic infiltrate and tumor microenvironment in the breast disease context. Finally, we demonstrate that the biochemical information reflected in the epithelial spectra might be clinically relevant for the grading purpose, suggesting potential to improve breast cancer management in the future., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

La présente étude, menée par une équipe interuniversitaire, répond à un appel d’offre initié par le Gouvernement de la Fédération Wallonie-Bruxelles, Cet appel mentionnait trois étapes principales. La première étape est centrée sur la description et l’analyse des modes et des mécanismes de financement public des institutions d’enseignement supérieur en Fédération Wallonie-Bruxelles. Cette étape concerne tant les institutions universitaires que les hautes écoles et les écoles supérieures des arts. La seconde étape se base sur la littérature scientifique pour décrire les modalités de financement envisageables et les pratiques menées à l’étranger et en Communauté flamande en matière de démocratisation de l’enseignement supérieur. Les travaux menés dans le cadre des deux premières étapes ont permis de soutenir la mise à l’étude d’indicateurs pertinents dans le cadre de la différenciation du financement de l’enseignement supérieur et d’identifier, à travers l’étude des différences de répartition des populations cible au sein des établissements d’enseignement supérieur, la manière dont les moyens peuvent être distribués.

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Imaging preclinical and clinical - Abstract 95P, info:eu-repo/semantics/published

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Over the past few decades, Fourier transform infrared (FTIR) spectroscopy coupled to microscopy has been recognized as an emerging and potentially powerful tool in cancer research and diagnosis. For this purpose, histological analyses performed by pathologists are mostly carried out on biopsied tissue that undergoes the formalin-fixation and paraffin-embedding (FFPE) procedure. This processing method ensures an optimal and permanent preservation of the samples, making FFPE-archived tissue an extremely valuable source for retrospective studies. Nevertheless, as highlighted by previous studies, this fixation procedure significantly changes the principal constituents of cells, resulting in important effects on their infrared (IR) spectrum. Despite the chemical and spectral influence of FFPE processing, some studies demonstrate that FTIR imaging allows precise identification of the different cell types present in biopsied tissue, indicating that the FFPE process preserves spectral differences between distinct cell types. In this study, we investigated whether this is also the case for closely related cell lines. We analyzed spectra from 8 cancerous epithelial cell lines: 4 breast cancer cell lines and 4 melanoma cell lines. For each cell line, we harvested cells at subconfluence and divided them into two sets. We first tested the "original" capability of FTIR imaging to identify these closely related cell lines on cells just dried on BaF2 slides. We then repeated the test after submitting the cells to the FFPE procedure. Our results show that the IR spectra of FFPE processed cancerous cell lines undergo small but significant changes due to the treatment. The spectral modifications were interpreted as a potential decrease in the phospholipid content and protein denaturation, in line with the scientific literature on the topic. Nevertheless, unsupervised analyses showed that spectral proximities and distances between closely related cell lines were mostly, but not entirel, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Cahier réalisé à la suite de la recherche confiée au CERB, en 2011, par l’Institut Bruxellois de Statistique et d’Analyse, à l’initiative du Ministre-président de la Région de Bruxelles-Capitale intitulée : « Définition de la classe moyenne bruxelloise et harmonisation conjointe des mesures visant à maintenir les ménages de la classe moyenne dans la Région de Bruxelles-Capitale ou à y renforcer leur présence ».

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Systemic approaches such as metabolomics are increasingly needed to improve the development of novel drugs. In this paper, we suggest a new strategy based on infrared spectroscopy which probes the global chemical composition of a sample. Seven cell lines from three tumour types were investigated and exposed to four classical anticancer drugs belonging to two classes characterized by a unique mechanism. First, each cell line was considered separately and a hierarchical clustering was built for the seven cell lines. Spectra clustered according to the drug mechanism of action for all the cell lines tested. Second, the similarities among drug mechanism spectral fingerprints were investigated for all the cell lines simultaneously. Difference spectra (the mean spectrum of the corresponding untreated cell line was subtracted) were computed so that the particular contribution of every cell line was eliminated and only the drug-induced differences could be compared. The hierarchical clustering shows a clear tendency to distinguish the two modes of action, revealing a very similar type of response to molecules with a similar mechanism. High throughput systems with 96-well plates are now available and a well established bioassay could be developed in order to provide an objective classifier for potential anticancer drugs., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Fiscal federalism is meant to benefit from both the advantages of centralization and decentralization in public revenues and expenditures, the optimal allocation of competencies between levels of governement depending on the nature of revenues, public goods or services. For historical, political or practical reasons, this optimal allocation is not always attainable. Therefore, fiscal federalism may raise new issues in efficiency or equity, in the form of spill-over effects, harmful fiscal competition or fiscal imbalance. To tend to the optimum, it is necessary to evaluate the extent of inefficiencies or inequities and to design corrective mechanisms in order to minimize them. This thesis adopts such an approach in four different situations. First, we measure empirically and dynamically the presence of fiscal competition between Belgian municipalities. The analysis reveals the existence of fiscal competition, but with a rather slow pace of adjustment of taxe rates over time. This pace depends on the mobility of tax bases and on the similarity of neighboring municipalities with respect to some socio-economic characteristics. Second, we evaluate the effects of the Belgian fiscal equalization mechanism on equity. This analysis shows the existence of a poverty trap at the level of regions and proposes a range of solutions, inspired by equalization mechanisms applied in other federal States. Third, we analyse the case of multiple States emitting multiple pollutants where a trade-off exists between producing goods and minimizing pollution. We propose a form of inter-State transfers such that all States adopt a behaviour leading to the collective optimum. To be sustainable, the collective optimum must be individually rational. We show that this condition is respected with the proposed transfer formula. Fourth, we examine the case of harmful fiscal competition between two countries differing in size, the small country being seen as a fiscal heaven. In order to reach the coll, Le fédéralisme fiscal a pour objectif de bénéficier à la fois des avantages de la centralisation et des avantages de la décentralisation des revenus et dépenses publiques. La répartition optimale des compétences entre différents niveaux de pouvoir est déterminée par la nature des revenus, dépenses et biens et services publics. Pour des raisons historiques, politiques ou pratiques, cette répartition optimale n'est pas toujours accessible. En conséquence, les avantages du fédéralisme fiscal peuvent s'accompagner de problèmes d'efficacité ou d'équité sous la forme d'effets de débordement, de concurrence fiscale dommageable ou de déséquilibre fiscal. Pour tendre vers l'optimum, il convient dès lors d'évaluer l'ampleur des inefficacités et inéquités et de concevoir des mécanismes correctifs pour les atténuer. Cette thèse applique cette démarche à quatre situations particulières. Premièrement, nous mesurons la présence de concurrence fiscale entre les communes belges, de façon empirique et dynamique. L'analyse met en lumière l'existence d'une concurrence fiscale certaine, mais avec une vitesse d'ajustement des taux de taxation relativement faible dans le temps. Cette vitesse d'ajustement dépend de la mobilité des bases imposables et de la similitude des communes voisines en termes de caractéristiques socio-économiques. Deuxièmement, nous évaluons les effets redistributifs et incitatifs du mécanisme belge de péréquation financière. Cette analyse démontre la présence d'un effet de " piège à pauvreté " au niveau des Régions et propose une série de solutions pour y remédier, en s'inspirant de mécanismes étrangers. Troisièmement, nous analysons le cas de multiples Etats émettant de multiples polluants, dans un contexte où un arbitrage doit être effectué entre la production de biens et la minimisation de la pollution. Nous proposons une forme de transferts à appliquer entre Etats de sorte que tous les Etats sont amenés à adopter un comportement menant à l'optimum collectif. Pou, (ECON 3)--UCL, 2006

The purpose of this paper is to test econometrically the existence of fiscal interactions between Belgian municipalities. At the time of writing, the motivation was to provide scientific support to the lively debate on fiscal competition that took place among Belgian politicians in the late nineties. Two types of taxes are considered, for which Belgian municipalities have the decision power as to rates: the 'centimes additionnels' on the personal income tax and the 'pr©♭compte immobilier' which is a property tax. A dynamic adjustment model is specified and estimated using panel data for 598 municipalities over 15 years. The empirical results obtained bear upon two main points: (i) Some interaction definitely has prevailed between the municipalities' fiscal choices made during the observation period, for both taxes; (ii) However, the adjustment reactions to the other municipalities' fiscal choices have occurred over time at the very low yearly pace of 6% and 10%, respectively, of the discrepancy between the actual rates and the preferred rates.

The purpose of this paper is to test econometrically the existence of fiscal interactions between Belgian municipalities. At the time of writing, the motivation was to provide scientific support to the lively debate on fiscal competition that took place among Belgian politicians in the late nineties. Two types of taxes are considered, for which Belgian municipalities have the decision power as to rates: the 'centimes additionnels' on the personal income tax and the 'pr©♭compte immobilier' which is a property tax. A dynamic adjustment model is specified and estimated using panel data for 598 municipalities over 15 years. The empirical results obtained bear upon two main points: (i) Some interaction definitely has prevailed between the municipalities' fiscal choices made during the observation period, for both taxes; (ii) However, the adjustment reactions to the other municipalities' fiscal choices have occurred over time at the very low yearly pace of 6% and 10%, respectively, of the discrepancy between the actual rates and the preferred rates.

We analyze the two-country model of fiscal competition of Kanbur and Keen (1993) where countries differ in size and use a commodity tax to reach their objective of revenue maximization. Due to fiscal externalities, the non-cooperative outcome is inefficient. Besides, the international optimum could be individually irrational for the smaller country compared to the non-cooperative equilibrium. The purpose of this paper is to examine whether the international optimum can be reached and sustained by means of financial transfers between the countries as suggested in another context by Chander and Tulkens (1995, 1997). We show that with transfers of a specific form internationally optimal fiscal cooperation is indeed individually rational for both countries and, in that sense, sustainable. Furthermore, we show that these transfers can be such that the optimal outcome is, under some conditions, a dominant strategy for both countries.

For simple economic models of transfrontier pollution, Chander and Tulkens (1995) and (1997) have offered a formula for transfers to sustain international cooperation on a voluntary basis and which deter coalitionnal free-riding under some reasonable behaviours of countries not in the coalition. Their scheme rests on the assumption that pollution is a scalar. Relaxing this assumption, interesting interactions among pollutants arise that call for a new formula. In this paper we extend Chander and Tulkens formula for this more realistic multidimensional context, and thereby enhance the pratical and theoretical relevance of their seminal analysis.

Nous testons économétriquement l’existence d’interactions fiscales entre les communes belges pour deux types d’impôts : les additionnels à l’impôt sur le revenu des personnes physiques (IPP) et au précompte immobilier (PrI). Un modèle dynamique est spécifié et estimé sur la base de données en panel provenant des 589 communes du pays sur 15 ans. Les résultats révèlent d’une part qu’il existe une interaction certaine entre les communes dans leurs choix des taux des deux impôts. D’autre part, leurs ajustements en réaction aux taux des autres communes se font à un rythme lent : l’écart entre le taux pratiqué et le taux souhaité en raison des interactions ne se réduit annuellement que de 6 % pour le PrI et de 10 % pour l’IPP., Dynamics of Tax Interactions Among Belgium’s Communes, 1984-1997. The authors test econometrically for the existence of tax interactions among Belgium’s local authorities (communes) for two types of taxes, the local component of personal income tax (additionnels à l’impôt sur le revenu des personnes physiques, IPP) and the property tax (précompte immobilier, PRI). Adynamic model is specified and estimated on the basis of panel data from the country’s 589 communes over a 15-year period. The results show a definite interaction among the communes in setting the rates of the two taxes. Further, their adjustments to changes in rates in other communes are slow : the gap between the actual rate and the rate desired because of the interactions is reduced annually by only 6% for the PRI and only 10% for the IPP.